WorldWideScience

Sample records for association study ewas

  1. An Environment-Wide Association Study (EWAS on type 2 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Chirag J Patel

    Full Text Available BACKGROUND: Type 2 Diabetes (T2D and other chronic diseases are caused by a complex combination of many genetic and environmental factors. Few methods are available to comprehensively associate specific physical environmental factors with disease. We conducted a pilot Environmental-Wide Association Study (EWAS, in which epidemiological data are comprehensively and systematically interpreted in a manner analogous to a Genome Wide Association Study (GWAS. METHODS AND FINDINGS: We performed multiple cross-sectional analyses associating 266 unique environmental factors with clinical status for T2D defined by fasting blood sugar (FBG concentration > or =126 mg/dL. We utilized available Centers for Disease Control (CDC National Health and Nutrition Examination Survey (NHANES cohorts from years 1999 to 2006. Within cohort sample numbers ranged from 503 to 3,318. Logistic regression models were adjusted for age, sex, body mass index (BMI, ethnicity, and an estimate of socioeconomic status (SES. As in GWAS, multiple comparisons were controlled and significant findings were validated with other cohorts. We discovered significant associations for the pesticide-derivative heptachlor epoxide (adjusted OR in three combined cohorts of 1.7 for a 1 SD change in exposure amount; p<0.001, and the vitamin gamma-tocopherol (adjusted OR 1.5; p<0.001. Higher concentrations of polychlorinated biphenyls (PCBs such as PCB170 (adjusted OR 2.2; p<0.001 were also found. Protective factors associated with T2D included beta-carotenes (adjusted OR 0.6; p<0.001. CONCLUSIONS AND SIGNIFICANCE: Despite difficulty in ascertaining causality, the potential for novel factors of large effect associated with T2D justify the use of EWAS to create hypotheses regarding the broad contribution of the environment to disease. Even in this study based on prior collected epidemiological measures, environmental factors can be found with effect sizes comparable to the best loci yet found by GWAS.

  2. Karakterisering van het Etimologiewoordeboek van Afrikaans (EWA

    Directory of Open Access Journals (Sweden)

    Fons Moerdijk

    2011-10-01

    Full Text Available

    Samenvatting: Zesendertig jaar na Afrikaanse etimologieë van Boshoff en Nienaber verscheener in 2003 een nieuw etymologisch woordenboek van het Afrikaans: het Etimologiewoordeboek vanAfrikaans (EWA. Tussen die twee woordenboeken bestaat een wezenlijk verschil. Het werk vanBoshoff en Nienaber is vrijwel alleen toegankelijk voor specialisten en niet specifiek bedoeld vooreen breed publiek. EWA is juist allereerst bestemd voor de leek die zich interesseert voor de oorsprongen de geschiedenis van de eigen taal. Daarnaast biedt het ook de etymoloog en historischtaalkundige een hoop gegevens en inspiratie voor nader onderzoek. Als etymologisch woordenboekbezit EWA een aantal bijzondere, eigen kenmerken. De selectie van de woorden is bepaalddoor het beoogde gebruikerspubliek. Als gevolg daarvan bevat EWA verscheidene typen woordendie in traditionele etymologische woordenboeken doorgaans veronachtzaamd worden, zoals afleidingen,samenstellingen, neologismen en gemeenzame spreektaalwoorden. De artikelstructuurwordt gekenmerkt door een hoge graad van uniformiteit en consistentie. Het accent ligt op dezogenaamde etymologia proxima, de etymologie waarbij men één stap teruggaat en de meestdirecte herkomst van het woord biedt. Voorts is speciale aandacht besteed aan polysemie: nietalleen de herkomst van de dominante betekenis van een woord wordt gegeven, maar ook die vanzijn eventuele andere betekenis(sen. Benoemingsmotieven komen ook veelvuldig aan bod. In eeneventuele tweede druk zouden opvallende verschillen in vorm of betekenis altijd verklaard of inieder geval besproken moeten worden. Dat blijft nu nogal eens achterwege. Ook zou voorafgaandaan zo'n volgende editie meer onderzoek naar woordhistorisch materiaal uit primaire bronnenvoor met name de 17de–19de eeuw verricht moeten worden. Het zou mooi zijn als deze eersteuitgave van EWA de aanleiding tot een dergelijk onderzoek zou vormen.

    Sleutelwoorden: BENOEMINGSMOTIEF, ETYMOLOGIA PROXIMA

  3. Quantification of clay minerals by combined EWA/XRD method

    Institute of Scientific and Technical Information of China (English)

    XU; Jianhong; (徐建红); XU; Jianhong; (徐建红); T.; R.; Astin; PAN; Mao; (潘懋)

    2001-01-01

    Illite has been considered the main constraint on permeability in the Morecambe Gas Field, East Irish Sea, UK. Previous research has emphasized the morphology rather than the amount of clay minerals. By applying a new method of clay mineral quantification, EWA/XRD, and applying statistical analysis methods, we are able to establish a quantitative model of illite distribution in the field. The result also leads to a better understanding of permeability distribution in reservoir sandstones.

  4. Uncertainty in vertical extrapolation of wind statistics: shear-exponent and WAsP/EWA methods

    DEFF Research Database (Denmark)

    Kelly, Mark C.

    for uncertainties inherent in determination of (wind) shear exponents, and subsequent vertical extrapolation of wind speeds. The report further outlines application of the theory and results of Kelly & Troen (2014-6) for gauging the uncertainty inherent in use of the European Wind Atlas (EWA) / WAsP method...

  5. EWA Detection Effectiveness Based on SEA Method%基于效能分析方法的预警机探测效能研究

    Institute of Scientific and Technical Information of China (English)

    粘松雷; 严建钢; 林云

    2012-01-01

    在预警机巡逻航线分析的基础上,运用系统效能分析的基本原理,对跑道型巡逻航线探测效能问题进行了研究,重点研究了强效区的探测模型和弱效区的系统映射模型.通过算例仿真对模型的各个因素的影响效果进行了分析.%Based on early warning aircraft(EWA) cruising course analysis, the detection effectiveness cruising along racetrack is studied by using the basic principle of system effecectivess analysis ( SEA ) , The detection model of areas of high probability and system mapping of areas of low probability are specially studied. The influence effect of each factor of the model is analyzed with simulation calculation.

  6. Fish Census Data from Annual Surveys at Selected Shallow-water Sites Near the Barber's Point Sewage Outfall, Ewa, Oahu, Hawaii, 1991 - 2010 (NODC Accession 0073346)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Honouliuli Wastewater Treatment Plant (WWTP) located in Ewa, Oahu, Hawaii, near Barbers Point (Kalaeloa) has been in operation since 1982. It releases...

  7. HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT

    OpenAIRE

    Shuo Wang; Jieyun Song; Yide Yang; Yining Zhang; Haijun Wang; Jun Ma

    2015-01-01

    Gene polymorphisms associated so far with body mass index (BMI) can explain only 1.18-1.45% of observed variation in BMI. Recent studies suggest that epigenetic modifications, especially DNA methylation, could contribute to explain part of the missing heritability, and two epigenetic genome-wide analysis studies (EWAS) have reported that Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) methylation was associated with BMI or BMI change. We therefore assessed whether the HIF3A methylation is as...

  8. Epigenome-Wide Association Study of Tic Disorders.

    Science.gov (United States)

    Zilhão, Nuno R; Padmanabhuni, Shanmukha S; Pagliaroli, Luca; Barta, Csaba; Smit, Dirk J A; Cath, Danielle; Nivard, Michel G; Baselmans, Bart M L; van Dongen, Jenny; Paschou, Peristera; Boomsma, Dorret I

    2015-12-01

    Tic disorders are moderately heritable common psychiatric disorders that can be highly troubling, both in childhood and in adulthood. In this study, we report results obtained in the first epigenome-wide association study (EWAS) of tic disorders. The subjects are participants in surveys at the Netherlands Twin Register (NTR) and the NTR biobank project. Tic disorders were measured with a self-report version of the Yale Global Tic Severity Scale Abbreviated version (YGTSS-ABBR), included in the 8th wave NTR data collection (2008). DNA methylation data consisted of 411,169 autosomal methylation sites assessed by the Illumina Infinium HumanMethylation450 BeadChip Kit (HM450k array). Phenotype and DNA methylation data were available in 1,678 subjects (mean age = 41.5). No probes reached genome-wide significance (p tic disorders. The top significantly enriched gene ontology (GO) terms among higher ranking methylation sites included anatomical structure morphogenesis (GO:0009653, p = 4.6 × 10-(15)) developmental process (GO:0032502, p = 2.96 × 10(-12)), and cellular developmental process (GO:0048869, p = 1.96 × 10(-12)). Overall, these results provide a first insight into the epigenetic mechanisms of tic disorders. This first study assesses the role of DNA methylation in tic disorders, and it lays the foundations for future work aiming to unravel the biological mechanisms underlying the architecture of this disorder.

  9. New Nordic Exceptionalism: Jeuno JE Kim and Ewa Einhorn's The United Nations of Norden and other realist utopias

    Directory of Open Access Journals (Sweden)

    Mathias Danbolt

    2016-11-01

    Full Text Available At the 2009 Nordic Culture Forum summit in Berlin that centered on the profiling and branding of the Nordic region in a globalized world, one presenter stood out from the crowd. The lobbyist Annika Sigurdardottir delivered a speech that called for the establishment of “The United Nations of Norden”: A Nordic union that would gather the nations and restore Norden's role as the “moral superpower of the world.” Sigurdardottir's presentation generated such a heated debate that the organizers had to intervene and reveal that the speech was a performance made by the artists Jeuno JE Kim and Ewa Einhorn. This article takes Kim and Einhorn's intervention as a starting point for a critical discussion of the history and politics of Nordic image-building. The article suggests that the reason Kim and Einhorn's speech passed as a serious proposal was due to its meticulous mimicking of two discursive formations that have been central to the debates on the branding of Nordicity over the last decades: on the one hand, the discourse of “Nordic exceptionalism,” that since the 1960s has been central to the promotion of a Nordic political, socio-economic, and internationalist “third way” model, and, on the other hand, the discourse on the “New Nordic,” that emerged out of the New Nordic Food-movement in the early 2000s, and which has given art and culture a privileged role in the international re-fashioning of the Nordic brand. Through an analysis of Kim and Einhorn's United Nations of Norden (UNN-performance, the article examines the historical development and ideological underpinnings of the image of Nordic unity at play in the discourses of Nordic exceptionalism and the New Nordic. By focusing on how the UNN-project puts pressure on the role of utopian imaginaries in the construction of Nordic self-images, the article describes the emergence of a discursive framework of New Nordic Exceptionalism.

  10. Interindividual methylomic variation across blood, cortex, and cerebellum: implications for epigenetic studies of neurological and neuropsychiatric phenotypes.

    Science.gov (United States)

    Hannon, Eilis; Lunnon, Katie; Schalkwyk, Leonard; Mill, Jonathan

    2015-01-01

    Given the tissue-specific nature of epigenetic processes, the assessment of disease-relevant tissue is an important consideration for epigenome-wide association studies (EWAS). Little is known about whether easily accessible tissues, such as whole blood, can be used to address questions about interindividual epigenomic variation in inaccessible tissues, such as the brain. We quantified DNA methylation in matched DNA samples isolated from whole blood and 4 brain regions (prefrontal cortex, entorhinal cortex, superior temporal gyrus, and cerebellum) from 122 individuals. We explored co-variation between tissues and the extent to which methylomic variation in blood is predictive of interindividual variation identified in the brain. For the majority of DNA methylation sites, interindividual variation in whole blood is not a strong predictor of interindividual variation in the brain, although the relationship with cortical regions is stronger than with the cerebellum. Variation at a subset of probes is strongly correlated across tissues, even in instances when the actual level of DNA methylation is significantly different between them. A substantial proportion of this co-variation, however, is likely to result from genetic influences. Our data suggest that for the majority of the genome, a blood-based EWAS for disorders where brain is presumed to be the primary tissue of interest will give limited information relating to underlying pathological processes. These results do not, however, discount the utility of using a blood-based EWAS to identify biomarkers of disease phenotypes manifest in the brain. We have generated a searchable database for the interpretation of data from blood-based EWAS analyses ( http://epigenetics.essex.ac.uk/bloodbrain/).

  11. Sharing Water with Nature: Insights on Environmental Water Allocation from a Case Study of the Murrumbidgee Catchment, Australia

    Directory of Open Access Journals (Sweden)

    Becky Swainson

    2011-02-01

    Full Text Available Human use of freshwater resources has placed enormous stress on aquatic ecosystems in many regions of the world. At one time, this was considered an acceptable price to pay for economic growth and development. Nowadays, however, many societies are seeking a better balance between healthy aquatic ecosystems and viable economies. Unfortunately, historically, water allocation systems have privileged human uses over the environment. Thus, jurisdictions seeking to ensure that adequate water is available for the environment must typically deal with the fact that economies and communities have become dependent on water. Additionally, they must often layer institutions for environmental water allocation (EWA on top of already complex institutional systems. This paper explores EWA in a jurisdiction – New South Wales (NSW, Australia – where water scarcity has become a priority. Using an in-depth case study of EWA in the Murrumbidgee catchment, NSW, we characterise the NSW approach to EWA with the goal of highlighting the myriad challenges encountered in EWA planning and implementation. Sharing water between people and the environment, we conclude, is much more than just a scientific and technical challenge. EWA in water-scarce regions involves reshaping regional economies and societies. Thus, political and socio-economic considerations must be identified and accounted for from the outset of planning and decision-making processes.

  12. Differentially methylated DNA regions in monozygotic twin pairs discordant for rheumatoid arthritis.An epigenome - wide study.

    Directory of Open Access Journals (Sweden)

    Anders Jørgen Svendsen

    2016-11-01

    Full Text Available Objectives: In an explorative epigenome-wide association study (EWAS to search for gene independent, differentially methylated DNA positions (DMPs and regions (DMRs associated with rheumatoid arthritis (RA by studying monozygotic (MZ twin pairs discordant for rheumatoid arthritis.Methods: Genomic DNA was isolated from whole blood samples from 28 monozygotic (MZ twin pairs discordant for RA. DNA methylation was measured using the HumanMethylation450 BeadChips. Smoking, anti-cyclic citrullinated peptide antibodies and immunosuppressive treatment were included as covariates. Pathway analysis was performed using GREAT.Results: Smoking was significantly associated with hypomethylation of a DMR overlapping the promoter region of the RNF5 and the AGPAT1, which are implicated in inflammation and autoimmunity, whereas DMARD treatment induced hypermethylation of the same region. Additionally, the promotor region of both S100A6 and EFCAB4B were hypomethylated and both genes have previously been associated with RA. We replicated several candidate genes identified in a previous EWAS in treatment naïve RA singletons. Gene set analysis indicated the involvement of immunologic signatures and cancer-related pathways in RA.Conclusion: We identified several differentially methylated regions associated with RA which may represent environmental effects or consequences of the disease and plausible biological pathways pertinent to the pathogenesis of rheumatoid arthritis

  13. Medication-wide association studies

    NARCIS (Netherlands)

    P.B. Ryan (Patrick); D. Madigan (David); P.E. Stang (Paul); M.J. Schuemie (Martijn); G. Hripcsak (G.)

    2013-01-01

    textabstractUndiscovered side effects of drugs can have a profound effect on the health of the nation, and electronic health-care databases offer opportunities to speed up the discovery of these side effects. We applied a "medication-wide association study" approach that combined multivariate analys

  14. Association studies in consanguineous populations

    Energy Technology Data Exchange (ETDEWEB)

    Genin, E.; Clerget-Darpous, F. [Institut National d`Etudes Demographiques, Paris (France)

    1996-04-01

    To study the genetic determinism of multifactorial diseases in large panmictic populations, a strategy consists in looking for an association with markers closely linked to candidate genes. A distribution of marker genotypes different in patients and controls may indicate that the candidate gene is involved in the disease. In panmictic populations, the power to detect the role of a candidate gene depends on the gametic disequilibrium with the marker locus. In consanguineous populations, we show that it depends on the inbreeding coefficient F as well. Inbreeding increases the power to detect the role of a recessive or quasi-recessive disease-susceptibility factor. The gain in power turns out to be greater for small values of the gametic disequilibrium. Moreover, even in the absence of gametic disequilibrium, the presence of inbreeding may allow to detect the role of a recessive factor. Ignoring inbreeding when it exists may lead to reject falsely a recessive model if the mode of inheritance is inferred on the distribution of genotypes among patients. 5 refs., 6 figs., 1 tab.

  15. eFORGE : A Tool for Identifying Cell Type-Specific Signal in Epigenomic Data

    NARCIS (Netherlands)

    Breeze, Charles E.; Paul, Dirk S.; van Dongen, Jenny; Butcher, Lee M.; Ambrose, John C.; Barrett, James E.; Lowe, Robert; Rakyan, Vardhman K.; Iotchkova, Valentina; Frontini, Mattia; Downes, Kate; Ouwehand, Willem H.; Laperle, Jonathan; Jacques, Pierre-ETienne; Bourque, Guillaume; Bergmann, Anke K.; Siebert, Reiner; Vellenga, Edo; Saeed, Sadia; Matarese, Filomena; Martens, Joost H. A.; Stunnenberg, Hendrik G.; Teschendorff, Andrew E.; Herrero, Javier; Birney, Ewan; Dunham, Ian; Beck, Stephan

    2016-01-01

    Epigenome-wide association studies (EWAS) provide an alternative approach for studying human disease through consideration of non-genetic variants such as altered DNA methylation. To advance the complex interpretation of EWAS, we developed eFORGE (http://eforge.cs.ucl.ac.uk/), a new stand-alone and

  16. Maternal Smoking during Pregnancy and DNA-Methylation in Children at Age 5.5 Years: Epigenome-Wide-Analysis in the European Childhood Obesity Project (CHOP)-Study

    Science.gov (United States)

    Rzehak, Peter; Saffery, Richard; Reischl, Eva; Covic, Marcela; Wahl, Simone; Grote, Veit; Xhonneux, Annick; Langhendries, Jean-Paul; Ferre, Natalia; Closa-Monasterolo, Ricardo; Verduci, Elvira; Riva, Enrica; Socha, Piotr; Gruszfeld, Dariusz; Koletzko, Berthold

    2016-01-01

    Mounting evidence links prenatal exposure to maternal tobacco smoking with disruption of DNA methylation (DNAm) profile in the blood of infants. However, data on the postnatal stability of such DNAm signatures in childhood, as assessed by Epigenome Wide Association Studies (EWAS), are scarce. Objectives of this study were to investigate DNAm signatures associated with in utero tobacco smoke exposure beyond the 12th week of gestation in whole blood of children at age 5.5 years, to replicate previous findings in young European and American children and to assess their biological role by exploring databases and enrichment analysis. DNA methylation was measured in blood of 366 children of the multicentre European Childhood Obesity Project Study using the Illumina Infinium HM450 Beadchip (HM450K). An EWAS was conducted using linear regression of methylation values at each CpG site against in utero smoke exposure, adjusted for study characteristics, biological and technical effects. Methylation levels at five HM450K probes in MYO1G (cg12803068, cg22132788, cg19089201), CNTNAP2 (cg25949550), and FRMD4A (cg11813497) showed differential methylation that reached epigenome-wide significance according to the false-discovery-rate (FDR) criteria (q-value<0.05). Whereas cg25949550 showed decreased methylation (-2% DNAm ß-value), increased methylation was observed for the other probes (9%: cg12803068; 5%: cg22132788; 4%: cg19089201 and 4%: cg11813497) in exposed relative to non-exposed subjects. This study thus replicates previous findings in children ages 3 to 5, 7 and 17 and confirms the postnatal stability of MYO1G, CNTNAP2 and FRMD4A differential methylation. The role of this differential methylation in mediating childhood phenotypes, previously associated with maternal smoking, requires further investigation. PMID:27171005

  17. HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT.

    Directory of Open Access Journals (Sweden)

    Shuo Wang

    Full Text Available Gene polymorphisms associated so far with body mass index (BMI can explain only 1.18-1.45% of observed variation in BMI. Recent studies suggest that epigenetic modifications, especially DNA methylation, could contribute to explain part of the missing heritability, and two epigenetic genome-wide analysis studies (EWAS have reported that Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A methylation was associated with BMI or BMI change. We therefore assessed whether the HIF3A methylation is associated with obesity and other obesity-related phenotypes in Chinese children. The subjects included 110 severe obese cases aged 7-17y and 110 normal-weight controls matched by age and gender for measurement of blood DNA methylation levels at the HIF3A gene locus using the Sequenom's MassARRAY system. We observed significantly higher methylation levels in obese children than in controls at positions 46801642 and 46801699 in HIF3A gene (P<0.05, and found positive associations between methylation and alanine aminotransferase (ALT levels adjusted by gender, age and BMI at the position 46801699 (r = 0.226, P = 0.007. These results suggest that HIF3A DNA methylation is associated with childhood obesity, and has a BMI-independent association with ALT. The results provide evidence for identifying epigenetic factors of elivated ALT and may be useful for risk assessment and personalized medicine of liver diseases such as non-alcoholic fatty liver disease (NAFLD.

  18. Genetic association studies in lumbar disc degeneration

    DEFF Research Database (Denmark)

    Eskola, Pasi J; Lemmelä, Susanna; Kjaer, Per;

    2012-01-01

    Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans....

  19. SOCIAL PARTICIPATION IN THE ENVIRONMENTAL FLOW ASSESSMENT: THE SÃO FRANCISCO RIVER CASE STUDY

    Directory of Open Access Journals (Sweden)

    Yvonilde Dantas Pinto Medeiros

    2013-03-01

    Full Text Available Traditionally, water resource management has been developed using an essentially technical approach. Currently, public opinion on water resource management is formed as a result of growing environmental concerns and social conflicts arising from poorly planned actions. Environmental problems are complex and have multiple dimensions, including social and economic. Therefore, the inclusion of a human dimension in integrated assessment methodologies is required for the introduction of new elements to the water management planning process. Environmental water allocation (EWA is understood as the quantity, quality and distribution of water required for the maintenance of the functions and processes of aquatic ecosystems on which people depend. Within the various holistic assessment methodologies, the Building Block Methodology (BBM was found to be the most suitable, in the Brazilian context, for maintaining and restoring essential elements of the natural flow regime. This article describes the process of social participation in the environmental flow assessment (EFA for the Sao Francisco River, and compares it with some of the lessons learned from EFA in other parts of the world. The process involved multiple stakeholders who have conflicting interests. BBM was used to guide the field interviews, to incorporate the empirical observations by the local population and to guide the methodological procedures of the multidisciplinary team. The results of the study indicate the effectiveness of this holistic approach in organizing the elements to be evaluated. It also facilitated important contributions to the establishment of a dialogue between the actors to achieve a better understanding of the multiple aspects involved in the decisions associated with the EWA.

  20. HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT.

    Science.gov (United States)

    Wang, Shuo; Song, Jieyun; Yang, Yide; Zhang, Yining; Wang, Haijun; Ma, Jun

    2015-01-01

    Gene polymorphisms associated so far with body mass index (BMI) can explain only 1.18-1.45% of observed variation in BMI. Recent studies suggest that epigenetic modifications, especially DNA methylation, could contribute to explain part of the missing heritability, and two epigenetic genome-wide analysis studies (EWAS) have reported that Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) methylation was associated with BMI or BMI change. We therefore assessed whether the HIF3A methylation is associated with obesity and other obesity-related phenotypes in Chinese children. The subjects included 110 severe obese cases aged 7-17y and 110 normal-weight controls matched by age and gender for measurement of blood DNA methylation levels at the HIF3A gene locus using the Sequenom's MassARRAY system. We observed significantly higher methylation levels in obese children than in controls at positions 46801642 and 46801699 in HIF3A gene (Pobesity, and has a BMI-independent association with ALT. The results provide evidence for identifying epigenetic factors of elivated ALT and may be useful for risk assessment and personalized medicine of liver diseases such as non-alcoholic fatty liver disease (NAFLD).

  1. Identification of type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis.

    Directory of Open Access Journals (Sweden)

    Vardhman K Rakyan

    2011-09-01

    Full Text Available Monozygotic (MZ twin pair discordance for childhood-onset Type 1 Diabetes (T1D is ∼50%, implicating roles for genetic and non-genetic factors in the aetiology of this complex autoimmune disease. Although significant progress has been made in elucidating the genetics of T1D in recent years, the non-genetic component has remained poorly defined. We hypothesized that epigenetic variation could underlie some of the non-genetic component of T1D aetiology and, thus, performed an epigenome-wide association study (EWAS for this disease. We generated genome-wide DNA methylation profiles of purified CD14+ monocytes (an immune effector cell type relevant to T1D pathogenesis from 15 T1D-discordant MZ twin pairs. This identified 132 different CpG sites at which the direction of the intra-MZ pair DNA methylation difference significantly correlated with the diabetic state, i.e. T1D-associated methylation variable positions (T1D-MVPs. We confirmed these T1D-MVPs display statistically significant intra-MZ pair DNA methylation differences in the expected direction in an independent set of T1D-discordant MZ pairs (P = 0.035. Then, to establish the temporal origins of the T1D-MVPs, we generated two further genome-wide datasets and established that, when compared with controls, T1D-MVPs are enriched in singletons both before (P = 0.001 and at (P = 0.015 disease diagnosis, and also in singletons positive for diabetes-associated autoantibodies but disease-free even after 12 years follow-up (P = 0.0023. Combined, these results suggest that T1D-MVPs arise very early in the etiological process that leads to overt T1D. Our EWAS of T1D represents an important contribution toward understanding the etiological role of epigenetic variation in type 1 diabetes, and it is also the first systematic analysis of the temporal origins of disease-associated epigenetic variation for any human complex disease.

  2. Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants

    OpenAIRE

    Allum, Fiona; Shao, Xiaojian; Guénard, Frédéric; Simon, Marie Michelle; Busche, Stephan; Caron, Maxime; Lambourne, John; Lessard, Julie; Tandre, Karolina; Hedman, Åsa K.; Kwan, Tony; Ge, Bing; Rönnblom, Lars; McCarthy, Mark I; Deloukas, Panos

    2015-01-01

    This is the final version. It was first published by NPG at http://www.nature.com/ncomms/2015/150529/ncomms8211/full/ncomms8211.html#abstract Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequenci...

  3. Associative visual agnosia: a case study.

    Science.gov (United States)

    Charnallet, A; Carbonnel, S; David, D; Moreaud, O

    2008-01-01

    We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study, an alternative account in the framework of (non abstractive) episodic models of memory.

  4. Associative Visual Agnosia: A Case Study

    OpenAIRE

    A. Charnallet; S. Carbonnel; David, D.; Moreaud, O.

    2008-01-01

    We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study [1], an alternative account in the framework of (non abstractive) episodic models of memory [4].

  5. Understanding Salesforce Behavior using Genetic Association Studies

    NARCIS (Netherlands)

    W.E. van den Berg (Wouter)

    2014-01-01

    markdownabstract__Abstract__ Using genetic association studies, this thesis aims to investigate the drivers of successful customer-salesperson interactions in a context where knowledge development has become crucial to the value creation process. Central to this thesis is the developing role of the

  6. A Comparative Study of Sparse Associative Memories

    Science.gov (United States)

    Gripon, Vincent; Heusel, Judith; Löwe, Matthias; Vermet, Franck

    2016-07-01

    We study various models of associative memories with sparse information, i.e. a pattern to be stored is a random string of 0s and 1s with about log N 1s, only. We compare different synaptic weights, architectures and retrieval mechanisms to shed light on the influence of the various parameters on the storage capacity.

  7. Functional analysis of variance for association studies.

    Directory of Open Access Journals (Sweden)

    Olga A Vsevolozhskaya

    Full Text Available While progress has been made in identifying common genetic variants associated with human diseases, for most of common complex diseases, the identified genetic variants only account for a small proportion of heritability. Challenges remain in finding additional unknown genetic variants predisposing to complex diseases. With the advance in next-generation sequencing technologies, sequencing studies have become commonplace in genetic research. The ongoing exome-sequencing and whole-genome-sequencing studies generate a massive amount of sequencing variants and allow researchers to comprehensively investigate their role in human diseases. The discovery of new disease-associated variants can be enhanced by utilizing powerful and computationally efficient statistical methods. In this paper, we propose a functional analysis of variance (FANOVA method for testing an association of sequence variants in a genomic region with a qualitative trait. The FANOVA has a number of advantages: (1 it tests for a joint effect of gene variants, including both common and rare; (2 it fully utilizes linkage disequilibrium and genetic position information; and (3 allows for either protective or risk-increasing causal variants. Through simulations, we show that FANOVA outperform two popularly used methods - SKAT and a previously proposed method based on functional linear models (FLM, - especially if a sample size of a study is small and/or sequence variants have low to moderate effects. We conduct an empirical study by applying three methods (FANOVA, SKAT and FLM to sequencing data from Dallas Heart Study. While SKAT and FLM respectively detected ANGPTL 4 and ANGPTL 3 associated with obesity, FANOVA was able to identify both genes associated with obesity.

  8. Associative Visual Agnosia: A Case Study

    Directory of Open Access Journals (Sweden)

    A. Charnallet

    2008-01-01

    Full Text Available We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study [1], an alternative account in the framework of (non abstractive episodic models of memory [4].

  9. Gastroschisis and associated defects: an international study.

    LENUS (Irish Health Repository)

    Mastroiacovo, Pierpaolo

    2007-04-01

    Our objective was to evaluate the frequency and type of malformations associated with gastroschisis in a large pool of international data, to identify malformation patterns, and to evaluate the role of maternal age in non-isolated cases. Case-by-case information from 24 registries, all members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), were evaluated. After the exclusion of other abdominal wall defects cases were classified as: (a) isolated; (b) recognizable syndrome, chromosomal or not; (c) multiple congenital anomalies (MCA). Our results showed that out of 3,322 total cases 469 non-isolated cases were registered (14.1%): 41 chromosomal syndromes, 24 other syndromes, and 404 MCA. Among MCA four groups of anomalies were most frequent: CNS (4.5%), cardio-vascular (2.5%), limb (2.2%), and kidney anomalies (1.9%). No similar patterns emerged except two patterns resembling limb-body wall complex and OEIS. In both of them the gastroschisis could be however misclassified. Chromosomal trisomies and possibly non-syndromic MCA are associated with an older maternal age more than isolated cases. On consideration of our data and the most valid studies published in the literature, the best estimate of the proportion of gastroschisis associated with major unrelated defects is about 10%, with a few cases associated to recognizable syndromes. Recognized syndromes with gastroschisis seem to be so exceptional that the well documented and validated cases are worth being published as interesting case report. An appropriate case definition in etiological studies should include only isolated gastroschisis after an appropriate definition of isolated and non-isolated cases and a thorough case-by-case review.

  10. A Study on Associative Neural Memories

    OpenAIRE

    B.D.C.N.Prasad; P. E. S. N. Krishna Prasad; Sagar Yeruva; P Sita Rama Murty

    2011-01-01

    Memory plays a major role in Artificial Neural Networks. Without memory, Neural Network can not be learned itself. One of the primary concepts of memory in neural networks is Associative neural memories. A survey has been made on associative neural memories such as Simple associative memories (SAM), Dynamic associative memories (DAM), Bidirectional Associative memories (BAM), Hopfield memories, Context Sensitive Auto-associative memories (CSAM) and so on. These memories can be applied in vari...

  11. Studying risk factors associated with Human Leptospirosis

    Directory of Open Access Journals (Sweden)

    Ramachandra Kamath

    2014-01-01

    Full Text Available Background: Leptospirosis is one of the most under diagnosed and underreported disease in both developed and developing countries including India. It is established that environmental conditions and occupational habit of the individuals put them at risk of acquiring disease, which varies from community to community. Various seroprevalence studies across the world have documented emerging situation of this neglected tropical disease, but limited have probed to identify the risk factors, especially in India. Objectives: The objective of this study was to identify the environmental and occupational risk factors associated with the disease in Udupi District. Materials and Methods: This population-based case-control study was carried out in Udupi, a District in Southern India from April 2012 until August 2012. Udupi is considered to be endemic for Leptospirosis and reported 116 confirmed cases in the year 2011. Seventy of 116 laboratory confirmed cases and 140 sex matched neighborhood healthy controls participated in the study. A predesigned, semi-structured and validated questionnaire was used for data collection through house to house visit and observations were noted about environmental conditions. Univariate analysis followed by multivariate analysis (back ward conditional logistic regression was performed by using STATA version 9.2 (StataCorp, College Station, TX, USA to identify potential risk factors. Results: Occupational factors such as outdoor activities (matched odds ratio [OR] of 3.95, 95% confidence interval [CI]: 1.19-13.0, presence of cut or wound at body parts during work (matched OR: 4.88, CI: 1.83-13.02 and environmental factors such as contact with rodents through using the food materials ate by rat (matched OR: 4.29, CI: 1.45-12.73 and contact with soil or water contaminated with urine of rat (matched OR: 4.58, CI: 1.43-14.67 were the risk factors identified to be associated with disease. Conclusion: Leptospirosis is still

  12. 'Smoking genes': a genetic association study.

    Directory of Open Access Journals (Sweden)

    Zoraida Verde

    Full Text Available Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A [rs1801272], CYP2A6*9 (-48T>G [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T [rs8192789], CYP2A13*3 (7520C>G, CYP2A13*4 (579G>A, CYP2A13*7 (578C>T [rs72552266], CYP2B6*4 (785A>G, CYP2B6*9 (516G>T, CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126 and ethnically matched never smokers (controls, N = 80. The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both PA (Taq1A polymorphisms was 3.60 (95%CI: 1.75, 7.44 and 2.63 (95%CI: 1.41, 4.89 respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65. We found a significant genotype effect (all P≤0.017 for the following smoking-related phenotypes: (i cigarettes smoked per day and CYP2A13*3; (ii pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A; (iii nicotine dependence (assessed with the Fagestrom test and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5, serotoninergic (HTR2A, opioid (OPRM1 or cannabinoid receptors (CNR1.

  13. Genetics in psychiatry: common variant association studies

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D

    2010-03-01

    Full Text Available Abstract Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data.

  14. Association study of nonsynonymous single nucleotide polymorphisms in schizophrenia

    DEFF Research Database (Denmark)

    Carrera, Noa; Arrojo, Manuel; Sanjuán, Julio

    2012-01-01

    Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, ...

  15. The Danish Association for Science and Technology Studies

    DEFF Research Database (Denmark)

    A presentation of the Danish Association for Science and Technology Studies (DASTS). Organization, experiences, challenges and future developments.......A presentation of the Danish Association for Science and Technology Studies (DASTS). Organization, experiences, challenges and future developments....

  16. Archaeological and Paleontological Investigation at Kalaeloa (Barber’s Point), Honouliuli, ’EWA, O’Ahu Island, Federal Study Areas 1a and 1b, and State of Hawaii Optional Area 1,

    Science.gov (United States)

    1981-07-01

    DIAMOND HEAD 8 - EUCALYPTUS FOREST TRAINING AREA 30-FT DE RUSSY 9 -KAWAILOA TRAINING AREA 31-FT ARMSTRONG I0-KAHUKU TRAINING CAMP AND AREA 32-SAND ISLAND...evidence. In essence , paleo-malacological analysis is based upon the assumption that the specific composition of a fossil landsnail assemblage should

  17. A Candidate Gene Association Study of 77 Polymorphisms in Migraine

    OpenAIRE

    Schürks, Markus; Kurth, Tobias; Buring, Julie E.; Zee, Robert Y.L.

    2009-01-01

    Population-based studies have established an association between migraine and cardiovascular disease (CVD). We sought to investigate whether genetic variants implicated in CVD are associated with migraine. We performed an association study among 25,713 women, participating in the Women’s Health Study, with information on 77 previously characterized polymorphisms. Migraine and migraine aura status were self-reported. We used logistic regression to investigate the genotype-migraine association....

  18. Ergonomic analysis in the manual transport of loads: a case study in a cement production company

    Directory of Open Access Journals (Sweden)

    Jarbas Rocha Martins

    2017-03-01

    Full Text Available This study aims to analyze the manual transport activity of 50kg bags in a cement production company by means of ergonomic work analysis (EWA, identifying environmental factors and loaders’ working conditions. In order for EWA to take place, photographic records, videos and interviews were performed. It covered aspects related to lifting, transportation and handling of cement bags, as well as observations of loaders’ posture while performing the activity. In this sense, both qualitative and quantitative aspects were taken into account, which were evidenced by the use of instruments for determining the concentration of agents in the environment. In addition, some management tools, such as the cause and effect diagram, and interviews conducted during the field research were used. It was found that the high rate of absenteeism in the activity is related to the strict control of productivity, the excessive lifting and manual transport of weights, and repetitive trunk flexion movements. The results shown by the EWA made it possible to propose preventive measures and some changes in the work environment.

  19. Sensitivity studies associated with dosimetry experiment interpretation

    Energy Technology Data Exchange (ETDEWEB)

    Bourganel, S.; Soldevila, M. [CEA/DANS/DM2S/SERMA, CEA Saclay, 91191, Gif sur Yvette (France); Ferrer, A.; Gregoire, G.; Destouches, C.; Beretz, D. [CEA/DEN-CAD/DER/SPEX, CEA Cadarache, F13108, Saint Paul lez Durance (France)

    2011-07-01

    Document available in abstract form only, full text of document follows: Interpretation of reactor dosimetry experiments with C/E comparison requires precise knowledge of parameters involved in modeling. Some parameters have more weight than others on the calculated values. So, sensitivity studies should be conducted to verify the importance of these parameters. The conclusions of these studies are used to refine the experiment modeling, or to correct uncertainty calculations. The results of these sensitivity studies allow a post-irradiation analysis, which can justify the discarding of some atypical C/M values. Derived uncertainties may be improved by the sensitivity analyses. Beyond classical parameters as geometry or composition, this paper describes some specific sensitivity studies conducted for dosimetry irradiation in reactor, and presents conclusions. These studies are based on dosimeters irradiated in the EOLE reactor facility at Cadarache CEA center. Conclusions drawn from these studies are generic and can be applied to any dosimetry study. Calculations performed for these studies were realized using TRIPOLI-4 Monte Carlo code. (authors)

  20. Genome-wide association study of multiplex schizophrenia pedigrees

    DEFF Research Database (Denmark)

    Levinson, Douglas F; Shi, Jianxin; Wang, Kai;

    2012-01-01

    The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs).......The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs)....

  1. CCNA Cisco Certified Network Associate Study Guide

    CERN Document Server

    Lammle, Todd

    2011-01-01

    Learn from the Best - Cisco Networking Authority Todd LammleWritten by Cisco networking authority Todd Lammle, this comprehensive guide has been completely updated to reflect the latest CCNA 640-802 exam. Todd's straightforward style provides lively examples, hands on and written labs, easy-to-understand analogies, and real-world scenarios that will not only help you prepare for the exam, but also give you a solid foundation as a Cisco networking professional.This Study Guide teaches you how toDescribe how a network worksConfigure, verify and troubleshoot a switch with VLANs and interswitch co

  2. Cancer genetic association studies in the genome-wide age

    OpenAIRE

    Savage, Sharon A

    2008-01-01

    Genome-wide association studies of hundreds of thousands of SNPs have led to a deluge of studies of genetic variation in cancer and other common diseases. Large case–control and cohort studies have identified novel SNPs as markers of cancer risk. Genome-wide association study SNP data have also advanced understanding of population-specific genetic variation. While studies of risk profiles, combinations of SNPs that may increase cancer risk, are not yet clinically applicable, future, large-sca...

  3. Genetic association studies in drug-induced liver injury.

    Science.gov (United States)

    Daly, Ann K; Day, Chris P

    2009-11-01

    Genetic studies on drug-induced liver injury (DILI) have proved challenging, both because of their rarity and their difficulty in replicating observed effects. However, significant progress has now been achieved by both candidate-gene and genome-wide association studies. These two approaches are considered in detail, together with examples of DILI due to specific drugs where consistent associations have been reported. Particular consideration is given to associations between antituberculosis drug-related liver injury and the "slow acetylator" genotype for N-acetyltransferase 2, amoxicillin/clavulanate-related liver injury, and the human leukocyte antigen (HLA) class II DRB1*1501 allele and flucloxacillin-related injury and the HLA class I B*5701 allele. Although these associations are drug-specific, the possibility that additional, more general susceptibility genes for DILI exist requires further investigation, ideally by genome-wide association studies involving international collaboration. The possibility of interethnic variation in susceptibility to DILI also requires further study.

  4. Novel Loci Associated with Usual Sleep Duration: The CHARGE Consortium Genome-Wide Association Study

    Science.gov (United States)

    Gottlieb, Daniel J.; Hek, Karin; Chen, Ting-hsu; Watson, Nathaniel F.; Eiriksdottir, Gudny; Byrne, Enda M.; Cornelis, Marilyn; Warby, Simon C.; Bandinelli, Stefania; Cherkas, Lynn; Evans, Daniel S.; Grabe, Hans J.; Lahti, Jari; Li, Man; Lehtimäki, Terho; Lumley, Thomas; Marciante, Kristin D.; Pérusse, Louis; Psaty, Bruce M.; Robbins, John; Tranah, Gregory J.; Vink, Jacqueline M.; Wilk, Jemma B.; Stafford, Jeanette M.; Bellis, Claire; Biffar, Reiner; Bouchard, Claude; Cade, Brian; Curhan, Gary C.; Eriksson, Johan G.; Ewert, Ralf; Ferrucci, Luigi; Fülöp, Tibor; Gehrman, Philip R.; Goodloe, Robert; Harris, Tamara B.; Heath, Andrew C.; Hernandez, Dena; Hofman, Albert; Hottenga, Jouke-Jan; Hunter, David J.; Jensen, Majken K.; Johnson, Andrew D.; Kähönen, Mika; Kao, Linda; Kraft, Peter; Larkin, Emma K.; Lauderdale, Diane S.; Luik, Annemarie I.; Medici, Marco; Montgomery, Grant W.; Palotie, Aarno; Patel, Sanjay R.; Pistis, Giorgio; Porcu, Eleonora; Quaye, Lydia; Raitakari, Olli; Redline, Susan; Rimm, Eric B.; Rotter, Jerome I.; Smith, Albert V.; Spector, Tim D.; Teumer, Alexander; Uitterlinden, André G.; Vohl, Marie-Claude; Widen, Elisabeth; Willemsen, Gonneke; Young, Terry; Zhang, Xiaoling; Liu, Yongmei; Blangero, John; Boomsma, Dorret I.; Gudnason, Vilmundur; Hu, Frank; Mangino, Massimo; Martin, Nicholas G.; O’Connor, George T.; Stone, Katie L.; Tanaka, Toshiko; Viikari, Jorma; Gharib, Sina A.; Punjabi, Naresh M.; Räikkönen, Katri; Völzke, Henry; Mignot, Emmanuel; Tiemeier, Henning

    2015-01-01

    Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study of usual sleep duration was conducted using 18 population-based cohorts totaling 47,180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35–80 kb upstream from the thyroid-specific transcription factor PAX8 (lowest p=1.1 ×10−9). This finding was replicated in an African-American sample of 4771 individuals (lowest p=9.3 × 10−4). The strongest combined association was at rs1823125 (p=1.5 × 10−10, minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 minutes longer per night. The alleles associated with longer sleep duration were associated in previous genome-wide association studies with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease. PMID:25469926

  5. Genome-Wide Association Study of Polymorphisms Predisposing to Bronchiolitis

    Science.gov (United States)

    Pasanen, Anu; Karjalainen, Minna K.; Bont, Louis; Piippo-Savolainen, Eija; Ruotsalainen, Marja; Goksör, Emma; Kumawat, Kuldeep; Hodemaekers, Hennie; Nuolivirta, Kirsi; Jartti, Tuomas; Wennergren, Göran; Hallman, Mikko; Rämet, Mika; Korppi, Matti

    2017-01-01

    Bronchiolitis is a major cause of hospitalization among infants. Severe bronchiolitis is associated with later asthma, suggesting a common genetic predisposition. Genetic background of bronchiolitis is not well characterized. To identify polymorphisms associated with bronchiolitis, we conducted a genome-wide association study (GWAS) in which 5,300,000 single nucleotide polymorphisms (SNPs) were tested for association in a Finnish–Swedish population of 217 children hospitalized for bronchiolitis and 778 controls. The most promising SNPs (n = 77) were genotyped in a Dutch replication population of 416 cases and 432 controls. Finally, we used a set of 202 Finnish bronchiolitis cases to further investigate candidate SNPs. We did not detect genome-wide significant associations, but several suggestive association signals (p bronchiolitis. These preliminary findings require further validation in a larger sample size. PMID:28139761

  6. Genome-wide association study of clinical dimensions of schizophrenia

    DEFF Research Database (Denmark)

    Fanous, Ayman H; Zhou, Baiyu; Aggen, Steven H;

    2012-01-01

    Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia....

  7. Current approaches of genome-wide association studies

    Institute of Scientific and Technical Information of China (English)

    Jianfeng Xu

    2008-01-01

    @@ With rapid advances in high-throughput genotyping technology and the great increase in information available on SNPs throughout the genuine, genuine-wide association(GWA) studies have now become feasible.

  8. Association between erectile dysfunction and chronic periodontitis: A clinical study

    Directory of Open Access Journals (Sweden)

    Ranjit Singh Uppal

    2014-01-01

    Conclusion: It may be concluded that chronic periodontitis and ED are associated with each other. However, further large scale studies with confounder analysis and longitudinal follow-up are warranted to explore the link between these two diseases.

  9. Toward a Taxonomy for Multi-Omics Science? Terminology Development for Whole Genome Study Approaches by Omics Technology and Hierarchy.

    Science.gov (United States)

    Pirih, Nina; Kunej, Tanja

    2017-01-01

    Omics is a form of high-throughput systems science. However, taxonomies for omics studies are limited, inviting us to rethink new ways in which we classify, prioritize, and rank various omics systems science studies. In this overarching context, the genome-wide study approaches have proliferated in number and popularity over the past decade. However, their hierarchy is not well organized and the development of attendant terminology is not controlled. In the present study, we searched the literature in PubMed and the Web of Science databases published from March 1999 to September 2016 using the keywords, including genome-wide, association, whole genome, transcriptome-wide, metabolome, epigenome, and phenome. We identified the whole genome study approaches and sorted them according to the omics technology types (genomics, proteomics, and so on) and hierarchy. Thirty-four studies from over 90 publications were sorted into 10 omics groups: DNA level, transcriptomics, proteomics, interactomics, metabolomics, epigenomics, miRNomics/ncRNomics, phenomics, environmental omics, and pharmacogenomics. We suggest here modifications of terminology for study approaches, which share the same acronyms such as EWAS for epigenome-wide association and environment-wide association studies, and MWAS for methylome-wide association and metabolome-wide association studies. Taken together, our study presented here provides the first systematic review and analyses of whole genome approaches and presents a baseline for further controlled terminology development, with a view to a new taxonomy for omics and multi-omics studies in the future. Finally, we call for greater dialogue and collaboration across diverse omics knowledge domains and applications, for example, across plants, animals, clinical medicine, and ecology.

  10. Genome-wide association studies and contribution to cardiovascular physiology.

    Science.gov (United States)

    Munroe, Patricia B; Tinker, Andrew

    2015-09-01

    The study of family pedigrees with rare monogenic cardiovascular disorders has revealed new molecular players in physiological processes. Genome-wide association studies of complex traits with a heritable component may afford a similar and potentially intellectually richer opportunity. In this review we focus on the interpretation of genetic associations and the issue of causality in relation to known and potentially new physiology. We mainly discuss cardiometabolic traits as it reflects our personal interests, but the issues pertain broadly in many other disciplines. We also describe some of the resources that are now available that may expedite follow up of genetic association signals into observations on causal mechanisms and pathophysiology.

  11. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height

    Science.gov (United States)

    Lanktree, Matthew B.; Guo, Yiran; Murtaza, Muhammed; Glessner, Joseph T.; Bailey, Swneke D.; Onland-Moret, N. Charlotte; Lettre, Guillaume; Ongen, Halit; Rajagopalan, Ramakrishnan; Johnson, Toby; Shen, Haiqing; Nelson, Christopher P.; Klopp, Norman; Baumert, Jens; Padmanabhan, Sandosh; Pankratz, Nathan; Pankow, James S.; Shah, Sonia; Taylor, Kira; Barnard, John; Peters, Bas J.; M. Maloney, Cliona; Lobmeyer, Maximilian T.; Stanton, Alice; Zafarmand, M. Hadi; Romaine, Simon P.R.; Mehta, Amar; van Iperen, Erik P.A.; Gong, Yan; Price, Tom S.; Smith, Erin N.; Kim, Cecilia E.; Li, Yun R.; Asselbergs, Folkert W.; Atwood, Larry D.; Bailey, Kristian M.; Bhatt, Deepak; Bauer, Florianne; Behr, Elijah R.; Bhangale, Tushar; Boer, Jolanda M.A.; Boehm, Bernhard O.; Bradfield, Jonathan P.; Brown, Morris; Braund, Peter S.; Burton, Paul R.; Carty, Cara; Chandrupatla, Hareesh R.; Chen, Wei; Connell, John; Dalgeorgou, Chrysoula; Boer, Anthonius de; Drenos, Fotios; Elbers, Clara C.; Fang, James C.; Fox, Caroline S.; Frackelton, Edward C.; Fuchs, Barry; Furlong, Clement E.; Gibson, Quince; Gieger, Christian; Goel, Anuj; Grobbee, Diederik E.; Hastie, Claire; Howard, Philip J.; Huang, Guan-Hua; Johnson, W. Craig; Li, Qing; Kleber, Marcus E.; Klein, Barbara E.K.; Klein, Ronald; Kooperberg, Charles; Ky, Bonnie; LaCroix, Andrea; Lanken, Paul; Lathrop, Mark; Li, Mingyao; Marshall, Vanessa; Melander, Olle; Mentch, Frank D.; J. Meyer, Nuala; Monda, Keri L.; Montpetit, Alexandre; Murugesan, Gurunathan; Nakayama, Karen; Nondahl, Dave; Onipinla, Abiodun; Rafelt, Suzanne; Newhouse, Stephen J.; Otieno, F. George; Patel, Sanjey R.; Putt, Mary E.; Rodriguez, Santiago; Safa, Radwan N.; Sawyer, Douglas B.; Schreiner, Pamela J.; Simpson, Claire; Sivapalaratnam, Suthesh; Srinivasan, Sathanur R.; Suver, Christine; Swergold, Gary; Sweitzer, Nancy K.; Thomas, Kelly A.; Thorand, Barbara; Timpson, Nicholas J.; Tischfield, Sam; Tobin, Martin; Tomaszweski, Maciej; Verschuren, W.M. Monique; Wallace, Chris; Winkelmann, Bernhard; Zhang, Haitao; Zheng, Dongling; Zhang, Li; Zmuda, Joseph M.; Clarke, Robert; Balmforth, Anthony J.; Danesh, John; Day, Ian N.; Schork, Nicholas J.; de Bakker, Paul I.W.; Delles, Christian; Duggan, David; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofker, Marten H.; Humphries, Steve E.; Kivimaki, Mika; Lawlor, Debbie A.; Kottke-Marchant, Kandice; Mega, Jessica L.; Mitchell, Braxton D.; Morrow, David A.; Palmen, Jutta; Redline, Susan; Shields, Denis C.; Shuldiner, Alan R.; Sleiman, Patrick M.; Smith, George Davey; Farrall, Martin; Jamshidi, Yalda; Christiani, David C.; Casas, Juan P.; Hall, Alistair S.; Doevendans, Pieter A.; D. Christie, Jason; Berenson, Gerald S.; Murray, Sarah S.; Illig, Thomas; Dorn, Gerald W.; Cappola, Thomas P.; Boerwinkle, Eric; Sever, Peter; Rader, Daniel J.; Reilly, Muredach P.; Caulfield, Mark; Talmud, Philippa J.; Topol, Eric; Engert, James C.; Wang, Kai; Dominiczak, Anna; Hamsten, Anders; Curtis, Sean P.; Silverstein, Roy L.; Lange, Leslie A.; Sabatine, Marc S.; Trip, Mieke; Saleheen, Danish; Peden, John F.; Cruickshanks, Karen J.; März, Winfried; O'Connell, Jeffrey R.; Klungel, Olaf H.; Wijmenga, Cisca; Maitland-van der Zee, Anke Hilse; Schadt, Eric E.; Johnson, Julie A.; Jarvik, Gail P.; Papanicolaou, George J.; Grant, Struan F.A.; Munroe, Patricia B.; North, Kari E.; Samani, Nilesh J.; Koenig, Wolfgang; Gaunt, Tom R.; Anand, Sonia S.; van der Schouw, Yvonne T.; Soranzo, Nicole; FitzGerald, Garret A.; Reiner, Alex; Hegele, Robert A.; Hakonarson, Hakon; Keating, Brendan J.

    2011-01-01

    Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10−6), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10−8). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10−11). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait. PMID:21194676

  12. Genetic association studies in lumbar disc degeneration: a systematic review.

    Directory of Open Access Journals (Sweden)

    Pasi J Eskola

    Full Text Available OBJECTIVE: Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI in humans. METHODS: A systematic literature search was conducted in MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database and The Human Genome Epidemiology Network for information published between 1990-2011 addressing genes and lumbar disc degeneration. Two investigators independently identified studies to determine inclusion, after which they performed data extraction and analysis. The level of cumulative genetic association evidence was analyzed according to The HuGENet Working Group guidelines. RESULTS: Fifty-two studies were included for review. Forty-eight studies reported at least one positive association between a genetic marker and lumbar disc degeneration. The phenotype definition of lumbar disc degeneration was highly variable between the studies and replications were inconsistent. Most of the associations presented with a weak level of evidence. The level of evidence was moderate for ASPN (D-repeat, COL11A1 (rs1676486, GDF5 (rs143383, SKT (rs16924573, THBS2 (rs9406328 and MMP9 (rs17576. CONCLUSIONS: Based on this first extensive systematic review on the topic, the credibility of reported genetic associations is mostly weak. Clear definition of lumbar disc degeneration phenotypes and large population-based cohorts are needed. An international consortium is needed to standardize genetic association studies in relation to disc degeneration.

  13. Genome-wide association study of serum selenium concentrations

    DEFF Research Database (Denmark)

    Gong, Jian; Hsu, Li; Harrison, Tabitha

    2013-01-01

    Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated...... this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening and the Women’s Health Initiative (WHI). We...... tested association between 2,474,333 single nucleotide polymorphisms (SNPs) and serum selenium concentrations using linear regression models. In the first stage (PLCO) 41 SNPs clustered in 15 regions had p

  14. SNP CHARACTERISTICS PREDICT REPLICATION SUCCESS IN ASSOCIATION STUDIES

    Science.gov (United States)

    Gorlov, Ivan P.; Moore, Jason H.; Peng, Bo; Jin, Jennifer L.; Gorlova, Olga Y.; Amos, Christopher I.

    2014-01-01

    Successful independent replication is the most direct approach for distinguishing real genotype-disease associations from false discoveries in Genome Wide Association Studies (GWAS). Selecting SNPs for replication has been primarily based on p-values from the discovery stage, although additional characteristics of SNPs may be used to improve replication success. We used disease-associated SNPs from more than 2,000 published GWASs to identify predictors of SNP reproducibility. SNP reproducibility was defined as a proportion of successful replications among all replication attempts. The study reporting association for the first time was considered to be discovery and all consequent studies targeting the same phenotype replications. We found that −Log(P), where P is a p-value from the discovery study, is the strongest predictor of the SNP reproducibility. Other significant predictors include type of the SNP (e.g. missense vs intronic SNPs) and minor allele frequency. Features of the genes linked to the disease-associated SNP also predict SNP reproducibility. Based on empirically defined rules, we developed a reproducibility score (RS) to predict SNP reproducibility independently of −Log(P). We used data from two lung cancer GWAS studies as well as recently reported disease-associated SNPs to validate RS. Minus Log(P) outperforms RS when the very top SNPs are selected, while RS works better with relaxed selection criteria. In conclusion, we propose an empirical model to predict SNP reproducibility, which can be used to select SNPs for validation and prioritization. PMID:25273843

  15. Prediction of disease and phenotype associations from genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Stephanie N Lewis

    Full Text Available BACKGROUND: Genome wide association studies (GWAS have proven useful as a method for identifying genetic variations associated with diseases. In this study, we analyzed GWAS data for 61 diseases and phenotypes to elucidate common associations based on single nucleotide polymorphisms (SNP. The study was an expansion on a previous study on identifying disease associations via data from a single GWAS on seven diseases. METHODOLOGY/PRINCIPAL FINDINGS: Adjustments to the originally reported study included expansion of the SNP dataset using Linkage Disequilibrium (LD and refinement of the four levels of analysis to encompass SNP, SNP block, gene, and pathway level comparisons. A pair-wise comparison between diseases and phenotypes was performed at each level and the Jaccard similarity index was used to measure the degree of association between two diseases/phenotypes. Disease relatedness networks (DRNs were used to visualize our results. We saw predominant relatedness between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis for the first three levels of analysis. Expected relatedness was also seen between lipid- and blood-related traits. CONCLUSIONS/SIGNIFICANCE: The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis can be validated by clinical studies. The diseases have been proposed to share a systemic inflammation phenotype that can result in progression of additional diseases in patients with one of these three diseases. We also noticed unexpected relationships between metabolic and neurological diseases at the pathway comparison level. The less significant relationships found between diseases require a more detailed literature review to determine validity of the predictions. The results from this study serve as a first step towards a better understanding of seemingly unrelated diseases and phenotypes with similar symptoms or modes of treatment.

  16. Association between cancer and contact allergy: a linkage study

    DEFF Research Database (Denmark)

    Engkilde, Kaare; Thyssen, Jacob P; Menné, Torkil;

    2011-01-01

    and cancer, few have looked into the association between cancer and contact allergy, a type IV allergy. By linking two clinical databases, the authors investigate the possible association between contact allergy and cancer. Methods Record linkage of two different registers was performed: (1) a tertiary...... by logistic regression analysis. Results An inverse association between contact allergy and non-melanoma skin- and breast cancer, respectively, was identified in both sexes, and an inverse trend for brain cancer was found in women with contact allergy. Additionally, a positive association between contact......Background Contact allergy is a prevalent disorder. It is estimated that about 20% of the general population are allergic to one or more of the chemicals that constitute the European baseline patch test panel. While many studies have investigated associations between type I allergic disorders...

  17. Allelic association studies of genome wide association data can reveal errors in marker position assignments

    Directory of Open Access Journals (Sweden)

    Curtis David

    2007-06-01

    Full Text Available Abstract Background Genome wide association (GWA studies provide the opportunity to develop new kinds of analysis. Analysing pairs of markers from separate regions might lead to the detection of allelic association which might indicate an interaction between nearby genes. Methods 396,591 markers typed in 541 subjects were studied. 7.8*1010 pairs of markers were screened and those showing initial evidence for allelic association were subjected to more thorough investigation along with 10 flanking markers on either side. Results No evidence was detected for interaction. However 6 markers appeared to have an incorrect map position according to NCBI Build 35. One of these was corrected in Build 36 and 2 were dropped. The remaining 3 were left with map positions inconsistent with their allelic association relationships. Discussion Although no interaction effects were detected the method was successful in identifying markers with probably incorrect map positions. Conclusion The study of allelic association can supplement other methods for assigning markers to particular map positions. Analyses of this type may usefully be applied to data from future GWA studies.

  18. Generalization of Rare Variant Association Tests for Longitudinal Family Studies.

    Science.gov (United States)

    Chien, Li-Chu; Hsu, Fang-Chi; Bowden, Donald W; Chiu, Yen-Feng

    2016-02-01

    Given the functional relevance of many rare variants, their identification is frequently critical for dissecting disease etiology. Functional variants are likely to be aggregated in family studies enriched with affected members, and this aggregation increases the statistical power to detect rare variants associated with a trait of interest. Longitudinal family studies provide additional information for identifying genetic and environmental factors associated with disease over time. However, methods to analyze rare variants in longitudinal family data remain fairly limited. These methods should be capable of accounting for different sources of correlations and handling large amounts of sequencing data efficiently. To identify rare variants associated with a phenotype in longitudinal family studies, we extended pedigree-based burden (BT) and kernel (KS) association tests to genetic longitudinal studies. Generalized estimating equation (GEE) approaches were used to generalize the pedigree-based BT and KS to multiple correlated phenotypes under the generalized linear model framework, adjusting for fixed effects of confounding factors. These tests accounted for complex correlations between repeated measures of the same phenotype (serial correlations) and between individuals in the same family (familial correlations). We conducted comprehensive simulation studies to compare the proposed tests with mixed-effects models and marginal models, using GEEs under various configurations. When the proposed tests were applied to data from the Diabetes Heart Study, we found exome variants of POMGNT1 and JAK1 genes were associated with type 2 diabetes.

  19. Power analysis for genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Klein Robert J

    2007-08-01

    Full Text Available Abstract Background Genome-wide association studies are a promising new tool for deciphering the genetics of complex diseases. To choose the proper sample size and genotyping platform for such studies, power calculations that take into account genetic model, tag SNP selection, and the population of interest are required. Results The power of genome-wide association studies can be computed using a set of tag SNPs and a large number of genotyped SNPs in a representative population, such as available through the HapMap project. As expected, power increases with increasing sample size and effect size. Power also depends on the tag SNPs selected. In some cases, more power is obtained by genotyping more individuals at fewer SNPs than fewer individuals at more SNPs. Conclusion Genome-wide association studies should be designed thoughtfully, with the choice of genotyping platform and sample size being determined from careful power calculations.

  20. Associations of heart failure with sleep quality: The rotterdam study

    NARCIS (Netherlands)

    L.A. Zuurbier (Lisette); A.I. Luik (Annemarie); M.J.G. Leening (Maarten); A. Hofman (Albert); R. Freak-Poli (Rosanne); O.H. Franco (Oscar); B.H. Stricker; H.W. Tiemeier (Henning)

    2015-01-01

    textabstractStudy Objectives: The prevalence of sleep disturbances and heart failure increases with age. We aimed to evaluate the associations of incident heart failure and cardiac dysfunction with changes in sleep quality. Methods: This prospective population-based study was conducted in the Rotter

  1. A genome-wide association study of anorexia nervosa

    NARCIS (Netherlands)

    Boraska, V; Franklin, C S; Floyd, J A B; Thornton, L M; Huckins, L M; Southam, L; Rayner, N W; Tachmazidou, I; Klump, K L; Treasure, J; Lewis, C M; Schmidt, U; Tozzi, F; Kiezebrink, K; Hebebrand, J; Gorwood, P; Adan, R A H; Kas, M J H; Favaro, A; Santonastaso, P; Fernández-Aranda, F; Gratacos, M; Rybakowski, F; Dmitrzak-Weglarz, M; Kaprio, J; Keski-Rahkonen, A; Raevuori, A; Van Furth, E F; Slof-Op 't Landt, M C T; Hudson, J I; Reichborn-Kjennerud, T; Knudsen, G P S; Monteleone, P; Kaplan, A S; Karwautz, A; Hakonarson, H; Berrettini, W H; Guo, Y; Li, D; Schork, N J; Komaki, G; Ando, T; Inoko, H; Esko, T; Fischer, K; Männik, K; Metspalu, A; Baker, J H; Cone, R D; Dackor, J; DeSocio, J E; Hilliard, C E; O'Toole, J K; Pantel, J; Szatkiewicz, J P; Taico, C; Zerwas, S; Trace, S E; Davis, O S P; Helder, S; Bühren, K; Burghardt, R; de Zwaan, M; Egberts, K; Ehrlich, S; Herpertz-Dahlmann, B; Herzog, W; Imgart, H; Scherag, A; Scherag, S; Zipfel, S; Boni, C; Ramoz, N; Versini, A; Brandys, M K; Danner, U N; de Kovel, C; Hendriks, J; Koeleman, B P C; Ophoff, R A; Strengman, E; van Elburg, Annemarie; Bruson, A; Clementi, M; Degortes, D; Forzan, M; Tenconi, E; Docampo, E; Escaramís, G; Jiménez-Murcia, S; Lissowska, J; Rajewski, A; Szeszenia-Dabrowska, N; Slopien, A; Hauser, J; Karhunen, L; Meulenbelt, I; Slagboom, P E; Tortorella, A; Maj, M; Dedoussis, G; Dikeos, D; Gonidakis, F; Tziouvas, K; Tsitsika, A; Papezova, H; Slachtova, L; Martaskova, D; Kennedy, J L; Levitan, R D; Yilmaz, Z; Huemer, J; Koubek, D; Merl, E; Wagner, G; Lichtenstein, P; Breen, G; Cohen-Woods, S; Farmer, A; McGuffin, P; Cichon, S; Giegling, I; Herms, S; Rujescu, D; Schreiber, S; Wichmann, H-E; Dina, C; Sladek, R; Gambaro, G; Soranzo, N; Julia, A; Marsal, S; Rabionet, R; Gaborieau, V; Dick, D M; Palotie, A; Ripatti, S; Widén, E; Andreassen, O A; Espeseth, T; Lundervold, A; Reinvang, I; Steen, V M; Le Hellard, S; Mattingsdal, M; Ntalla, I; Bencko, V; Foretova, L; Janout, V; Navratilova, M; Gallinger, S; Pinto, D; Scherer, S W; Aschauer, H; Carlberg, L; Schosser, A; Alfredsson, L; Ding, B; Klareskog, L; Padyukov, L; Courtet, P; Guillaume, S; Jaussent, I; Finan, C; Kalsi, G; Roberts, M; Logan, D W; Peltonen, L; Ritchie, G R S; Barrett, J C; Estivill, X; Hinney, A; Sullivan, P F; Collier, D A; Zeggini, E; Bulik, C M

    2014-01-01

    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countri

  2. Genome-Wide Association Studies of the Human Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Emily R Davenport

    Full Text Available The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both. These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%. For example, we identified an association between a taxon known to affect obesity (genus Akkermansia and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7. Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.

  3. Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants.

    Science.gov (United States)

    Allum, Fiona; Shao, Xiaojian; Guénard, Frédéric; Simon, Marie-Michelle; Busche, Stephan; Caron, Maxime; Lambourne, John; Lessard, Julie; Tandre, Karolina; Hedman, Åsa K; Kwan, Tony; Ge, Bing; Rönnblom, Lars; McCarthy, Mark I; Deloukas, Panos; Richmond, Todd; Burgess, Daniel; Spector, Timothy D; Tchernof, André; Marceau, Simon; Lathrop, Mark; Vohl, Marie-Claude; Pastinen, Tomi; Grundberg, Elin

    2015-05-29

    Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequencing functional methylomes, while simultaneously providing genetic variation information. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adipose tissue (AT) samples and public databases to design AT-specific panels. We establish its efficiency for high-density interrogation of methylome variability by systematic comparisons with other approaches and demonstrate its applicability by identifying novel methylation variation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol, including at CD36. Our more comprehensive AT panel assesses tissue methylation and genotypes in parallel at ∼4 and ∼3 M sites, respectively. Our study demonstrates that MCC-Seq provides comparable accuracy to alternative approaches but enables more efficient cataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS.

  4. Evolutionary triangulation: informing genetic association studies with evolutionary evidence.

    Science.gov (United States)

    Huang, Minjun; Graham, Britney E; Zhang, Ge; Harder, Reed; Kodaman, Nuri; Moore, Jason H; Muglia, Louis; Williams, Scott M

    2016-01-01

    Genetic studies of human diseases have identified many variants associated with pathogenesis and severity. However, most studies have used only statistical association to assess putative relationships to disease, and ignored other factors for evaluation. For example, evolution is a factor that has shaped disease risk, changing allele frequencies as human populations migrated into and inhabited new environments. Since many common variants differ among populations in frequency, as does disease prevalence, we hypothesized that patterns of disease and population structure, taken together, will inform association studies. Thus, the population distributions of allelic risk variants should reflect the distributions of their associated diseases. Evolutionary Triangulation (ET) exploits this evolutionary differentiation by comparing population structure among three populations with variable patterns of disease prevalence. By selecting populations based on patterns where two have similar rates of disease that differ substantially from a third, we performed a proof of principle analysis for this method. We examined three disease phenotypes, lactase persistence, melanoma, and Type 2 diabetes mellitus. We show that for lactase persistence, a phenotype with a simple genetic architecture, ET identifies the key gene, lactase. For melanoma, ET identifies several genes associated with this disease and/or phenotypes related to it, such as skin color genes. ET was less obviously successful for Type 2 diabetes mellitus, perhaps because of the small effect sizes in known risk loci and recent environmental changes that have altered disease risk. Alternatively, ET may have revealed new genes involved in conferring disease risk for diabetes that did not meet nominal GWAS significance thresholds. We also compared ET to another method used to filter for phenotype associated genes, population branch statistic (PBS), and show that ET performs better in identifying genes known to associate with

  5. Genome-wide association study of circulating retinol levels.

    Science.gov (United States)

    Mondul, Alison M; Yu, Kai; Wheeler, William; Zhang, Hong; Weinstein, Stephanie J; Major, Jacqueline M; Cornelis, Marilyn C; Männistö, Satu; Hazra, Aditi; Hsing, Ann W; Jacobs, Kevin B; Eliassen, Heather; Tanaka, Toshiko; Reding, Douglas J; Hendrickson, Sara; Ferrucci, Luigi; Virtamo, Jarmo; Hunter, David J; Chanock, Stephen J; Kraft, Peter; Albanes, Demetrius

    2011-12-01

    Retinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide association study of 5006 Caucasian individuals drawn from two cohorts of men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We identified two independent single-nucleotide polymorphisms associated with circulating retinol levels, which are located near the transthyretin (TTR) and retinol binding protein 4 (RBP4) genes which encode major carrier proteins of retinol: rs1667255 (P =2.30× 10(-17)) and rs10882272 (P =6.04× 10(-12)). We replicated the association with rs10882272 in RBP4 in independent samples from the Nurses' Health Study and the Invecchiare in Chianti Study (InCHIANTI) that included 3792 women and 504 men (P =9.49× 10(-5)), but found no association for retinol with rs1667255 in TTR among women, thus suggesting evidence for gender dimorphism (P-interaction=1.31× 10(-5)). Discovery of common genetic variants associated with serum retinol levels may provide further insight into the contribution of retinol and other vitamin A compounds to the development of cancer and other complex diseases.

  6. Planning and executing a genome wide association study (GWAS).

    Science.gov (United States)

    Sale, Michèle M; Mychaleckyj, Josyf C; Chen, Wei-Min

    2009-01-01

    In recent years, genome-wide association approaches have proven a powerful and successful strategy to identify genetic contributors to complex traits, including a number of endocrine disorders. Their success has meant that genome wide association studies (GWAS) are fast becoming the default study design for discovery of new genetic variants that influence a clinical trait or phenotype. This chapter focuses on a number of key elements that require consideration for the successful conduct of a GWAS. Although many of the considerations are common to any genetic study, the greater cost, extreme multiple testing, and greater openness to data sharing require specific awareness and planning by investigators. In the section on designing a GWAS, we reflect on ethical considerations, study design, selection of phenotype/s, power considerations, sample tracking and storage issues, and genotyping product selection. During execution, important considerations include DNA quantity and preparation, genotyping methods, quality control checks of genotype data, in silico genotyping (imputation), tests of association, and replication of association signals. Although the field of human genetics is rapidly evolving, recent experiences can help guide an investigator in making practical and methodological choices that will eventually determine the overall quality of GWAS results. Given the investment to recruit patient populations or cohorts that are powered for a GWAS, and the still substantial costs associated with genotyping, it is helpful to be aware of these aspects to maximize the likelihood of success, especially where there is an opportunity for implementing them prospectively.

  7. Recommendations for using standardised phenotypes in genetic association studies

    Directory of Open Access Journals (Sweden)

    Naylor Melissa G

    2009-07-01

    Full Text Available Abstract Genetic association studies of complex traits often rely on standardised quantitative phenotypes, such as percentage of predicted forced expiratory volume and body mass index to measure an underlying trait of interest (eg lung function, obesity. These phenotypes are appealing because they provide an easy mechanism for comparing subjects, although such standardisations may not be the best way to control for confounders and other covariates. We recommend adjusting raw or standardised phenotypes within the study population via regression. We illustrate through simulation that optimal power in both population- and family-based association tests is attained by using the residuals from within-study adjustment as the complex trait phenotype. An application of family-based association analysis of forced expiratory volume in one second, and obesity in the Childhood Asthma Management Program data, illustrates that power is maintained or increased when adjusted phenotype residuals are used instead of typical standardised quantitative phenotypes.

  8. Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study

    NARCIS (Netherlands)

    Gottlieb, D.J.; Hek, K.; Chen, T.H.; Watson, N.F.; Eiriksdottir, G.; Byrne, E.M.; Cornelis, M.; Warby, S.C.; Bandinelli, S.; Cherkas, L.; Evans, D.S.; Grabe, H.J.; Lahti, J.; Li, M.; Lehtimaki, T.; Lumley, T.; Marciante, K.D.; Pérusse, L.; Psaty, B.M.; Robbins, J.; Tranah, G.J.; Vink, J.M.; Wilk, J.B.; Stafford, J.M.; Bellis, C.; Biffar, R.; Bouchard, C.; Cade, B.; Curhan, G.C.; Eriksson, J.G.; Ewert, R.; Ferrucci, L.; Fulop, T.; Gehrman, P.R.; Goodloe, R.; Harris, T.B.; Heath, A.C.; Hernandez, D.G.; Hofman, A.; Hottenga, J.J.; Hunter, D.J.; Jensen, M.K.; Johnson, A.D.; Kahonen, M.; Kao, L.; Kraft, P.; Larkin, E.K.; Lauderdale, D.S.; Luik, A.I.; Medici, M.; Montgomery, G.W.; Palotie, A.; Patel, S.R.; Pistis, G.; Porcu, E.; Quaye, L.; Raitakari, O.; Redline, S.; Rimm, E.B.; Rotter, J.I.; Smith, A.V.; Spector, T.D.; Teumer, A.; Uitterlinden, A.G.; Vohl, M.C.; Widen, E.; Willemsen, G.; Young, T.; Zhang, X.; Liu, Y.; Blangero, J.; Boomsma, D.I.; Gudnason, V.; Hu, F.; Mangino, M.; Martin, N.G.; O'Connor, G.T.; Stone, K.L.; Tanaka, T.; Viikari, J.; Gharib, S.A.; Punjabi, N.M.; Raikkonen, K.; Völzke, H.; Mignot, E.; Tiemeier, H.

    2015-01-01

    Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based c

  9. Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study

    NARCIS (Netherlands)

    D.J. Gottlieb (Daniel J); K. Hek (Karin); T.-H. Chen; N.F. Watson; G. Eiriksdottir (Gudny); E.M. Byrne; M. Cornelis (Marilyn); S.C. Warby; S. Bandinelli; L. Cherkas (Lynn); D.S. Evans (Daniel); H.J. Grabe (Hans Jörgen); J. Lahti (Jari); M. Li (Man); T. Lehtimäki (Terho); T. Lumley (Thomas); K. Marciante (Kristin); L. Perusse (Louis); B.M. Psaty (Bruce); J. Robbins; G.J. Tranah (Gregory); J.M. Vink; J.B. Wilk; J.M. Stafford; C. Bellis (Claire); R. Biffar; C. Bouchard (Claude); B. Cade; G.C. Curhan (Gary); J. Eriksson; R. Ewert; L. Ferrucci (Luigi); T. Fülöp; P.R. Gehrman (Philip); R. Goodloe (Robert); T.B. Harris (Tamara B.); A.C. Heath (Andrew C.); D.G. Hernandez (Dena); A. Hofman (Albert); J.J. Hottenga (Jouke Jan); D. Hunter (David); M.K. Jensen (Majken K.); A.D. Johnson (Andrew); M. Kähönen (Mika); W.H.L. Kao (Wen); P. Kraft (Peter); E.K. Larkin; D.S. Lauderdale; A.I. Luik (Annemarie I); M. Medici; G.W. Montgomery (Grant W.); A. Palotie; S.R. Patel (Sanjay); G. Pistis (Giorgio); E. Porcu; L. Quaye (Lydia); O. Raitakari (Olli); S. Redline (Susan); E.B. Rimm (Eric B.); J.I. Rotter; A.V. Smith; T.D. Spector (Timothy); A. Teumer (Alexander); A.G. Uitterlinden (André); M.-C. Vohl (Marie-Claude); E. Widen; G.A.H.M. Willemsen (Gonneke); T.L. Young (Terri L.); X. Zhang; Y. Liu; J. Blangero (John); D.I. Boomsma (Dorret); V. Gudnason (Vilmundur); F. Hu; M. Mangino; N.G. Martin (Nicholas); G.T. O'Connor (George); K.L. Stone (Katie L); T. Tanaka; J. Viikari (Jorma); S.A. Gharib (Sina); N.M. Punjabi (Naresh); K. Räikkönen (Katri); H. Völzke (Henry); E. Mignot; H.W. Tiemeier (Henning)

    2015-01-01

    textabstractUsual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 popula

  10. Association study in eating disorders : TPH2 associates with anorexia nervosa and self-induced vomiting

    NARCIS (Netherlands)

    't Landt, M. C. T. Slof-Op; Meulenbelt, I.; Bartels, M.; Suchiman, E.; Middeldorp, C. M.; Houwing-Duistermaat, J. J.; van Trier, J.; Onkenhout, E. J.; Vink, J. M.; van Beijsterveldt, C. E. M.; Brandys, M. K.; Sanders, N.; Zipfel, S.; Herpertz-Dahlmann, B.; Klampfl, K.; Fleischhaker, C.; Zeeck, A.; de Zwaan, M.; Herpertz, S.; Ehrlich, S.; van Elburg, A. A.; Adan, R. A. H.; Scherag, S.; Hinney, A.; Hebebrand, J.; Boomsma, D. I.; van Furth, E. F.; Slagboom, P. E.; Herzog, W.

    2011-01-01

    Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of t

  11. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    Okbay, Aysu; Beauchamp, Jonathan P.; Fontana, Mark Alan; Lee, James J.; Pers, Tune H.; Rietveld, Cornelius A.; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S. Fleur W.; Oskarsson, Sven; Pickrell, Joseph K.; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S.; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H.; Concas, Maria Pina; Derringer, Jaime; Furlotte, Nicholas A.; Galesloot, Tessel E.; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M.; Harris, Sarah E.; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E.; Kaasik, Kadri; Kalafati, Ioanna P.; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J.; de Leeuw, Christiaan; Lind, Penelope A.; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B.; van der Most, Peter J.; Oldmeadow, Christopher; Payton, Antony; Pervjakova, Natalia; Peyrot, Wouter J.; Qian, Yong; Raitakari, Olli; Rueedi, Rico; Salvi, Erika; Schmidt, Brge; Schraut, Katharina E.; Shi, Jianxin; Smith, Albert V.; Poot, Raymond A.; St Pourcain, Beate; Teumer, Alexander; Thorleifsson, Gudmar; Verweij, Niek; Vuckovic, Dragana; Wellmann, Juergen; Westra, Harm-Jan; Yang, Jingyun; Zhao, Wei; Zhu, Zhihong; Alizadeh, Behrooz Z.; Amin, Najaf; Bakshi, Andrew; Baumeister, Sebastian E.; Biino, Ginevra; Bonnelykke, Klaus; Boyle, Patricia A.; Campbell, Harry; Cappuccio, Francesco P.; Davies, Gail; De Neve, Jan-Emmanuel; Deloukas, Panos; Demuth, Ilja; Ding, Jun; Eibich, Peter; Eisele, Lewin; Eklund, Niina; Evans, David M.; Faul, Jessica D.; Feitosa, Mary F.; Forstner, Andreas J.; Gandin, Ilaria; Gunnarsson, Bjarni; Halldorsson, Bjarni V.; Harris, Tamara B.; Heath, Andrew C.; Hocking, Lynne J.; Holliday, Elizabeth G.; Homuth, Georg; Horan, Michael A.; Hottenga, Jouke-Jan; de Jager, Philip L.; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika A.; Kahonen, Mika; Kanoni, Stavroula; Keltigangas-Jarvinen, Liisa; Kiemeney, Lambertus A. L. M.; Kolcic, Ivana; Koskinen, Seppo; Kraja, Aldi T.; Kroh, Martin; Kutalik, Zoltan; Latvala, Antti; Launer, Lenore J.; Lebreton, Mael P.; Levinson, Douglas F.; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C. M.; Loukola, Anu; Madden, Pamela A.; Magi, Reedik; Maki-Opas, Tomi; Marioni, Riccardo E.; Marques-Vidal, Pedro; Meddens, Gerardus A.; McMahon, George; Meisinger, Christa; Meitinger, Thomas; Milaneschi, Yusplitri; Milani, Lili; Montgomery, Grant W.; Myhre, Ronny; Nelson, Christopher P.; Nyholt, Dale R.; Ollier, William E. R.; Palotie, Aarno; Paternoster, Lavinia; Pedersen, Nancy L.; Petrovic, Katja E.; Porteous, David J.; Raikkonen, Katri; Ring, Susan M.; Robino, Antonietta; Rostapshova, Olga; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sanders, Alan R.; Sarin, Antti-Pekka; Schmidt, Helena; Scott, Rodney J.; Smith, Blair H.; Smith, Jennifer A.; Staessen, Jan A.; Steinhagen-Thiessen, Elisabeth; Strauch, Konstantin; Terracciano, Antonio; Tobin, Martin D.; Ulivi, Sheila; Vaccargiu, Simona; Quaye, Lydia; van Rooij, Frank J. A.; Venturini, Cristina; Vinkhuyzen, Anna A. E.; Volker, Uwe; Volzke, Henry; Vonk, Judith M.; Waage, Johannes; Ware, Erin B.; Willemsen, Gonneke; Attia, John R.; Bennett, David A.; Berger, Klaus; Bertram, Lars; Bisgaard, Hans; Boomsma, Dorret I.; Borecki, Ingrid B.; Bultmann, Ute; Chabris, Christopher F.; Cucca, Francesco; Cusi, Daniele; Deary, Ian J.; Dedoussis, George V.; van Duijn, Cornelia M.; Eriksson, Johan G.; Franke, Barbara; Franke, Lude; Gasparini, Paolo; Gejman, Pablo V.; Gieger, Christian; Grabe, Hans-Jorgen; Gratten, Jacob; Groenen, Patrick J. F.; Gudnason, Vilmundur; van der Harst, Pim; Hayward, Caroline; Hinds, David A.; Hoffmann, Wolfgang; Hyppnen, Elina; Iacono, William G.; Jacobsson, Bo; Jarvelin, Marjo-Riitta; Jockel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L. R.; Lehtimaki, Terho; Lehrer, Steven F.; Magnusson, Patrik K. E.; Martin, Nicholas G.; McGue, Matt; Metspalu, Andres; Pendleton, Neil; Penninx, Brenda W. J. H.; Perola, Markus; Pirastu, Nicola; Pirastu, Mario; Polasek, Ozren; Posthuma, Danielle; Power, Christine; Province, Michael A.; Samani, Nilesh J.; Schlessinger, David; Schmidt, Reinhold; Sorensen, Thorkild I. A.; Spector, Tim D.; Stefansson, Kari; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tiemeier, Henning; Tung, Joyce Y.; Uitterlinden, Andre G.; Vitart, Veronique; Vollenweider, Peter; Weir, David R.; Wilson, James F.; Wright, Alan F.; Conley, Dalton C.; Krueger, Robert F.; Smith, George Davey; Hofman, Albert; Laibson, David I.; Medland, Sarah E.; Meyer, Michelle N.; Yang, Jian; Johannesson, Magnus; Visscher, Peter M.; Esko, Tonu; Koellinger, Philipp D.; Cesarini, David; Benjamin, Daniel J.

    2016-01-01

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends

  12. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

    NARCIS (Netherlands)

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and it

  13. Genome-wide association study identifies four loci associated with eruption of permanent teeth

    DEFF Research Database (Denmark)

    Geller, Frank; Feenstra, Bjarke; Zhang, Hao

    2011-01-01

    The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years...

  14. Genome-wide association study reveals regions associated with gestation length in two pig populations

    NARCIS (Netherlands)

    Hidalgo, A.M.; Lopes, M.S.; Harlizius, B.; Bastiaansen, J.W.M.

    2016-01-01

    Reproduction traits, such as gestation length (GLE), play an important role in dam line breeding in pigs. The objective of our study was to identify single nucleotide polymorphisms (SNPs) that are associated with GLE in two pig populations. Genotypes and deregressed breeding values were available

  15. Genome-Wide Association Study of Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Naomi Ogawa

    2010-01-01

    Full Text Available Coronary artery disease (CAD is a multifactorial disease with environmental and genetic determinants. The genetic determinants of CAD have previously been explored by the candidate gene approach. Recently, the data from the International HapMap Project and the development of dense genotyping chips have enabled us to perform genome-wide association studies (GWAS on a large number of subjects without bias towards any particular candidate genes. In 2007, three chip-based GWAS simultaneously revealed the significant association between common variants on chromosome 9p21 and CAD. This association was replicated among other ethnic groups and also in a meta-analysis. Further investigations have detected several other candidate loci associated with CAD. The chip-based GWAS approach has identified novel and unbiased genetic determinants of CAD and these insights provide the important direction to better understand the pathogenesis of CAD and to develop new and improved preventive measures and treatments for CAD.

  16. Genome-Wide Association Study of Meiotic Recombination Phenotypes

    Science.gov (United States)

    Begum, Ferdouse; Chowdhury, Reshmi; Cheung, Vivian G.; Sherman, Stephanie L.; Feingold, Eleanor

    2016-01-01

    Meiotic recombination is an essential step in gametogenesis, and is one that also generates genetic diversity. Genome-wide association studies (GWAS) and molecular studies have identified genes that influence of human meiotic recombination. RNF212 is associated with total or average number of recombination events, and PRDM9 is associated with the locations of hotspots, or sequences where crossing over appears to cluster. In addition, a common inversion on chromosome 17 is strongly associated with recombination. Other genes have been identified by GWAS, but those results have not been replicated. In this study, using new datasets, we characterized additional recombination phenotypes to uncover novel candidates and further dissect the role of already known loci. We used three datasets totaling 1562 two-generation families, including 3108 parents with 4304 children. We estimated five different recombination phenotypes including two novel phenotypes (average recombination counts within recombination hotspots and outside of hotspots) using dense SNP array genotype data. We then performed gender-specific and combined-sex genome-wide association studies (GWAS) meta-analyses. We replicated associations for several previously reported recombination genes, including RNF212 and PRDM9. By looking specifically at recombination events outside of hotspots, we showed for the first time that PRDM9 has different effects in males and females. We identified several new candidate loci, particularly for recombination events outside of hotspots. These include regions near the genes SPINK6, EVC2, ARHGAP25, and DLGAP2. This study expands our understanding of human meiotic recombination by characterizing additional features that vary across individuals, and identifying regulatory variants influencing the numbers and locations of recombination events. PMID:27733454

  17. Replication of genetic association studies in aortic stenosis in adults.

    Science.gov (United States)

    Gaudreault, Nathalie; Ducharme, Valérie; Lamontagne, Maxime; Guauque-Olarte, Sandra; Mathieu, Patrick; Pibarot, Philippe; Bossé, Yohan

    2011-11-01

    Only a handful of studies have attempted to unravel the genetic architecture of calcific aortic valve stenosis (AS). The goal of this study was to validate genes previously associated with AS. Seven genes were assessed: APOB, APOE, CTGF, IL10, PTH, TGFB1, and VDR. Each gene was tested for a comprehensive set of single-nucleotide polymorphisms (SNPs). SNPs were genotyped in 457 patients who underwent surgical aortic valve replacement, and allele frequencies were compared to 3,294 controls. A missense mutation in the APOB gene was significantly associated with AS (rs1042031, E4181K, p = 0.00001). A second SNP located 5.6 kilobases downstream of the APOB stop codon was also associated with the disease (rs6725189, p = 0.000013). Six SNPs surrounding the IL10 locus were strongly associated with AS (0.02 > p > 6.2 × 10⁻¹¹). The most compelling association for IL10 was found with a promoter polymorphism (rs1800872) well known to regulate the production of the encoded anti-inflammatory cytokine. The frequency of the low-producing allele was greater in cases compared to controls (30% vs 20%, p = 6.2 × 10⁻¹¹). SNPs in PTH, TGFB1, and VDR had nominal p values <0.05 but did not resist Bonferroni correction. In conclusion, this study suggests that subjects carrying specific polymorphisms in the IL10 and APOB genes are at higher risk for developing AS.

  18. Susceptibility to chronic mucus hypersecretion, a genome wide association study.

    Directory of Open Access Journals (Sweden)

    Akkelies E Dijkstra

    Full Text Available BACKGROUND: Chronic mucus hypersecretion (CMH is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA study of CMH in Caucasian populations. METHODS: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years. Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP. RESULTS: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10(-6, OR = 1.17, located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1 on chromosome 3. The risk allele (G was associated with higher mRNA expression of SATB1 (4.3×10(-9 in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. CONCLUSIONS: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.

  19. Susceptibility to Chronic Mucus Hypersecretion, a Genome Wide Association Study

    Science.gov (United States)

    Dijkstra, Akkelies E.; Smolonska, Joanna; van den Berge, Maarten; Wijmenga, Ciska; Zanen, Pieter; Luinge, Marjan A.; Platteel, Mathieu; Lammers, Jan-Willem; Dahlback, Magnus; Tosh, Kerrie; Hiemstra, Pieter S.; Sterk, Peter J.; Spira, Avi; Vestbo, Jorgen; Nordestgaard, Borge G.; Benn, Marianne; Nielsen, Sune F.; Dahl, Morten; Verschuren, W. Monique; Picavet, H. Susan J.; Smit, Henriette A.; Owsijewitsch, Michael; Kauczor, Hans U.; de Koning, Harry J.; Nizankowska-Mogilnicka, Eva; Mejza, Filip; Nastalek, Pawel; van Diemen, Cleo C.; Cho, Michael H.; Silverman, Edwin K.; Crapo, James D.; Beaty, Terri H.; Lomas, David A.; Bakke, Per; Gulsvik, Amund; Bossé, Yohan; Obeidat, M. A.; Loth, Daan W.; Lahousse, Lies; Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Andre; Stricker, Bruno H.; Brusselle, Guy G.; van Duijn, Cornelia M.; Brouwer, Uilke; Koppelman, Gerard H.; Vonk, Judith M.; Nawijn, Martijn C.; Groen, Harry J. M.; Timens, Wim; Boezen, H. Marike; Postma, Dirkje S.

    2014-01-01

    Background Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP). Results A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10−6, OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3×10−9) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH. PMID:24714607

  20. Genome-wide association study reveals regions associated with gestation length in two pig populations.

    Science.gov (United States)

    Hidalgo, A M; Lopes, M S; Harlizius, B; Bastiaansen, J W M

    2016-04-01

    Reproduction traits, such as gestation length (GLE), play an important role in dam line breeding in pigs. The objective of our study was to identify single nucleotide polymorphisms (SNPs) that are associated with GLE in two pig populations. Genotypes and deregressed breeding values were available for 2081 Dutch Landrace-based (DL) and 2301 Large White-based (LW) pigs. We identified two QTL regions for GLE, one in each population. For DL, three associated SNPs were detected in one QTL region spanning 0.52 Mbp on Sus scrofa chromosome (SSC) 2. For LW, four associated SNPs were detected in one region of 0.14 Mbp on SSC5. The region on SSC2 contains the heparin-binding EGF-like growth factor (HBEGF) gene, which promotes embryo implantation and has been described to be involved in embryo survival throughout gestation. The associated SNP can be used for marker-assisted selection in the studied populations, and further studies of the HBEGF gene are warranted to investigate its role in GLE.

  1. Genome-wide association studies and resting heart rate

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas

    2016-01-01

    Genome-wide association studies (GWASs) have revolutionized the search for genetic variants regulating resting heart rate. In the last 10 years, GWASs have led to the identification of at least 21 novel heart rate loci. These discoveries have provided valuable insights into the mechanisms...... and pathways that regulate heart rate and link heart rate to cardiovascular morbidity and mortality. GWASs capture majority of genetic variation in a population sample by utilizing high-throughput genotyping chips measuring genotypes for up to several millions of SNPs across the genome in thousands...... of individuals. This allows the identification of the strongest heart rate associated signals at genome-wide level. While GWASs provide robust statistical evidence of the association of a given genetic locus with heart rate, they are only the starting point for detailed follow-up studies to locate the causal...

  2. Genome-wide association study of relative telomere length.

    Science.gov (United States)

    Prescott, Jennifer; Kraft, Peter; Chasman, Daniel I; Savage, Sharon A; Mirabello, Lisa; Berndt, Sonja I; Weissfeld, Joel L; Han, Jiali; Hayes, Richard B; Chanock, Stephen J; Hunter, David J; De Vivo, Immaculata

    2011-05-10

    Telomere function is essential to maintaining the physical integrity of linear chromosomes and healthy human aging. The probability of forming proper telomere structures depends on the length of the telomeric DNA tract. We attempted to identify common genetic variants associated with log relative telomere length using genome-wide genotyping data on 3,554 individuals from the Nurses' Health Study and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that took part in the National Cancer Institute Cancer Genetic Markers of Susceptibility initiative for breast and prostate cancer. After genotyping 64 independent SNPs selected for replication in additional Nurses' Health Study and Women's Genome Health Study participants, we did not identify genome-wide significant loci; however, we replicated the inverse association of log relative telomere length with the minor allele variant [C] of rs16847897 at the TERC locus (per allele β = -0.03, P = 0.003) identified by a previous genome-wide association study. We did not find evidence for an association with variants at the OBFC1 locus or other loci reported to be associated with telomere length. With this sample size we had >80% power to detect β estimates as small as ±0.10 for SNPs with minor allele frequencies of ≥0.15 at genome-wide significance. However, power is greatly reduced for β estimates smaller than ±0.10, such as those for variants at the TERC locus. In general, common genetic variants associated with telomere length homeostasis have been difficult to detect. Potential biological and technical issues are discussed.

  3. Genome-wide association study of relative telomere length.

    Directory of Open Access Journals (Sweden)

    Jennifer Prescott

    Full Text Available Telomere function is essential to maintaining the physical integrity of linear chromosomes and healthy human aging. The probability of forming proper telomere structures depends on the length of the telomeric DNA tract. We attempted to identify common genetic variants associated with log relative telomere length using genome-wide genotyping data on 3,554 individuals from the Nurses' Health Study and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that took part in the National Cancer Institute Cancer Genetic Markers of Susceptibility initiative for breast and prostate cancer. After genotyping 64 independent SNPs selected for replication in additional Nurses' Health Study and Women's Genome Health Study participants, we did not identify genome-wide significant loci; however, we replicated the inverse association of log relative telomere length with the minor allele variant [C] of rs16847897 at the TERC locus (per allele β = -0.03, P = 0.003 identified by a previous genome-wide association study. We did not find evidence for an association with variants at the OBFC1 locus or other loci reported to be associated with telomere length. With this sample size we had >80% power to detect β estimates as small as ±0.10 for SNPs with minor allele frequencies of ≥0.15 at genome-wide significance. However, power is greatly reduced for β estimates smaller than ±0.10, such as those for variants at the TERC locus. In general, common genetic variants associated with telomere length homeostasis have been difficult to detect. Potential biological and technical issues are discussed.

  4. Genome-wide association studies in nephrology: using known associations for data checks.

    Science.gov (United States)

    Wuttke, Matthias; Schaefer, Franz; Wong, Craig S; Köttgen, Anna

    2015-02-01

    Prior to conducting genome-wide association studies (GWAS) of renal traits and diseases, systematic checks to ensure data integrity and analytical work flow should be conducted. Using positive controls (ie, known associations between a single-nucleotide polymorphism [SNP] and a corresponding trait) allows for identifying errors that are not apparent solely from global evaluation of summary statistics. Strong genetic control associations of chronic kidney disease (CKD), as derived from GWAS, are lacking in the non-African ancestry CKD population; thus, in this perspective, we provide examples of and considerations for using positive controls among patients with CKD. Using data from individuals with CKD who participated in the CRIC (Chronic Renal Insufficiency Cohort) Study or PediGFR (Pediatric Investigation for Genetic Factors Linked to Renal Progression) Consortium, we evaluated 2 kinds of positive control traits: traits unrelated to kidney function (bilirubin level and body height) and those related to kidney function (cystatin C and urate levels). For the former, the proportion of variance in the control trait that is explained by the control SNP is the main determinant of the strength of the observable association, irrespective of adjustment for kidney function. For the latter, adjustment for kidney function can be effective in uncovering known associations among patients with CKD. For instance, in 1,092 participants in the PediGFR Consortium, the P value for the association of cystatin C concentrations and rs911119 in the CST3 gene decreased from 2.7×10(-3) to 2.4×10(-8) upon adjustment for serum creatinine-based estimated glomerular filtration rate. In this perspective, we give recommendations for the appropriate selection of control traits and SNPs that can be used for data checks prior to conducting GWAS among patients with CKD.

  5. Clinical study on antibody-associated limbic encephalitis

    Directory of Open Access Journals (Sweden)

    WANG Jia-wei

    2013-01-01

    Full Text Available In recent years, the antibody-associated limbic encephalitis (LE has attracted attentions of more and more clinicians. The associated antibodies mainly act on neuronal cell surface antigens, including the N-methyl-D-aspartate (NMDA receptor, the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA receptor, the γ-aminobutyric acid B (GABAB receptor, leucine-rich glioma-inactivated 1 (LGI1 and contactin-associated protein-like 2 (Caspr2 and so on. The clinical manifestation is primarily defined by the subacute onset of short-term memory loss, seizures, confusion and psychiatric symptoms suggesting the involvement of the limbic system. These severe and protracted disorders can affect children and young adults, occurring with or without tumor association. Routine detection of serum and cerebrospinal fluid (CSF and imaging tests show no specificity, but associated antibodies can be detected in serum and (or CSF. The patients respond well to tumor resection and immunotherapies, including corticosteroids, intravenous immunoglobulin (IVIg, plasma exchange or combination of them, but may relapse. This article aims to study the clinical features and treatment of antibody-associated limbic encephalitis and to improve the diagnosis and prognosis of these diseases.

  6. Genome-wide association studies in asthma: progress and pitfalls

    Directory of Open Access Journals (Sweden)

    March ME

    2015-01-01

    Full Text Available Michael E March,1 Patrick MA Sleiman,1,2 Hakon Hakonarson1,2 1Center for Applied Genomics, Children's Hospital of Philadelphia Research Institute, 2Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Abstract: Genetic studies of asthma have revealed that there is considerable heritability to the phenotype. An extensive history of candidate-gene studies has identified a long list of genes associated with immune function that are potentially involved in asthma pathogenesis. However, many of the results of candidate-gene studies have failed to be replicated, leaving in question the true impact of the implicated biological pathways on asthma. With the advent of genome-wide association studies, geneticists are able to examine the association of hundreds of thousands of genetic markers with a phenotype, allowing the hypothesis-free identification of variants associated with disease. Many such studies examining asthma or related phenotypes have been published, and several themes have begun to emerge regarding the biological pathways underpinning asthma. The results of many genome-wide association studies have currently not been replicated, and the large sample sizes required for this experimental strategy invoke difficulties with sample stratification and phenotypic heterogeneity. Recently, large collaborative groups of researchers have formed consortia focused on asthma, with the goals of sharing material and data and standardizing diagnosis and experimental methods. Additionally, research has begun to focus on genetic variants that affect the response to asthma medications and on the biology that generates the heterogeneity in the asthma phenotype. As this work progresses, it will move asthma patients closer to more specific, personalized medicine. Keywords: asthma, genetics, GWAS, pharmacogenetics, biomarkers

  7. Genome-wide association study identifies five new schizophrenia loci

    DEFF Research Database (Denmark)

    Ripke, Stephan; Sanders, Alan R; Kendler, Kenneth S;

    2011-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yiel...

  8. Genome-Wide Association Study of Serum Selenium Concentrations

    Directory of Open Access Journals (Sweden)

    Ulrike Peters

    2013-05-01

    Full Text Available Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO Cancer Screening and the Women’s Health Initiative (WHI. We tested association between 2,474,333 single nucleotide polymorphisms (SNPs and serum selenium concentrations using linear regression models. In the first stage (PLCO 41 SNPs clustered in 15 regions had p < 1 × 10−5. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003 in the second stage (WHI. Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11 and had p between 2.62 × 10−7 and 4.04 × 10−7 in the combined analysis (PLCO + WHI. Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations.

  9. Genome-wide association study identifies five new schizophrenia loci

    NARCIS (Netherlands)

    Ripke, Stephan; Sanders, Alan R.; Kendler, Kenneth S.; Levinson, Douglas F.; Sklar, Pamela; Holmans, Peter A.; Lin, Dan-Yu; Duan, Jubao; Ophoff, Roel A.; Andreassen, Ole A.; Scolnick, Edward; Cichon, Sven; Clair, David St.; Corvin, Aiden; Gurling, Hugh; Werge, Thomas; Rujescu, Dan; Blackwood, Douglas H. R.; Pato, Carlos N.; Malhotra, Anil K.; Purcell, Shaun; Dudbridge, Frank; Neale, Benjamin M.; Rossin, Lizzy; Visscher, Peter M.; Posthuma, Danielle; Ruderfer, Douglas M.; Fanous, Ayman; Stefansson, Hreinn; Steinberg, Stacy; Mowry, Bryan J.; Golimbet, Vera; De Hert, Marc; Jonsson, Erik G.; Bitter, Istvan; Pietilainen, Olli P. H.; Collier, David A.; Tosato, Sarah; Agartz, Ingrid; Albus, Margot; Alexander, Madeline; Amdur, Richard L.; Amin, Farooq; Bass, Nicholas; Bergen, Sarah E.; Black, Donald W.; Borglum, Anders D.; Brown, Matthew A.; Bruggeman, Richard; Buccola, Nancy G.; Byerley, William F.; Cahn, Wiepke; Cantor, Rita M.; Carr, Vaughan J.; Catts, Stanley V.; Choudhury, Khalid; Cloninger, C. Robert; Cormican, Paul; Craddock, Nicholas; Danoy, Patrick A.; Datta, Susmita; De Haan, Lieuwe; Demontis, Ditte; Dikeos, Dimitris; Djurovic, Srdjan; Donnelly, Peter; Donohoe, Gary; Duong, Linh; Dwyer, Sarah; Fink-Jensen, Anders; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Georgieva, Lyudmila; Giegling, Ina; Gill, Michael; Glenthoj, Birte; Godard, Stephanie; Hamshere, Marian; Hansen, Mark; Hansen, Thomas; Hartmann, Annette M.; Henskens, Frans A.; Hougaard, David M.; Hultman, Christina M.; Ingason, Andres; Jablensky, Assen V.; Jakobsen, Klaus D.; Jay, Maurice; Juergens, Gesche; Kahn, Renes; Keller, Matthew C.; Kenis, Gunter; Kenny, Elaine; Kim, Yunjung; Kirov, George K.; Konnerth, Heike; Konte, Bettina; Krabbendam, Lydia; Krasucki, Robert; Lasseter, Virginia K.; Laurent, Claudine; Lawrence, Jacob; Lencz, Todd; Lerer, F. Bernard; Liang, Kung-Yee; Lichtenstein, Paul; Lieberman, Jeffrey A.; Linszen, Don H.; Lonnqvist, Jouko; Loughland, Carmel M.; Maclean, Alan W.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Malloy, Pat; Mattheisen, Manuel; Mattingsdal, Morten; McGhee, Kevin A.; McGrath, John J.; McIntosh, Andrew; McLean, Duncan E.; McQuillin, Andrew; Melle, Ingrid; Michie, Patricia T.; Milanova, Vihra; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Moskvina, Valentina; Muglia, Pierandrea; Myin-Germeys, Inez; Nertney, Deborah A.; Nestadt, Gerald; Nielsen, Jimmi; Nikolov, Ivan; Nordentoft, Merete; Norton, Nadine; Noethen, Markus M.; O'Dushlaine, Colm T.; Olincy, Ann; Olsen, Line; O'Neill, F. Anthony; Orntoft, Torben F.; Owen, Michael J.; Pantelis, Christos; Papadimitriou, George; Pato, Michele T.; Peltonen, Leena; Petursson, Hannes; Pickard, Ben; Pimm, Jonathan; Pulver, Ann E.; Puri, Vinay; Quested, Digby; Quinn, Emma M.; Rasmussen, Henrik B.; Rethelyi, Janos M.; Ribble, Robert; Rietschel, Marcella; Riley, Brien P.; Ruggeri, Mirella; Schall, Ulrich; Schulze, Thomas G.; Schwab, Sibylle G.; Scott, Rodney J.; Shi, Jianxin; Sigurdsson, Engilbert; Silverman, Jeremy M.; Spencer, Chris C. A.; Stefansson, Kari; Strange, Amy; Strengman, Eric; Stroup, T. Scott; Suvisaari, Jaana; Terenius, Lars; Thirumalai, Srinivasa; Thygesen, Johan H.; Timm, Sally; Toncheva, Draga; van den Oord, Edwin; van Os, Jim; van Winkel, Ruud; Veldink, Jan; Walsh, Dermot; Wang, August G.; Wiersma, Durk; Wildenauer, Dieter B.; Williams, Hywel J.; Williams, Nigel M.; Wormley, Brandon; Zammit, Stan; Sullivan, Patrick F.; O'Donovan, Michael C.; Daly, Mark J.; Gejman, Pablo V.

    2011-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded

  10. Dental trauma in association with maxillofacial fractures: an epidemiological study

    NARCIS (Netherlands)

    Ruslin, M.; Wolff, J.; Boffano, P.; Brand, H.S.; Forouzanfar, T.

    2015-01-01

    Aim The aim of this study was to retrospectively investigate the incidence and associated factors of dental trauma in patients with maxillofacial fractures at the VU Medical Center in Amsterdam. Material and methods Data from 707 patients who were treated surgically for maxillofacial fractures were

  11. A study of type-1 diabetes associated autoantibodies in schizophrenia.

    Science.gov (United States)

    Hallford, Philomena; Clair, David St; Halley, Lorna; Mustard, Colette; Wei, Jun

    2016-10-01

    Epidemiological studies revealed an association between type-1 diabetes (T1D) and schizophrenia but the findings reported to date have been controversial. To clarify the inconsistency across studies, T1D-associated autoantibodies were examined in plasma samples collected from 272 patients with schizophrenia and 276 control subjects. An in-house enzyme-linked immunosorbent assay (ELISA) was developed using three linear peptide antigens, one of which was derived from glutamic acid decarboxylase (GAD) and two were derived from insulinoma-associated antigen 2 (IA2). Mann-Whitney U test showed a significant decrease in the levels of plasma IgG against the IA2b antigen in schizophrenia patients as compared to control subjects (Z=-3.54, p=0.0007), while no significant difference was found between these two groups either in anti-IA2a IgG levels (Z=-1.62, p=0.105) or in anti-GAD IgG levels (Z=-1.63, p=0.104). Linear regression analysis indicated no association of antipsychotic medication with the levels of plasma IgG against IA2a, IA2b or GAD, while the levels of plasma IgG for these 3 peptide antigens were significantly correlated with each other. Binary logistic regression showed that neither the DQ2.5 variant nor the DQ8 variant was associated with circulating levels of 3 T1D-associated autoantibodies in both the patient group and the control group. The coefficient of variation was 10.7% for anti-IA2a IgG assay, 10.1% for anti-IA2b IgG assay and 10.7% for anti-GAD IgG assay. The present work suggests that T1D-associated antibodies are unlikely to confer risk of schizophrenia and that the in-house ELISA developed with linear peptide antigens is highly reproducible.

  12. Ventilator associated pneumonia and transfusion, is there really an association? (the NAVTRA study

    Directory of Open Access Journals (Sweden)

    Gonzalez Marco

    2006-07-01

    Full Text Available Abstract Background Anemic syndrome is a frequent problem in intensive care units. The most probable etiology is the suppression of the erythropoietin response due to the direct effects of cytokines, as well as frequent blood sampling. Transfusions are not free of complications, therefore transfusion reactions are estimated to occur in 2% of the total packed red blood cells (pRBCs transfused. In the past several years, several trials had tried to compare the restrictive with the more liberal use of transfusions, and they were found to be equally effective. Nosocomial pneumonia is the most common nosocomial infection in intensive care units; the prevalence is 47% with an attributive mortality of 33%. There are multiple risk factors for the development of nosocomial pneumonia. Colonization of the upper airways is the most important pathophysiological factor but there are other factors implicated like, sedation techniques, inappropriate use of antibiotics and recumbent positioning. A secondary analysis of the CRIT study describes transfusion therapy and its practices in the United States. They found that transfusion practice is an independent risk factor for the development of nosocomial pneumonia. Methods This is a multicenter, prospective cohort study in different intensive care units in Colombia. A total of 474 patients were selected who had more than 48 hours of mechanical ventilation. The primary objective is to try to demonstrate the hypothetical relationship between the use of transfusions and nosocomial pneumonia. Secondly, we will try to determine which other factors are implicated in the development of pneumonia in intensive care units and describe the incidence of pneumonia and transfusion practices. Discussion Ventilator associated pneumonia is a primary problem in the intensive care unit, multiple factors have been associated with its presence in this study we try to explore the possible association between pneumonia and transfusion

  13. Genome-wide association studies in pediatric endocrinology.

    Science.gov (United States)

    Dauber, Andrew; Hirschhorn, Joel N

    2011-01-01

    Genome-wide association (GWA) studies are a powerful tool for understanding the genetic underpinnings of human disease. In this article, we briefly review the role and findings of GWA studies in type 1 diabetes, stature, pubertal timing, obesity, and vitamin D deficiency. We then discuss the present and future implications of these findings with regards to disease prediction, uncovering basic biology, and the development of novel therapeutic agents.

  14. Genome-Wide Association Study of Down Syndrome-Associated Atrioventricular Septal Defects.

    Science.gov (United States)

    Ramachandran, Dhanya; Zeng, Zhen; Locke, Adam E; Mulle, Jennifer G; Bean, Lora J H; Rosser, Tracie C; Dooley, Kenneth J; Cua, Clifford L; Capone, George T; Reeves, Roger H; Maslen, Cheryl L; Cutler, David J; Feingold, Eleanor; Sherman, Stephanie L; Zwick, Michael E

    2015-07-20

    The goal of this study was to identify the contribution of common genetic variants to Down syndrome-associated atrioventricular septal defect, a severe heart abnormality. Compared with the euploid population, infants with Down syndrome, or trisomy 21, have a 2000-fold increased risk of presenting with atrioventricular septal defects. The cause of this increased risk remains elusive. Here we present data from the largest heart study conducted to date on a trisomic background by using a carefully characterized collection of individuals from extreme ends of the phenotypic spectrum. We performed a genome-wide association study using logistic regression analysis on 452 individuals with Down syndrome, consisting of 210 cases with complete atrioventricular septal defects and 242 controls with structurally normal hearts. No individual variant achieved genome-wide significance. We identified four disomic regions (1p36.3, 5p15.31, 8q22.3, and 17q22) and two trisomic regions on chromosome 21 (around PDXK and KCNJ6 genes) that merit further investigation in large replication studies. Our data show that a few common genetic variants of large effect size (odds ratio >2.0) do not account for the elevated risk of Down syndrome-associated atrioventricular septal defects. Instead, multiple variants of low-to-moderate effect sizes may contribute to this elevated risk, highlighting the complex genetic architecture of atrioventricular septal defects even in the highly susceptible Down syndrome population.

  15. Genome-wide association studies in pediatric chronic kidney disease.

    Science.gov (United States)

    Gupta, Jayanta; Kanetsky, Peter A; Wuttke, Matthias; Köttgen, Anna; Schaefer, Franz; Wong, Craig S

    2016-08-01

    The genome-wide association study (GWAS) has become an established scientific method that provides an unbiased screen for genetic loci potentially associated with phenotypes of clinical interest, such as chronic kidney disease (CKD). Thus, GWAS provides opportunities to gain new perspectives regarding the genetic architecture of CKD progression by identifying new candidate genes and targets for intervention. As such, it has become an important arm of translational science providing a complementary line of investigation to identify novel therapeutics to treat CKD. In this review, we describe the method and the challenges of performing GWAS in the pediatric CKD population. We also provide an overview of successful GWAS for kidney disease, and we discuss the established pediatric CKD cohorts in North America and Europe that are poised to identify genetic risk variants associated with CKD progression.

  16. Methods for Analyzing Multivariate Phenotypes in Genetic Association Studies

    Directory of Open Access Journals (Sweden)

    Qiong Yang

    2012-01-01

    Full Text Available Multivariate phenotypes are frequently encountered in genetic association studies. The purpose of analyzing multivariate phenotypes usually includes discovery of novel genetic variants of pleiotropy effects, that is, affecting multiple phenotypes, and the ultimate goal of uncovering the underlying genetic mechanism. In recent years, there have been new method development and application of existing statistical methods to such phenotypes. In this paper, we provide a review of the available methods for analyzing association between a single marker and a multivariate phenotype consisting of the same type of components (e.g., all continuous or all categorical or different types of components (e.g., some are continuous and others are categorical. We also reviewed causal inference methods designed to test whether the detected association with the multivariate phenotype is truly pleiotropy or the genetic marker exerts its effects on some phenotypes through affecting the others.

  17. Study on multimers and their structures in molecular association mixture

    Institute of Scientific and Technical Information of China (English)

    NI Yi; DOU XiaoMing; ZHAO HaiYing; YIN GuangZhong; YAMAGUCHI Yoshinori; OZAKI Yukihiro

    2007-01-01

    Self-association system of (R)-1,3-butanediol in dilute carbon tetrachloride (CCl4) solution is studied as a model of molecular association mixture. Analysis methods including FSMWEFA (fixed-size moving window evolving factor analysis) combined with PCA (principal component analysis), SIMPLISMA (simple-to-use interactive self-modeling mixture analysis), and ITTFA (iterative target transformation factor analysis) are adopted to resolve infrared spectra of (R)-1,3-butanediol solution. Association number and equilibrium constant are computed. (R)-1,3-butanediol in dilute inert solution is determined as a monomer-trimer equilibrium system. Theoretical investigation of trimer structures is carried out with DFT (density functional theory), and structural factors are analyzed.

  18. Study on multimers and their structures in molecular association mixture

    Institute of Scientific and Technical Information of China (English)

    YAMAGUCHI; Yoshinori; OZAKI; Yukihiro

    2007-01-01

    Self-association system of(R)-1,3-butanediol in dilute carbon tetrachloride(CCl4)solution is studied as a model of molecular association mixture.Analysis methods including FSMWEFA(fixed-size moving window evolving factor analysis)combined with PCA(principal component analysis),SIMPLISMA (simple-to-use interactive self-modeling mixture analysis),and ITTFA(iterative target transformation factor analysis)are adopted to resolve infrared spectra of(R)-1,3-butanediol solution.Association number and equilibrium constant are computed.(R)-1,3-butanediol in dilute inert solution is determined as a monomer-trimer equilibrium system.Theoretical investigation of trimer structures is carried out with DFT(density functional theory),and structural factors are analyzed.

  19. Disease-Concordant Twins Empower Genetic Association Studies

    DEFF Research Database (Denmark)

    Tan, Qihua; Li, Weilong; Vandin, Fabio

    2017-01-01

    Genome-wide association studies with moderate sample sizes are underpowered, especially when testing SNP alleles with low allele counts, a situation that may lead to high frequency of false-positive results and lack of replication in independent studies. Related individuals, such as twin pairs...... concordant for a disease, should confer increased power in genetic association analysis because of their genetic relatedness. We conducted a computer simulation study to explore the power advantage of the disease-concordant twin design, which uses singletons from disease-concordant twin pairs as cases...... and ordinary healthy samples as controls. We examined the power gain of the twin-based design for various scenarios (i.e., cases from monozygotic and dizygotic twin pairs concordant for a disease) and compared the power with the ordinary case-control design with cases collected from the unrelated patient...

  20. Genome-wide association study identifies four loci associated with eruption of permanent teeth.

    Directory of Open Access Journals (Sweden)

    Frank Geller

    2011-09-01

    Full Text Available The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years, analyzed as age-adjusted standard deviation score averaged over multiple time points, based on childhood records for 5,104 women from the Danish National Birth Cohort. Four loci showed association at P<5×10(-8 and were replicated in four independent study groups from the United States and Denmark with a total of 3,762 individuals; all combined P-values were below 10(-11. Two loci agreed with previous findings in primary tooth eruption and were also known to influence height and breast cancer, respectively. The two other loci pointed to genomic regions without any previous significant genome-wide association study results. The intronic SNP rs7924176 in ADK could be linked to gene expression in monocytes. The combined effect of the four genetic variants was most pronounced between age 10 and 12 years, where children with 6 to 8 delayed tooth eruption alleles had on average 3.5 (95% confidence interval: 2.9-4.1 fewer permanent teeth than children with 0 or 1 of these alleles.

  1. Liposomes- and ethosomes-associated distamycins: a comparative study.

    Science.gov (United States)

    Cortesi, Rita; Romagnoli, Romeo; Drechsler, Markus; Menegatti, Enea; Zaid, Abdel N; Ravani, Laura; Esposito, Elisabetta

    2010-12-01

    The present article describes a comparative study of the performances of liposomes and ethosomes as specialized delivery systems for distamycin A (DA) and two of its derivatives. Liposomes and ethosomes were prepared by classical methods, extruded through polycarbonate filters, and characterized in terms of dimensions, morphology, and encapsulation efficiency. It was found that DA was associated with vesicles (either liposomes or ethosomes) by around 16.0%, while both derivatives of DA showed a percentage of association around 80% in the case of liposomes and around 50% in the case of ethosomes. In vitro antiproliferative activity experiments performed on cultured human and mouse leukemic cells demonstrated that vesicles were able to increase the activity of both derivatives of DA. In addition, it was demonstrated that the aging of both liposomes- and ethosomes-associated distamycin suspensions did not heavily influence the vesicle size, while all samples showed a relevant drug leakage with time. Moreover, according to the different physicochemical characteristics of DA and its derivatives (i.e., log P), vesicle-associated DA showed the highest loss of drug with respect to both its derivatives. In conclusion, the enhancement of drug activity expressed by these specialized delivery systems-associated DD could be interesting to obtain an efficient therapeutic effect aimed at reducing or minimizing toxic effects occurring with distamycins administration.

  2. Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat

    Science.gov (United States)

    Sung, Yun Ju; Pérusse, Louis; Sarzynski, Mark A.; Fornage, Myriam; Sidney, Steve; Sternfeld, Barbara; Rice, Treva; Terry, Gregg; Jacobs, David R.; Katzmarzyk, Peter; Curran, Joanne E; Carr, John Jeffrey; Blangero, John; Ghosh, Sujoy; Després, Jean-Pierre; Rankinen, Tuomo; Rao, D.C.; Bouchard, Claude

    2015-01-01

    Background To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR). Subjects and Methods Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT-BMI) or without (TRAIT) adjustment for BMI, and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2,513 subjects of European descent were available for the discovery phase. For replication, 2,171 European Americans and 772 African Americans were available. Results A total of 52 SNPs encompassing 7 loci showed suggestive evidence of association (p < 1.0 × 10−6) with abdominal fat in the sex-combined analyses. The strongest evidence was found on chromosome 7p14.3 between a SNP near BBS9 gene and VAT (rs12374818; p= 1.10 × 10−7), an association that was replicated (p = 0.02). For the BMI-adjusted trait, the strongest evidence of association was found between a SNP near CYCSP30 and VAT-BMI (rs10506943; p= 2.42 × 10−7). Our sex-specific analyses identified one genome-wide significant (p < 5.0 × 10−8) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (p = 3.97 × 10−8 to 1.13 × 10−8). The THNSL2 gene previously associated with VAT in women was also replicated (p= 0.006). The six gene/loci showing the strongest evidence of association with VAT or VAT-BMI were interrogated for their functional links with obesity and inflammation using the Biograph knowledge-mining software. Genes showing the closest functional links with obesity and inflammation were ADCY8 and KCNK9, respectively. Conclusions Our results provide evidence for new loci influencing abdominal visceral (BBS9, ADCY8, KCNK9) and subcutaneous (MLLT10/DNAJC1/EBLN1) fat, and confirmed a locus (THNSL2

  3. Genome-wide association study identifies genetic loci associated with iron deficiency.

    Directory of Open Access Journals (Sweden)

    Christine E McLaren

    Full Text Available The existence of multiple inherited disorders of iron metabolism in man, rodents and other vertebrates suggests genetic contributions to iron deficiency. To identify new genomic locations associated with iron deficiency, a genome-wide association study (GWAS was performed using DNA collected from white men aged≥25 y and women≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS Study with serum ferritin (SF≤12 µg/L (cases and iron replete controls (SF>100 µg/L in men, SF>50 µg/L in women. Regression analysis was used to examine the association between case-control status (336 cases, 343 controls and quantitative serum iron measures and 331,060 single nucleotide polymorphism (SNP genotypes, with replication analyses performed in a sample of 71 cases and 161 controls from a population of white male and female veterans screened at a US Veterans Affairs (VA medical center. Five SNPs identified in the GWAS met genome-wide statistical significance for association with at least one iron measure, rs2698530 on chr. 2p14; rs3811647 on chr. 3q22, a known SNP in the transferrin (TF gene region; rs1800562 on chr. 6p22, the C282Y mutation in the HFE gene; rs7787204 on chr. 7p21; and rs987710 on chr. 22q11 (GWAS observed P<1.51×10(-7 for all. An association between total iron binding capacity and SNP rs3811647 in the TF gene (GWAS observed P=7.0×10(-9, corrected P=0.012 was replicated within the VA samples (observed P=0.012. Associations with the C282Y mutation in the HFE gene also were replicated. The joint analysis of the HEIRS and VA samples revealed strong associations between rs2698530 on chr. 2p14 and iron status outcomes. These results confirm a previously-described TF polymorphism and implicate one potential new locus as a target for gene identification.

  4. Evaluation of Genome Wide Association Study Associated Type 2 Diabetes Susceptibility Loci in Sub Saharan Africans

    Science.gov (United States)

    Adeyemo, Adebowale A.; Tekola-Ayele, Fasil; Doumatey, Ayo P.; Bentley, Amy R.; Chen, Guanjie; Huang, Hanxia; Zhou, Jie; Shriner, Daniel; Fasanmade, Olufemi; Okafor, Godfrey; Eghan, Benjamin; Agyenim-Boateng, Kofi; Adeleye, Jokotade; Balogun, Williams; Elkahloun, Abdel; Chandrasekharappa, Settara; Owusu, Samuel; Amoah, Albert; Acheampong, Joseph; Johnson, Thomas; Oli, Johnnie; Adebamowo, Clement; Collins, Francis; Dunston, Georgia; Rotimi, Charles N.

    2015-01-01

    Genome wide association studies (GWAS) for type 2 diabetes (T2D) undertaken in European and Asian ancestry populations have yielded dozens of robustly associated loci. However, the genomics of T2D remains largely understudied in sub-Saharan Africa (SSA), where rates of T2D are increasing dramatically and where the environmental background is quite different than in these previous studies. Here, we evaluate 106 reported T2D GWAS loci in continental Africans. We tested each of these SNPs, and SNPs in linkage disequilibrium (LD) with these index SNPs, for an association with T2D in order to assess transferability and to fine map the loci leveraging the generally reduced LD of African genomes. The study included 1775 unrelated Africans (1035 T2D cases, 740 controls; mean age 54 years; 59% female) enrolled in Nigeria, Ghana, and Kenya as part of the Africa America Diabetes Mellitus (AADM) study. All samples were genotyped on the Affymetrix Axiom PanAFR SNP array. Forty-one of the tested loci showed transferability to this African sample (p < 0.05, same direction of effect), 11 at the exact reported SNP and 30 others at SNPs in LD with the reported SNP (after adjustment for the number of tested SNPs). TCF7L2 SNP rs7903146 was the most significant locus in this study (p = 1.61 × 10−8). Most of the loci that showed transferability were successfully fine-mapped, i.e., localized to smaller haplotypes than in the original reports. The findings indicate that the genetic architecture of T2D in SSA is characterized by several risk loci shared with non-African ancestral populations and that data from African populations may facilitate fine mapping of risk loci. The study provides an important resource for meta-analysis of African ancestry populations and transferability of novel loci. PMID:26635871

  5. Genome-wide association study identifies 74 loci associated with educational attainment

    Science.gov (United States)

    Okbay, Aysu; Beauchamp, Jonathan P.; Fontana, Mark A.; Lee, James J.; Pers, Tune H.; Rietveld, Cornelius A.; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S. Fleur W.; Oskarsson, Sven; Pickrell, Joseph K.; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S.; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H.; Concas, Maria Pina; Derringer, Jaime; Furlotte, Nicholas A.; Galesloot, Tessel E.; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M.; Harris, Sarah E.; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E.; Kaasik, Kadri; Kalafati, Ioanna P.; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J.; de Leeuw, Christiaan; Lind, Penelope A.; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B.; van der Most, Peter J.; Oldmeadow, Christopher; Payton, Antony; Pervjakova, Natalia; Peyrot, Wouter J.; Qian, Yong; Raitakari, Olli; Rueedi, Rico; Salvi, Erika; Schmidt, Börge; Schraut, Katharina E.; Shi, Jianxin; Smith, Albert V.; Poot, Raymond A.; Pourcain, Beate; Teumer, Alexander; Thorleifsson, Gudmar; Verweij, Niek; Vuckovic, Dragana; Wellmann, Juergen; Westra, Harm-Jan; Yang, Jingyun; Zhao, Wei; Zhu, Zhihong; Alizadeh, Behrooz Z.; Amin, Najaf; Bakshi, Andrew; Baumeister, Sebastian E.; Biino, Ginevra; Bønnelykke, Klaus; Boyle, Patricia A.; Campbell, Harry; Cappuccio, Francesco P.; Davies, Gail; De Neve, Jan-Emmanuel; Deloukas, Panos; Demuth, Ilja; Ding, Jun; Eibich, Peter; Eisele, Lewin; Eklund, Niina; Evans68, David M.; Faul, Jessica D.; Feitosa, Mary F.; Forstner, Andreas J.; Gandin, Ilaria; Gunnarsson, Bjarni; Halldórsson, Bjarni V.; Harris, Tamara B.; Heath, Andrew C.; Hocking, Lynne J.; Holliday, Elizabeth G.; Homuth, Georg; Horan, Michael A.; Hottenga, Jouke-Jan; de Jager, Philip L.; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika A.; Kähönen, Mika; Kanoni, Stavroula; Keltigangas-Järvinen, Liisa; Kiemeney, Lambertus A.L.M.; Kolcic, Ivana; Koskinen, Seppo; Kraja, Aldi T.; Kroh, Martin; Kutalik, Zoltan; Latvala, Antti; Launer, Lenore J.; Lebreton, Maël P.; Levinson, Douglas F.; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C.M.; Loukola, Anu; Madden, Pamela A.; Mägi, Reedik; Mäki-Opas, Tomi; Marioni, Riccardo E.; Marques-Vidal, Pedro; Meddens, Gerardus A.; McMahon, George; Meisinger, Christa; Meitinger, Thomas; Milaneschi, Yusplitri; Milani, Lili; Montgomery, Grant W.; Myhre, Ronny; Nelson, Christopher P.; Nyholt, Dale R.; Ollier, William E.R.; Palotie, Aarno; Paternoster, Lavinia; Pedersen, Nancy L.; Petrovic, Katja E.; Porteous, David J.; Räikkönen, Katri; Ring, Susan M.; Robino, Antonietta; Rostapshova, Olga; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sanders, Alan R.; Sarin, Antti-Pekka; Schmidt, Helena; Scott, Rodney J.; Smith, Blair H.; Smith, Jennifer A.; Staessen, Jan A.; Steinhagen-Thiessen, Elisabeth; Strauch, Konstantin; Terracciano, Antonio; Tobin, Martin D.; Ulivi, Sheila; Vaccargiu, Simona; Quaye, Lydia; van Rooij, Frank J.A.; Venturini, Cristina; Vinkhuyzen, Anna A.E.; Völker, Uwe; Völzke, Henry; Vonk, Judith M.; Vozzi, Diego; Waage, Johannes; Ware, Erin B.; Willemsen, Gonneke; Attia, John R.; Bennett, David A.; Berger, Klaus; Bertram, Lars; Bisgaard, Hans; Boomsma, Dorret I.; Borecki, Ingrid B.; Bultmann, Ute; Chabris, Christopher F.; Cucca, Francesco; Cusi, Daniele; Deary, Ian J.; Dedoussis, George V.; van Duijn, Cornelia M.; Eriksson, Johan G.; Franke, Barbara; Franke, Lude; Gasparini, Paolo; Gejman, Pablo V.; Gieger, Christian; Grabe, Hans-Jörgen; Gratten, Jacob; Groenen, Patrick J.F.; Gudnason, Vilmundur; van der Harst, Pim; Hayward, Caroline; Hinds, David A.; Hoffmann, Wolfgang; Hyppönen, Elina; Iacono, William G.; Jacobsson, Bo; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L.R.; Lehtimäki, Terho; Lehrer, Steven F.; Magnusson, Patrik K.E.; Martin, Nicholas G.; McGue, Matt; Metspalu, Andres; Pendleton, Neil; Penninx, Brenda W.J.H.; Perola, Markus; Pirastu, Nicola; Pirastu, Mario; Polasek, Ozren; Posthuma, Danielle; Power, Christine; Province, Michael A.; Samani, Nilesh J.; Schlessinger, David; Schmidt, Reinhold; Sørensen, Thorkild I.A.; Spector, Tim D.; Stefansson, Kari; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tiemeier, Henning; Tung, Joyce Y.; Uitterlinden, André G.; Vitart, Veronique; Vollenweider, Peter; Weir, David R.; Wilson, James F.; Wright, Alan F.; Conley, Dalton C.; Krueger, Robert F.; Smith, George Davey; Hofman, Albert; Laibson, David I.; Medland, Sarah E.; Meyer, Michelle N.; Yang, Jian; Johannesson, Magnus; Visscher, Peter M.; Esko, Tõnu; Koellinger, Philipp D.; Cesarini, David; Benjamin, Daniel J.

    2016-01-01

    Summary Educational attainment (EA) is strongly influenced by social and other environmental factors, but genetic factors are also estimated to account for at least 20% of the variation across individuals1. We report the results of a genome-wide association study (GWAS) for EA that extends our earlier discovery sample1,2 of 101,069 individuals to 293,723 individuals, and a replication in an independent sample of 111,349 individuals from the UK Biobank. We now identify 74 genome-wide significant loci associated with number of years of schooling completed. Single-nucleotide polymorphisms (SNPs) associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioral phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because EA is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric disease. PMID:27225129

  6. A whole-genome association study for pig reproductive traits.

    Science.gov (United States)

    Onteru, S K; Fan, B; Du, Z-Q; Garrick, D J; Stalder, K J; Rothschild, M F

    2012-02-01

    A whole-genome association study was performed for reproductive traits in commercial sows using the PorcineSNP60 BeadChip and Bayesian statistical methods. The traits included total number born (TNB), number born alive (NBA), number of stillborn (SB), number of mummified foetuses at birth (MUM) and gestation length (GL) in each of the first three parities. We report the associations of informative QTL and the genes within the QTL for each reproductive trait in different parities. These results provide evidence of gene effects having temporal impacts on reproductive traits in different parities. Many QTL identified in this study are new for pig reproductive traits. Around 48% of total genes located in the identified QTL regions were predicted to be involved in placental functions. The genomic regions containing genes important for foetal developmental (e.g. MEF2C) and uterine functions (e.g. PLSCR4) were associated with TNB and NBA in the first two parities. Similarly, QTL in other foetal developmental (e.g. HNRNPD and AHR) and placental (e.g. RELL1 and CD96) genes were associated with SB and MUM in different parities. The QTL with genes related to utero-placental blood flow (e.g. VEGFA) and hematopoiesis (e.g. MAFB) were associated with GL differences among sows in this population. Pathway analyses using genes within QTL identified some modest underlying biological pathways, which are interesting candidates (e.g. the nucleotide metabolism pathway for SB) for pig reproductive traits in different parities. Further validation studies on large populations are warranted to improve our understanding of the complex genetic architecture for pig reproductive traits.

  7. A study of associated congenital anomalies with biliary atresia

    Directory of Open Access Journals (Sweden)

    Lucky Gupta

    2016-01-01

    Full Text Available Background/Purpose: This study aims to analyze the incidence and type of various associated anomalies among infants with extrahepatic biliary atresia (EHBA, compare their frequency with those quoted in the existing literature and assess their role in the overall management. Materials and Methods: A retrospective study was performed on 137 infants who underwent the Kasai procedure for EHBA during the past 12 years. The medical records were reviewed for the incidence and type of associated anomalies in addition to the details of the management of the EHBA. Results: Of the137 infants, 40 (29.2% were diagnosed as having 58 anomalies. The majority of patients had presented in the 3 rd month of life; mean age was 81 ± 33 days (range = 20-150 days. There were 32 males and 8 females; boys with EHBA had a higher incidence of associated anomalies. Of these 40 patients, 22 (37.9% had vascular anomalies, 13 patients (22.4% had hernias (umbilical-10, inguinal-3, 7 patients (12.1% had intestinal malrotation, 4 patients (6.8% had choledochal cyst, 1 patient (1.7% had Meckel′s diverticulum, 3 patients (5% had undergone prior treatment for jejunoileal atresias (jejunal-2, ileal-1, 2 patients (3.4% had undergone prior treatment for esophageal atresia and tracheoesophageal fistula, 2 patients (3.4% had spleniculi, and 2 patients (3.4% were diagnosed as having situs inversus. Conclusions: The most common associated anomalies in our study were related to the vascular variation at the porta hepatis and the digestive system. The existence of anomalies in distantly developing anatomic regions in patients with EHBA supports the possibility of a "generalized" insult during embryogenesis rather than a "localized" defect. In addition, male infants were observed to have significantly more associated anomalies as compared with the female infants in contrast to earlier reports.

  8. Association studies in common endocrine diseases (review article

    Directory of Open Access Journals (Sweden)

    Akrami SM

    2007-05-01

    Full Text Available Our understanding of the pathogenesis of endocrine disorders increase rapidly by genetic studies at the molecular level. Common endocrine disorders such as diabetes mellitus, obesity, osteoporosis, dyslipidemia and cancer follow the multifactorial model in the genetic aspect. This review tries to clarify the approach in molecular studies of such diseases for clinicians in different specialties. How to evaluate a possible association between a single nucleotide polymorphism and an endocrinopathy or its complication is the main concern of this review. Two approaches for gene mapping will be discussed as well as main challenges regarding each approach. All such genetic studies ideally include some test of the association between genome sequence variation and the phenotype of interest such as the trait itself, the presence of a given complication, or measures of some endocrinopathy-related intermediate trait. Despite different advances in this analysis, there are major concerns regarding the overall performance and robustness of genetic association studies. By using powerful new high-throughput methods, further insights to molecular basis of such endocrine disorders can be expected. Close correlation between geneticists and clinicians can effectively bridge between basic sciences and clinical investigations.

  9. Insights into kidney diseases from genome-wide association studies.

    Science.gov (United States)

    Wuttke, Matthias; Köttgen, Anna

    2016-09-01

    Over the past decade, genome-wide association studies (GWAS) have considerably improved our understanding of the genetic basis of kidney function and disease. Population-based studies, used to investigate traits that define chronic kidney disease (CKD), have identified >50 genomic regions in which common genetic variants associate with estimated glomerular filtration rate or urinary albumin-to-creatinine ratio. Case-control studies, used to study specific CKD aetiologies, have yielded risk loci for specific kidney diseases such as IgA nephropathy and membranous nephropathy. In this Review, we summarize important findings from GWAS and clinical and experimental follow-up studies. We also compare risk allele frequency, effect sizes, and specificity in GWAS of CKD-defining traits and GWAS of specific CKD aetiologies and the implications for study design. Genomic regions identified in GWAS of CKD-defining traits can contain causal genes for monogenic kidney diseases. Population-based research on kidney function traits can therefore generate insights into more severe forms of kidney diseases. Experimental follow-up studies have begun to identify causal genes and variants, which are potential therapeutic targets, and suggest mechanisms underlying the high allele frequency of causal variants. GWAS are thus a useful approach to advance knowledge in nephrology.

  10. Lipid nanotechnologies for structural studies of membrane-associated proteins.

    Science.gov (United States)

    Stoilova-McPhie, Svetla; Grushin, Kirill; Dalm, Daniela; Miller, Jaimy

    2014-11-01

    We present a methodology of lipid nanotubes (LNT) and nanodisks technologies optimized in our laboratory for structural studies of membrane-associated proteins at close to physiological conditions. The application of these lipid nanotechnologies for structure determination by cryo-electron microscopy (cryo-EM) is fundamental for understanding and modulating their function. The LNTs in our studies are single bilayer galactosylceramide based nanotubes of ∼20 nm inner diameter and a few microns in length, that self-assemble in aqueous solutions. The lipid nanodisks (NDs) are self-assembled discoid lipid bilayers of ∼10 nm diameter, which are stabilized in aqueous solutions by a belt of amphipathic helical scaffold proteins. By combining LNT and ND technologies, we can examine structurally how the membrane curvature and lipid composition modulates the function of the membrane-associated proteins. As proof of principle, we have engineered these lipid nanotechnologies to mimic the activated platelet's phosphtaidylserine rich membrane and have successfully assembled functional membrane-bound coagulation factor VIII in vitro for structure determination by cryo-EM. The macromolecular organization of the proteins bound to ND and LNT are further defined by fitting the known atomic structures within the calculated three-dimensional maps. The combination of LNT and ND technologies offers a means to control the design and assembly of a wide range of functional membrane-associated proteins and complexes for structural studies by cryo-EM. The presented results confirm the suitability of the developed methodology for studying the functional structure of membrane-associated proteins, such as the coagulation factors, at a close to physiological environment.

  11. Facial dermatosis associated with Demodex: a case-control study*

    OpenAIRE

    Zhao, Ya-e; Peng, Yan; Wang, Xiang-lan; Wu, Li-ping; Wang, Mei; Yan, Hu-ling; Xiao, Sheng-xiang

    2011-01-01

    Demodex has been considered to be related with multiple skin disorders, but controversy persists. In this case-control study, a survey was conducted with 860 dermatosis patients aged 12 to 84 years in Xi’an, China to identify the association between facial dermatosis and Demodex. Amongst the patients, 539 suffered from facial dermatosis and 321 suffered from non-facial dermatosis. Demodex mites were sampled and examined using the skin pressurization method. Multivariate regression analysis wa...

  12. A Pooled Genome-Wide Association Study of Asperger Syndrome.

    Directory of Open Access Journals (Sweden)

    Varun Warrier

    Full Text Available Asperger Syndrome (AS is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC, which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448 were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448 lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

  13. A Pooled Genome-Wide Association Study of Asperger Syndrome.

    Science.gov (United States)

    Warrier, Varun; Chakrabarti, Bhismadev; Murphy, Laura; Chan, Allen; Craig, Ian; Mallya, Uma; Lakatošová, Silvia; Rehnstrom, Karola; Peltonen, Leena; Wheelwright, Sally; Allison, Carrie; Fisher, Simon E; Baron-Cohen, Simon

    2015-01-01

    Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

  14. Adult Learning Open University Determinants (ALOUD) study: Psychological factors associated with study success

    NARCIS (Netherlands)

    Neroni, Joyce; De Groot, Renate; Kirschner, Paul A.

    2013-01-01

    Neroni, J., De Groot, R. H. M., & Kirschner, P. A. (2012, 7 November). Adult Learning Open University Determinants (ALOUD) study: Psychological factors associated with study success. Poster presentation at the International ICO Fall School, Girona, Spain.

  15. Adult Learning Open University Determinants study (ALOUD): Biological lifestyle factors associated with study success

    NARCIS (Netherlands)

    Gijselaers, Jérôme; De Groot, Renate; Kirschner, Paul A.

    2012-01-01

    Gijselaers, H. J. M., De Groot, R. H. M., & Kirschner, P. A. (2012, 7 November). Adult Learning Open University Determinants study (ALOUD): Biological lifestyle factors associated with study success. Poster presentation at the International ICO Fall School, Girona, Spain.

  16. Multiethnic genetic association studies improve power for locus discovery.

    Directory of Open Access Journals (Sweden)

    Sara L Pulit

    Full Text Available To date, genome-wide association studies have focused almost exclusively on populations of European ancestry. These studies continue with the advent of next-generation sequencing, designed to systematically catalog and test low-frequency variation for a role in disease. A complementary approach would be to focus further efforts on cohorts of multiple ethnicities. This leverages the idea that population genetic drift may have elevated some variants to higher allele frequency in different populations, boosting statistical power to detect an association. Based on empirical allele frequency distributions from eleven populations represented in HapMap Phase 3 and the 1000 Genomes Project, we simulate a range of genetic models to quantify the power of association studies in multiple ethnicities relative to studies that exclusively focus on samples of European ancestry. In each of these simulations, a first phase of GWAS in exclusively European samples is followed by a second GWAS phase in any of the other populations (including a multiethnic design. We find that nontrivial power gains can be achieved by conducting future whole-genome studies in worldwide populations, where, in particular, African populations contribute the largest relative power gains for low-frequency alleles (<5% of moderate effect that suffer from low power in samples of European descent. Our results emphasize the importance of broadening genetic studies to worldwide populations to ensure efficient discovery of genetic loci contributing to phenotypic trait variability, especially for those traits for which large numbers of samples of European ancestry have already been collected and tested.

  17. A statistical study of post-flare-associated CME events

    Science.gov (United States)

    Youssef, M.; Mawad, R.; shaltout, Mosalam

    2013-04-01

    We present a statistical study of post-flare-associated CMEs (PFA-CMEs) during the period from 1996 to 2010. By investigating all CMEs and X-ray flares, respectively, in the LASCO and GOES archives, we found 15875 CMEs of which masses are well measured and 25112 X-ray flares of which positions are determined from their optical counterparts. Under certain temporal and spatial criteria of these CMEs and solar flare events, 291PFA-CMEs events have been selected. Linking the flare fluxes with CME speeds of these paired events, we found that there is a reasonable positive linear relation between the CME linear speed and associated flare flux. The results show also the CME width increases as the flux of its associated solar flare increases. Besides we found that there is a fine positive linear relation between the CME mass and its width. Matching the flare fluxes with CME masses of these paired events, we find the CME mass increases as the flux of its associated solar flare increases. Finally we find the PFA-CME events are in regular more decelerated than the other CMEs.

  18. [Association study of telomere length with idiopathic male infertility].

    Science.gov (United States)

    Shuyuan, Liu; Changjun, Zhang; Haiying, Peng; Xiaoqin, Huang; Hao, Sun; Keqin, Lin; Kai, Huang; Jiayou, Chu; Zhaoqing, Yang

    2015-11-01

    Telomeres are evolutionary conserved, multifunctional DNA-protein complexes located at the ends of eukaryotic chromosomes. Telomeres maintain chromosome stability and genome integrity and also play an important role in meiosis which aid in synapsis, homologous recombination, and segregation. Sperm telomere has been reported to play an important role in fertilization and embryo development. Nowadays, the association between telomere and reproduction is one of the major areas of interest, however whether sperm telomere associated with male infertility is not clear. In this study, in order to find out the association between Chinese idiopathic infertility and sperm telomere length, we analyzed the difference of sperm telomere length between idiopathic infertile men and normal fertile men, as well as the correlations between sperm telomere length and human semen characteristics. We analyzed 126 Chinese idiopathic infertile men and 138 normal fertile men for sperm telomere length by using quantitative PCR. We found that the relative sperm mean telomere length of infertile men was significantly shorter than that of fertile men (2.894 ± 0.115 vs. 4.016 ± 0.603, P=5.097 x 10⁻⁵). Both sperm count and semen progressive motility are related with telomere length. Our results suggest that sperm telomere length is associated with idiopathic male infertility of China and we proposed the possibility that shorter telomeres in sperm chromosome will reduce spermatogenesis and sperm functions, which finally affected the fertility of male.

  19. A Photometric Study of Stars in the MBM 12 Association

    Science.gov (United States)

    Herbst, William; Williams, Eric C.; Hawley, Wendy P.

    2004-03-01

    We have monitored four fields containing nine previously identified members of the MBM 12 association to search for photometric variability and periodicity in these pre-main-sequence stars. Seven of the nine are found to be variable and definite periodicity (of 1.2, 2.6, and 6.2 days) is found for three of them, including the classical T Tauri star LkHα 264. Two other members are possibly periodic, but each requires confirmation. In addition, a ``field'' star that is associated with the X-ray source RX J0255.9+2005 was discovered to be a variable with a period of 4.2 days. Our results indicate that the photometric variability characteristics of the known MBM 12 association members are typical of what is found in roughly few-million-year-old stellar groups such as IC 348, supporting arguments for a similar age. In particular, there is a mix of periodic and nonperiodic variables with typical amplitudes (in Cousins I) of 0.1-0.5 mag, in addition to a small number of larger amplitude variables. The periods, as a group, are somewhat shorter than in IC 348, but when allowance is made for the known dependence of period on mass in pre-main-sequence stars the difference may not be significant. Our data confirm and illustrate the value of photometric monitoring as a tool for identifying likely association members and for studying rotation in extremely young stellar groups.

  20. Poor replication validity of biomedical association studies reported by newspapers

    Science.gov (United States)

    Smith, Andy; Boraud, Thomas; Gonon, François

    2017-01-01

    Objective To investigate the replication validity of biomedical association studies covered by newspapers. Methods We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Results Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Conclusion Journalists

  1. [Genome-wide association study for adolescent idiopathic scoliosis].

    Science.gov (United States)

    Ogura, Yoji; Kou, Ikuyo; Scoliosis, Japan; Matsumoto, Morio; Watanabe, Kota; Ikegawa, Shiro

    2016-04-01

    Adolescent idiopathic scoliosis(AIS)is a polygenic disease. Genome-wide association studies(GWASs)have been performed for a lot of polygenic diseases. For AIS, we conducted GWAS and identified the first AIS locus near LBX1. After the discovery, we have extended our study by increasing the numbers of subjects and SNPs. In total, our Japanese GWAS has identified four susceptibility genes. GWASs for AIS have also been performed in the USA and China, which identified one and three susceptibility genes, respectively. Here we review GWASs in Japan and abroad and functional analysis to clarify the pathomechanism of AIS.

  2. Factors associated with incomplete small bowel capsule endoscopy studies

    Institute of Scientific and Technical Information of China (English)

    Mitchell; M; Lee; Andrew; Jacques; Eric; Lam; Ricky; Kwok; Pardis; Lakzadeh; Ajit; Sandhar; Brandon; Segal; Sigrid; Svarta; Joanna; Law; Robert; Enns

    2010-01-01

    AIM:To identify patient risk factors associated with incomplete small bowel capsule endoscopy(CE) studies.METHODS:Data from all CE procedures performed at St.Paul's Hospital in Vancouver,British Columbia,Canada,between December 2001 and June 2008 were collected and analyzed on a retrospective basis.Data collection for complete and incomplete CE study groups included patient demographics as well as a number of potential risk factors for incomplete CE including indication for the procedure,hospitalization,dia...

  3. Genome-wide association study of antisocial personality disorder

    Science.gov (United States)

    Rautiainen, M-R; Paunio, T; Repo-Tiihonen, E; Virkkunen, M; Ollila, H M; Sulkava, S; Jolanki, O; Palotie, A; Tiihonen, J

    2016-01-01

    The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53–3.14), P=1.9 × 10-5). Two polymorphisms at 6p21.2 LINC00951–LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37–1.85), P=1.6 × 10−9) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (β=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder. PMID:27598967

  4. Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study.

    Directory of Open Access Journals (Sweden)

    Giuseppe Matullo

    Full Text Available Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM, a rare aggressive tumor. Nevertheless, only 5-17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes, causing at most a 2-3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14. Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52-95.28. These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos.

  5. Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study.

    Science.gov (United States)

    Matullo, Giuseppe; Guarrera, Simonetta; Betti, Marta; Fiorito, Giovanni; Ferrante, Daniela; Voglino, Floriana; Cadby, Gemma; Di Gaetano, Cornelia; Rosa, Fabio; Russo, Alessia; Hirvonen, Ari; Casalone, Elisabetta; Tunesi, Sara; Padoan, Marina; Giordano, Mara; Aspesi, Anna; Casadio, Caterina; Ardissone, Francesco; Ruffini, Enrico; Betta, Pier Giacomo; Libener, Roberta; Guaschino, Roberto; Piccolini, Ezio; Neri, Monica; Musk, Arthur W B; de Klerk, Nicholas H; Hui, Jennie; Beilby, John; James, Alan L; Creaney, Jenette; Robinson, Bruce W; Mukherjee, Sutapa; Palmer, Lyle J; Mirabelli, Dario; Ugolini, Donatella; Bonassi, Stefano; Magnani, Corrado; Dianzani, Irma

    2013-01-01

    Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5-17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2-3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14). Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52-95.28). These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos.

  6. Genome-wide association study and premature ovarian failure.

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    Christin-Maitre, S; Tachdjian, G

    2010-05-01

    Premature ovarian failure (POF) is defined as an amenorrhea for more than 4months, associated with elevated gonadotropins, usually higher than 20mIU/ml, occurring in a woman before the age of 40. Some candidate genes have been identified in the past 15years, such as FOXL2, FSHR, BMP15, GDF9, Xfra premutation. However, POF etiology remains unknown in more than 90% of cases. The first strategy to identify candidate gene, apart from studying genes involved in ovarian failure in animal models, relies on the study of X chromosome deletions and X;autosome translocations in patients. The second strategy is based on linkage analysis, the third one on Comparative Genomic Hybridization (CGH) array. The latest strategy relies on Genome-Wide Association Studies (GWAS). This technique consists in screening single nucleotide polymorphisms (SNPs) in patients and controls. So far, three studies have been performed and have identified different loci potentially linked to POF, such as PTHB1 and ADAMTS19. However, replications in independent cohorts need to be performed. GWAS studies on large cohorts of women with POF should find new candidate genes in the near future.

  7. Genome-wide association study identifies multiple loci associated with bladder cancer risk

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    Figueroa, Jonine D.; Ye, Yuanqing; Siddiq, Afshan; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Prokunina-Olsson, Ludmila; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Dinney, Colin P.; Malats, Núria; Baris, Dalsu; Purdue, Mark; Jacobs, Eric J.; Albanes, Demetrius; Wang, Zhaoming; Deng, Xiang; Chung, Charles C.; Tang, Wei; Bas Bueno-de-Mesquita, H.; Trichopoulos, Dimitrios; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth; Tjønneland, Anne; Brenan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Rodabough, Rebecca; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Chen, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Kamat, Ashish M.; Lerner, Seth P.; Barton Grossman, H.; Lin, Jie; Gu, Jian; Pu, Xia; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Kogevinas, Manolis; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Schwenn, Molly; Karagas, Margaret R.; Johnson, Alison; Schned, Alan; Armenti, Karla R.; Hosain, G.M.; Andriole, Gerald; Grubb, Robert; Black, Amanda; Ryan Diver, W.; Gapstur, Susan M.; Weinstein, Stephanie J.; Virtamo, Jarmo; Haiman, Chris A.; Landi, Maria T.; Caporaso, Neil; Fraumeni, Joseph F.; Vineis, Paolo; Wu, Xifeng; Silverman, Debra T.; Chanock, Stephen; Rothman, Nathaniel

    2014-01-01

    Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10−5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10−9) and rs907611 on 11p15.5 (P = 4.11 × 10−8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10−7) and rs4510656 on 6p22.3 (P = 6.98 × 10−7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis. PMID:24163127

  8. STUDY OF ASSOCIATION OF DIABETIC MACULOPATHY WITH HYPERLIPIDEMIA

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    Sivaramareddy

    2015-12-01

    Full Text Available BACKGROUND Diabetic maculopathy is the most common microvascular complication in diabetes, which can produce severe visual loss. Apart from diabetes, a number of systemic factor like hyperlipidemia has an important role in occurrence and progression of Diabetic Macular Edema. Thus control of these factors along with control of blood sugars can prevent or reverse the maculopathy and thereby restore the vision of diabetic patients. OBJECTIVES To study the association of diabetic maculopathy with Hyperlipidemia to highlight the effect of this factor on onset and/or progression of diabetic maculopathy. MATERIALS AND METHODS A cross-sectional comparative study was carried out in 100 diabetic patient with retinopathy more than 18 years attending Department of Ophthalmology. For all patients visual acuity, slit lamp examination, intraocular pressure, fundus examination was conducted. Patients were divided into 2 groups (Group1 - Retinopathy with maculopathy and Group 2 - Retinopathy without maculopathy. A detailed history of duration of diabetes, type of treatment, hyperlipidemia were taken from the patient. The significance of the hyperlipidemia was compared in both the groups involved in the study. RESULTS In the present study of 100 patients diagnosed with diabetic retinopathy, majority were males (54% in study group and 58% in control group by age 51-60 years. In the study group, majority (76% patients had duration of DM>10 years, whereas in control group majority of patients (70% had duration 5-10 years. The mean value of PPBS, HbA1C were significantly higher in study group than in control group. In this study among serum lipids, serum cholesterol, serum triglycerides, VLDL and LDL levels were significantly higher in study group compared to control group. CONCLUSION Diabetic maculopathy was significantly associated with hyperlipidemia. Thus early detection of this risk factor and their control prevent the development and progression of maculopathy

  9. Multiple Sclerosis Associated Risk Factors: A Case-Control Study

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    Jalal POOROLAJAL

    2015-11-01

    Full Text Available Background: Hamadan Province is one of the high-risk regions in Iran for Multiple sclerosis (MS. A majority of the epidemiological studies conducted in Iran addressing MS are descriptive. This study was conducted to assess MS and its associated risk factors in Hamadan Province, the west of Iran.Methods: This case-control study compared 100 patients with MS (case group and 100 patients with acute infectious diseases (control group from September 2013 to March 2014. A checklist was used to assess the demographic, medical, and family history of the patients. The Friedman-Rosenman questionnaire was also used to assess personality type. Statistical analysis was performed using logistic regression model with Stata 11 software program.Results: The adjusted odds ratio (OR estimate of MS was 4.37 (95% CI: 2.33, 8.20 for females compared to males; 0.15 (95% CI: 0.06, 0.43 for people aged above 50 years compared to aged 14 to 29 years; 0.44 (95% CI: 0.21, 0.91 for overweight or obese people compared to normal weights. Crude OR indicated a significant association between the occurrence of MS and exclusive breast feeding, season of birth, and smoking. However, the association was not statistically significant after adjustment for other covariates.Conclusion: The risk of MS is significantly lower in male gender, obese/overweight, and old people. Furthermore, non-smoking, non-exclusive breast-feeding, and born in autumn may increase the risk of MS but need further investigation. However, long-term large prospective cohort studies are needed to investigate the true effect of the potential risk factors on MS. Keywords: Multiple sclerosis, Risk factors, Case-control study, Iran

  10. Genome-Wide Association Study Identifies Novel Loci Associated With Diisocyanate-Induced Occupational Asthma

    Science.gov (United States)

    Yucesoy, Berran; Kaufman, Kenneth M.; Lummus, Zana L.; Weirauch, Matthew T.; Zhang, Ge; Cartier, André; Boulet, Louis-Philippe; Sastre, Joaquin; Quirce, Santiago; Tarlo, Susan M.; Cruz, Maria-Jesus; Munoz, Xavier; Harley, John B.; Bernstein, David I.

    2015-01-01

    Diisocyanates, reactive chemicals used to produce polyurethane products, are the most common causes of occupational asthma. The aim of this study is to identify susceptibility gene variants that could contribute to the pathogenesis of diisocyanate asthma (DA) using a Genome-Wide Association Study (GWAS) approach. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed in 74 diisocyanate-exposed workers with DA and 824 healthy controls using Omni-2.5 and Omni-5 SNP microarrays. We identified 11 SNPs that exceeded genome-wide significance; the strongest association was for the rs12913832 SNP located on chromosome 15, which has been mapped to the HERC2 gene (p = 6.94 × 10−14). Strong associations were also found for SNPs near the ODZ3 and CDH17 genes on chromosomes 4 and 8 (rs908084, p = 8.59 × 10−9 and rs2514805, p = 1.22 × 10−8, respectively). We also prioritized 38 SNPs with suggestive genome-wide significance (p < 1 × 10−6). Among them, 17 SNPs map to the PITPNC1, ACMSD, ZBTB16, ODZ3, and CDH17 gene loci. Functional genomics data indicate that 2 of the suggestive SNPs (rs2446823 and rs2446824) are located within putative binding sites for the CCAAT/Enhancer Binding Protein (CEBP) and Hepatocyte Nuclear Factor 4, Alpha transcription factors (TFs), respectively. This study identified SNPs mapping to the HERC2, CDH17, and ODZ3 genes as potential susceptibility loci for DA. Pathway analysis indicated that these genes are associated with antigen processing and presentation, and other immune pathways. Overlap of 2 suggestive SNPs with likely TF binding sites suggests possible roles in disruption of gene regulation. These results provide new insights into the genetic architecture of DA and serve as a basis for future functional and mechanistic studies. PMID:25918132

  11. Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension.

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    Sandosh Padmanabhan

    2010-10-01

    Full Text Available Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6 × 10⁻¹¹. The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91], reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027. In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003. In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

  12. A genome-wide association study in multiple system atrophy

    Science.gov (United States)

    Sailer, Anna; Nalls, Michael A.; Schulte, Claudia; Federoff, Monica; Price, T. Ryan; Lees, Andrew; Ross, Owen A.; Dickson, Dennis W.; Mok, Kin; Mencacci, Niccolo E.; Schottlaender, Lucia; Chelban, Viorica; Ling, Helen; O'Sullivan, Sean S.; Wood, Nicholas W.; Traynor, Bryan J.; Ferrucci, Luigi; Federoff, Howard J.; Mhyre, Timothy R.; Morris, Huw R.; Deuschl, Günther; Quinn, Niall; Widner, Hakan; Albanese, Alberto; Infante, Jon; Bhatia, Kailash P.; Poewe, Werner; Oertel, Wolfgang; Höglinger, Günter U.; Wüllner, Ullrich; Goldwurm, Stefano; Pellecchia, Maria Teresa; Ferreira, Joaquim; Tolosa, Eduardo; Bloem, Bastiaan R.; Rascol, Olivier; Meissner, Wassilios G.; Hardy, John A.; Revesz, Tamas; Holton, Janice L.; Gasser, Thomas; Wenning, Gregor K.; Singleton, Andrew B.

    2016-01-01

    Objective: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS). Methods: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed. Results: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 × 10−6, including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA. Conclusions: We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps. PMID:27629089

  13. Sincipital Encephaloceles: A Study of Associated Brain Malformations

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    Shashidhar Vedavyas Achar

    2016-01-01

    Full Text Available Objective: The aim of this study was to evaluate the associated intracranial malformations in patients with sincipital encephaloceles. Materials and Methods: A hospital-based cross-sectional study was conducted over 8 years from June 2007 to May 2015 on 28 patients. The patients were evaluated by either computed tomography or magnetic resonance imaging whichever was feasible. Encephaloceles were described with respect to their types, contents, and extensions. A note was made on the associated malformations with sincipital encephaloceles. Results: Fifty percent of the patients presented before the age of 3 years and both the sexes were affected equally. Nasofrontal encephalocele was the most common type seen in 13 patients (46.4%, and corpus callosal agenesis (12 patients was the most common associated malformation. Other malformations noted were arachnoid cyst (10 patients, hydrocephalus (7 patients, and agyria-pachygyria complex (2 patients. Conclusion: Capital Brain malformations are frequently encountered in children with sincipital encephaloceles. Detail radiological evaluation is necessary to plan treatment and also to prognosticate such rare malformations.

  14. A genome-wide association study of female sexual dysfunction.

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    Andrea Burri

    Full Text Available BACKGROUND: Female sexual dysfunction (FSD is an important but controversial problem with serious negative impact on women's quality of life. Data from twin studies have shown a genetic contribution to the development and maintenance of FSD. METHODOLOGY/PRINCIPAL FINDINGS: We performed a genome-wide association study (GWAS on 2.5 million single-nucleotide polymorphisms (SNPs in 1,104 female twins (25-81 years of age in a population-based register and phenotypic data on lifelong sexual functioning. Although none reached conventional genome-wide level of significance (10 × -8, we found strongly suggestive associations with the phenotypic dimension of arousal (rs13202860, P = 1.2 × 10(-7; rs1876525, P = 1.2 × 10(-7; and rs13209281 P = 8.3 × 10(-7 on chromosome 6, around 500 kb upstream of the locus HTR1E (5-hydroxytryptamine receptor 1E locus, related to the serotonin brain pathways. We could not replicate previously reported candidate SNPs associated with FSD in the DRD4, 5HT2A and IL-1B loci. CONCLUSIONS/SIGNIFICANCE: We report the first GWAS of FSD symptoms in humans. This has pointed to several "risk alleles" and the implication of the serotonin and GABA pathways. Ultimately, understanding key mechanisms via this research may lead to new FSD treatments and inform clinical practice and developments in psychiatric nosology.

  15. A genome-wide association study of heat stress-associated SNPs in catfish.

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    Jin, Y; Zhou, T; Geng, X; Liu, S; Chen, A; Yao, J; Jiang, C; Tan, S; Su, B; Liu, Z

    2017-04-01

    Heat tolerance is a complex and economically important trait for catfish genetic breeding programs. With global climate change, it is becoming an increasingly important trait. To better understand the molecular basis of heat stress, a genome-wide association study (GWAS) was carried out using the 250 K catfish SNP array with interspecific backcross progenies, which derived from crossing female channel catfish with male F1 hybrid catfish (female channel catfish × male blue catfish). Three significant associated SNPs were detected by performing an EMMAX approach for GWAS. The SNP located on linkage group 14 explained 12.1% of phenotypical variation. The other two SNPs, located on linkage group 16, explained 11.3 and 11.5% of phenotypical variation respectively. A total of 14 genes with heat stress related functions were detected within the significant associated regions. Among them, five genes-TRAF2, FBXW5, ANAPC2, UBR1 and KLHL29- have known functions in the protein degradation process through the ubiquitination pathway. Other genes related to heat stress include genes involved in protein biosynthesis (PRPF4 and SYNCRIP), protein folding (DNAJC25), molecule and iron transport (SLC25A46 and CLIC5), cytoskeletal reorganization (COL12A1) and energy metabolism (COX7A2, PLCB1 and PLCB4) processes. The results provide fundamental information about genes and pathways that is useful for further investigation into the molecular mechanisms of heat stress. The associated SNPs could be promising candidates for selecting heat-tolerant catfish lines after validating their effects on larger and various catfish populations.

  16. A genome-wide association study of optic disc parameters.

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    Wishal D Ramdas

    2010-06-01

    Full Text Available The optic nerve head is involved in many ophthalmic disorders, including common diseases such as myopia and open-angle glaucoma. Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio (VCDR. Both are highly heritable but genetically largely undetermined. We performed a meta-analysis of genome-wide association (GWA data to identify genetic variants associated with optic disc area and VCDR. The gene discovery included 7,360 unrelated individuals from the population-based Rotterdam Study I and Rotterdam Study II cohorts. These cohorts revealed two genome-wide significant loci for optic disc area, rs1192415 on chromosome 1p22 (p = 6.72x10(-19 within 117 kb of the CDC7 gene and rs1900004 on chromosome 10q21.3-q22.1 (p = 2.67x10(-33 within 10 kb of the ATOH7 gene. They revealed two genome-wide significant loci for VCDR, rs1063192 on chromosome 9p21 (p = 6.15x10(-11 in the CDKN2B gene and rs10483727 on chromosome 14q22.3-q23 (p = 2.93x10(-10 within 40 kbp of the SIX1 gene. Findings were replicated in two independent Dutch cohorts (Rotterdam Study III and Erasmus Rucphen Family study; N = 3,612, and the TwinsUK cohort (N = 843. Meta-analysis with the replication cohorts confirmed the four loci and revealed a third locus at 16q12.1 associated with optic disc area, and four other loci at 11q13, 13q13, 17q23 (borderline significant, and 22q12.1 for VCDR. ATOH7 was also associated with VCDR independent of optic disc area. Three of the loci were marginally associated with open-angle glaucoma. The protein pathways in which the loci of optic disc area are involved overlap with those identified for VCDR, suggesting a common genetic origin.

  17. Feasibility study for banking loan using association rule mining classifier

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    Agus Sasmito Aribowo

    2015-03-01

    Full Text Available The problem of bad loans in the koperasi can be reduced if the koperasi can detect whether member can complete the mortgage debt or decline. The method used for identify characteristic patterns of prospective lenders in this study, called Association Rule Mining Classifier. Pattern of credit member will be converted into knowledge and used to classify other creditors. Classification process would separate creditors into two groups: good credit and bad credit groups. Research using prototyping for implementing the design into an application using programming language and development tool. The process of association rule mining using Weighted Itemset Tidset (WIT–tree methods. The results shown that the method can predict the prospective customer credit. Training data set using 120 customers who already know their credit history. Data test used 61 customers who apply for credit. The results concluded that 42 customers will be paying off their loans and 19 clients are decline

  18. Technological issues and experimental design of gene association studies.

    Science.gov (United States)

    Distefano, Johanna K; Taverna, Darin M

    2011-01-01

    Genome-wide association studies (GWAS), in which thousands of single-nucleotide polymorphisms (SNPs) spanning the genome are genotyped in individuals who are phenotypically well characterized, -currently represent the most popular strategy for identifying gene regions associated with common -diseases and related quantitative traits. Improvements in technology and throughput capability, development of powerful statistical tools, and more widespread acceptance of pooling-based genotyping approaches have led to greater utilization of GWAS in human genetics research. However, important considerations for optimal experimental design, including selection of the most appropriate genotyping platform, can enhance the utility of the approach even further. This chapter reviews experimental and technological issues that may affect the success of GWAS findings and proposes strategies for developing the most comprehensive, logical, and cost-effective approaches for genotyping given the population of interest.

  19. Study on acute burn injury survivors and the associated issues

    Institute of Scientific and Technical Information of China (English)

    Jonathan Bayuo; Pius Agbenorku; Richcane Amankwa

    2016-01-01

    Objective: To explore the phenomenon of surviving burn injury and its associated issues and concerns. Methods: A cross sectional survey approach was utilized to obtain data from one hundred burn survivors who were purposely selected. Descriptive statistics and content analysis were used to analyze data. Results: Findings from the study indicate that burns from flames stood out as a major cause of burns. Physical discomfort/pain, anxiety, needing assistance in meeting self-care needs, financial and social limitations were identified as the major impact of the injury. Furthermore, participants perceived the existence of societal stigma. In addition, hope in God or a spiritual being as well as family support were the two key resources participants relied on to cope effectively. Conclusions: Surviving burn injury is associated with varied physical, social and psy-chological factors and survivors may need professional assistance to fully adjust after discharge.

  20. Facial dermatosis associated with Demodex: a case-control study.

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    Zhao, Ya-e; Peng, Yan; Wang, Xiang-lan; Wu, Li-ping; Wang, Mei; Yan, Hu-ling; Xiao, Sheng-xiang

    2011-12-01

    Demodex has been considered to be related with multiple skin disorders, but controversy persists. In this case-control study, a survey was conducted with 860 dermatosis patients aged 12 to 84 years in Xi'an, China to identify the association between facial dermatosis and Demodex. Amongst the patients, 539 suffered from facial dermatosis and 321 suffered from non-facial dermatosis. Demodex mites were sampled and examined using the skin pressurization method. Multivariate regression analysis was applied to analyze the association between facial dermatosis and Demodex infestation, and to identify the risk factors of Demodex infestation. The results showed that total detection rate of Demodex was 43.0%. Patients aged above 30 years had higher odds of Demodex infestation than those under 30 years. Compared to patients with neutral skin, patients with mixed, oily, or dry skin were more likely to be infested with Demodex (odds ratios (ORs) were 2.5, 2.4, and 1.6, respectively). Moreover, Demodex infestation was found to be statistically associated with rosacea (OR=8.1), steroid-induced dermatitis (OR=2.7), seborrheic dermatitis (OR=2.2), and primary irritation dermatitis (OR=2.1). In particular, ORs calculated from the severe infestation (≥5 mites/cm(2)) rate were significantly higher than those of the total rate. Therefore, we concluded that Demodex is associated with rosacea, steroid-induced dermatitis, seborrheic dermatitis, and primary irritation dermatitis. The rate of severe infestation is found to be more correlated with various dermatosis than the total infestation rate. The risk factors of Demodex infestation, age, and skin types were identified. Our study also suggested that good hygiene practice might reduce the chances of demodicosis and Demodex infestation.

  1. Facial dermatosis associated with Demodex: a case-control study

    Institute of Scientific and Technical Information of China (English)

    Ya-e ZHAO; Yah PENG; Xiang-lan WANG; Li-ping WU; Mei WANG; Hu-ling YAN; Sheng-xiang XIAO

    2011-01-01

    Demodex has been considered to be related with multiple skin disorders,but controversy persists.In this case-control study,a survey was conducted with 860 dermatosis patients aged 12 to 84 years in Xi'an,China to identify the association between facial dermatosis and Demodex.Amongst the patients,539 suffered from facial dermatosis and 321 suffered from non-facial dermatosis.Demodex mites were sampled and examined using the skin pressurization method.Multivariate regression analysis was applied to analyze the association between facial dermatosis and Demodex infestation,and to identify the risk factors of Demodex infestation.The results showed that total detection rate of Demodex was 43.0%.Patients aged above 30 years had higher odds of Demodex infestation than those under 30 years.Compared to patients with neutral skin,patients with mixed,oily,or dry skin were more likely to be infested with Demodex (odds ratios (ORs) were 2.5,2.4,and 1.6,respectively).Moreover,Demodex infestation was found to be statistically associated with rosacea (OR=8.1),steroid-induced dermatitis (OR=2.7),seborrheic dermatitis (OR=2.2),and primary irritation dermatitis (OR=2.1).In particular,ORs calculated from the severe infestation (≥5 mites/cm2) rate were significantly higher than those of the total rate.Therefore,we concluded that Demodex is associated with rosacea,steroid-induced dermatitis,seborrheic dermatitis,and primary irritation dermatitis.The rate of severe infestation is found to be more correlated with various dermatosis than the total infestation rate.The risk factors of Demodex infestation,age,and skin types were identified.Our study also suggested that good hygiene practice might reduce the chances of demodicosis and Demodex infestation.

  2. Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes

    Science.gov (United States)

    Tin, Adrienne; Sorice, Rossella; Gorski, Mathias; Yeo, Nan Cher; Chu, Audrey Y.; Li, Man; Li, Yong; Mijatovic, Vladan; Ko, Yi-An; Taliun, Daniel; Luciani, Alessandro; Chen, Ming-Huei; Yang, Qiong; Foster, Meredith C.; Olden, Matthias; Hiraki, Linda T.; Tayo, Bamidele O.; Fuchsberger, Christian; Dieffenbach, Aida Karina; Shuldiner, Alan R.; Smith, Albert V.; Zappa, Allison M.; Lupo, Antonio; Kollerits, Barbara; Ponte, Belen; Stengel, Bénédicte; Krämer, Bernhard K.; Paulweber, Bernhard; Mitchell, Braxton D.; Hayward, Caroline; Helmer, Catherine; Meisinger, Christa; Gieger, Christian; Shaffer, Christian M.; Müller, Christian; Langenberg, Claudia; Ackermann, Daniel; Siscovick, David; Boerwinkle, Eric; Kronenberg, Florian; Ehret, Georg B.; Homuth, Georg; Waeber, Gerard; Navis, Gerjan; Gambaro, Giovanni; Malerba, Giovanni; Eiriksdottir, Gudny; Li, Guo; Wichmann, H. Erich; Grallert, Harald; Wallaschofski, Henri; Völzke, Henry; Brenner, Herrmann; Kramer, Holly; Leach, I. Mateo; Rudan, Igor; Hillege, Hans L.; Beckmann, Jacques S.; Lambert, Jean Charles; Luan, Jian'an; Zhao, Jing Hua; Chalmers, John; Coresh, Josef; Denny, Joshua C.; Butterbach, Katja; Launer, Lenore J.; Ferrucci, Luigi; Kedenko, Lyudmyla; Haun, Margot; Metzger, Marie; Woodward, Mark; Hoffman, Matthew J.; Nauck, Matthias; Waldenberger, Melanie; Pruijm, Menno; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Wareham, Nicholas J.; Endlich, Nicole; Soranzo, Nicole; Polasek, Ozren; van der Harst, Pim; Pramstaller, Peter Paul; Vollenweider, Peter; Wild, Philipp S.; Gansevoort, Ron T.; Rettig, Rainer; Biffar, Reiner; Carroll, Robert J.; Katz, Ronit; Loos, Ruth J.F.; Hwang, Shih-Jen; Coassin, Stefan; Bergmann, Sven; Rosas, Sylvia E.; Stracke, Sylvia; Harris, Tamara B.; Corre, Tanguy; Zeller, Tanja; Illig, Thomas; Aspelund, Thor; Tanaka, Toshiko; Lendeckel, Uwe; Völker, Uwe; Gudnason, Vilmundur; Chouraki, Vincent; Koenig, Wolfgang; Kutalik, Zoltan; O'Connell, Jeffrey R.; Parsa, Afshin; Heid, Iris M.; Paterson, Andrew D.; de Boer, Ian H.; Devuyst, Olivier; Lazar, Jozef; Endlich, Karlhans; Susztak, Katalin; Tremblay, Johanne; Hamet, Pavel; Jacob, Howard J.; Böger, Carsten A.

    2016-01-01

    Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10−10). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10–7) and 13% for RAB38/CTSC (P = 5.8 × 10−7). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria. PMID:26631737

  3. Identification of Promising Mutants Associated with Egg Production Traits Revealed by Genome-Wide Association Study.

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    Jingwei Yuan

    Full Text Available Egg number (EN, egg laying rate (LR and age at first egg (AFE are important production traits related to egg production in poultry industry. To better understand the knowledge of genetic architecture of dynamic EN during the whole laying cycle and provide the precise positions of associated variants for EN, LR and AFE, laying records from 21 to 72 weeks of age were collected individually for 1,534 F2 hens produced by reciprocal crosses between White Leghorn and Dongxiang Blue-shelled chicken, and their genotypes were assayed by chicken 600 K Affymetrix high density genotyping arrays. Subsequently, pedigree and SNP-based genetic parameters were estimated and a genome-wide association study (GWAS was conducted on EN, LR and AFE. The heritability estimates were similar between pedigree and SNP-based estimates varying from 0.17 to 0.36. In the GWA analysis, we identified nine genome-wide significant loci associated with EN of the laying periods from 21 to 26 weeks, 27 to 36 weeks and 37 to 72 weeks. Analysis of GTF2A1 and CLSPN suggested that they influenced the function of ovary and uterus, and may be considered as relevant candidates. The identified SNP rs314448799 for accumulative EN from 21 to 40 weeks on chromosome 5 created phenotypic differences of 6.86 eggs between two homozygous genotypes, which could be potentially applied to the molecular breeding for EN selection. Moreover, our finding showed that LR was a moderate polygenic trait. The suggestive significant region on chromosome 16 for AFE suggested the relationship between sex maturity and immune in the current population. The present study comprehensively evaluates the role of genetic variants in the development of egg laying. The findings will be helpful to investigation of causative genes function and future marker-assisted selection and genomic selection in chickens.

  4. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

    DEFF Research Database (Denmark)

    Evangelou, Evangelos; Kerkhof, Hanneke J; Styrkarsdottir, Unnur

    2014-01-01

    Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects.......Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects....

  5. Genome-wide association study identified a narrow chromosome 1 region associated with chicken growth traits.

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    Liang Xie

    Full Text Available Chicken growth traits are important economic traits in broilers. A large number of studies are available on finding genetic factors affecting chicken growth. However, most of these studies identified chromosome regions containing putative quantitative trait loci and finding causal mutations is still a challenge. In this genome-wide association study (GWAS, we identified a narrow 1.5 Mb region (173.5-175 Mb of chicken (Gallus gallus chromosome (GGA 1 to be strongly associated with chicken growth using 47,678 SNPs and 489 F2 chickens. The growth traits included aggregate body weight (BW at 0-90 d of age measured weekly, biweekly average daily gains (ADG derived from weekly body weight, and breast muscle weight (BMW, leg muscle weight (LMW and wing weight (WW at 90 d of age. Five SNPs in the 1.5 Mb KPNA3-FOXO1A region at GGA1 had the highest significant effects for all growth traits in this study, including a SNP at 8.9 Kb upstream of FOXO1A for BW at 22-48 d and 70 d, a SNP at 1.9 Kb downstream of FOXO1A for WW, a SNP at 20.9 Kb downstream of ENSGALG00000022732 for ADG at 29-42 d, a SNP in INTS6 for BW at 90 d, and a SNP in KPNA3 for BMW and LMW. The 1.5 Mb KPNA3-FOXO1A region contained two microRNA genes that could bind to messenger ribonucleic acid (mRNA of IGF1, FOXO1A and KPNA3. It was further indicated that the 1.5 Mb GGA1 region had the strongest effects on chicken growth during 22-42 d.

  6. A genome wide association study of mathematical ability reveals an association at chromosome 3q29, a locus associated with autism and learning difficulties: a preliminary study.

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    Simon Baron-Cohen

    Full Text Available Mathematical ability is heritable, but few studies have directly investigated its molecular genetic basis. Here we aimed to identify specific genetic contributions to variation in mathematical ability. We carried out a genome wide association scan using pooled DNA in two groups of U.K. samples, based on end of secondary/high school national academic exam achievement: high (n = 419 versus low (n = 183 mathematical ability while controlling for their verbal ability. Significant differences in allele frequencies between these groups were searched for in 906,600 SNPs using the Affymetrix GeneChip Human Mapping version 6.0 array. After meeting a threshold of p<1.5×10(-5, 12 SNPs from the pooled association analysis were individually genotyped in 542 of the participants and analyzed to validate the initial associations (lowest p-value 1.14 ×10(-6. In this analysis, one of the SNPs (rs789859 showed significant association after Bonferroni correction, and four (rs10873824, rs4144887, rs12130910 rs2809115 were nominally significant (lowest p-value 3.278 × 10(-4. Three of the SNPs of interest are located within, or near to, known genes (FAM43A, SFT2D1, C14orf64. The SNP that showed the strongest association, rs789859, is located in a region on chromosome 3q29 that has been previously linked to learning difficulties and autism. rs789859 lies 1.3 kbp downstream of LSG1, and 700 bp upstream of FAM43A, mapping within the potential promoter/regulatory region of the latter. To our knowledge, this is only the second study to investigate the association of genetic variants with mathematical ability, and it highlights a number of interesting markers for future study.

  7. Genome-wide association studies in pharmacogenomics of antidepressants.

    Science.gov (United States)

    Lin, Eugene; Lane, Hsien-Yuan

    2015-01-01

    Major depressive disorder (MDD) is one of the most common psychiatric disorders worldwide. Doctors must prescribe antidepressants based on educated guesses due to the fact that it is unmanageable to predict the effectiveness of any particular antidepressant in an individual patient. With the recent advent of scientific research, the genome-wide association study (GWAS) is extensively employed to analyze hundreds of thousands of single nucleotide polymorphisms by high-throughput genotyping technologies. In addition to the candidate-gene approach, the GWAS approach has recently been utilized to investigate the determinants of antidepressant response to therapy. In this study, we reviewed GWAS studies, their limitations and future directions with respect to the pharmacogenomics of antidepressants in MDD.

  8. Association between diabetes and tuberculosis: case-control study

    Science.gov (United States)

    Pereira, Susan Martins; de Araújo, Gleide Santos; Santos, Carlos Antônio de Souza Teles; de Oliveira, Maeli Gomes; Barreto, Maurício Lima

    2016-01-01

    ABSTRACT OBJECTIVE To test the association between diabetes and tuberculosis. METHODS It is a case-control study, matched by age and sex. We included 323 new cases of tuberculosis with positive results for bacilloscopy. The controls were 323 respiratory symptomatic patients with negative bacilloscopy, from the same health services, such as: ambulatory cases from three referral hospitals and six basic health units responsible for the notifications of new cases of tuberculosis in Salvador, Bahia. Data collection occurred between 2008 and 2010. The instruments used were structured interview, including clinical data, capillary blood glucose (during fasting or postprandial), and the CAGE questionnaire for screening of abusive consumption of alcohol. Descriptive, exploratory, and multivariate analysis was performed using conditional logistic regression. RESULTS The average age of the cases was 38.5 (SD = 14.2) years and of the controls, 38.5 (SD = 14.3) years. Among cases and controls, most subjects (61%) were male. In univariate analysis we found association between the occurrence of diabetes and tuberculosis (OR = 2.37; 95%CI 1.04–5.42), which remained statistically significant after adjustment for potential confounders (OR = 3.12; 95%CI 1.12–7.94). CONCLUSIONS The association between diabetes and tuberculosis can hinder the control of tuberculosis, contributing to the maintainance of the disease burden. The situation demands increasing early detection of diabetes among people with tuberculosis, in an attempt to improve disease control strategies. PMID:28099656

  9. Association between diabetes and tuberculosis: case-control study

    Directory of Open Access Journals (Sweden)

    Susan Martins Pereira

    Full Text Available ABSTRACT OBJECTIVE To test the association between diabetes and tuberculosis. METHODS It is a case-control study, matched by age and sex. We included 323 new cases of tuberculosis with positive results for bacilloscopy. The controls were 323 respiratory symptomatic patients with negative bacilloscopy, from the same health services, such as: ambulatory cases from three referral hospitals and six basic health units responsible for the notifications of new cases of tuberculosis in Salvador, Bahia. Data collection occurred between 2008 and 2010. The instruments used were structured interview, including clinical data, capillary blood glucose (during fasting or postprandial, and the CAGE questionnaire for screening of abusive consumption of alcohol. Descriptive, exploratory, and multivariate analysis was performed using conditional logistic regression. RESULTS The average age of the cases was 38.5 (SD = 14.2 years and of the controls, 38.5 (SD = 14.3 years. Among cases and controls, most subjects (61% were male. In univariate analysis we found association between the occurrence of diabetes and tuberculosis (OR = 2.37; 95%CI 1.04–5.42, which remained statistically significant after adjustment for potential confounders (OR = 3.12; 95%CI 1.12–7.94. CONCLUSIONS The association between diabetes and tuberculosis can hinder the control of tuberculosis, contributing to the maintainance of the disease burden. The situation demands increasing early detection of diabetes among people with tuberculosis, in an attempt to improve disease control strategies.

  10. Methods for Analyzing Multivariate Phenotypes in Genetic Association Studies.

    Science.gov (United States)

    Yang, Qiong; Wang, Yuanjia

    2012-05-01

    This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Multivariate phenotypes are frequently encountered in genetic association studies. The purpose of analyzing multivariate phenotypes usually includes discovery of novel genetic variants of pleiotropy effects, that is, affecting multiple phenotypes, and the ultimate goal of uncovering the underlying genetic mechanism. In recent years, there have been new method development and application of existing statistical methods to such phenotypes. In this paper, we provide a review of the available methods for analyzing association between a single marker and a multivariate phenotype consisting of the same type of components (e.g., all continuous or all categorical) or different types of components (e.g., some are continuous and others are categorical). We also reviewed causal inference methods designed to test whether the detected association with the multivariate phenotype is truly pleiotropy or the genetic marker exerts its effects on some phenotypes through affecting the others.

  11. Detecting rare variants in case-parents association studies.

    Directory of Open Access Journals (Sweden)

    Kuang-Fu Cheng

    Full Text Available Despite the success of genome-wide association studies (GWASs in detecting common variants (minor allele frequency ≥0.05 many suggested that rare variants also contribute to the genetic architecture of diseases. Recently, researchers demonstrated that rare variants can show a strong stratification which may not be corrected by using existing methods. In this paper, we focus on a case-parents study and consider methods for testing group-wise association between multiple rare (and common variants in a gene region and a disease. All tests depend on the numbers of transmitted mutant alleles from parents to their diseased children across variants and hence they are robust to the effect of population stratification. We use extensive simulation studies to compare the performance of four competing tests: the largest single-variant transmission disequilibrium test (TDT, multivariable test, combined TDT, and a likelihood ratio test based on a random-effects model. We find that the likelihood ratio test is most powerful in a wide range of settings and there is no negative impact to its power performance when common variants are also included in the analysis. If deleterious and protective variants are simultaneously analyzed, the likelihood ratio test was generally insensitive to the effect directionality, unless the effects are extremely inconsistent in one direction.

  12. Factors associated with pharmacy student interest in international study.

    Science.gov (United States)

    Owen, Chelsea; Breheny, Patrick; Ingram, Richard; Pfeifle, William; Cain, Jeff; Ryan, Melody

    2013-04-12

    OBJECTIVES. To examine the interest of pharmacy students in international study, the demographic factors and involvement characteristics associated with that interest, and the perceived advantages and barriers of engaging in international opportunities during pharmacy school. METHODS. A self-administered electronic survey instrument was distributed to first-, second-, and third-year pharmacy students at the University of Kentucky College of Pharmacy. RESULTS. There were 192 total respondents, for a response rate of 50.9%. Seventy-two percent reported interest in international study. Previous international study experience (p=0.001), previous international travel experience (p=0.002), year in pharmacy school (p=0.03), level of academic involvement (pinternational study interest. Positive influences to international study included desire to travel and availability of scholarships. Perceived barriers included an inability to pay expenses and lack of foreign language knowledge. CONCLUSIONS. The needs and interests of pharmacy students should be considered in the development and expansion of internationalization programs in order to effectively optimize global partnerships and available international experiences. Colleges and schools of pharmacy should engage students early in the curriculum when interest in study-abroad opportunities is highest and seek to alleviate concerns about expenses as a primary influence on study-abroad decisions through provision of financial assistance.

  13. Genome Wide Association Study Identifies New Loci Associated with Undesired Coat Color Phenotypes in Saanen Goats.

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    Pauline Marie Martin

    Full Text Available This paper reports a quantitative genetics and genomic analysis of undesirable coat color patterns in goats. Two undesirable coat colors have routinely been recorded for the past 15 years in French Saanen goats. One fifth of Saanen females have been phenotyped "pink" (8.0% or "pink neck" (11.5% and consequently have not been included in the breeding program as elite animals. Heritability of the binary "pink" and "pink neck" phenotype, estimated from 103,443 females was 0.26 for "pink" and 0.21 for "pink neck". Genome wide association studies (using haplotypes or single SNPs were implemented using a daughter design of 810 Saanen goats sired by 9 Artificial Insemination bucks genotyped with the goatSNP50 chip. A highly significant signal (-log10pvalue = 10.2 was associated with the "pink neck" phenotype on chromosome 11, suggesting the presence of a major gene. Highly significant signals for the "pink" phenotype were found on chromosomes 5 and 13 (-log10p values of 7.2 and, 7.7 respectively. The most significant SNP on chromosome 13 was in the ASIP gene region, well known for its association with coat color phenotypes. Nine significant signals were also found for both traits. The highest signal for each trait was detected by both single SNP and haplotype approaches, whereas the smaller signals were not consistently detected by the two methods. Altogether these results demonstrated a strong genetic control of the "pink" and "pink neck" phenotypes in French Saanen goats suggesting that SNP information could be used to identify and remove undesired colored animals from the breeding program.

  14. Genome-wide association study of colorectal cancer in Hispanics

    Science.gov (United States)

    Schmit, Stephanie L.; Schumacher, Fredrick R.; Edlund, Christopher K.; Conti, David V.; Ihenacho, Ugonna; Wan, Peggy; Van Den Berg, David; Casey, Graham; Fortini, Barbara K.; Lenz, Heinz-Josef; Tusié-Luna, Teresa; Aguilar-Salinas, Carlos A.; Moreno-Macías, Hortensia; Huerta-Chagoya, Alicia; Ordóñez-Sánchez, María Luisa; Rodríguez-Guillén, Rosario; Cruz-Bautista, Ivette; Rodríguez-Torres, Maribel; Muñóz-Hernández, Linda Liliana; Arellano-Campos, Olimpia; Gómez, Donají; Alvirde, Ulices; González-Villalpando, Clicerio; González-Villalpando, María Elena; Le Marchand, Loic; Haiman, Christopher A.; Figueiredo, Jane C.

    2016-01-01

    Genome-wide association studies (GWAS) have identified 58 susceptibility alleles across 37 regions associated with the risk of colorectal cancer (CRC) with P < 5×10−8. Most studies have been conducted in non-Hispanic whites and East Asians; however, the generalizability of these findings and the potential for ethnic-specific risk variation in Hispanic and Latino (HL) individuals have been largely understudied. We describe the first GWAS of common genetic variation contributing to CRC risk in HL (1611 CRC cases and 4330 controls). We also examine known susceptibility alleles and implement imputation-based fine-mapping to identify potential ethnicity-specific association signals in known risk regions. We discovered 17 variants across 4 independent regions that merit further investigation due to suggestive CRC associations (P < 1×10−6) at 1p34.3 (rs7528276; Odds Ratio (OR) = 1.86 [95% confidence interval (CI): 1.47–2.36); P = 2.5×10−7], 2q23.3 (rs1367374; OR = 1.37 (95% CI: 1.21–1.55); P = 4.0×10−7), 14q24.2 (rs143046984; OR = 1.65 (95% CI: 1.36–2.01); P = 4.1×10−7) and 16q12.2 [rs142319636; OR = 1.69 (95% CI: 1.37–2.08); P=7.8×10−7]. Among the 57 previously published CRC susceptibility alleles with minor allele frequency ≥1%, 76.5% of SNPs had a consistent direction of effect and 19 (33.3%) were nominally statistically significant (P < 0.05). Further, rs185423955 and rs60892987 were identified as novel secondary susceptibility variants at 3q26.2 (P = 5.3×10–5) and 11q12.2 (P = 6.8×10−5), respectively. Our findings demonstrate the importance of fine mapping in HL. These results are informative for variant prioritization in functional studies and future risk prediction modeling in minority populations. PMID:27207650

  15. A genome-wide association study of anorexia nervosa.

    Science.gov (United States)

    Boraska, V; Franklin, C S; Floyd, J A B; Thornton, L M; Huckins, L M; Southam, L; Rayner, N W; Tachmazidou, I; Klump, K L; Treasure, J; Lewis, C M; Schmidt, U; Tozzi, F; Kiezebrink, K; Hebebrand, J; Gorwood, P; Adan, R A H; Kas, M J H; Favaro, A; Santonastaso, P; Fernández-Aranda, F; Gratacos, M; Rybakowski, F; Dmitrzak-Weglarz, M; Kaprio, J; Keski-Rahkonen, A; Raevuori, A; Van Furth, E F; Slof-Op 't Landt, M C T; Hudson, J I; Reichborn-Kjennerud, T; Knudsen, G P S; Monteleone, P; Kaplan, A S; Karwautz, A; Hakonarson, H; Berrettini, W H; Guo, Y; Li, D; Schork, N J; Komaki, G; Ando, T; Inoko, H; Esko, T; Fischer, K; Männik, K; Metspalu, A; Baker, J H; Cone, R D; Dackor, J; DeSocio, J E; Hilliard, C E; O'Toole, J K; Pantel, J; Szatkiewicz, J P; Taico, C; Zerwas, S; Trace, S E; Davis, O S P; Helder, S; Bühren, K; Burghardt, R; de Zwaan, M; Egberts, K; Ehrlich, S; Herpertz-Dahlmann, B; Herzog, W; Imgart, H; Scherag, A; Scherag, S; Zipfel, S; Boni, C; Ramoz, N; Versini, A; Brandys, M K; Danner, U N; de Kovel, C; Hendriks, J; Koeleman, B P C; Ophoff, R A; Strengman, E; van Elburg, A A; Bruson, A; Clementi, M; Degortes, D; Forzan, M; Tenconi, E; Docampo, E; Escaramís, G; Jiménez-Murcia, S; Lissowska, J; Rajewski, A; Szeszenia-Dabrowska, N; Slopien, A; Hauser, J; Karhunen, L; Meulenbelt, I; Slagboom, P E; Tortorella, A; Maj, M; Dedoussis, G; Dikeos, D; Gonidakis, F; Tziouvas, K; Tsitsika, A; Papezova, H; Slachtova, L; Martaskova, D; Kennedy, J L; Levitan, R D; Yilmaz, Z; Huemer, J; Koubek, D; Merl, E; Wagner, G; Lichtenstein, P; Breen, G; Cohen-Woods, S; Farmer, A; McGuffin, P; Cichon, S; Giegling, I; Herms, S; Rujescu, D; Schreiber, S; Wichmann, H-E; Dina, C; Sladek, R; Gambaro, G; Soranzo, N; Julia, A; Marsal, S; Rabionet, R; Gaborieau, V; Dick, D M; Palotie, A; Ripatti, S; Widén, E; Andreassen, O A; Espeseth, T; Lundervold, A; Reinvang, I; Steen, V M; Le Hellard, S; Mattingsdal, M; Ntalla, I; Bencko, V; Foretova, L; Janout, V; Navratilova, M; Gallinger, S; Pinto, D; Scherer, S W; Aschauer, H; Carlberg, L; Schosser, A; Alfredsson, L; Ding, B; Klareskog, L; Padyukov, L; Courtet, P; Guillaume, S; Jaussent, I; Finan, C; Kalsi, G; Roberts, M; Logan, D W; Peltonen, L; Ritchie, G R S; Barrett, J C; Estivill, X; Hinney, A; Sullivan, P F; Collier, D A; Zeggini, E; Bulik, C M

    2014-10-01

    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

  16. A genome-wide association study of anorexia nervosa

    Science.gov (United States)

    Boraska, Vesna; Franklin, Christopher S; Floyd, James AB; Thornton, Laura M; Huckins, Laura M; Southam, Lorraine; Rayner, N William; Tachmazidou, Ioanna; Klump, Kelly L; Treasure, Janet; Lewis, Cathryn M; Schmidt, Ulrike; Tozzi, Federica; Kiezebrink, Kirsty; Hebebrand, Johannes; Gorwood, Philip; Adan, Roger AH; Kas, Martien JH; Favaro, Angela; Santonastaso, Paolo; Fernández-Aranda, Fernando; Gratacos, Monica; Rybakowski, Filip; Dmitrzak-Weglarz, Monika; Kaprio, Jaakko; Keski-Rahkonen, Anna; Raevuori, Anu; Van Furth, Eric F; Landt, Margarita CT Slof-Op t; Hudson, James I; Reichborn-Kjennerud, Ted; Knudsen, Gun Peggy S; Monteleone, Palmiero; Kaplan, Allan S; Karwautz, Andreas; Hakonarson, Hakon; Berrettini, Wade H; Guo, Yiran; Li, Dong; Schork, Nicholas J.; Komaki, Gen; Ando, Tetsuya; Inoko, Hidetoshi; Esko, Tõnu; Fischer, Krista; Männik, Katrin; Metspalu, Andres; Baker, Jessica H; Cone, Roger D; Dackor, Jennifer; DeSocio, Janiece E; Hilliard, Christopher E; O'Toole, Julie K; Pantel, Jacques; Szatkiewicz, Jin P; Taico, Chrysecolla; Zerwas, Stephanie; Trace, Sara E; Davis, Oliver SP; Helder, Sietske; Bühren, Katharina; Burghardt, Roland; de Zwaan, Martina; Egberts, Karin; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Imgart, Hartmut; Scherag, André; Scherag, Susann; Zipfel, Stephan; Boni, Claudette; Ramoz, Nicolas; Versini, Audrey; Brandys, Marek K; Danner, Unna N; de Kovel, Carolien; Hendriks, Judith; Koeleman, Bobby PC; Ophoff, Roel A; Strengman, Eric; van Elburg, Annemarie A; Bruson, Alice; Clementi, Maurizio; Degortes, Daniela; Forzan, Monica; Tenconi, Elena; Docampo, Elisa; Escaramís, Geòrgia; Jiménez-Murcia, Susana; Lissowska, Jolanta; Rajewski, Andrzej; Szeszenia-Dabrowska, Neonila; Slopien, Agnieszka; Hauser, Joanna; Karhunen, Leila; Meulenbelt, Ingrid; Slagboom, P Eline; Tortorella, Alfonso; Maj, Mario; Dedoussis, George; Dikeos, Dimitris; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Tsitsika, Artemis; Papezova, Hana; Slachtova, Lenka; Martaskova, Debora; Kennedy, James L.; Levitan, Robert D.; Yilmaz, Zeynep; Huemer, Julia; Koubek, Doris; Merl, Elisabeth; Wagner, Gudrun; Lichtenstein, Paul; Breen, Gerome; Cohen-Woods, Sarah; Farmer, Anne; McGuffin, Peter; Cichon, Sven; Giegling, Ina; Herms, Stefan; Rujescu, Dan; Schreiber, Stefan; Wichmann, H-Erich; Dina, Christian; Sladek, Rob; Gambaro, Giovanni; Soranzo, Nicole; Julia, Antonio; Marsal, Sara; Rabionet, Raquel; Gaborieau, Valerie; Dick, Danielle M; Palotie, Aarno; Ripatti, Samuli; Widén, Elisabeth; Andreassen, Ole A; Espeseth, Thomas; Lundervold, Astri; Reinvang, Ivar; Steen, Vidar M; Le Hellard, Stephanie; Mattingsdal, Morten; Ntalla, Ioanna; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Navratilova, Marie; Gallinger, Steven; Pinto, Dalila; Scherer, Stephen; Aschauer, Harald; Carlberg, Laura; Schosser, Alexandra; Alfredsson, Lars; Ding, Bo; Klareskog, Lars; Padyukov, Leonid; Finan, Chris; Kalsi, Gursharan; Roberts, Marion; Logan, Darren W; Peltonen, Leena; Ritchie, Graham RS; Barrett, Jeffrey C; Estivill, Xavier; Hinney, Anke; Sullivan, Patrick F; Collier, David A; Zeggini, Eleftheria; Bulik, Cynthia M

    2015-01-01

    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10-7) in SOX2OT and rs17030795 (P=5.84×10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10-6) between CUL3 and FAM124B and rs1886797 (P=8.05×10-6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4×10-6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field. PMID:24514567

  17. An evolutionary framework for association testing in resequencing studies.

    Directory of Open Access Journals (Sweden)

    C Ryan King

    2010-11-01

    Full Text Available Sequencing technologies are becoming cheap enough to apply to large numbers of study participants and promise to provide new insights into human phenotypes by bringing to light rare and previously unknown genetic variants. We develop a new framework for the analysis of sequence data that incorporates all of the major features of previously proposed approaches, including those focused on allele counts and allele burden, but is both more general and more powerful. We harness population genetic theory to provide prior information on effect sizes and to create a pooling strategy for information from rare variants. Our method, EMMPAT (Evolutionary Mixed Model for Pooled Association Testing, generates a single test per gene (substantially reducing multiple testing concerns, facilitates graphical summaries, and improves the interpretation of results by allowing calculation of attributable variance. Simulations show that, relative to previously used approaches, our method increases the power to detect genes that affect phenotype when natural selection has kept alleles with large effect sizes rare. We demonstrate our approach on a population-based re-sequencing study of association between serum triglycerides and variation in ANGPTL4.

  18. Bipolar disorder and the pseudoautosomal region: An association study

    Energy Technology Data Exchange (ETDEWEB)

    Parsian, A.; Todd, R.D. [Washington Univ. School of Medicine, St. Louis, MO (United States)

    1994-03-15

    From family, adoption, and twin studies it is clear that genetic factors play an important role in the etiology of bipolar disorder (McGuffin and Katz: The Biology of Depression, Gaskell, London, 1986). Recently Yoneda et al. reported an association between an allele (A4) of a VNTR marker (DXYS20) for the pseudoautosomal region and bipolar disorder in a Japanese population. In order to test for this association in a Caucasian population, we have typed a sample of 52 subjects with bipolar disorder and 61 normal controls. The bipolar subjects are probands of multiple incidence families. The normal controls are an epidemiologically ascertained sample of middle-aged, unrelated individuals. The two groups were matched for sex and ethnic background. There were no significant differences in the allele or genotype frequencies of DXYS20 between the two groups. In particular, there was no significant difference in the frequency of the A4 allele in normal controls and bipolar patients (0.377 vs. 0.317, respectively). The prevalence of the A4 allele in bipolar patients and normal controls was 0.567 and 0.622, respectively. We were not able to replicate the results of the 1992 Yoneda et al. study. 15 refs., 2 tabs.

  19. A genome-wide association study of aging.

    Science.gov (United States)

    Walter, Stefan; Atzmon, Gil; Demerath, Ellen W; Garcia, Melissa E; Kaplan, Robert C; Kumari, Meena; Lunetta, Kathryn L; Milaneschi, Yuri; Tanaka, Toshiko; Tranah, Gregory J; Völker, Uwe; Yu, Lei; Arnold, Alice; Benjamin, Emelia J; Biffar, Reiner; Buchman, Aron S; Boerwinkle, Eric; Couper, David; De Jager, Philip L; Evans, Denis A; Harris, Tamara B; Hoffmann, Wolfgang; Hofman, Albert; Karasik, David; Kiel, Douglas P; Kocher, Thomas; Kuningas, Maris; Launer, Lenore J; Lohman, Kurt K; Lutsey, Pamela L; Mackenbach, Johan; Marciante, Kristin; Psaty, Bruce M; Reiman, Eric M; Rotter, Jerome I; Seshadri, Sudha; Shardell, Michelle D; Smith, Albert V; van Duijn, Cornelia; Walston, Jeremy; Zillikens, M Carola; Bandinelli, Stefania; Baumeister, Sebastian E; Bennett, David A; Ferrucci, Luigi; Gudnason, Vilmundur; Kivimaki, Mika; Liu, Yongmei; Murabito, Joanne M; Newman, Anne B; Tiemeier, Henning; Franceschini, Nora

    2011-11-01

    Human longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10(-8)). We found 14 independent SNPs that predicted risk of death, and 8 SNPs that predicted event-free survival (p < 10(-5)). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer's disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity.

  20. GPFrontend and GPGraphics: graphical analysis tools for genetic association studies

    Directory of Open Access Journals (Sweden)

    Schanze Denny

    2010-09-01

    Full Text Available Abstract Background Most software packages for whole genome association studies are non-graphical, purely text based programs originally designed to run with UNIX-like operating systems. Graphical output is often not intended or supposed to be performed with other command line tools, e.g. gnuplot. Results Using the Microsoft .NET 2.0 platform and Visual Studio 2005, we have created a graphical software package to analyze data from microarray whole genome association studies, both for a DNA-pooling based approach as well as regular single sample data. Part of this package was made to integrate with GenePool 0.8.2, a previously existing software suite for GNU/Linux systems, which we have modified to run in a Microsoft Windows environment. Further modifications cause it to generate some additional data. This enables GenePool to interact with the .NET parts created by us. The programs we developed are GPFrontend, a graphical user interface and frontend to use GenePool and create metadata files for it, and GPGraphics, a program to further analyze and graphically evaluate output of different WGA analysis programs, among them also GenePool. Conclusions Our programs enable regular MS Windows users without much experience in bioinformatics to easily visualize whole genome data from a variety of sources.

  1. Family Stigma Associated With Epilepsy: A Qualitative Study

    Science.gov (United States)

    Nabi Amjad, Reza; Nikbakht Nasrabadi, Alireza; Navab, Elham

    2017-01-01

    Introduction: Harmful nature of epilepsy can affect the patient and their parent. Stigma, arising from it, affects the patient and their family. To relieve it understanding the experiences of the parent are useful. This study was aimed at understanding the experiences of parent of child with epilepsy in Iran. Methods: In this interpretative phenomenological study, 10 parents who took care of their child with epilepsy were participated. Data were collected through in-depth semi-structured interviews. After transcription, data were analyzed using Van Manen’s method. Results: Family stigma emerged as a main theme in data analysis with three subthemes including becoming verbally abusive, a dull and heavy shadowed look, and associates interference. Conclusion: Family stigma is a major challenge for parents of child with epilepsy need to special attention by health system. Nurses, as a big part of the system, can play an important role to manage this problem. PMID:28299298

  2. STUDY OF ASSOCIATION OF DIABETIC MACULOPATHY WITH HYPERTENSION

    Directory of Open Access Journals (Sweden)

    Sivaramareddy

    2015-12-01

    Full Text Available BACKGROUND Diabetic retinopathy is a leading cause of blindness in adults and is unique in displaying a uniform epidemiology profile worldwide. Diabetic maculopathy is the most common microvascular complication in diabetes which can produce severe visual loss. Apart from diabetes, a number of systemic factor like hypertension, has an important role in occurrence and progression of DME. Thus control of these factors along with control of blood sugars can prevent or reverse the maculopathy and there by restore the vision of diabetic patients. OBJECTIVE To study the association of diabetic maculopathy with hypertension and to highlight the effect of this factor on onset and/or progression of diabetic maculopathy. METHODS A cross sectional two group comparative study was carried out in 100 diabetic patients with retinopathy more than 18 years attending the department of ophthalmology (Katuri medical college in the period of September 2012 to April 2014. For all patients, visual acuity with Snellen’s chart, slit lamp examination, intraocular pressure by applanation tonometry, fundus examination with direct, indirect ophthalmoscopy and 90D lens was conducted. Patients were divided into 2 groups (group1-Retinopathy with maculopathy and group 2- retinopathy without maculopathy. A detailed history of duration of diabetes, type of treatment, hypertension, taken from the patient. The significance of the hypertension was compared in both the groups involved in the study. RESULTS In the present study of 100 patients diagnosed with diabetic retinopathy, majority were males (54% in study group and 58% in control group by age 51-60 years. There was no significant difference in the age and gender distribution among two groups. Majority of the patients in the both groups were on treatment with anti-hypertensives (64% in the study group and 74% in control group. In this study, the mean value of SBP and DBP were significantly higher in study group compared to

  3. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations.

    Directory of Open Access Journals (Sweden)

    Ayşe Demirkan

    Full Text Available Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034 on plasma levels of 24 sphingomyelins (SPM, 9 ceramides (CER, 57 phosphatidylcholines (PC, 20 lysophosphatidylcholines (LPC, 27 phosphatidylethanolamines (PE, and 16 PE-based plasmalogens (PLPE, as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10(-204 and 10 loci for sphingolipids (smallest P-value = 3.10×10(-57. After a correction for multiple comparisons (P-value<2.2×10(-9, we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1 and two with sphingolipids (PLD2 and APOE explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3 suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2 to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our

  4. Comorbidities Associated with Obstructive Sleep Apnea: a Retrospective Study

    Science.gov (United States)

    Pinto, José Antonio; Ribeiro, Davi Knoll; Cavallini, Andre Freitas da Silva; Duarte, Caue; Freitas, Gabriel Santos

    2016-01-01

    Introduction Obstructive sleep apnea (OSA) is characterized by partial or complete recurrent upper airway obstruction during sleep. OSA brings many adverse consequences, such as hypertension, obesity, diabetes mellitus, cardiac and encephalic alterations, behavioral, among others, resulting in a significant source of public health care by generating a high financial and social impact. The importance of this assessment proves to be useful, because the incidence of patients with comorbidities associated with AOS has been increasing consistently and presents significant influence in natural disease history. Objective The objective of this study is to assess major comorbidities associated with obstructive sleep apnea (OSA) and prevalence in a group of patients diagnosed clinically and polysomnographically with OSA. Methods This is a retrospective study of 100 charts from patients previously diagnosed with OSA in our service between October 2010 and January 2013. Results We evaluated 100 patients with OSA (84 men and 16 women) with a mean age of 50.05 years (range 19–75 years). The prevalence of comorbidities were hypertension (39%), obesity (34%), depression (19%), gastroesophageal reflux disease (GERD) (18%), diabetes mellitus (15%), hypercholesterolemia (10%), asthma (4%), and no comorbidities (33%). Comorbidities occurred in 56.2% patients diagnosed with mild OSA, 67.6% with moderate OSA, and 70% of patients with severe OSA. Conclusion According to the current literature data and the values obtained in our paper, we can correlate through expressive values obesity with OSA and their apnea hypopnea index (AHI) values. However, despite significant prevalence of OSA with other comorbidities, our study could not render expressive significance values able to justify their correlations. PMID:27096019

  5. Comorbidities Associated with Obstructive Sleep Apnea: a Retrospective Study

    Directory of Open Access Journals (Sweden)

    Pinto, José Antonio

    2016-03-01

    Full Text Available Introduction Obstructive sleep apnea (OSA is characterized by partial or complete recurrent upper airway obstruction during sleep. OSA brings many adverse consequences, such as hypertension, obesity, diabetes mellitus, cardiac and encephalic alterations, behavioral, among others, resulting in a significant source of public health care by generating a high financial and social impact. The importance of this assessment proves to be useful, because the incidence of patients with comorbidities associated with AOS has been increasing consistently and presents significant influence in natural disease history. Objective The objective of this study is to assess major comorbidities associated with obstructive sleep apnea (OSA and prevalence in a group of patients diagnosed clinically and polysomnographically with OSA. Methods This is a retrospective study of 100 charts from patients previously diagnosed with OSA in our service between October 2010 and January 2013. Results We evaluated 100 patients with OSA (84 men and 16 women with a mean age of 50.05 years (range 19–75 years. The prevalence of comorbidities were hypertension (39%, obesity (34%, depression (19%, gastroesophageal reflux disease (GERD (18%, diabetes mellitus (15%, hypercholesterolemia (10%, asthma (4%, and no comorbidities (33%. Comorbidities occurred in 56.2% patients diagnosed with mild OSA, 67.6% with moderate OSA, and 70% of patients with severe OSA. Conclusion According to the current literature data and the values obtained in our paper, we can correlate through expressive values obesity with OSA and their apnea hypopnea index (AHI values. However, despite significant prevalence of OSA with other comorbidities, our study could not render expressive significance values able to justify their correlations.

  6. Tomographic Study of Ionospheric Effects Associated with a Solar Eclipse

    Institute of Scientific and Technical Information of China (English)

    Wu Xiong-bin; Xu Ji-sheng; Ma Shu-ying; Tian Mao

    2003-01-01

    This paper studies the ionospheric effects associ-ated with the solar eclipse of October 24th, 1995 by means of Computerized Ionospheric Tomography (CIT). Since the re-constructed profiles from experimental CIT are sporadically located in time, a time domain interpolation method based onSingular Value Decomposition (SVD) technique is proposed and applied to extract the ionospheric effects. The effects canbe extracted by comparison analysis between the interpolated CIT profiles of the eclipse days and that of the reference day that are time-aligned. A series of figs have been obtained showing the attenuation of photonization effect at low alti-tudes and the weakening of plasma's transportation process athigh altitudes, etc. The photonization effect recovered to nor-mal level soon after the last contact. The maximum electron density diminishing is observed about 2 h after the eclipse maximum and the effects seem vanished in the hours fol-lowed. Analysis on vertical TEC's latitudinal temporal variation gives similar conclusions.

  7. Mechanism study of goldenseal-associated DNA damage.

    Science.gov (United States)

    Chen, Si; Wan, Liqing; Couch, Letha; Lin, Haixia; Li, Yan; Dobrovolsky, Vasily N; Mei, Nan; Guo, Lei

    2013-07-31

    Goldenseal has been used for the treatment of a wide variety of ailments including gastrointestinal disturbances, urinary tract disorders, and inflammation. The five major alkaloid constituents in goldenseal are berberine, palmatine, hydrastine, hydrastinine, and canadine. When goldenseal was evaluated by the National Toxicology Program (NTP) in the standard 2-year bioassay, goldenseal induced an increase in liver tumors in rats and mice; however, the mechanism of goldenseal-associated liver carcinogenicity remains unknown. In this study, the toxicity of the five goldenseal alkaloid constituents was characterized, and their toxic potencies were compared. As measured by the Comet assay and the expression of γ-H2A.X, berberine, followed by palmatine, appeared to be the most potent DNA damage inducer in human hepatoma HepG2 cells. Berberine and palmatine suppressed the activities of both topoisomerase (Topo) I and II. In berberine-treated cells, DNA damage was shown to be directly associated with the inhibitory effect of Topo II, but not Topo I by silencing gene of Topo I or Topo II. In addition, DNA damage was also observed when cells were treated with commercially available goldenseal extracts and the extent of DNA damage was positively correlated to the berberine content. Our findings suggest that the Topo II inhibitory effect may contribute to berberine- and goldenseal-induced genotoxicity and tumorigenicity.

  8. Study of enteropathogens associated with paediatric gastroen-teritis

    Institute of Scientific and Technical Information of China (English)

    Maysaa El; Sayed Zaki

    2009-01-01

    Objective:To determine the etiology of acute diarrhea in children under 5 years of age and to improve knowl-edge of the etiology of gastrointestinal pathogens using traditional and molecular diagnostic techniques.Meth-ods:Various common enteropathogens (viral,bacterial and parasites)associated with diarrhea were investiga-ted by conventional and molecular techniques (PCR)for verotoxin present in Escherichia coli in 218 children less than 5 years of age admitted to Mansoura University Children hospital-Egypt.Results:The occurrence of enteropathogens identified was as follows:E.coli O157∶H7 38.8% followed by Salmonella Spp 29.4%,Aero-monas 20% and Shigella Spp 11.8%.Rotavirus was found in of samples 17.1%.Rotavirus was statistically significant in age <2 years old.The commonest parasites found were E.histolytica followed by Enterobius ver-micularis,Giardia lambia,Hymenolepis nana and Ascaries.Shigella and Salmonella isolates were tested for their susceptibility to common antimicrobial agents and most of the isolates were resistant to ampicillin and tri-methoprim /sulfamethoxazole.Conculsion:This study demonstrated that rotavirus,E.coli O157∶H7,Salmo-nella Spp,and Aeromonas were significant enteropathogens.Rotavirus was significantly associated with infan-tile gastroenteritis.The results highlight the value of using a combination of traditional and PCR techniques in the diagnosis of enteropathogens related to acute gastroenteritis in children.

  9. Genome-wide association study identifies five new schizophrenia loci.

    LENUS (Irish Health Repository)

    Ripke, Stephan

    2011-10-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).

  10. Semantically enabling a genome-wide association study database

    Directory of Open Access Journals (Sweden)

    Beck Tim

    2012-12-01

    Full Text Available Abstract Background The amount of data generated from genome-wide association studies (GWAS has grown rapidly, but considerations for GWAS phenotype data reuse and interchange have not kept pace. This impacts on the work of GWAS Central – a free and open access resource for the advanced querying and comparison of summary-level genetic association data. The benefits of employing ontologies for standardising and structuring data are widely accepted. The complex spectrum of observed human phenotypes (and traits, and the requirement for cross-species phenotype comparisons, calls for reflection on the most appropriate solution for the organisation of human phenotype data. The Semantic Web provides standards for the possibility of further integration of GWAS data and the ability to contribute to the web of Linked Data. Results A pragmatic consideration when applying phenotype ontologies to GWAS data is the ability to retrieve all data, at the most granular level possible, from querying a single ontology graph. We found the Medical Subject Headings (MeSH terminology suitable for describing all traits (diseases and medical signs and symptoms at various levels of granularity and the Human Phenotype Ontology (HPO most suitable for describing phenotypic abnormalities (medical signs and symptoms at the most granular level. Diseases within MeSH are mapped to HPO to infer the phenotypic abnormalities associated with diseases. Building on the rich semantic phenotype annotation layer, we are able to make cross-species phenotype comparisons and publish a core subset of GWAS data as RDF nanopublications. Conclusions We present a methodology for applying phenotype annotations to a comprehensive genome-wide association dataset and for ensuring compatibility with the Semantic Web. The annotations are used to assist with cross-species genotype and phenotype comparisons. However, further processing and deconstructions of terms may be required to facilitate automatic

  11. Tomographic Study of Ionospheric Effects Associated with a Solar Eclipse

    Institute of Scientific and Technical Information of China (English)

    WuXiong-bin; XuJi-sheng; MaShu-ying; TianMao

    2003-01-01

    This paper studies the ionospheric effects associated with the solar eclipse of October 24th, 1995 by means of Computerized Ionospheric Tomography (CIT). Since the reconstructed profiles from experimental CIT are sporadically located in time, a time domain interpolation method based on Singular Value Decomposition (SVD) technique is proposed and applied to extract the ionospheric effects. The effects can be extracted by comparison analysis between the interpolated CIT profiles of the eclipse days and that of the reference day that are time-aligned. A series of figs have been obtained showing the attenuation of photonization effect at low altitudes and the weakening of plasma's transportation process at high altitudes, etc. The photonization effect recovered to normal level soon after the last contact. The maximum electron density diminishing is observed about 2 h after the eclipse maximum and the effects seem vanished in the hours followed. Analysis on vertical TEC's latitudinal-temporal variation gives similar conclusions.

  12. Interleukin-1 gene complex in schizophrenia: an association study.

    Science.gov (United States)

    Saiz, Pilar A; Garcia-Portilla, Maria P; Arango, Celso; Morales, Blanca; Martinez-Barrondo, Sara; Alvarez, Victoria; Coto, Eliecer; Fernandez, Juan; Bousono, Manuel; Bobes, Julio

    2006-09-01

    The aim of this study is to investigate the association between three polymorphisms of the interleukin-1 (IL-1) gene complex and schizophrenia. We genotyped 228 outpatients with schizophrenia (DSM-IV criteria) and 419 unrelated healthy controls. The following polymorphisms were analyzed: IL-1alpha -889 C/T, IL-1beta +3953 C/T, and IL-1RA (86 bp)n. No significant differences in genotype or in allelic distribution of the Il-1alpha, IL-1beta, and IL-1RA polymorphisms were found. Estimated haplotype frequencies were similar in both groups. Our data do not suggest that genetically determined changes in the IL-1 gene complex confer increased susceptibility for schizophrenia.

  13. Statistical study of seismicity associated with geothermal reservoirs in California

    Energy Technology Data Exchange (ETDEWEB)

    Hadley, D.M.; Cavit, D.S.

    1982-01-01

    Statistical methods are outlined to separate spatially, temporally, and magnitude-dependent portions of both the random and non-random components of the seismicity. The methodology employed compares the seismicity distributions with a generalized Poisson distribution. Temporally related events are identified by the distribution of the interoccurrence times. The regions studied to date include the Imperial Valley, Coso, The Geysers, Lassen, and the San Jacinto fault. The spatial characteristics of the random and clustered components of the seismicity are diffuse and appear unsuitable for defining the areal extent of the reservoir. However, from the temporal characteristics of the seismicity associated with these regions a general discriminant was constructed that combines several physical parameters for identifying the presence of a geothermal system.

  14. Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis

    NARCIS (Netherlands)

    Natarajan, Pradeep; Bis, Joshua C; Bielak, Lawrence F; Cox, Amanda J; Dörr, Marcus; Feitosa, Mary F; Franceschini, Nora; Guo, Xiuqing; Hwang, Shih-Jen; Isaacs, Aaron; Jhun, Min A; Kavousi, Maryam; Li-Gao, Ruifang; Lyytikäinen, Leo-Pekka; Marioni, Riccardo E; Schminke, Ulf; Stitziel, Nathan O; Tada, Hayato; van Setten, Jessica; Smith, Albert V; Vojinovic, Dina; Yanek, Lisa R; Yao, Jie; Yerges-Armstrong, Laura M; Amin, Najaf; Baber, Usman; Borecki, Ingrid B; Carr, J Jeffrey; Chen, Yii-Der Ida; Cupples, L Adrienne; de Jong, Pim A; de Koning, Harry; de Vos, Bob D; Demirkan, Ayse; Fuster, Valentin; Franco, Oscar H; Goodarzi, Mark O; Harris, Tamara B; Heckbert, Susan R; Heiss, Gerardo; Hoffmann, Udo; Hofman, Albert; Išgum, Ivana; Jukema, J Wouter; Kähönen, Mika; Kardia, Sharon L R; Kral, Brian G; Launer, Lenore J; Massaro, Joseph; Mehran, Roxana; Mitchell, Braxton D; Mosley, Thomas H; de Mutsert, Renée; Newman, Anne B; Nguyen, Khanh-Dung; North, Kari E; O'Connell, Jeffrey R; Oudkerk, Matthijs; Pankow, James S; Peloso, Gina M; Post, Wendy; Province, Michael A; Raffield, Laura M; Raitakari, Olli T; Reilly, Dermot F; Rivadeneira, Fernando; Rosendaal, Frits; Sartori, Samantha; Taylor, Kent D; Teumer, Alexander; Trompet, Stella; Turner, Stephen T; Uitterlinden, André G; Vaidya, Dhananjay; van der Lugt, Aad; Völker, Uwe; Wardlaw, Joanna M; Wassel, Christina L; Weiss, Stefan; Wojczynski, Mary K; Becker, Diane M; Becker, Lewis C; Boerwinkle, Eric; Bowden, Donald W; Deary, Ian J; Dehghan, Abbas; Felix, Stephan B; Gudnason, Vilmundur; Lehtimäki, Terho; Mathias, Rasika; Mook-Kanamori, Dennis O; Psaty, Bruce M; Rader, Daniel J; Rotter, Jerome I; Wilson, James G; van Duijn, Cornelia M; Völzke, Henry; Kathiresan, Sekar; Peyser, Patricia A; O'Donnell, Christopher J

    2016-01-01

    BACKGROUND: -The burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease (CHD). We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the

  15. Sequence imputation of HPV16 genomes for genetic association studies.

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    Benjamin Smith

    Full Text Available BACKGROUND: Human Papillomavirus type 16 (HPV16 causes over half of all cervical cancer and some HPV16 variants are more oncogenic than others. The genetic basis for the extraordinary oncogenic properties of HPV16 compared to other HPVs is unknown. In addition, we neither know which nucleotides vary across and within HPV types and lineages, nor which of the single nucleotide polymorphisms (SNPs determine oncogenicity. METHODS: A reference set of 62 HPV16 complete genome sequences was established and used to examine patterns of evolutionary relatedness amongst variants using a pairwise identity heatmap and HPV16 phylogeny. A BLAST-based algorithm was developed to impute complete genome data from partial sequence information using the reference database. To interrogate the oncogenic risk of determined and imputed HPV16 SNPs, odds-ratios for each SNP were calculated in a case-control viral genome-wide association study (VWAS using biopsy confirmed high-grade cervix neoplasia and self-limited HPV16 infections from Guanacaste, Costa Rica. RESULTS: HPV16 variants display evolutionarily stable lineages that contain conserved diagnostic SNPs. The imputation algorithm indicated that an average of 97.5±1.03% of SNPs could be accurately imputed. The VWAS revealed specific HPV16 viral SNPs associated with variant lineages and elevated odds ratios; however, individual causal SNPs could not be distinguished with certainty due to the nature of HPV evolution. CONCLUSIONS: Conserved and lineage-specific SNPs can be imputed with a high degree of accuracy from limited viral polymorphic data due to the lack of recombination and the stochastic mechanism of variation accumulation in the HPV genome. However, to determine the role of novel variants or non-lineage-specific SNPs by VWAS will require direct sequence analysis. The investigation of patterns of genetic variation and the identification of diagnostic SNPs for lineages of HPV16 variants provides a valuable

  16. A genome-wide association study of pulmonary function measures in the Framingham Heart Study.

    Directory of Open Access Journals (Sweden)

    Jemma B Wilk

    2009-03-01

    Full Text Available The ratio of forced expiratory volume in one second to forced vital capacity (FEV(1/FVC is a measure used to diagnose airflow obstruction and is highly heritable. We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs associated with the FEV(1/FVC ratio, analyzed as a percent of the predicted value. Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction. Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV(1/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09. One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV(1/FVC (p-value = 2.0e-04. The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G associated with higher FEV(1/FVC ratio levels. Results from the Family Heart Study demonstrated that the association extended to FEV(1 and dichotomous airflow obstruction phenotypes, particularly among smokers. The SNP rs13147758 was associated with the percent predicted FEV(1/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript. The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP gene and several expressed sequence tags cloned from fetal lung. Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation.

  17. A strategy analysis for genetic association studies with known inbreeding

    Directory of Open Access Journals (Sweden)

    del Giacco Stefano

    2011-07-01

    Full Text Available Abstract Background Association studies consist in identifying the genetic variants which are related to a specific disease through the use of statistical multiple hypothesis testing or segregation analysis in pedigrees. This type of studies has been very successful in the case of Mendelian monogenic disorders while it has been less successful in identifying genetic variants related to complex diseases where the insurgence depends on the interactions between different genes and the environment. The current technology allows to genotype more than a million of markers and this number has been rapidly increasing in the last years with the imputation based on templates sets and whole genome sequencing. This type of data introduces a great amount of noise in the statistical analysis and usually requires a great number of samples. Current methods seldom take into account gene-gene and gene-environment interactions which are fundamental especially in complex diseases. In this paper we propose to use a non-parametric additive model to detect the genetic variants related to diseases which accounts for interactions of unknown order. Although this is not new to the current literature, we show that in an isolated population, where the most related subjects share also most of their genetic code, the use of additive models may be improved if the available genealogical tree is taken into account. Specifically, we form a sample of cases and controls with the highest inbreeding by means of the Hungarian method, and estimate the set of genes/environmental variables, associated with the disease, by means of Random Forest. Results We have evidence, from statistical theory, simulations and two applications, that we build a suitable procedure to eliminate stratification between cases and controls and that it also has enough precision in identifying genetic variants responsible for a disease. This procedure has been successfully used for the beta-thalassemia, which is

  18. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies

    DEFF Research Database (Denmark)

    Yang, Xiaohong R; Chang-Claude, Jenny; Goode, Ellen L;

    2011-01-01

    Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.......Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors....

  19. Genome-wide Association Study of Personality Traits in the Long Life Family Study

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    Harold T Bae

    2013-05-01

    Full Text Available Personality traits have been shown to be associated with longevity and healthy aging. In order to discover novel genetic modifiers associated with personality traits as related with longevity, we performed a genome-wide association study (GWAS on personality factors assessed by NEO-FFI in individuals enrolled in the Long Life Family Study (LLFS, a study of 583 families (N up to 4595 with clustering for longevity in the United States and Denmark. Three SNPs, in almost perfect LD, associated with agreeableness reached genome-wide significance (p<10-8 and replicated in an additional sample of 1279 LLFS subjects, although one (rs9650241 failed to replicate and the other two were not available in two independent replication cohorts, the Baltimore Longitudinal Study of Aging and the New England Centenarian Study. Based on 10,000,000 permutations, the empirical p-value of 2X10-7 was observed for the genome-wide significant SNPs. Seventeen SNPs that reached marginal statistical significance in the two previous GWASs (p-value < 10-4 and 10-5, were also marginally significantly associated in this study (p-value < 0.05, although none of the associations passed the Bonferroni correction. In addition, we tested age-by-SNP interactions and found some significant associations. Since scores of personality traits in LLFS subjects change in the oldest ages, and genetic factors outweigh environmental factors to achieve extreme ages, these age-by-SNP interactions could be a proxy for complex gene-gene interactions affecting personality traits and longevity.

  20. A study of Helicobacter pylori -associated gastritis patterns in Iraq and their association with strain virulence

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    Hussein Nawfal

    2009-01-01

    Full Text Available Background/Aim: Helicobacter pylori ( H. pylori infection causes peptic ulceration and gastric adenocarcinoma. In Iraq, gastric cancer is rare. We investigated whether infected adults had the antral-predominant pattern of H. pylori -associated gastritis, which does not predispose to cancer. Materials and Methods: We evaluated histopathological changes by the Sydney scoring system in gastric biopsies taken from 30 H. pylori -infected adults and studied the correlation of these changes with the virulence factors. The Mann-Whitney test was used for the comparison of histopathological data. The presence or absence of each pathological index was evaluated with respect to the possession of virulence factors by the infecting H. pylori strain using the χ2 test. Results: Gastric lymphocyte infiltration was more prominent in the antrum ( P = 0.01. Neutrophil infiltration was mild and gastric mucosal atrophy was rare. No relationship was found between virulence factors and histopathological changes. Conclusions: The mild pathology and antral-predominant gastritis help explain the low cancer rate in Iraq.

  1. Adult Learning Open University Determinants study (ALOUD): physical activity associated with study success

    NARCIS (Netherlands)

    Gijselaers, Jérôme; De Groot, Renate; Kirschner, Paul A.

    2013-01-01

    Gijselaers, H. J. M., De Groot, R. H. M., & Kirschner, P. A. (2013, 23 May). Adult Learning Open University Determinants study (ALOUD): physical activity associated with study success. Poster presentation at the annual meeting of the International Society for Behaviour on Nutrition and Physical Acti

  2. Methylome-wide Association Study of Atrial Fibrillation in Framingham Heart Study

    Science.gov (United States)

    Lin, Honghuang; Yin, Xiaoyan; Xie, Zhijun; Lunetta, Kathryn L.; Lubitz, Steven A.; Larson, Martin G.; Ko, Darae; Magnani, Jared W.; Mendelson, Michael M.; Liu, Chunyu; McManus, David D.; Levy, Daniel; Ellinor, Patrick T.; Benjamin, Emelia J.

    2017-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia, but little is known about the molecular mechanisms associated with AF arrhythmogenesis. DNA methylation is an important epigenetic mechanism that regulates gene expression and downstream biological processes. We hypothesize that DNA methylation might play an important role in the susceptibility to develop AF. A total of 2,639 participants from the Offspring Cohort of Framingham Heart Study were enrolled in the current study. These participants included 183 participants with prevalent AF and 220 with incident AF during up to 9 years follow up. Genome-wide methylation was profiled using the Illumina Infinium HumanMethylation450 BeadChip on blood-derived DNA collected during the eighth examination cycle (2005–2008). Two CpG sites were significantly associated with prevalent AF, and five CpGs were associated with incident AF after correction for multiple testing (FDR < 0.05). Fourteen previously reported genome-wide significant AF-related SNP were each associated with at least one CpG site; the most significant association was rs6490029 at the CUX2 locus and cg10833066 (P = 9.5 × 10−279). In summary, we performed genome-wide methylation profiling in a community-based cohort and identified seven methylation signatures associated with AF. Our study suggests that DNA methylation might play an important role in AF arrhythmogenesis. PMID:28067321

  3. Genome-Wide Association Study of Schizophrenia in Japanese Population

    Science.gov (United States)

    Yamada, Kazuo; Iwayama, Yoshimi; Hattori, Eiji; Iwamoto, Kazuya; Toyota, Tomoko; Ohnishi, Tetsuo; Ohba, Hisako; Maekawa, Motoko; Kato, Tadafumi; Yoshikawa, Takeo

    2011-01-01

    Schizophrenia is a devastating neuropsychiatric disorder with genetically complex traits. Genetic variants should explain a considerable portion of the risk for schizophrenia, and genome-wide association study (GWAS) is a potentially powerful tool for identifying the risk variants that underlie the disease. Here, we report the results of a three-stage analysis of three independent cohorts consisting of a total of 2,535 samples from Japanese and Chinese populations for searching schizophrenia susceptibility genes using a GWAS approach. Firstly, we examined 115,770 single nucleotide polymorphisms (SNPs) in 120 patient-parents trio samples from Japanese schizophrenia pedigrees. In stage II, we evaluated 1,632 SNPs (1,159 SNPs of p<0.01 and 473 SNPs of p<0.05 that located in previously reported linkage regions). The second sample consisted of 1,012 case-control samples of Japanese origin. The most significant p value was obtained for the SNP in the ELAVL2 [(embryonic lethal, abnormal vision, Drosophila)-like 2] gene located on 9p21.3 (p = 0.00087). In stage III, we scrutinized the ELAVL2 gene by genotyping gene-centric tagSNPs in the third sample set of 293 family samples (1,163 individuals) of Chinese descent and the SNP in the gene showed a nominal association with schizophrenia in Chinese population (p = 0.026). The current data in Asian population would be helpful for deciphering ethnic diversity of schizophrenia etiology. PMID:21674006

  4. Genome-wide association study of schizophrenia in Japanese population.

    Directory of Open Access Journals (Sweden)

    Kazuo Yamada

    Full Text Available Schizophrenia is a devastating neuropsychiatric disorder with genetically complex traits. Genetic variants should explain a considerable portion of the risk for schizophrenia, and genome-wide association study (GWAS is a potentially powerful tool for identifying the risk variants that underlie the disease. Here, we report the results of a three-stage analysis of three independent cohorts consisting of a total of 2,535 samples from Japanese and Chinese populations for searching schizophrenia susceptibility genes using a GWAS approach. Firstly, we examined 115,770 single nucleotide polymorphisms (SNPs in 120 patient-parents trio samples from Japanese schizophrenia pedigrees. In stage II, we evaluated 1,632 SNPs (1,159 SNPs of p<0.01 and 473 SNPs of p<0.05 that located in previously reported linkage regions. The second sample consisted of 1,012 case-control samples of Japanese origin. The most significant p value was obtained for the SNP in the ELAVL2 [(embryonic lethal, abnormal vision, Drosophila-like 2] gene located on 9p21.3 (p = 0.00087. In stage III, we scrutinized the ELAVL2 gene by genotyping gene-centric tagSNPs in the third sample set of 293 family samples (1,163 individuals of Chinese descent and the SNP in the gene showed a nominal association with schizophrenia in Chinese population (p = 0.026. The current data in Asian population would be helpful for deciphering ethnic diversity of schizophrenia etiology.

  5. Highway Expenditures and Associated Customer Satisfaction: A Case Study

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    Alexander Paz

    2016-01-01

    Full Text Available This study analyzes the satisfaction of the Nevadans with respect to their highway transportation system and the corresponding expenditures of Nevada Department of Transportation (NDOT. A survey questionnaire was designed to capture the opinions of the Nevadans (customers about a number of characteristics of their transportation system. Data from the financial data warehouse of the NDOT was used to evaluate expenditures. Multinomial probit models were estimated to study the correlations between customers’ opinion and the government expenditures in transportation. The results indicate the customer satisfaction is decreasing with respect to traffic safety throughout Northwestern and Southern Nevada highways. In addition, users of Northwestern highways are more likely to be satisfied, compared to their counterparts, with increasing construction spending to reduce the time taken to complete construction projects. In Southern Nevada highways, customers’ satisfaction increases with the expenditures associated with reduction of congestion. These insights are examples of the conclusions that were obtained as a consequence of simultaneously considering customer satisfaction and the corresponding expenditures in transportation.

  6. Genome-wide association study of proneness to anger.

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    Eric Mick

    Full Text Available BACKGROUND: Community samples suggest that approximately 1 in 20 children and adults exhibit clinically significant anger, hostility, and aggression. Individuals with dysregulated emotional control have a greater lifetime burden of psychiatric morbidity, severe impairment in role functioning, and premature mortality due to cardiovascular disease. METHODS: With publically available data secured from dbGaP, we conducted a genome-wide association study of proneness to anger using the Spielberger State-Trait Anger Scale in the Atherosclerosis Risk in Communities (ARIC study (n = 8,747. RESULTS: Subjects were, on average, 54 (range 45-64 years old at baseline enrollment, 47% (n = 4,117 were male, and all were of European descent by self-report. The mean Angry Temperament and Angry Reaction scores were 5.8 ± 1.8 and 7.6 ± 2.2. We observed a nominally significant finding (p = 2.9E-08, λ = 1.027 - corrected pgc = 2.2E-07, λ = 1.0015 on chromosome 6q21 in the gene coding for the non-receptor protein-tyrosine kinase, Fyn. CONCLUSIONS: Fyn interacts with NDMA receptors and inositol-1,4,5-trisphosphate (IP3-gated channels to regulate calcium influx and intracellular release in the post-synaptic density. These results suggest that signaling pathways regulating intracellular calcium homeostasis, which are relevant to memory, learning, and neuronal survival, may in part underlie the expression of Angry Temperament.

  7. Incidence of Pneumonia After Videofluoroscopic Swallowing Study and Associated Factors.

    Science.gov (United States)

    Jo, Hannae; Park, Jung-Gyoo; Min, David; Park, Hee-Won; Kang, Eun Kyoung; Lee, Kun-Jai; Baek, Sora

    2016-02-01

    Pneumonia after videofluoroscopic swallow study (VFSS) is sometimes considered to be caused by aspiration during VFSS; however, to our knowledge, a relationship between these events has not been clearly investigated. The aim of this study was to assess the incidence of VFSS-related pneumonia and related factors. Overall, 696 VFSS cases were retrospectively reviewed. Cases in which blood culture was performed within 3 days after VFSS due to newly developed infectious signs were considered as post-VFSS infection cases. Pneumonia was suspected when there was some evidence of respiratory infectious signs in clinical, radiological, and laboratory findings. The underlying disease, clinical signs, and VFSS findings of the pneumonia group were assessed. Among 696 cases, pneumonia was diagnosed in 15 patients. The patients in the pneumonia group tended to be older and had higher aspiration rate on VFSS than those in the non-pneumonia group. In the pneumonia group, 2 patients showed no aspiration during VFSS. In 6 patients, pneumonia developed after massive aspiration of gastric content in 5 patients and inappropriate oral feeding with risk of aspiration before VFSS in 1 patient. Only 7 patients (1.0 %) were finally determined as having VFSS-related pneumonia. In conclusion, the 72-h incidence of VFSS-related pneumonia was 1.0 %. Old age and severity of swallowing difficulty are associated with occurrence of pneumonia.

  8. A Retrospective Study of Congenital Cardiac Abnormality Associated with Scoliosis

    Science.gov (United States)

    Ucpunar, Hanifi; Sevencan, Ahmet; Balioglu, Mehmet Bulent; Albayrak, Akif; Polat, Veli

    2016-01-01

    Study Design Retrospective study. Purpose To identify the incidence of congenital cardiac abnormalities in patients who had scoliosis and underwent surgical treatment for scoliosis. Overview of Literature Congenital and idiopathic scoliosis (IS) are associated with cardiac abnormalities. We sought to establish and compare the incidence of congenital cardiac abnormalities in patients with idiopathic and congenital scoliosis (CS) who underwent surgical treatment for scoliosis. Methods Ninety consecutive scoliosis patients, who underwent surgical correction of scoliosis, were classified as CS (55 patients, 28 female [51%]) and IS (35 patients, 21 female [60%]). The complete data of the patients, including medical records, plain radiograph and transthoracic echocardiography were retrospectively assessed. Results We found that mitral valve prolapse was the most common cardiac abnormality in both patients with IS (nine patients, 26%) and CS (13 patients, 24%). Other congenital cardiac abnormalities were atrial septal aneurysm (23% of IS patients, 18% of CS patients), pulmonary insufficiency (20% of IS patients, 4% of CS patients), aortic insufficiency (17% of IS patients), atrial septal defect (11% of IS patients, 13% of CS patients), patent foramen ovale (15% of CS patients), dextrocardia (4% of CS patients), bicuspid aortic valve (3% of IS patients), aortic stenosis (2% of CS patients), ventricular septal defect (2% of CS patients), and cardiomyopathy (2% of CS patients). Conclusions We determined the increased incidence of congenital cardiac abnormalities among patients with congenital and IS. Mitral valve prolapse appeared to be the most prevalent congenital cardiac abnormality in both groups. PMID:27114761

  9. Study of Myelin Basic Protein Associated with Pediatric Systematic Epilepsy

    Institute of Scientific and Technical Information of China (English)

    Yang Sida; He Xin; Yang Yiyu; Zhu Huihua; He Dansha; Deng Weiyi

    2000-01-01

    Objective: To investigate the quantitative myelin basic protein (MBP) in cerebrospinal fluid (CSF) and serum in pediatric systematic epilepsy (SEP), study the relation between SEP and MBP, and the possibility predicating'the injury of myelin and blood-brain barrier (BBB) from pediatric SEP. Background: While tactors induced destroy of cerebral and Myelin, MBP was released out into CSF to increase its concentration. On the other hand, the BBB was involved to make serum MBP increased. The related studies had confirmed these viewpoints above. The test for quantitative MBP was recognized as the specific biochemical index, which diagnose if there is or not organic injury of cerebral and myelin. There was few reports about the studies of quantitative MBP in CSF and serum of EP, not mention to those published in domestic pediatric academia. Methods: 47 cases were studied during one month after the SEP attack, whose MBP in serum were quantitatively and 31 inside in CSF were also tested by easy MBP-ELISA method; the quantitative MBP in serum of 30 control cases and 10 in CSF were tested, too. Results: MBP values in CSF and serum of SEP pediatric patients were 2.95±0.61 ng/ml and 3.17±0.53 ng/ml; whereas 1.41 ±0.19 ng/ml and 1.30±0.04 ng/ml in control group. Both mean valves of MBP in CSF and serum in study group were significantly higher than control group (either P< 0.01). Discussion: In general, electrophysiological evidences supported the issue that epileptic episode was originated from abnormal electrical activities of nervous cells. Pathological studies revealed degeneration and necrosis of nerve existed in temporal epileptic focus, where there was morphological change of myelin. This study showed MBP values in CSF and serum of SEEP, during one month after attack, increased significantly; suggested there was changed component of MBP, while SEP could not be controled. Those above indicated the destroy of myelin, increasing of BBB permeability that induced its

  10. Association between sensory function and hop performance and self-reported outcomes in patients with anterior cruciate ligament injury

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    Cronström A

    2017-01-01

    Full Text Available Anna Cronström,1 Ewa M Roos,2 Eva Ageberg1 1Department of Health Sciences, Lund University, Lund, Sweden; 2Research Unit for Musculoskeletal Function and Physiotherapy, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark Background: In patients with anterior cruciate ligament (ACL deficiency (ACLD or reconstruction (ACLR, sensory deficits are commonly assessed as knee kinesthesia using time-consuming laboratory equipment. Portable equipment such as that used for evaluation of vibration sense would be preferable. In contrast to kinesthesia, vibration sense is not well studied in these patients. Objectives: 1 To study the association between kinesthesia and vibration sense to investigate if one sensory measurement can replace the other; and 2 to determine the clinical relevance by investigating associations between the sensory measurements and functional performance and patient-reported outcomes in patients with ACLD or ACLR. Methods: Twenty patients with ACLD and 33 patients with ACLR were assessed with knee kinesthesia, vibration sense, the one-leg hop test for distance, as well as the Knee injury and Osteoarthritis Outcome Score (KOOS and the Tegner Activity Scale. Results: There were no significant correlations between kinesthesia and vibration sense (r= –0.267, p>0.269 or between the sensory measures and hop performance (r= –0.351, p>0.199. In patients with ACLD, worse knee kinesthesia was associated with worse scores on KOOS subscales pain (r= –0.464, p=0.046 and activities of daily living (r= –0.491, p=0.033, and worse vibration sense was associated with worse scores on KOOS subscale quality of life (r= –0.469, p=0.037 and worse knee confidence (item Q3 from subscale quality of life (rs=0.436, p=0.054. In patients with ACLR, worse vibration sense was associated with worse scores on KOOS subscales pain (r= –0.402, p=0.020 and activities of daily living (r= –0.385, p=0

  11. Goitrogens And Goitre— A Clinicosocial Study Of Association

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    M Athar Ansari

    2003-06-01

    Full Text Available Research Problem : Is there any role of goitrogens in the causation of goitre?Objectives :    (1     To describe the intake of goitrogenic substances in goitrous and non-goitrous patients.(2 To find out the types and frequency of goitrogenic subtanccs in these patients.Study Design : Hospital-based Study by Questionnaire Method.                            •Setting : Endocrinology Out Patients Department, J.N.Medical college Hospital, A.M.U., Aligarh.Participants : Cases were patients having clinical features of iodine deficiency disorders (IDD and controls were not having goiter but they had other endocrinological disorders in the Endocrinology O.P.D. at J.N. Medical College Hospital, A.M.U., Aligarh.Study variables : Intake, type and frequency of goitrogenic substances.Outcome variables : Percentage of goitrous and nongoitrous patients consuming goitrogenic substances.Statistical Analysis : Chi-Square Test.Result : In goitrous patients, a dietary' history' of goitrogen intake was found in 93.85% patients while in nongoitrous patients, it was 76.92%, Commonly consumed vegetables having goitrogenic properties were Cabbage, Cauliflower and Lady’s finger. Intake was frequent (once a week in most of the goitrous patients while it was taken occasional (once fortnightly in most of the nongoitrous patients.Conclusion : Majority of the goitrous patients were consuming goitrogenic substances. Their role in the causation of goiter is clearly understood. However, for this further research activities should be carried out to find out the strength of association.

  12. ‘Smoking Genes’: A Genetic Association Study

    Science.gov (United States)

    Rodríguez González-Moro, José Miguel; de Lucas Ramos, Pilar; López Martín, Soledad; Bandrés, Fernando; Lucia, Alejandro; Gómez-Gallego, Félix

    2011-01-01

    Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence) with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A) [rs1801272], CYP2A6*9 (−48T>G) [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T) [rs8192789], CYP2A13*3 (7520C>G), CYP2A13*4 (579G>A), CYP2A13*7 (578C>T) [rs72552266], CYP2B6*4 (785A>G), CYP2B6*9 (516G>T), CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A) [rs1800497], 5HTT LPR, HTR2A −1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126) and ethnically matched never smokers (controls, N = 80). The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both PA (Taq1A) polymorphisms was 3.60 (95%CI: 1.75, 7.44) and 2.63 (95%CI: 1.41, 4.89) respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65). We found a significant genotype effect (all P≤0.017) for the following smoking-related phenotypes: (i) cigarettes smoked per day and CYP2A13*3; (ii) pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A); (iii) nicotine dependence (assessed with the Fagestrom test) and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms) are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5), serotoninergic (HTR2A), opioid (OPRM1) or cannabinoid receptors (CNR1). PMID:22046326

  13. An ecophysiological study of the Azolla filiculoides- Anabaena azollae association

    Science.gov (United States)

    van Kempen, Monique; Smolders, Fons; Speelman, Eveline; Reichart, Gert Jan; Barke, Judith; Brinkhuis, Henk; Lotter, Andy; Roelofs, Jan

    2010-05-01

    The long term effects of salinity stress on the growth, nutrient content and amino acid composition of the Azolla filiculoides - Anabaena azollae association was studied in a laboratory experiment. It was demonstrated that the symbiosis could tolerate salt stress up to 90 mM NaCl, even after a 100 day period of preconditioning at salt concentrations that were 30 mM NaCl lower. In the 120 mM NaCl treatment the Azolla filiculoides survived, but hardly any new biomass was produced. It was shown that during the experiment, A. filiculoides became increasingly efficient in excluding salt ions from the plant tissue and was thus able to increase its salt tolerance. The amino acid analysis revealed that the naturally occurring high glutamine concentration in the plants was strongly reduced at salt concentrations of 120 mM NaCl and higher. This was the result of the reduced nitrogenase activity at these salt concentrations, as was demonstrated in an acetylene reduction assay. We suggest that the high glutamine concentration in the plants might play a role in the osmoregulatory response against salt stress, enabling growth of the A. filiculoides -Anabaena azollae association up to 90 mM NaCl. In a mesocosm experiment it furthermore was demonstrated that Azolla might manipulate its own microenvironment when grown at elevated salt concentration (up to ~50 mmol•L-1) by promoting salinity stratification, especially when it has formed a dense cover at the water surface. Beside salt stress, we also studied the growth of Azolla filiculoides in response to elevated atmospheric carbon dioxide concentration, in combination with different light intensities and different pH of the nutrient solution. The results demonstrated that as compared to the control (ambient pCO2 concentrations), Azolla filiculoides was able to produce twice as much biomass at carbon dioxide concentrations that were five times as high as the ambient pCO2 concentration. However, it was also shown that this

  14. Genome-wide association study identifies 74 loci associated with educational attainment

    DEFF Research Database (Denmark)

    Okbay, Aysu; P. Beauchamp, Jonathan; Alan Fontana, Mark;

    2016-01-01

    -nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural...

  15. Study of acoustic correlates associate with emotional speech

    Science.gov (United States)

    Yildirim, Serdar; Lee, Sungbok; Lee, Chul Min; Bulut, Murtaza; Busso, Carlos; Kazemzadeh, Ebrahim; Narayanan, Shrikanth

    2004-10-01

    This study investigates the acoustic characteristics of four different emotions expressed in speech. The aim is to obtain detailed acoustic knowledge on how a speech signal is modulated by changes from neutral to a certain emotional state. Such knowledge is necessary for automatic emotion recognition and classification and emotional speech synthesis. Speech data obtained from two semi-professional actresses are analyzed and compared. Each subject produces 211 sentences with four different emotions; neutral, sad, angry, happy. We analyze changes in temporal and acoustic parameters such as magnitude and variability of segmental duration, fundamental frequency and the first three formant frequencies as a function of emotion. Acoustic differences among the emotions are also explored with mutual information computation, multidimensional scaling and acoustic likelihood comparison with normal speech. Results indicate that speech associated with anger and happiness is characterized by longer duration, shorter interword silence, higher pitch and rms energy with wider ranges. Sadness is distinguished from other emotions by lower rms energy and longer interword silence. Interestingly, the difference in formant pattern between [happiness/anger] and [neutral/sadness] are better reflected in back vowels such as /a/(/father/) than in front vowels. Detailed results on intra- and interspeaker variability will be reported.

  16. Suprathermal helium associated with corotating interaction regions: A case study

    Science.gov (United States)

    Yu, J.; Berger, L.; Wimmer-Schweingruber, R. F.; Hilchenbach, M.; Kallenbach, R.; Klecker, B.; Guo, J.

    2016-03-01

    Enhancements of suprathermal particles observed at 1AU often can be related to Corotating Interaction Regions (CIRs). The compression regions associated with CIRs and their driven shocks which typically form at a few AU distance to the Sun can efficiently accelerate particles. If accelerated at the trailing edge of a CIR these particles can travel sunward along the ambient magnetic field and thus enhanced fluxes can be observed even if the acceleration region has passed over the spacecraft. We have analysed a CIR that has been observed at L1 by ACE/SWICS and SOHO/CELIAS/STOF on days 207 and 208 in 2003. The combination of SWICS and STOF data allowed us to study suprathermal Helium ranging from its onset at solar wind bulk energies up to 330 keV/nuc. Here we present our results for the temporal evolution of the flux, energy spectra and the He+/He++ ratio. In particular we present observational evidence for a turnover of the energy spectra at lower energies after the CIR passage which has been theoretically predicted but never been observed so far.

  17. Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis

    NARCIS (Netherlands)

    Natarajan, Pradeep; Bis, Joshua C.; Bielak, Lawrence F.; Cox, Amanda J.; Dorr, Marcus; Feitosa, Mary F.; Franceschini, Nora; Guo, Xiuqing; Hwang, Shih-Jen; Isaacs, Aaron; Jhun, Min A.; Kavousi, Maryam; Li-Gao, Ruifang; Lyytikainen, Leo-Pekka; Marioni, Riccardo E.; Schminke, Ulf; Stitziel, Nathan O.; Tada, Hayato; van Setten, Jessica; Smith, Albert V.; Vojinovic, Dina; Yanek, Lisa R.; Yao, Jie; Yerges-Armstrong, Laura M.; Amin, Najaf; Baber, Usman; Borecki, Ingrid B.; Carr, J. Jeffrey; Chen, Yii-Der Ida; Cupples, L. Adrienne; de Jong, Pim A.; de Koning, Harry; de Vos, Bob D.; Demirkan, Ayse; Fuster, Valentin; Franco, Oscar H.; Goodarzi, Mark O.; Harris, Tamara B.; Heckbert, Susan R.; Heiss, Gerardo; Hoffmann, Udo; Hofman, Albert; Isgum, Ivana; Jukema, J. Wouter; Kahonen, Mika; Kardia, Sharon L. R.; Kral, Brian G.; Launer, Lenore J.; Massaro, Joe; Mehran, Roxana; Mitchell, Braxton D.; Jr, Thomas H. Mosley; de Mutsert, Renee; Newman, Anne B.; Nguyen, Khanh-dung; North, Kari E.; O'Connell, Jeffrey R.; Oudkerk, Matthijs; Pankow, James S.; Peloso, Gina M.; Post, Wendy; Province, Michael A.; Raffield, Laura M.; Raitakari, Olli T.; Reilly, Dermot F.; Rivadeneira, Fernando; Rosendaal, Frits; Sartori, Samantha; Taylor, Kent D.; Teumer, Alexander; Trompet, Stella; Turner, Stephen T.; Uitterlinden, Andre G.; Vaidya, Dhananjay; van der Lugt, Aad; Volker, Uwe; Wardlaw, Joanna M.; Wassel, Christina L.; Weiss, Stefan; Wojczynski, Mary K.; Becker, Diane M.; Becker, Lewis C.; Boerwinkle, Eric; Bowden, Donald W.; Deary, Ian J.; Dehghan, Abbas; Felix, Stephan B.; Gudnason, Vilmundur; Lehtimaki, Terho; Mathias, Rasika; Mook-Kanamori, Dennis O.; Psaty, Bruce M.; Rader, Daniel J.; Rotter, Jerome I.; Wilson, James G.; van Duijn, Cornelia M.; Volzke, Henry; Kathiresan, Sekar; Peyser, Patricia A.; O'Donnell, Christopher J.

    2016-01-01

    Background-The burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease. We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of

  18. Association between cancer and contact allergy: a linkage study

    DEFF Research Database (Denmark)

    Engkilde, Kaare; Thyssen, Jacob P; Menné, Torkil

    2011-01-01

    and cancer, few have looked into the association between cancer and contact allergy, a type IV allergy. By linking two clinical databases, the authors investigate the possible association between contact allergy and cancer. Methods Record linkage of two different registers was performed: (1) a tertiary...... hospital register of dermatitis patients patch tested for contact allergy and (2) a nationwide cancer register (the Danish Cancer Register). After linking the two registers, only cancer subtypes with 40 or more patients registered were included in the analysis. The final associations were evaluated...... by logistic regression analysis. Results An inverse association between contact allergy and non-melanoma skin- and breast cancer, respectively, was identified in both sexes, and an inverse trend for brain cancer was found in women with contact allergy. Additionally, a positive association between contact...

  19. Evaluating variations of genotype calling: a potential source of spurious associations in genome-wide association studies

    Indian Academy of Sciences (India)

    Xuixiao Hong; Zhenqiang Su; Weigong Ge; Leming Shi; Roger Perkins; Hong Fang; Donna Mendrick; Weida Tong

    2010-04-01

    Genome-wide association studies (GWAS) examine the entire human genome with the goal of identifying genetic variants (usually single nucleotide polymorphisms (SNPs)) that are associated with phenotypic traits such as disease status and drug response. The discordance of significantly associated SNPs for the same disease identified from different GWAS indicates that false associations exist in such results. In addition to the possible sources of spurious associations that have been investigated and discussed intensively, such as sample size and population stratification, an accurate and reproducible genotype calling algorithm is required for concordant GWAS results from different studies. However, variations of genotype calling of an algorithm and their effects on significantly associated SNPs identified in downstream association analyses have not been systematically investigated. In this paper, the variations of genotype calling using the Bayesian Robust Linear Model with Mahalanobis distance classifier (BRLMM) algorithm and the resulting influence on the lists of significantly associated SNPs were evaluated using the raw data of 270 HapMap samples analysed with the Affymetrix Human Mapping 500K Array Set (Affy500K) by changing algorithmic parameters. Modified were the Dynamic Model (DM) call confidence threshold (threshold) and the number of randomly selected SNPs (size). Comparative analysis of the calling results and the corresponding lists of significantly associated SNPs identified through association analysis revealed that algorithmic parameters used in BRLMM affected the genotype calls and the significantly associated SNPs. Both the threshold and the size affected the called genotypes and the lists of significantly associated SNPs in association analysis. The effect of the threshold was much larger than the effect of the size. Moreover, the heterozygous calls had lower consistency compared to the homozygous calls.

  20. Association of genetic variation with systolic and diastolic blood pressure among African Americans : the Candidate Gene Association Resource study

    NARCIS (Netherlands)

    Fox, Ervin R.; Young, J. Hunter; Li, Yali; Dreisbach, Albert W.; Keating, Brendan J.; Musani, Solomon K.; Liu, Kiang; Morrison, Alanna C.; Ganesh, Santhi; Kutlar, Abdullah; Ramachandran, Vasan S.; Polak, Josef F.; Fabsitz, Richard R.; Dries, Daniel L.; Farlow, Deborah N.; Redline, Susan; Adeyemo, Adebowale; Hirschorn, Joel N.; Sun, Yan V.; Wyatt, Sharon B.; Penman, Alan D.; Palmas, Walter; Rotter, Jerome I.; Townsend, Raymond R.; Doumatey, Ayo P.; Tayo, Bamidele O.; Mosley, Thomas H.; Lyon, Helen N.; Kang, Sun J.; Rotimi, Charles N.; Cooper, Richard S.; Franceschini, Nora; Curb, J. David; Martin, Lisa W.; Eaton, Charles B.; Kardia, Sharon L. R.; Taylor, Herman A.; Caulfield, Mark J.; Ehret, Georg B.; Johnson, Toby; Chakravarti, Aravinda; Zhu, Xiaofeng; Levy, Daniel

    2011-01-01

    The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unkno

  1. Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer

    NARCIS (Netherlands)

    Rafnar, T.; Sulem, P.; Thorleifsson, G.; Vermeulen, S.; Helgason, H.; Saemundsdottir, J.; Gudjonsson, S.A.; Sigurdsson, A.; Stacey, S.N.; Gudmundsson, J.; Johannsdottir, H.; Alexiusdottir, K.; Petursdottir, V.; Nikulasson, S.; Geirsson, G.; Jonsson, T.; Aben, K.K.H.; Grotenhuis, A.J.; Verhaegh, G.W.C.T.; Dudek, A.M.D.; Witjes, J.A.; Heijden, A.G. van der; Vrieling, A.; Galesloot, T.E.; Juan, A. de; Panadero, A.; Rivera, F.; Hurst, C.; Bishop, D.T.; Sak, S.C.; Choudhury, A.; Teo, M.T.; Arici, C.; Carta, A.; Toninelli, E.; Verdier, P. de; Rudnai, P.; Gurzau, E; Koppova, K.; Keur, K.A. van der; Lurkin, I.; Goossens, M.; Kellen, E.; Guarrera, S.; Russo, A.; Critelli, R.; Sacerdote, C.; Vineis, P.; Krucker, C.; Zeegers, M.P.; Gerullis, H.; Ovsiannikov, D.; Volkert, F.; Hengstler, J.G.; Selinski, S.; Magnusson, O.T.; Masson, G.; Kong, A.; Gudbjartsson, D.; Lindblom, A.; Zwarthoff, E.; Porru, S.; Golka, K.; Buntinx, F.; Matullo, G.; Kumar, R.; Mayordomo, J.I.; Steineck, D.G.; Kiltie, A.E.; Jonsson, E.; Radvanyi, F.; Knowles, M.A.; Thorsteinsdottir, U.; Kiemeney, B.; Stefansson, K.

    2014-01-01

    Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC ca

  2. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

    NARCIS (Netherlands)

    E. Evangelou (Evangelos); J.M. Kerkhof (Hanneke); U. Styrkarsdottir (Unnur); E.E. Ntzani (Evangelia); S.D. Bos (Steffan); T. Esko (Tõnu); D.S. Evans (Daniel); S. Metrustry (Sarah); K. Panoutsopoulou (Kalliope); Y.F.M. Ramos (Yolande); G. Thorleifsson (Gudmar); K.K. Tsilidis (Konstantinos); N.K. Arden (Nigel); N. Aslam (Nadim); N. Bellamy (Nicholas); F. Birrell (Fraser); F.J. Blanco; A.J. Carr (Andrew Jonathan); K. Chapman (Kay); A.G. Day-Williams (Aaron); P. Deloukas (Panagiotis); M. Doherty (Michael); G. Engström; H.T. Helgadottir (Hafdis); A. Hofman (Albert); T. Ingvarsson (Torvaldur); H. Jonsson (Helgi); A. Keis (Aime); J.C. Keurentjes (J. Christiaan); M. Kloppenburg (Margreet); P.A. Lind (Penelope); A. McCaskie (Andrew); N.G. Martin; A.L. Milani (Alfredo); G.W. Montgomery; R.G.H.H. Nelissen (Rob); M.C. Nevitt (Michael); P. Nilsson (Peter); W.E.R. Ollier (William); N. Parimi (Neeta); A. Rai (Ashok); S.H. Ralston; M.R. Reed (Mike); J.A. Riancho (José); F. Rivadeneira Ramirez (Fernando); C. Rodriguez-Fontenla (Cristina); L. Southam (Lorraine); U. Thorsteinsdottir (Unnur); A. Tsezou (Aspasia); G.A. Wallis (Gillian); J.M. Wilkinson (Mark); A. Gonzalez (Antonio); N.E. Lane; L.S. Lohmander (Stefan); J. Loughlin (John); A. Metspalu (Andres); A.G. Uitterlinden (André); I. Jonsdottir (Ingileif); J-A. Zwart (John-Anker); P.E. Slagboom (Eline); E. Zeggini (Eleftheria); I. Meulenbelt (Ingrid); J.P.A. Ioannidis (John); T.D. Spector (Timothy); J.B.J. van Meurs (Joyce); A.M. Valdes (Ana Maria)

    2013-01-01

    textabstractObjectives: Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods: We performed a two-stage meta-analysis

  3. Genome-wide association study identifies eight loci associated with blood pressure.

    Science.gov (United States)

    Newton-Cheh, Christopher; Johnson, Toby; Gateva, Vesela; Tobin, Martin D; Bochud, Murielle; Coin, Lachlan; Najjar, Samer S; Zhao, Jing Hua; Heath, Simon C; Eyheramendy, Susana; Papadakis, Konstantinos; Voight, Benjamin F; Scott, Laura J; Zhang, Feng; Farrall, Martin; Tanaka, Toshiko; Wallace, Chris; Chambers, John C; Khaw, Kay-Tee; Nilsson, Peter; van der Harst, Pim; Polidoro, Silvia; Grobbee, Diederick E; Onland-Moret, N Charlotte; Bots, Michiel L; Wain, Louise V; Elliott, Katherine S; Teumer, Alexander; Luan, Jian'an; Lucas, Gavin; Kuusisto, Johanna; Burton, Paul R; Hadley, David; McArdle, Wendy L; Brown, Morris; Dominiczak, Anna; Newhouse, Stephen J; Samani, Nilesh J; Webster, John; Zeggini, Eleftheria; Beckmann, Jacques S; Bergmann, Sven; Lim, Noha; Song, Kijoung; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M; Yuan, Xin; Groop, Leif; Orho-Melander, Marju; Allione, Alessandra; Di Gregorio, Alessandra; Guarrera, Simonetta; Panico, Salvatore; Ricceri, Fulvio; Romanazzi, Valeria; Sacerdote, Carlotta; Vineis, Paolo; Barroso, Inês; Sandhu, Manjinder S; Luben, Robert N; Crawford, Gabriel J; Jousilahti, Pekka; Perola, Markus; Boehnke, Michael; Bonnycastle, Lori L; Collins, Francis S; Jackson, Anne U; Mohlke, Karen L; Stringham, Heather M; Valle, Timo T; Willer, Cristen J; Bergman, Richard N; Morken, Mario A; Döring, Angela; Gieger, Christian; Illig, Thomas; Meitinger, Thomas; Org, Elin; Pfeufer, Arne; Wichmann, H Erich; Kathiresan, Sekar; Marrugat, Jaume; O'Donnell, Christopher J; Schwartz, Stephen M; Siscovick, David S; Subirana, Isaac; Freimer, Nelson B; Hartikainen, Anna-Liisa; McCarthy, Mark I; O'Reilly, Paul F; Peltonen, Leena; Pouta, Anneli; de Jong, Paul E; Snieder, Harold; van Gilst, Wiek H; Clarke, Robert; Goel, Anuj; Hamsten, Anders; Peden, John F; Seedorf, Udo; Syvänen, Ann-Christine; Tognoni, Giovanni; Lakatta, Edward G; Sanna, Serena; Scheet, Paul; Schlessinger, David; Scuteri, Angelo; Dörr, Marcus; Ernst, Florian; Felix, Stephan B; Homuth, Georg; Lorbeer, Roberto; Reffelmann, Thorsten; Rettig, Rainer; Völker, Uwe; Galan, Pilar; Gut, Ivo G; Hercberg, Serge; Lathrop, G Mark; Zelenika, Diana; Deloukas, Panos; Soranzo, Nicole; Williams, Frances M; Zhai, Guangju; Salomaa, Veikko; Laakso, Markku; Elosua, Roberto; Forouhi, Nita G; Völzke, Henry; Uiterwaal, Cuno S; van der Schouw, Yvonne T; Numans, Mattijs E; Matullo, Giuseppe; Navis, Gerjan; Berglund, Göran; Bingham, Sheila A; Kooner, Jaspal S; Connell, John M; Bandinelli, Stefania; Ferrucci, Luigi; Watkins, Hugh; Spector, Tim D; Tuomilehto, Jaakko; Altshuler, David; Strachan, David P; Laan, Maris; Meneton, Pierre; Wareham, Nicholas J; Uda, Manuela; Jarvelin, Marjo-Riitta; Mooser, Vincent; Melander, Olle; Loos, Ruth J F; Elliott, Paul; Abecasis, Gonçalo R; Caulfield, Mark; Munroe, Patricia B

    2009-06-01

    Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

  4. [Arteriovenous malformation-glioma association: study of four cases].

    Science.gov (United States)

    Borges, Lia Raquel R; Malheiros, Suzana M F; Pelaez, Maria Paula; Stávale, João Norberto; Santos, Adrialdo J; Carrete, Henrique; Nogueira, Roberto Gomes; Ferraz, Fernando A P; Gabbai, Alberto A

    2003-06-01

    We reviewed the clinical presentation, imaging and histopathologic findings in 4 patients with the diagnosis of arteriovenous malformation associated with glioma that were operated on from 1991 to 2000 in our institution. Four patients (2 males; age between 15 and 52 years) presented with progressive headache with clinical evidence of intracranial hypertension (in 3) and partial seizures (in 1). CT scan showed a brain tumor without any detectable pathologic vessels. Histologic examination revealed astrocytic tumors associated with arteriovenous malformation. No patient presented the vascular component intermixed with the tumor. The arteriovenous-glioma association is rare and must be identified by a clear demarcation between the malformation and the tumor.

  5. Study of Associated α Particle Imaging Technique for Explosives Detection

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The explosive detecting technique about neutron mainly include the thermal neutron analysis (TNA), the fast neutron analysis (FNA), the pulse fast and thermal neutron analysis (PFTNA) and the associated α particle imaging technique about fast neutron (API).

  6. A Genomewide Association Study of Early Spontaneous Preterm Delivery

    Science.gov (United States)

    Zhang, Heping; Baldwin, Don A.; Bukowski, Radek K.; Parry, Samuel; Xu, Yaji; Song, Chi; Andrews, William W.; Saade, George R.; Esplin, M. Sean; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John; Varner, Michael; Biggio, Joseph R.

    2015-01-01

    Preterm birth is the leading cause of infant morbidity and mortality. Despite extensive research, the genetic contributions to spontaneous preterm birth (SPTB) are not well understood. Term controls were matched with cases by race/ethnicity, maternal age, and parity prior to recruitment. Genotyping was performed using Affymetrix SNP Array 6.0 assays. Statistical analyses utilized PLINK to compare allele occurrence rates between case and control groups, and incorporated quality control and multiple-testing adjustments. We analyzed DNA samples from mother-infant pairs from early SPTB cases (200/7 to 336/7 weeks, 959 women and 979 neonates) and term delivery controls (390/7 to 416/7 weeks, 960 women and 985 neonates). For validation purposes, we included an independent validation cohort consisting of early SPTB cases (293 mothers and 243 infants) and term controls (200 mothers and 149 infants). Clustering analysis revealed no population stratification. Multiple maternal SNPs were identified with association p-values between 10E-5 and 10E-6. The most significant maternal SNP was rs17053026 on chromosome 3 with an odds ratio (OR) 0.44 with a p-value of 1.0E-06. Two neonatal SNPs reached the genome-wide significance threshold, including rs17527054 on chromosome 6p22 with a p-value of 2.7E-12 and rs3777722 on chromosome 6q27 with a p-value of 1.4E-10. However, we could not replicate these findings after adjusting for multiple comparisons in a validation cohort. This is the first report of a genomewide case-control study to identify single nucleotide polymorphisms (SNPs) that correlate with SPTB. PMID:25599974

  7. Susceptibility to Chronic Mucus Hypersecretion, a Genome Wide Association Study

    DEFF Research Database (Denmark)

    Dijkstra, Akkelies E; Smolonska, Joanna; van den Berge, Maarten;

    2014-01-01

    (SNP). RESULTS: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10(-6), OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression...

  8. Genome-wide association study identifies eight loci associated with blood pressure

    NARCIS (Netherlands)

    Newton-Cheh, Christopher; Johnson, Toby; Gateva, Vesela; Tobin, Martin D.; Bochud, Murielle; Coin, Lachlan; Najjar, Samer S.; Zhao, Jing Hua; Heath, Simon C.; Eyheramendy, Susana; Papadakis, Konstantinos; Voight, Benjamin F.; Scott, Laura J.; Zhang, Feng; Farrall, Martin; Tanaka, Toshiko; Wallace, Chris; Chambers, John C.; Khaw, Kay-Tee; Nilsson, Peter; van der Harst, Pim; Polidoro, Silvia; Grobbee, Diederick E.; Onland-Moret, N. Charlotte; Bots, Michiel L.; Wain, Louise V.; Elliott, Katherine S.; Teumer, Alexander; Luan, Jian'an; Lucas, Gavin; Kuusisto, Johanna; Burton, Paul R.; Hadley, David; McArdle, Wendy L.; Brown, Morris; Dominiczak, Anna; Newhouse, Stephen J.; Samani, Nilesh J.; Webster, John; Zeggini, Eleftheria; Beckmann, Jacques S.; Bergmann, Sven; Lim, Noha; Song, Kijoung; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M.; Yuan, Xin; Groop, Leif; Orho-Melander, Marju; Allione, Alessandra; Di Gregorio, Alessandra; Guarrera, Simonetta; Panico, Salvatore; Ricceri, Fulvio; Romanazzi, Valeria; Sacerdote, Carlotta; Vineis, Paolo; Barroso, Ines; Sandhu, Manjinder S.; Luben, Robert N.; Crawford, Gabriel J.; Jousilahti, Pekka; Perola, Markus; Boehnke, Michael; Bonnycastle, Lori L.; Collins, Francis S.; Jackson, Anne U.; Mohlke, Karen L.; Stringham, Heather M.; Valle, Timo T.; Willer, Cristen J.; Bergman, Richard N.; Morken, Mario A.; Doering, Angela; Gieger, Christian; Illig, Thomas; Meitinger, Thomas; Org, Elin; Pfeufer, Arne; Wichmann, H. Erich; Kathiresan, Sekar; Marrugat, Jaume; O'Donnell, Christopher J.; Schwartz, Stephen M.; Siscovick, David S.; Subirana, Isaac; Freimer, Nelson B.; Hartikainen, Anna-Liisa; McCarthy, Mark I.; O'Reilly, Paul F.; Peltonen, Leena; Pouta, Anneli; de Jong, Paul E.; Snieder, Harold; van Gilst, Wiek H.; Clarke, Robert; Goel, Anuj; Hamsten, Anders; Peden, John F.; Seedorf, Udo; Syvanen, Ann-Christine; Tognoni, Giovanni; Lakatta, Edward G.; Sanna, Serena; Scheet, Paul; Schlessinger, David; Scuteri, Angelo; Doerr, Marcus; Ernst, Florian; Felix, Stephan B.; Homuth, Georg; Lorbeer, Roberto; Reffelmann, Thorsten; Rettig, Rainer; Voelker, Uwe; Galan, Pilar; Gut, Ivo G.; Hercberg, Serge; Lathrop, G. Mark; Zelenika, Diana; Deloukas, Panos; Soranzo, Nicole; Williams, Frances M.; Zhai, Guangju; Salomaa, Veikko; Laakso, Markku; Elosua, Roberto; Forouhi, Nita G.; Volzke, Henry; Uiterwaal, Cuno S.; van der Schouw, Yvonne T.; Numans, Mattijs E.; Matullo, Giuseppe; Navis, Gerjan; Berglund, Goran; Bingham, Sheila A.; Kooner, Jaspal S.; Connell, John M.; Bandinelli, Stefania; Ferrucci, Luigi; Watkins, Hugh; Spector, Tim D.; Tuomilehto, Jaakko; Altshuler, David; Strachan, David P.; Laan, Maris; Meneton, Pierre; Wareham, Nicholas J.; Uda, Manuela; Jarvelin, Marjo-Riitta; Mooser, Vincent; Melander, Olle; Loos, Ruth J. F.; Elliott, Paul; Abecasis, Goncalo R.; Caulfield, Mark; Munroe, Patricia B.

    2009-01-01

    Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure

  9. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height

    NARCIS (Netherlands)

    Lanktree, Matthew B.; Guo, Yiran; Murtaza, Muhammed; Glessner, Joseph T.; Bailey, Swneke D.; Onland-Moret, N. Charlotte; Lettre, Guillaume; Ongen, Halit; Rajagopalan, Ramakrishnan; Johnson, Toby; Shen, Haiqing; Nelson, Christopher P.; Klopp, Norman; Baumert, Jens; Padmanabhan, Sandosh; Pankratz, Nathan; Pankow, James S.; Shah, Sonia; Taylor, Kira; Barnard, John; Peters, Bas J.; Maloney, Cliona M.; Lobmeyer, Maximilian T.; Stanton, Alice; Zafarmand, M. Hadi; Romaine, Simon P. R.; Mehta, Amar; van Iperen, Erik P. A.; Gong, Yan; Price, Tom S.; Smith, Erin N.; Kim, Cecilia E.; Li, Yun R.; Asselbergs, Folkert W.; Atwood, Larry D.; Bailey, Kristian M.; Bhatt, Deepak; Bauer, Florianne; Behr, Elijah R.; Bhangale, Tushar; Boer, Jolanda M. A.; Boehm, Bernhard O.; Bradfield, Jonathan P.; Brown, Morris; Braund, Peter S.; Burton, Paul R.; Carty, Cara; Chandrupatla, Hareesh R.; Chen, Wei; Connell, John; Dalgeorgou, Chrysoula; de Boer, Anthonius; Drenos, Fotios; Elbers, Clara C.; Fang, James C.; Fox, Caroline S.; Frackelton, Edward C.; Fuchs, Barry; Furlong, Clement E.; Gibson, Quince; Gieger, Christian; Goe, Anuj; Grobbee, Diederik E.; Hastie, Claire; Howard, Philip J.; Huang, Guan-Hua; Johnson, W. Craig; Li, Qing; Kleber, Marcus E.; Klein, Barbara E. K.; Klein, Ronald; Kooperberg, Charles; Ky, Bonnie; LaCroix, Andrea; Lanken, Paul; Lathrop, Mark; Li, Mingyao; Marshal, Vanessa; Melander, Olle; Mentch, Frank D.; Meyer, Nuala J.; Monda, Keri L.; Montpetit, Alexandre; Murugesan, Gurunathan; Nakayama, Karen; Nondah, Dave; Onipinla, Abiodun; Rafelt, Suzanne; Newhouse, Stephen J.; Otieno, F. George; Patel, Sanjey R.; Putt, Mary E.; Rodriguez, Santiago; Safa, Radwan N.; Sawyer, Douglas B.; Schreiner, Pamela J.; Simpson, Claire; Sivapalaratnam, Suthesh; Srinivasan, Sathanur R.; Suver, Christine; Swergold, Gary; Sweitzer, Nancy K.; Thomas, Kelly A.; Thorand, Barbara; Timpson, Nicholas J.; Tischfield, Sam; Tobin, Martin; Tomaszweski, Maciej; Verschuren, W. M. Monique; Wallace, Chris; Winkelmann, Bernhard; Zhang, Haitao; Zheng, Dongling; Zhang, Li; Zmuda, Joseph M.; Clarke, Robert; Balmforth, Anthony J.; Danesh, John; Day, Ian N.; Schork, Nicholas J.; de Bakker, Paul I. W.; Delles, Christian; Duggan, David; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofker, Marten H.; Humphries, Steve E.; Kivimaki, Mika; Lawlor, Debbie A.; Kottke-Marchant, Kandice; Mega, Jessica L.; Mitchell, Braxton D.; Morrow, David A.; Palmen, Jutta; Redline, Susan; Shields, Denis C.; Shuldiner, Alan R.; Sleiman, Patrick M.; Smith, George Davey; Farrall, Martin; Jamshidi, Yalda; Christiani, David C.; Casas, Juan P.; Hall, Alistair S.; Doevendans, Pieter A.; Christie, Jason D.; Berenson, Gerald S.; Murray, Sarah S.; Illig, Thomas; Dorn, Gerald W.; Cappola, Thomas P.; Boerwinkle, Eric; Sever, Peter; Rader, Daniel J.; Reilly, Muredach P.; Caulfield, Mark; Talmud, Philippa J.; Topol, Eric; Engert, James C.; Wang, Kai; Dominiczak, Anna; Hamsten, Anders; Curtis, Sean P.; Silverstein, Roy L.; Lange, Leslie A.; Sabatine, Marc S.; Trip, Mieke; Saleheen, Danish; Peden, John F.; Cruickshanks, Karen J.; Maerz, Winfried; O'Connell, Jeffrey R.; Klungel, Olaf H.; Wijmenga, Cisca; Maitland-van der Zee, Anke Hilse; Schadt, Eric E.; Johnson, Julie A.; Jarvik, Gail P.; Papanicolaou, George J.; Watkins, Hugh; Grant, Struan F. A.; Munroe, Patricia B.; North, Kari E.; Samani, Nilesh J.; Koenig, Wolfgang; Gaunt, Tom R.; Anand, Sonia S.; van der Schouw, Yvonne T.; Kumari, Meena; Soranzo, Nicole; FitzGerald, Garret A.; Reiner, Alex; Hegele, Robert A.; Hakonarson, Hakon; Keating, Brendan J.

    2011-01-01

    Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and

  10. Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes

    NARCIS (Netherlands)

    Teumer, Alexander; Tin, Adrienne; Sorice, Rossella; Gorski, Mathias; Yeo, Nan Cher; Chu, Audrey Y; Li, Man; Li, Yong; Mijatovic, Vladan; Ko, Yi-An; Taliun, Daniel; Luciani, Alessandro; Chen, Ming-Huei; Yang, Qiong; Foster, Meredith C; Olden, Matthias; Hiraki, Linda T; Tayo, Bamidele O; Fuchsberger, Christian; Dieffenbach, Aida Karina; Shuldiner, Alan R; Smith, Albert V; Zappa, Allison M; Lupo, Antonio; Kollerits, Barbara; Ponte, Belen; Stengel, Bénédicte; Krämer, Bernhard K; Paulweber, Bernhard; Mitchell, Braxton D; Hayward, Caroline; Helmer, Catherine; Meisinger, Christa; Gieger, Christian; Shaffer, Christian M; Müller, Christian; Langenberg, Claudia; Ackermann, Daniel; Siscovick, David; Boerwinkle, Eric; Kronenberg, Florian; Ehret, Georg B; Homuth, Georg; Waeber, Gerard; Navis, Gerjan; Gambaro, Giovanni; Malerba, Giovanni; Eiriksdottir, Gudny; Li, Guo; Wichmann, H Erich; Grallert, Harald; Wallaschofski, Henri; Völzke, Henry; Brenner, Herrmann; Kramer, Holly; Mateo Leach, I; Rudan, Igor; Hillege, Hans L; Beckmann, Jacques S; Lambert, Jean Charles; Luan, Jian'an; Zhao, Jing Hua; Chalmers, John; Coresh, Josef; Denny, Joshua C; Butterbach, Katja; Launer, Lenore J; Ferrucci, Luigi; Kedenko, Lyudmyla; Haun, Margot; Metzger, Marie; Woodward, Mark; Hoffman, Matthew J; Nauck, Matthias; Waldenberger, Melanie; Pruijm, Menno; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Wareham, Nicholas J; Endlich, Nicole; Soranzo, Nicole; Polasek, Ozren; van der Harst, Pim; Pramstaller, Peter Paul; Vollenweider, Peter; Wild, Philipp S; Gansevoort, Ron T; Rettig, Rainer; Biffar, Reiner; Carroll, Robert J; Katz, Ronit; Loos, Ruth J F; Hwang, Shih-Jen; Coassin, Stefan; Bergmann, Sven; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Corre, Tanguy; Zeller, Tanja; Illig, Thomas; Aspelund, Thor; Tanaka, Toshiko; Lendeckel, Uwe; Völker, Uwe; Gudnason, Vilmundur; Chouraki, Vincent; Koenig, Wolfgang; Kutalik, Zoltan; O'Connell, Jeffrey R; Parsa, Afshin; Heid, Iris M; Paterson, Andrew D; de Boer, Ian H; Devuyst, Olivier; Lazar, Jozef; Endlich, Karlhans; Susztak, Katalin; Tremblay, Johanne; Hamet, Pavel; Jacob, Howard J; Böger, Carsten A; Fox, Caroline S; Pattaro, Cristian; Köttgen, Anna

    2016-01-01

    Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-an

  11. Further studies on HTLV-I associated myelopathy in Argentina.

    Science.gov (United States)

    Gonzalez, L A; Villa, A M; Kohler, G; Garcea, O; Kremenchutzky, M; Caceres, F; Sanz, O P; Sica, R E

    1998-01-01

    We report 10 HTLV-I virus seropositive subjects, eight of them with HTLV-I associated myelopathy (HAM), two of them also infected with HIV as well as two asymptomatic HTLV-I+ relatives of two unrelated patients. HTLV-I is endemic in several tropical areas, where it causes different neurological diseases. Only few patients have been reported in our country since 1994. We studied 8 patients, who fulfilled the clinical criteria for chronic spastic paraplegia, and 2 other non-symptomatic HTLV-I seropositive relatives, with electromyography (EMG), motor and sensory conduction velocities (NCV), somatosensory, visual and brainstem auditory evoked potentials (SSEP, VEP and BAEP), Magnetic Resonance Images (MRI) and cerobrospinal fluid (CSF) analysis. The latter was carried out only in seven symptomatic patients. In every case positive ELISA tests for HTLV-I/II were confirmed by Western Blot. The two asymptomatic persons were clinically and electromyographically assessed, one of them was also submitted to SSEPs studies. Three patients were males. Patient's ages ranged from 5 to 65 years old. All symptomatic patients showed muscular weakness, spasticity with pyramidal signs and sphincter disturbances. Five of them had paresthesias and 2 had burning pain on their feet. The EMGs and the NCVs were normal in 7 patients and in the 2 asymptomatic ones. SSEPs, obtained by stimulating the posterior tibial nerves, were impaired in 7 patients and in the asymptomatic person who received the procedure. The 7 symptomatic patients who underwent lumbar puncture had positive tests for HTLV-I in CSF, 3 out of these 7 patients had also high protein levels and 4 had increased number of lymphocytes. In 2 patients intrathecal IgG production could also be demonstrated. MRI were normal in 7 patients and in the 2 asymptomatics, the exception being a female who had bilateral hyperintense lesions in cerebral white matter in T2. In conclusion, tropical spastic paraparesis is apparently a rare disorder

  12. Recent advances in the study of HPV-associated carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Liyan; Jin; Zhi-Xiang; Xu

    2015-01-01

    Human papillomaviruses(HPVs) cause virtually all cervical cancers, the second leading cause of death by cancer among women, as well as other anogenital cancers and a subset of head and neck cancers. Approximately half of women, who develop cervical cancer die from it. Despite the optimism that has accompanied the introduction of prophylactic vaccines to prevent some HPV infections, the relatively modest uptake of the vaccine, especially in the developing world, and the very high fraction of men and women who are already infected, means that HPV-associated disease will remain as a significant public health problem for decades. In this review, we summarize some recent findings on HPV-associated carcinogenesis, such as mi RNAs in HPV-associated cancers, implication of stem cells in the biology and therapy of HPV-positive cancers, HPV vaccines, targeted therapy of cervical cancer, and drug treatment for HPV-induced intraepithelial neoplasias.

  13. Association of bacteria and viruses with wheezy episodes in young children: prospective birth cohort study

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Hermansen, Mette Northman; Bønnelykke, Klaus;

    2010-01-01

    To study the association between wheezy symptoms in young children and the presence of bacteria in the airways.......To study the association between wheezy symptoms in young children and the presence of bacteria in the airways....

  14. Worrying affects associative fear learning: a startle fear conditioning study

    NARCIS (Netherlands)

    F.J. Gazendam; M. Kindt

    2012-01-01

    A valuable experimental model for the pathogenesis of anxiety disorders is that they originate from a learned association between an intrinsically non-aversive event (Conditioned Stimulus, CS) and an anticipated disaster (Unconditioned Stimulus, UCS). Most anxiety disorders, however, do not evolve f

  15. Small bowel angiodysplasia and novel disease associations: a cohort study.

    LENUS (Irish Health Repository)

    Holleran, Grainne

    2013-04-01

    Gastrointestinal angiodysplasias recurrently bleed, accounting for 3-5% of obscure gastrointestinal bleeding. The advent of small bowel capsule endoscopy (SBCE) has led to an increased recognition of small bowel angiodysplasias (SBAs) but little is known about their etiology. Previous small cohorts and case reports suggest an equal gender incidence and associations with cardiovascular disease, renal impairment, and coagulopathies.

  16. Inverse association between dairy intake and hypertension: the Rotterdam Study

    NARCIS (Netherlands)

    Engberink, M.F.; Hendriksen, M.A.H.; Schouten, E.G.; Rooij, van F.J.A.; Hofman, A.; Witteman, J.C.; Geleijnse, J.M.

    2009-01-01

    Background: Little is known about the effect of different types of dairy food products on the development of hypertension. Objective: The objective was to determine whether the incidence of hypertension in older Dutch subjects is associated with intake of dairy products. Design: We examined the rela

  17. A Genome-Wide Association Study of Depressive Symptoms

    NARCIS (Netherlands)

    Hek, Karin; Demirkan, Ayse; Lahti, Jari; Terracciano, Antonio; Teumer, Alexander; Cornelis, Marilyn C.; Amin, Najaf; Bakshis, Erin; Baumert, Jens; Ding, Jingzhong; Liu, Yongmei; Marciante, Kristin; Meirelles, Osorio; Nalls, Michael A.; Sun, Yan V.; Vogelzangs, Nicole; Yu, Lei; Bandinelli, Stefania; Benjamin, Emelia J.; Bennett, David A.; Boomsma, Dorret; Cannas, Alessandra; Coker, Laura H.; de Geus, Eco; De Jager, Philip L.; Diez-Roux, Ana V.; Purcell, Shaun; Hu, Frank B.; Rimm, Eric B.; Hunter, David J.; Jensen, Majken K.; Curhan, Gary; Rice, Kenneth; Penman, Alan D.; Rotter, Jerome I.; Sotoodehnia, Nona; Emeny, Rebecca; Eriksson, Johan G.; Evans, Denis A.; Ferrucci, Luigi; Fornage, Myriam; Gudnason, Vilmundur; Hofman, Albert; Illig, Thomas; Kardia, Sharon; Kelly-Hayes, Margaret; Koenen, Karestan; Kraft, Peter; Kuningas, Maris; Massaro, Joseph M.; Melzer, David; Mulas, Antonella; Mulder, Cornelis L.; Murray, Anna; Oostra, Ben A.; Palotie, Aarno; Penninx, Brenda; Petersmann, Astrid; Pilling, Luke C.; Psaty, Bruce; Rawal, Rajesh; Reiman, Eric M.; Schulz, Andrea; Shulman, Joshua M.; Singleton, Andrew B.; Smith, Albert V.; Sutin, Angelina R.; Uitterlinden, Andre G.; Voelzke, Henry; Widen, Elisabeth; Yaffe, Kristine; Zonderman, Alan B.; Cucca, Francesco; Harris, Tamara; Ladwig, Karl-Heinz; Llewellyn, David J.; Raikkonen, Katri; Tanaka, Toshiko; van Duijn, Cornelia M.; Grabe, Hans J.; Launer, Lenore J.; Lunetta, Kathryn L.; Mosley, Thomas H.; Newman, Anne B.; Tiemeier, Henning; Murabito, Joanne

    2013-01-01

    Background: Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. Methods: In t

  18. A genome-wide association study of depressive symptoms

    NARCIS (Netherlands)

    K. Hek (Karin); A. Demirkan (Ayşe); J. Lahti (Jari); A. Terracciano; A. Teumer (Alexander); M. Cornelis (Marilyn); N. Amin (Najaf); E. Bakshis (Erin); J. Baumert (Jens); J. Ding (Jinhui); Y. Liu (Yongmei); K. Marciante (Kristin); O. Meirelles; M.A. Nalls (Michael); Y.V. Sun (Yan); N. Vogelzangs (Nicole); L. Yu (Lei); S. Bandinelli (Stefania); E.J. Benjamin (Emelia); D.A. Bennett (David); D.I. Boomsma (Dorret); A. Cannas; L.H. Coker (Laura); E.J.C. de Geus (Eco); P.L. de Jager (Philip); A.V. Diez-Roux (Ana); S. Purcell (Shaun); F.B. Hu (Frank); E. Rimm; D.J. Hunter (David); M.K. Jensen (Majken); G.C. Curhan (Gary); K.M. Rice (Kenneth); A.D. Penman (Alan); J.I. Rotter (Jerome); N. Sotoodehnia (Nona); R. Emeny (Rebecca); J.G. Eriksson (Johan); D.A. Evans (Denis); L. Ferrucci (Luigi); M. Fornage (Myriam); V. Gudnason (Vilmundur); A. Hofman (Albert); T. Illig (Thomas); S.L.R. Kardia (Sharon); M. Kelly-Hayes (Margaret); M.E. Koenen (Marjorie); P. Kraft (Peter); M. Kuningas (Maris); J. Massaro (Joseph); D. Melzer (David); A. Mulas (Antonella); C.L. Mulder (Niels); A. Murray (Anna); B.A. Oostra (Ben); A. Palotie (Aarno); B.W.J.H. Penninx (Brenda); A. Petersmann (Astrid); L.C. Pilling (Luke); B.M. Psaty (Bruce); R. Rawal (R.); E.M. Reiman (Eric); A. Schulz (Ansgar); L. Shulman (Lee); A.B. Singleton (Andrew); G.D. Smith; A.R. Sutin; A.G. Uitterlinden (André); H. Völzke (Henry); E. Widen (Elisabeth); K. Yaffe (Kristine); A.B. Zonderman (Alan); F. Cucca (Francesco); T.B. Harris (Tamara); K.-H. Ladwig (Karl-Heinz); D.J. Llewellyn (David); K. Räikkönen (Katri); T. Tanaka (Toshiko); C.M. van Duijn (Cock); H.J. Grabe (Hans Jörgen); L.J. Launer (Lenore); K.L. Lunetta (Kathryn); T.H. Mosley (Thomas); A.B. Newman (Anne); H.W. Tiemeier (Henning); J. Murabito (Joanne)

    2013-01-01

    textabstractBackground: Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. M

  19. Gender & Education Association: A Case Study in Feminist Education?

    Science.gov (United States)

    David, Miriam E.

    2015-01-01

    This article focuses on feminist activist academics who were instrumental in creating the UK Gender & Education Association at the turn of the twenty-first century. Drawing on my own intellectual biography (David, M. E. 2003. "Personal and Political: Feminisms, Sociology and Family Lives" Stoke-on-Trent. Trentham Books.) linked to…

  20. New Association Takes "Big Tent" Approach to Studying Native Peoples

    Science.gov (United States)

    Schmidt, Peter

    2009-01-01

    Although several academic associations in the United States devote at least some part of their annual conferences to research on American Indians, many scholars of indigenous populations have long felt they lacked an intellectual home, a place where they could gather with large numbers of people who share their interests. A fledgling organization,…

  1. Occupation, Personality, and Accidents: An Exploratory Study of Aggregate Associations

    Science.gov (United States)

    2005-05-09

    better prediction of behavioral criteria (Mershon & Gorsuch , 1988; Hogan & Holland, 2003). One reason is that associations to criteria are not...Publications. Mershon, B., & Gorsuch , R. L. (1988). Number of factors in the personality sphere: Does increase in factors increase predictability

  2. A Bayesian multilocus association method: allowing for higher-order interaction in association studies

    DEFF Research Database (Denmark)

    Albrechtsen, Anders; Castella, Sofie; Andersen, Gitte;

    2007-01-01

    conditions. We present a new powerful statistical model for analyzing and interpreting genomic data that influence multifactorial phenotypic traits with a complex and likely polygenic inheritance. The new method is based on Markov chain Monte Carlo (MCMC) and allows for identification of sets of SNPs...... and environmental factors that when combined increase disease risk or change the distribution of a quantitative trait. Using simulations, we show that the MCMC method can detect disease association when multiple, interacting SNPs are present in the data. When applying the method on real large-scale data from...

  3. The study of slip line field and upper bound method based on associated flow and non-associated flow rules

    Institute of Scientific and Technical Information of China (English)

    Zheng Yingren; Deng Chujian; Wang Jinglin

    2010-01-01

    At present,associated flow rule of traditional plastic theory is adopted in the slip line field theory and upper bound method of geotechnical materials.So the stress characteristic line conforms to the velocity line.It is proved that geotechnical materials do not abide by the associated flow rule.It is impossible for the stress characteristic line to conform to the velocity line.Generalized plastic mechanics theoretically proved that plastic potential surface intersects the Mohr-Coulomb yield surface with an angle,so that the velocity line must be studied by non-associated flow rule.According to limit analysis theory,the theory of slip line field is put forward in this paper,and then the ultimate boating capacity of strip footing is obtained based on the associated flow rule and the non-associated flow rule individually.These two results are identical since the ultimate bearing capacity is independent of flow rule.On the contrary,the velocity fields of associated and non-associated flow rules are different which shows the velocity field based on the associated flow rule is incorrect.

  4. Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk

    DEFF Research Database (Denmark)

    Orr, Nick; Lemnrau, Alina; Cooke, Rosie

    2012-01-01

    We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P...... = 3.02 × 10(-13); odds ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P = 3.87 × 10(-15); OR = 1.50)....

  5. Epidemiological studies of esophageal cancer in the era of genome-wide association studies

    Institute of Scientific and Technical Information of China (English)

    An-Hui; Wang; Yuan; Liu; Bo; Wang; Yi-Xuan; He; Ye-Xian; Fang; Yong-Ping; Yan

    2014-01-01

    Esophageal cancer(EC) caused about 395000 deaths in 2010. China has the most cases of EC and EC is the fourth leading cause of cancer death in China. Esophageal squamous cell carcinoma(ESCC) is the predominant histologic type(90%-95%), while the incidence of esophageal adenocarcinoma(EAC) remains extremely low in China. Traditional epidemiological studies have revealed that environmental carcinogens are risk factors for EC. Molecular epidemiological studies revealed that susceptibility to EC is influenced by both environmental and genetic risk factors. Of all the risk factors for EC, some are associated with the risk of ESCC and others with the risk of EAC. However, the details and mechanisms of risk factors involved in the process for EC are unclear. The advanced methods and techniques used in human genome studies bring a great opportunity for researchers to explore and identify the details of those risk factors or susceptibility genes involved inthe process of EC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era to the era of genome wide association studies(GWAS). Here we review the epidemiological studies of EC(especially ESCC) in the era of GWAS, and provide an overview of the general risk factors and those genomic variants(genes, SNPs, miRNAs, proteins) involved in the process of ESCC.

  6. A statistical perspective on association studies of psychiatric disorders

    DEFF Research Database (Denmark)

    Foldager, Leslie

    2014-01-01

    and 2 were motivated by the hypothesis that defects of the immune system may increase risk of psychiatric disorders. We consider two components from the lectin pathway of activation: mannan-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) via continuous traits (protein level...... accepted genome-wide threshold for single-marker association tests has become 5e-8 but searching for interactions genome-wide results in drastically many more tests and thus the need of an even lower p-value threshold. Lowering the threshold comes at the unfortunate but inevitable expense of increasing...... for significance. Yet, in paper 6 we propose the Landscape method to summarise a series of sequentially ordered test values without the need of more or less arbitrary prior grouping....

  7. An association study between the norepinephrine transporter gene and depression

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette N; Jacobsen, Iben S; Grynderup, Matias B;

    2013-01-01

    A2 for solute carrier 6 family member 2). The gene is responsible for the reuptake of norepinephrine and dopamine into presynaptic nerve terminals and the norepinephrine system appears to play an important role in depression. We therefore analyzed genetic variants within SLC6A2 for association......A potential approach for identification of candidate genes for depression is characterization of chromosomal rearrangements. Through analysis of a chromosome translocation in an individual with recurrent depression, we identified a potential candidate gene: the norepinephrine transporter (NET; SLC6...... with depression in 408 affected and 559 control individuals from Denmark. After quality control of the genotypes, 31 of 45 single nucleotide polymorphisms (SNPs) were left for analyses. One SNP showed a nominal association with depression but did not survive correction for multiple testing. The results from our...

  8. A Photometric Study of Stars in the MBM 12 Association

    CERN Document Server

    Herbst, W; Hawley, W P; Herbst, William; Williams, Eric C.; Hawley, Wendy P.

    2004-01-01

    We have monitored four fields containing nine previously identified members of the MBM 12 association to search for photometric variability and periodicity in these pre-main sequence stars. Seven of the nine are found to be variable and definite periodicity (of 1.2, 2.6 and 6.2 days) is found for three of them, including the classical T Tauri star LkH-alpha 264. Two other members are possibly periodic but each requires confirmation. In addition, a "field" star that is associated with the X-ray source RX J0255.9+2005 was discovered to be a variable with a period of 4.2 days. Our results indicate that the photometric variability characteristics of the known MBM 12 association members are typical of what is found in ~few My old stellar groups such as IC 348, supporting arguments for a similar age. In particular, there is a mix of periodic and non-periodic variables with typical amplitudes (in Cousins I) of 0.1-0.5 mag, in addition to a small number of larger amplitude variables. The periods, as a group, are some...

  9. [Genomwide association studies on obesity: what can we learn from these studies].

    Science.gov (United States)

    Kronenberg, Florian; Paulweber, Bernhard; Lamina, Claudia

    2016-03-01

    The introduction of genome-wide association studies resulted in a tremendous increase in the number of genes associated with obesity and related phenotypes (BMI, waist and waist-hip-ratio). Despite this enormous gain in knowledge the search for genes is only started since only a small fraction of the heritability of these phenotypes is explained yet: each single gene of the 97 hitherto known BMI-associated genes and 49 waist-hip-ratio-associated genes explains only a tiny fraction of the variance of these phenotypes. Sex-specific differences are mainly known for waist-hip-ratio and ̴40% of the genes showed only an effect in women but no or a markedly smaller effect in men. The functional characterization of the identified genes will take a lot of time. It is unclear whether and how fast the findings will result in therapeutic consequences. It is of utmost importance that we understand the involved mechanisms before new therapeutic strategies can be developed.

  10. Genome-wide population-based association study of extremely overweight young adults--the GOYA study

    DEFF Research Database (Denmark)

    Paternoster, Lavinia; Evans, David M; Nøhr, Ellen Aagaard

    2011-01-01

    Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining ∼1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight...

  11. Worrying affects associative fear learning: a startle fear conditioning study.

    Directory of Open Access Journals (Sweden)

    Femke J Gazendam

    Full Text Available A valuable experimental model for the pathogenesis of anxiety disorders is that they originate from a learned association between an intrinsically non-aversive event (Conditioned Stimulus, CS and an anticipated disaster (Unconditioned Stimulus, UCS. Most anxiety disorders, however, do not evolve from a traumatic experience. Insights from neuroscience show that memory can be modified post-learning, which may elucidate how pathological fear can develop after relatively mild aversive events. Worrying--a process frequently observed in anxiety disorders--is a potential candidate to strengthen the formation of fear memory after learning. Here we tested in a discriminative fear conditioning procedure whether worry strengthens associative fear memory. Participants were randomly assigned to either a Worry (n = 23 or Control condition (n = 25. After fear acquisition, the participants in the Worry condition processed six worrisome questions regarding the personal aversive consequences of an electric stimulus (UCS, whereas the Control condition received difficult but neutral questions. Subsequently, extinction, reinstatement and re-extinction of fear were tested. Conditioned responding was measured by fear-potentiated startle (FPS, skin conductance (SCR and UCS expectancy ratings. Our main results demonstrate that worrying resulted in increased fear responses (FPS to both the feared stimulus (CS(+ and the originally safe stimulus (CS(-, whereas FPS remained unchanged in the Control condition. In addition, worrying impaired both extinction and re-extinction learning of UCS expectancy. The implication of our findings is that they show how worry may contribute to the development of anxiety disorders by affecting associative fear learning.

  12. A Study of Association Strategies in Middle School Vocabulary Learning

    Institute of Scientific and Technical Information of China (English)

    李娜

    2013-01-01

    English for a long time, they still find their vocabulary insufficient. Because of the lack of vocabulary, they cannot understand the meaning of a sentence or cannot understand what others say. And their desire to learn is very strong. Therefore, possessing the efficient strategies of vocabulary learning is especially important. From this point, according to the investigation, this paper is intended to discuss the efficiency of the association methods in middle school vocabulary learning. Only when teachers adopt the appropriate strategies can they make a productive classroom teaching and arouse students’ learning interest.

  13. A study on the mixed jaw lesions associated with teeth

    Energy Technology Data Exchange (ETDEWEB)

    Nah, Kyung Soo [Dept. of Dental Radiology, College of Dentistry, Pusan National University, Pusan (Korea, Republic of)

    2000-03-15

    1. Retrospectively evaluate the accuracy of tentative diagnosis or impression from the clinico-radiographic materials of jaw lesions which showed mixed lesions associated with teeth. 2. To observe the diagnostic importance of the calcified part of the lesions which appear as radiopaque areas. 14 cases of jaw lesions which showed mixed lesions associated with teeth were reviewed. These lesions were mostly diagnosed as adenomatoid odontogenic tumors (6 cases) or calcifying odontogenic cysts with (4 cases) or without odontomas (4 cases). The calcified elements of the lesions which demonstrated various sizes and patterns of radiopaque shadows resembled odontoid tissues in some cases but could not be defined in some other cases radiographically. The final histopathologic diagnosis confirmed adenomatoid odontogenic tumors in 4 of the 6 cases. The remaining 2 cases turned out to be odontoma and ameloblastic fibroodontoma. The 4 cases of calcifying odontogenic cysts with odontomas were correct in 3 cases but remaining 1 case was just odontoma. The 4 cases of calcifying odontogenic cysts were proved to be odontogenic keratocyst, calcified peripheral fibroma, unicystic ameloblastoma and squamous cell carcinoma. The diagnostic accuracy of the adenomatoid odontogenic tumors and calcifying odontogenic cysts were high when the lesions show typical appearance. The calcifications which show radiopaque areas could be odontomas or dystrophic calficifations or remnants of bone fragments from resorption.

  14. Brain Activity Associated with Emoticons: An fMRI Study

    Science.gov (United States)

    Yuasa, Masahide; Saito, Keiichi; Mukawa, Naoki

    In this paper, we describe that brain activities associated with emoticons by using fMRI. In communication over a computer network, we use abstract faces such as computer graphics (CG) avatars and emoticons. These faces convey users' emotions and enrich their communications. However, the manner in which these faces influence the mental process is as yet unknown. The human brain may perceive the abstract face in an entirely different manner, depending on its level of reality. We conducted an experiment using fMRI in order to investigate the effects of emoticons. The results show that right inferior frontal gyrus, which associated with nonverbal communication, is activated by emoticons. Since the emoticons were created to reflect the real human facial expressions as accurately as possible, we believed that they would activate the right fusiform gyrus. However, this region was not found to be activated during the experiment. This finding is useful in understanding how abstract faces affect our behaviors and decision-making in communication over a computer network.

  15. Study of Single Top Quarks in Association with Vector Bosons

    CERN Document Server

    Leggat, Duncan Alexander

    2015-01-01

    The search for single top production in association with a massive electroweak vector bosonusing data collected by the CMS detector at the Large Hadron Collider is presented. Twoanalyses are discussed: the search for a single top produced in association with a W boson(tW production) and the search for t-channel single top production with a radiated Zboson (tZq production). Both analyses make use of proton-proton collision data at acentre-of-mass energy of 8 TeV, and focus on the leptonic decays of the vector bosons. Acut and count based approach is employed for the tW search, searching for a final statecontaining two leptons, two neutrinos and a jet originating from the decay of a b-quark.The main backgrounds to be understood and controlled in this analysis are those arisingfrom the production of top quark pairs and Z bosons with one or more jets. Using a set ofdata corresponding to an integrated luminosity of 12.2 fb−1 , a production cross section of33.9 ± 8.6 pb was measured for the process. This corres...

  16. A study of pattern recovery in recurrent correlation associative memories.

    Science.gov (United States)

    Wilson, R C; Hancock, E R

    2003-01-01

    In this paper, we analyze the recurrent correlation associative memory (RCAM) model of Chiueh and Goodman (1990, 1991). This is an associative memory in which stored binary memory patterns are recalled via an iterative update rule. The update of the individual pattern-bits is controlled by an excitation function, which takes as its argument the inner product between the stored memory patterns and the input patterns. Our contribution is to analyze the dynamics of pattern recall when the input patterns are corrupted by noise of a relatively unrestricted class. We show how to identify the excitation function which maximizes the separation (the Fisher discriminant) between the uncorrupted realization of the noisy input pattern and the remaining patterns residing in the memory. The excitation function which gives maximum separation is exponential when the input bit-errors follow a binomial distribution. We develop an expression for the expectation value of bit-error probability on the input pattern after one iteration. We show how to identify the excitation function which minimizes the bit-error probability. The relationship between the excitation functions which result from the two different approaches is examined for a binomial distribution of bit-errors. We develop a semiempirical approach to the modeling of the dynamics of the RCAM.

  17. Outcomes of Global Education: External and Internal Change Associated with Study Abroad

    Science.gov (United States)

    Miller-Perrin, Cindy; Thompson, Don

    2014-01-01

    This chapter provides an overview of external and internal changes associated with collegiate study abroad experiences. A brief review of the research literature is included along with recent research that sheds light on potential mechanisms associated with study abroad-related change. Recommendations for enhancing outcomes associated with study…

  18. Structural Studies of Adeno-Associated Virus Serotype 8 Capsid Transitions Associated with Endosomal Trafficking

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Hyun-Joo; Gurda, Brittney L.; McKenna, Robert; Potter, Mark; Byrne, Barry; Salganik, Maxim; Muzyczka, Nicholas; Agbandje-McKenna, Mavis (Florida)

    2012-09-17

    The single-stranded DNA (ssDNA) parvoviruses enter host cells through receptor-mediated endocytosis, and infection depends on processing in the early to late endosome as well as in the lysosome prior to nuclear entry for replication. However, the mechanisms of capsid endosomal processing, including the effects of low pH, are poorly understood. To gain insight into the structural transitions required for this essential step in infection, the crystal structures of empty and green fluorescent protein (GFP) gene-packaged adeno-associated virus serotype 8 (AAV8) have been determined at pH values of 6.0, 5.5, and 4.0 and then at pH 7.5 after incubation at pH 4.0, mimicking the conditions encountered during endocytic trafficking. While the capsid viral protein (VP) topologies of all the structures were similar, significant amino acid side chain conformational rearrangements were observed on (i) the interior surface of the capsid under the icosahedral 3-fold axis near ordered nucleic acid density that was lost concomitant with the conformational change as pH was reduced and (ii) the exterior capsid surface close to the icosahedral 2-fold depression. The 3-fold change is consistent with DNA release from an ordering interaction on the inside surface of the capsid at low pH values and suggests transitions that likely trigger the capsid for genome uncoating. The surface change results in disruption of VP-VP interface interactions and a decrease in buried surface area between VP monomers. This disruption points to capsid destabilization which may (i) release VP1 amino acids for its phospholipase A2 function for endosomal escape and nuclear localization signals for nuclear targeting and (ii) trigger genome uncoating.

  19. Structural studies of adeno-associated virus serotype 8 capsid transitions associated with endosomal trafficking.

    Science.gov (United States)

    Nam, Hyun-Joo; Gurda, Brittney L; McKenna, Robert; Potter, Mark; Byrne, Barry; Salganik, Maxim; Muzyczka, Nicholas; Agbandje-McKenna, Mavis

    2011-11-01

    The single-stranded DNA (ssDNA) parvoviruses enter host cells through receptor-mediated endocytosis, and infection depends on processing in the early to late endosome as well as in the lysosome prior to nuclear entry for replication. However, the mechanisms of capsid endosomal processing, including the effects of low pH, are poorly understood. To gain insight into the structural transitions required for this essential step in infection, the crystal structures of empty and green fluorescent protein (GFP) gene-packaged adeno-associated virus serotype 8 (AAV8) have been determined at pH values of 6.0, 5.5, and 4.0 and then at pH 7.5 after incubation at pH 4.0, mimicking the conditions encountered during endocytic trafficking. While the capsid viral protein (VP) topologies of all the structures were similar, significant amino acid side chain conformational rearrangements were observed on (i) the interior surface of the capsid under the icosahedral 3-fold axis near ordered nucleic acid density that was lost concomitant with the conformational change as pH was reduced and (ii) the exterior capsid surface close to the icosahedral 2-fold depression. The 3-fold change is consistent with DNA release from an ordering interaction on the inside surface of the capsid at low pH values and suggests transitions that likely trigger the capsid for genome uncoating. The surface change results in disruption of VP-VP interface interactions and a decrease in buried surface area between VP monomers. This disruption points to capsid destabilization which may (i) release VP1 amino acids for its phospholipase A2 function for endosomal escape and nuclear localization signals for nuclear targeting and (ii) trigger genome uncoating.

  20. Study on the Customer targeting using Association Rule Mining

    Directory of Open Access Journals (Sweden)

    Surendiran.R

    2010-10-01

    Full Text Available Data mining is one of the widest area where many researches takes place to mine desired and hidden data. There are many different approaches to find the hidden data. This paper deals with Frequent Pattern growth algorithm which follows association rule concept togroup the required data items. Using this method of mining time can be reduced to a greater extent. This paper contains implementation of a real time system; the implementation is about making a survey on the group of people and their mobile connection’s service providers.End result contains the set of people from a particular age group with their support and confidence for the service provider they have chosen. Based on which any decisions can be made by service providers to enhance their business and attain many customers.

  1. Genome-wide Association Study of Obsessive-Compulsive Disorder

    Science.gov (United States)

    Stewart, S Evelyn; Yu, Dongmei; Scharf, Jeremiah M; Neale, Benjamin M; Fagerness, Jesen A; Mathews, Carol A; Arnold, Paul D; Evans, Patrick D; Gamazon, Eric R; Osiecki, Lisa; McGrath, Lauren; Haddad, Stephen; Crane, Jacquelyn; Hezel, Dianne; Illman, Cornelia; Mayerfeld, Catherine; Konkashbaev, Anuar; Liu, Chunyu; Pluzhnikov, Anna; Tikhomirov, Anna; Edlund, Christopher K; Rauch, Scott L; Moessner, Rainald; Falkai, Peter; Maier, Wolfgang; Ruhrmann, Stephan; Grabe, Hans-Jörgen; Lennertz, Leonard; Wagner, Michael; Bellodi, Laura; Cavallini, Maria Cristina; Richter, Margaret A; Cook, Edwin H; Kennedy, James L; Rosenberg, David; Stein, Dan J; Hemmings, Sian MJ; Lochner, Christine; Azzam, Amin; Chavira, Denise A; Fournier, Eduardo; Garrido, Helena; Sheppard, Brooke; Umaña, Paul; Murphy, Dennis L; Wendland, Jens R; Veenstra-VanderWeele, Jeremy; Denys, Damiaan; Blom, Rianne; Deforce, Dieter; Van Nieuwerburgh, Filip; Westenberg, Herman GM; Walitza, Susanne; Egberts, Karin; Renner, Tobias; Miguel, Euripedes Constantino; Cappi, Carolina; Hounie, Ana G; Conceição do Rosário, Maria; Sampaio, Aline S; Vallada, Homero; Nicolini, Humberto; Lanzagorta, Nuria; Camarena, Beatriz; Delorme, Richard; Leboyer, Marion; Pato, Carlos N; Pato, Michele T; Voyiaziakis, Emanuel; Heutink, Peter; Cath, Danielle C; Posthuma, Danielle; Smit, Jan H; Samuels, Jack; Bienvenu, O Joseph; Cullen, Bernadette; Fyer, Abby J; Grados, Marco A; Greenberg, Benjamin D; McCracken, James T; Riddle, Mark A; Wang, Ying; Coric, Vladimir; Leckman, James F; Bloch, Michael; Pittenger, Christopher; Eapen, Valsamma; Black, Donald W; Ophoff, Roel A; Strengman, Eric; Cusi, Daniele; Turiel, Maurizio; Frau, Francesca; Macciardi, Fabio; Gibbs, J Raphael; Cookson, Mark R; Singleton, Andrew; Hardy, John; Crenshaw, Andrew T; Parkin, Melissa A; Mirel, Daniel B; Conti, David V; Purcell, Shaun; Nestadt, Gerald; Hanna, Gregory L; Jenike, Michael A; Knowles, James A; Cox, Nancy; Pauls, David L

    2014-01-01

    Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1,465 cases, 5,557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9,657 X-chromosome SNPs. Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two p-values were located within DLGAP1 (p=2.49×10-6 and p=3.44×10-6), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a p-value=3.84 × 10-8. However, when trios were meta-analyzed with the combined case-control samples, the p-value for this variant was 3.62×10-5, losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation-QTLs (p<0.001) and frontal lobe eQTLs (p=0.001) was observed within the top-ranked SNPs (p<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD. PMID:22889921

  2. Avidity Studies in Anisakis simplex-Associated Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Carmen Cuéllar

    2013-01-01

    Full Text Available Gastroallergic anisakiasis (GAA and Anisakis-sensitization-associated chronic urticaria (CU+ differ with respect to specific IgE levels. We hypothesised different immunoglobulin avidities in both entities as well as their dependence on TI and fish consumption. 16 patients with GAA and 17 patients with CU+ were included, and immunoglobulin levels were analysed by CAP (Phadia. IgE and IgG avidity indexes (AvIgE and AvIgG, resp. were also determined. IgG avidity was higher in GAA than in CU+ (P=0.035, whereas there was a tendency to lower IgE avidity in GAA (P=0.095. When analysing all patients, AvIgG was positively correlated with specific IgE, IgG, and IgG4 as well as total IgE (Rho between 0.66 and 0.71; P<0.002, but AvIgE was negatively correlated with specific IgE (Rho −0.57; P<0.001, specific IgG4 (Rho −0.38; P<0.05, and total IgE (Rho 0.66; P<0.001. In GAA, weekly fish consumption was positively associated with AvIgE (Rho 0.51; P=0.05. A multivariate regression showed that time interval was the main explaining factor for AvIgE in GAA. We could show a differential behaviour of immunoglobulin isotype avidities in both entities and their dependence on fish-eating habits as well as on the time elapsed to the last parasitic episode.

  3. Facility design and associated services for the study of amphibians.

    Science.gov (United States)

    Browne, Robert K; Odum, R Andrew; Herman, Timothy; Zippel, Kevin

    2007-01-01

    The role of facilities and associated services for amphibians has recently undergone diversification. Amphibians traditionally used as research models adjust well to captivity and thrive with established husbandry techniques. However, it is now necessary to maintain hundreds of novel amphibian species in captive breeding, conservation research, and biomedical research programs. These diverse species have a very wide range of husbandry requirements, and in many cases the ultimate survival of threatened species will depend on captive populations. Two critical factors have emerged in the maintenance of amphibians, stringent quarantine and high-quality water. Because exotic diseases such as chytridiomycosis have devastated both natural and captive populations of amphibians, facilities must provide stringent quarantine. The provision of high-quality water is also essential to maintain amphibian health and condition due to the intimate physiological relationship of amphibians to their aquatic environment. Fortunately, novel technologies backed by recent advances in the scientific knowledge of amphibian biology and disease management are available to overcome these challenges. For example, automation can increase the reliability of quarantine and maintain water quality, with a corresponding decrease in handling and the associated disease-transfer risk. It is essential to build facilities with appropriate nontoxic waterproof materials and to provide quarantined amphibian rooms for each population. Other spaces and services include live feed rooms, quarantine stations, isolation rooms, laboratory space, technical support systems, reliable energy and water supplies, high-quality feed, and security. Good husbandry techniques must include reliable and species-specific management by trained staff members who receive support from the administration. It is possible to improve husbandry techniques for many species by sharing knowledge through common information systems. Overall

  4. Candidate genes for obesity-susceptibility show enriched association within a large genome-wide association study for BMI

    Science.gov (United States)

    Vimaleswaran, Karani S.; Tachmazidou, Ioanna; Zhao, Jing Hua; Hirschhorn, Joel N.; Dudbridge, Frank; Loos, Ruth J.F.

    2012-01-01

    Before the advent of genome-wide association studies (GWASs), hundreds of candidate genes for obesity-susceptibility had been identified through a variety of approaches. We examined whether those obesity candidate genes are enriched for associations with body mass index (BMI) compared with non-candidate genes by using data from a large-scale GWAS. A thorough literature search identified 547 candidate genes for obesity-susceptibility based on evidence from animal studies, Mendelian syndromes, linkage studies, genetic association studies and expression studies. Genomic regions were defined to include the genes ±10 kb of flanking sequence around candidate and non-candidate genes. We used summary statistics publicly available from the discovery stage of the genome-wide meta-analysis for BMI performed by the genetic investigation of anthropometric traits consortium in 123 564 individuals. Hypergeometric, rank tail-strength and gene-set enrichment analysis tests were used to test for the enrichment of association in candidate compared with non-candidate genes. The hypergeometric test of enrichment was not significant at the 5% P-value quantile (P = 0.35), but was nominally significant at the 25% quantile (P = 0.015). The rank tail-strength and gene-set enrichment tests were nominally significant for the full set of genes and borderline significant for the subset without SNPs at P < 10−7. Taken together, the observed evidence for enrichment suggests that the candidate gene approach retains some value. However, the degree of enrichment is small despite the extensive number of candidate genes and the large sample size. Studies that focus on candidate genes have only slightly increased chances of detecting associations, and are likely to miss many true effects in non-candidate genes, at least for obesity-related traits. PMID:22791748

  5. Recent advances in human gene-longevity association studies

    DEFF Research Database (Denmark)

    De Benedictis, G; Tan, Q; Jeune, B;

    2001-01-01

    % of the variation in life span is genetically determined. Taking advantage of recent developments in molecular biology, researchers are now searching for candidate genes that might have an influence on life span. The data on unrelated individuals emerging from an ever-increasing number of centenarian studies makes......This paper reviews the recent literature on genes and longevity. The influence of genes on human life span has been confirmed in studies of life span correlation between related individuals based on family and twin data. Results from major twin studies indicate that approximately 25...

  6. A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough

    DEFF Research Database (Denmark)

    Mosley, J D; Shaffer, C M; Van Driest, S L;

    2016-01-01

    The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects di...

  7. Associations of Breast Cancer Risk Factors With Tumor Subtypes : A Pooled Analysis From the Breast Cancer Association Consortium Studies

    NARCIS (Netherlands)

    Yang, Xiaohong R.; Chang-Claude, Jenny; Goode, Ellen L.; Couch, Fergus J.; Nevanlinna, Heli; Milne, Roger L.; Gaudet, Mia; Schmidt, Marjanka K.; Broeks, Annegien; Cox, Angela; Fasching, Peter A.; Hein, Rebecca; Spurdle, Amanda B.; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomaeki, Kristiina; Heikkilae, Paeivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van 't Veer, Laura J.; Van Leeuwen, Flora E.; Andrulis, Irene L.; Glendon, Gord; Knight, Julia A.; Mulligan, Anna Marie; O'Malley, Frances P.; Weerasooriya, Nayana; John, Esther M.; Beckmann, Matthias W.; Hartmann, Arndt; Weihbrecht, Sebastian B.; Wachter, David L.; Jud, Sebastian M. S.; Loehberg, Christian R.; Baglietto, Laura; English, Dallas R.; Giles, Graham G.; McLean, Catriona A.; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E.; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E.; Connley, Daniel; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; Doerk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H.; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Perez, Jose Ignacio; Menendez Rodriguez, Primitiva; Zamora, Pilar; Bentez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Bruening, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M.; Tapper, William J.; Gerty, Sue M.; Sawyer, Elinor J.; Tomlinson, Ian P.; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yang, Show-Lin; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubinski, Jan; Huzarski, Tomasz; Byrski, Tomasz; Gorski, Bohdan; Gronwald, Jacek; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M. A.; Collee, Margriet; Wang-Gohrke, Shan; Pylkaes, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Paeivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E.; Orsted, David Dynnes; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Borge G.; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E.; Hunter, David J.; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; Mckay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P. E. A.; Tollenaar, R. A. E. M.; Seynaeve, C.; Dite, Gillian S.; Apicella, Carmel; Hopper, John L.; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D.; Southey, Melissa C.; Humphreys, Manjeet K.; Easton, Douglas; Pharoah, Paul; Sherman, Mark E.; Garcia-Closas, Montserrat

    2011-01-01

    Background Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35 568 invasive breast cancer case patients f

  8. A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough

    NARCIS (Netherlands)

    Mosley, J D; Shaffer, C M; Van Driest, S L; Weeke, P E; Wells, Q S; Karnes, J H; Velez Edwards, D R; Wei, W-Q; Teixeira, P L; Bastarache, L; Crawford, D C; Li, R; Manolio, T A; Bottinger, E P; McCarty, C A; Linneman, J G; Brilliant, M H; Pacheco, J A; Thompson, W; Chisholm, R L; Jarvik, G P; Crosslin, D R; Carrell, D S; Baldwin, E; Ralston, J; Larson, E B; Grafton, J; Scrol, A; Jouni, H; Kullo, I J; Tromp, G; Borthwick, K M; Kuivaniemi, H; Carey, D J; Ritchie, M D; Bradford, Y; Verma, S S; Chute, C G; Veluchamy, A; Siddiqui, M K; Palmer, C N A; Doney, A; Mahmoud Pour, Seyed Hamidreza; Maitland-van der Zee, A H; Morris, A D; Denny, J C; Roden, D M

    2015-01-01

    The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagn

  9. Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease

    NARCIS (Netherlands)

    Hansel, Nadia N.; Pare, Peter D.; Rafaels, Nicholas; Sin, Don D.; Sandford, Andrew; Daley, Denise; Vergara, Candelaria; Huang, Lili; Elliott, W. Mark; Pascoe, Chris D.; Arsenault, Bryna A.; Postma, Dirkje S.; Boezen, Marieke H.; Bosse, Yohan; van den Berge, Maarten; Hiemstra, Pieter S.; Cho, Michael H.; Litonjua, Augusto A.; Sparrow, David; Ober, Carole; Wise, Robert A.; Connett, John; Neptune, Enid R.; Beaty, Terri H.; Ruczinski, Ingo; Mathias, Rasika A.; Barnes, Kathleen C.

    2015-01-01

    Increased airway responsiveness is linked to lung function decline and mortality in subjects with chronic obstructive pulmonary disease (COPD); however, the genetic contribution to airway responsiveness remains largely unknown. A genome-wide association study (GWAS) was performed using the Illumina

  10. To Be or Not to Be Associated: Power study of four statistical modeling approaches to identify parasite associations in cross-sectional studies

    Directory of Open Access Journals (Sweden)

    Elise eVaumourin

    2014-05-01

    Full Text Available A growing number of studies are reporting simultaneous infections by parasites in many different hosts. The detection of whether these parasites are significantly associated is important in medicine and epidemiology. Numerous approaches to detect associations are available, but only a few provide statistical tests. Furthermore, they generally test for an overall detection of association and do not identify which parasite is associated with which other one. Here, we developed a new approach, the association screening approach, to detect the overall and the detail of multi-parasite associations. We studied the power of this new approach and of three other known ones (i.e. the generalized chi-square, the network and the multinomial GLM approaches to identify parasite associations either due to parasite interactions or to confounding factors. We applied these four approaches to detect associations within two populations of multi-infected hosts: 1 rodents infected with Bartonella sp., Babesia microti and Anaplasma phagocytophilum and 2 bovine population infected with Theileria sp. and Babesia sp.. We found that the best power is obtained with the screening model and the generalized chi-square test. The differentiation between associations, which are due to confounding factors and parasite interactions was not possible. The screening approach significantly identified associations between Bartonella doshiae and B. microti, and between T. parva, T. mutans and T. velifera. Thus, the screening approach was relevant to test the overall presence of parasite associations and identify the parasite combinations that are significantly over- or under-represented. Unravelling whether the associations are due to real biological interactions or confounding factors should be further investigated. Nevertheless, in the age of genomics and the advent of new technologies, it is a considerable asset to speed up researches focusing on the mechanisms driving interactions

  11. Association of Genome-Wide Association Study (GWAS) Identified SNPs and Risk of Breast Cancer in an Indian Population

    Science.gov (United States)

    Nagrani, Rajini; Mhatre, Sharayu; Rajaraman, Preetha; Chatterjee, Nilanjan; Akbari, Mohammad R.; Boffetta, Paolo; Brennan, Paul; Badwe, Rajendra; Gupta, Sudeep; Dikshit, Rajesh

    2017-01-01

    To date, no studies have investigated the association of the GWAS-identified SNPs with BC risk in Indian population. We investigated the association of 30 previously reported and replicated BC susceptibility SNPs in 1,204 cases and 1,212 controls from a hospital based case-control study conducted at the Tata Memorial Hospital, Mumbai. As a measure of total susceptibility burden, the polygenic risk score (PRS) for each individual was defined by the weighted sum of genotypes from 21 independent SNPs with weights derived from previously published estimates of association odds-ratios. Logistic regression models were used to assess risk associated with individual SNPs and overall PRS, and stratified by menopausal and receptor status. A total of 11 SNPs from eight genomic regions (FGFR2, 9q31.2, MAP3K, CCND1, ZM1Z1, RAD51L11, ESR1 and UST) showed statistically significant (p-value ≤ 0.05) evidence of association, either overall or when stratified by menopausal status or hormone receptor status. BC SNPs previously identified in Caucasian population showed evidence of replication in the Indian population mainly with respect to risk of postmenopausal and hormone receptor positive BC. PMID:28098224

  12. The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature

    Directory of Open Access Journals (Sweden)

    Frackelton Edward C

    2010-06-01

    Full Text Available Abstract Background Human height is considered highly heritable and correlated with certain disorders, such as type 2 diabetes and cancer. Despite environmental influences, genetic factors are known to play an important role in stature determination. A number of genetic determinants of adult height have already been established through genome wide association studies. Methods To examine 51 single nucleotide polymorphisms (SNPs corresponding to the 46 previously reported genomic loci for height in 8,184 European American children with height measurements. We leveraged genotyping data from our ongoing GWA study of height variation in children in order to query the 51 SNPs in this pediatric cohort. Results Sixteen of these SNPs yielded at least nominally significant association to height, representing fifteen different loci including EFEMP1-PNPT1, GPR126, C6orf173, SPAG17, Histone class 1, HLA class III and GDF5-UQCC. Other loci revealed no evidence for association, including HMGA1 and HMGA2. For the 16 associated variants, the genotype score explained 1.64% of the total variation for height z-score. Conclusion Among 46 loci that have been reported to associate with adult height to date, at least 15 also contribute to the determination of height in childhood.

  13. CCNA Cisco Certified Network Associate Deluxe Study Guide

    CERN Document Server

    Lammle, Todd

    2011-01-01

    Deluxe Edition of Best-Selling CCNA Study GuideThis comprehensive, enhanced version of the Sybex CCNA Study Guide provides certification candidates with the additional tools they need to prepare for this popular exam. With additional bonus exams and flashcards, as well as the exclusive CCNA Virtual Lab, Platinum Edition, this comprehensive guide has been completely updated to reflect the latest CCNA 640-802 exam. Written by Cisco Authority Todd Lammle, whose straightforward style provides lively examples, hands-on and written labs, easy-to-understand analogies, and real-world scenarios that wi

  14. Genomewide Association Study of African Children Identifies Association of SCHIP1 and PDE8A with Facial Size and Shape

    Science.gov (United States)

    Manyama, Mange; Kimwaga, Emmanuel; Mathayo, Joshua; Larson, Jacinda R.; Liberton, Denise K.; Lukowiak, Ken; Riccardi, Sheri L.; Li, Mao; Williams, Trevor; Li, Hong; Jones, Kenneth L.; Klein, Ophir D.; Santorico, Stephanie A.; Hallgrimsson, Benedikt; Spritz, Richard A.

    2016-01-01

    The human face is a complex assemblage of highly variable yet clearly heritable anatomic structures that together make each of us unique, distinguishable, and recognizable. Relatively little is known about the genetic underpinnings of normal human facial variation. To address this, we carried out a large genomewide association study and two independent replication studies of Bantu African children and adolescents from Mwanza, Tanzania, a region that is both genetically and environmentally relatively homogeneous. We tested for genetic association of facial shape and size phenotypes derived from 3D imaging and automated landmarking of standard facial morphometric points. SNPs within genes SCHIP1 and PDE8A were associated with measures of facial size in both the GWAS and replication cohorts and passed a stringent genomewide significance threshold adjusted for multiple testing of 34 correlated traits. For both SCHIP1 and PDE8A, we demonstrated clear expression in the developing mouse face by both whole-mount in situ hybridization and RNA-seq, supporting their involvement in facial morphogenesis. Ten additional loci demonstrated suggestive association with various measures of facial shape. Our findings, which differ from those in previous studies of European-derived whites, augment understanding of the genetic basis of normal facial development, and provide insights relevant to both human disease and forensics. PMID:27560698

  15. TMPRSS9 and GRIN2B are associated with neuroticism: a genome-wide association study in a European sample.

    Science.gov (United States)

    Aragam, Nagesh; Wang, Ke-Sheng; Anderson, James L; Liu, Xuefeng

    2013-06-01

    Major depression disorder (MDD) is a complex and chronic disease that ranks fourth as cause of disability worldwide. About 14 million adults in the USA are believed to have MDD, and an estimated 75 % attempt suicide making MDD a major public health problem. Neuroticism has been recognized as an endophenotype of MDD; however, few genome-wide association (GWA) analyses of neuroticism as a quantitative trait have been reported to date. The aim of this study is to identify genome-wide genetic variants affecting neuroticism using a European sample. A linear regression model was used to analyze the association with neuroticism as a continuous trait in the Netherlands Study of Depression and Anxiety and Netherlands Twin Registry population-based sample of 2,748 individuals with Perlegen 600K single nucleotide polymorphisms (SNPs). In addition, the neuroticism-associated genes/loci of the top 20 SNPs (p personality disorder (ASPD) in an Australian twin family study. Through GWA analysis, 32 neuroticism-associated SNPs (p neuroticism. Our findings provide a basis for replication in other populations to elucidate the potential role of these genetic variants in neuroticism and MDD along with a possible relationship between ASPD and neuroticism.

  16. Hypertrophic scarring is associated with epidermal abnormalities : An immunohistochemical study

    NARCIS (Netherlands)

    Adriessen, MP; Niessen, FB; Van de Kerkhof, PC; Schalkwijk, J

    1998-01-01

    The role of epidermal keratinocytes in the early phases of normal unimpaired wound healing has been studied extensively. However, little is known about the cell biological processes in the epidermis and the basal membrane zone during the later phases of dermal matrix formation and remodelling of the

  17. STUDY OF VARIABLES ASSOCIATED WITH FINAL GRADES IN MATHEMATICS COURSES.

    Science.gov (United States)

    DAVIS, ELTON C.; RISSER, JOHN J.

    THIS STUDY WAS CONDUCTED IN ORDER TO DETERMINE THE RELATIVE VALUE OF PREVIOUS GRADES IN MATHEMATICS COURSES, THE OVERALL HIGH SCHOOL GRADE POINT AVERAGE, AND THE PLACEMENT TEST IN MATHEMATICS DEVELOPED AT THE COLLEGE AS PREDICTORS OF ACHIEVEMENT IN INTRODUCTORY AND INTERMEDIATE ALGEBRA, IN COLLEGE ALGEBRA, IN TRIGONOMETRY, AND IN ANALYTIC GEOMETRY…

  18. Risk Factors Associated with Outcome in Liver Retransplantation : Multicentric Study

    NARCIS (Netherlands)

    Mattos, Rogerio O.; Linhares, Marcelo M.; Matos, Delcio; Adam, Rene; Bismuth, Henri; Castaing, Denis; Konietzko, Achim; Lerut, Jan; Porte, Robert J.; Neville, Jamieson; Azoulay, Daniel

    2015-01-01

    Background/Aims: To externally validate the predictive mathematical model of survival designed by Linhares et al. (2006). Methodology: This retrospective study was conducted on 217 individuals submitted to liver retransplantation from January 2000 to December 2008 in four European centers. The follo

  19. Genetic Association Analysis under Complex Survey Sampling: The Hispanic Community Health Study/Study of Latinos

    Science.gov (United States)

    Lin, Dan-Yu; Tao, Ran; Kalsbeek, William D.; Zeng, Donglin; Gonzalez, Franklyn; Fernández-Rhodes, Lindsay; Graff, Mariaelisa; Koch, Gary G.; North, Kari E.; Heiss, Gerardo

    2014-01-01

    The cohort design allows investigators to explore the genetic basis of a variety of diseases and traits in a single study while avoiding major weaknesses of the case-control design. Most cohort studies employ multistage cluster sampling with unequal probabilities to conveniently select participants with desired characteristics, and participants from different clusters might be genetically related. Analysis that ignores the complex sampling design can yield biased estimation of the genetic association and inflation of the type I error. Herein, we develop weighted estimators that reflect unequal selection probabilities and differential nonresponse rates, and we derive variance estimators that properly account for the sampling design and the potential relatedness of participants in different sampling units. We compare, both analytically and numerically, the performance of the proposed weighted estimators with unweighted estimators that disregard the sampling design. We demonstrate the usefulness of the proposed methods through analysis of MetaboChip data in the Hispanic Community Health Study/Study of Latinos, which is the largest health study of the Hispanic/Latino population in the United States aimed at identifying risk factors for various diseases and determining the role of genes and environment in the occurrence of diseases. We provide guidelines on the use of weighted and unweighted estimators, as well as the relevant software. PMID:25480034

  20. Study of an association of gout and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    I I Pol'skaya

    2011-06-01

    Full Text Available The paper considers the problem of comorbidity of gout and metabolic syndrome. It gives the data of the authors' study that has revealed the high prevalence of metabolic syndrome in patients with primary chronic gout, as well as a substantially higher cardiovascular risk in patients with the concomitance of these diseases. A role of hyperuricemia as an independent cardiovascular risk factor is demonstrated

  1. Fibromyalgia: is there association between balance and pain? a pilot study

    OpenAIRE

    2014-01-01

    Studies of balance and risk factors for falling typically focus on the elderly population or on individuals with musculoskeletal pain. Although fibromyalgia is associated with intrinsic factors that predispose to falls (pain, depression, fatigue), few studies have researched balance and falls in this syndrome. The aim of this study was to verify the association between balance, balance self-efficacy and pain in women with and without fibromyalgia, and verify the association between Berg Balan...

  2. Association study of FOXO3A SNPs and aging phenotypes in Danish oldest-old individuals

    DEFF Research Database (Denmark)

    Soerensen, Mette; Nygaard, Marianne; Dato, Serena

    2015-01-01

    FOXO3A variation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether FOXO3A variation also associates with aging-related traits. Here, we investigate the association of 15 FOXO3A tagging single nucleotide polymorphisms (SNPs) in 1088 olde...

  3. The Cultural Roots of Teacher Associations: A Case Study from India

    Science.gov (United States)

    Padwad, Amol

    2016-01-01

    Teacher associations (TAs) are communities located in complex cultural spaces that may affect their functioning, vision, priorities, and policies. This case study of the English Language Teachers' Association of India (ELTAI) attempts to examine the relationship between the Association and the cultural space it inhabits, with specific reference to…

  4. Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

    DEFF Research Database (Denmark)

    Kote-Jarai, Zsofia; Olama, Ali Amin Al; Giles, Graham G;

    2011-01-01

    of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations...

  5. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

    NARCIS (Netherlands)

    Chambers, John C; Zhang, Weihua; Sehmi, Joban; Li, Xinzhong; Wass, Mark N; Van der Harst, Pim; Holm, Hilma; Sanna, Serena; Kavousi, Maryam; Baumeister, Sebastian E; Coin, Lachlan J; Deng, Guohong; Gieger, Christian; Heard-Costa, Nancy L; Hottenga, Jouke-Jan; Kühnel, Brigitte; Kumar, Vinod; Lagou, Vasiliki; Liang, Liming; Luan, Jian'an; Vidal, Pedro Marques; Mateo Leach, Irene; O'Reilly, Paul F; Peden, John F; Rahmioglu, Nilufer; Soininen, Pasi; Speliotes, Elizabeth K; Yuan, Xin; Thorleifsson, Gudmar; Alizadeh, Behrooz Z; Atwood, Larry D; Borecki, Ingrid B; Brown, Morris J; Charoen, Pimphen; Cucca, Francesco; Das, Debashish; de Geus, Eco J C; Dixon, Anna L; Döring, Angela; Ehret, Georg; Eyjolfsson, Gudmundur I; Farrall, Martin; Forouhi, Nita G; Friedrich, Nele; Goessling, Wolfram; Gudbjartsson, Daniel F; Harris, Tamara B; Hartikainen, Anna-Liisa; Heath, Simon; Hirschfield, Gideon M; Hofman, Albert; Homuth, Georg; Hyppönen, Elina; Janssen, Harry L A; Johnson, Toby; Kangas, Antti J; Kema, Ido P; Kühn, Jens P; Lai, Sandra; Lathrop, Mark; Lerch, Markus M; Li, Yun; Liang, T Jake; Lin, Jing-Ping; Loos, Ruth J F; Martin, Nicholas G; Moffatt, Miriam F; Montgomery, Grant W; Munroe, Patricia B; Musunuru, Kiran; Nakamura, Yusuke; O'Donnell, Christopher J; Olafsson, Isleifur; Penninx, Brenda W; Pouta, Anneli; Prins, Bram P; Prokopenko, Inga; Puls, Ralf; Ruokonen, Aimo; Savolainen, Markku J; Schlessinger, David; Schouten, Jeoffrey N L; Seedorf, Udo; Sen-Chowdhry, Srijita; Siminovitch, Katherine A; Smit, Johannes H; Spector, Timothy D; Tan, Wenting; Teslovich, Tanya M; Tukiainen, Taru; Uitterlinden, Andre G; Van der Klauw, Melanie M; Vasan, Ramachandran S; Wallace, Chris; Wallaschofski, Henri; Wichmann, H-Erich; Willemsen, Gonneke; Würtz, Peter; Xu, Chun; Yerges-Armstrong, Laura M; Abecasis, Goncalo R; Ahmadi, Kourosh R; Boomsma, Dorret I; Caulfield, Mark; Cookson, William O; van Duijn, Cornelia M; Froguel, Philippe; Matsuda, Koichi; McCarthy, Mark I; Meisinger, Christa; Mooser, Vincent; Pietiläinen, Kirsi H; Schumann, Gunter; Snieder, Harold; Sternberg, Michael J E; Stolk, Ronald P; Thomas, Howard C; Thorsteinsdottir, Unnur; Uda, Manuela; Waeber, Gérard; Wareham, Nicholas J; Waterworth, Dawn M; Watkins, Hugh; Whitfield, John B; Witteman, Jacqueline C M; Wolffenbuttel, Bruce H R; Fox, Caroline S; Ala-Korpela, Mika; Stefansson, Kari; Vollenweider, Peter; Völzke, Henry; Schadt, Eric E; Scott, James; Järvelin, Marjo-Riitta; Elliott, Paul; Kooner, Jaspal S

    2011-01-01

    Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190))

  6. APOLIPOPROTEIN E GENE POLYMORPHISMS ARE NOT ASSOCIATED WITH DIABETIC RETINOPATHY: THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY

    Science.gov (United States)

    PURPOSE: Polymorphism of the apolipoprotein E (APOE) gene has been associated with dyslipidemia and cardiovascular disease. This study examines the association of APOE polymorphisms and diabetic retinopathy. DESIGN: Population-based cross-sectional study. METHODS: We studied 1,398 people aged 49 to ...

  7. A study of association between dental health status and pregnancy

    Directory of Open Access Journals (Sweden)

    Bhavana Gupta

    2013-08-01

    Results: In the study the prevalence of dental caries, gingivitis and periodontal disease were 90%, 98% and 90.33% respectively. The antenatal cases with poor oral hygiene were 2.5 times more likely to have dental caries. OR 0.0138, 95% CI (0.0033 to 0.0570 Z statistic 5.908, P<0.0001.The antenatal cases with poor oral hygiene were 20 times more likely to have gingivitis (OR 0.0045, 95% CI (0.0006-0.0365 Z statistic 5.077, P<0.0001. [Int J Reprod Contracept Obstet Gynecol 2013; 2(4.000: 521-523

  8. Factors Associated with Involvement in Bullying: A Study in Nicaragua

    Directory of Open Access Journals (Sweden)

    Eva M. Romera

    2011-07-01

    Full Text Available School bullying is one of the main problems affecting the quality of peer relationships in schools and in general the coexistence. At European level, there are scientific findings that indicate its nature, characteristics and factors related to its involvement. However, in poor and developing countries, where the problem is more serious, there is a high degree of awareness on this matter. The present study aimed to identify what factors may be influencing the occurrence of bullying in a representative sample of primary schools in the Nicaraguan capital. For this propose, 3042 students from Managua and its metropolitan area were explored with instruments comparable to those used in Europe. A multinomial logistic regression analysis indicated that being a boy, to show antisocial behaviors and attitudes and contact with drugs were the three factors most related with the role of aggressor, as well as negative relationships had a significant influence on involvement in this phenomenon, either as a victim, aggressor or victimized aggressor. Results are discussed in relation to the profiles of aggressor and victim of bullying in international studies focusing on differences in developed countries.

  9. Is Isolated Aphasia Associated with Atrial Fibrillation A Prospective Study

    Directory of Open Access Journals (Sweden)

    Carlijn P.A. Giesbers

    2014-07-01

    Full Text Available Background: A cardioembolic source, usually atrial fibrillation (AF, is detected in 14-30% of strokes. If AF is found, anticoagulation therapy provides a substantial decrease of the risk of recurrent cerebrovascular ischemic events. AF is often paroxysmal, and extensive diagnostic procedures may be necessary to detect it in patients. Considering cost-effectiveness and patient burden, however, not every suspected patient can be thoroughly screened. Therefore, the identification of risk factors for AF may be helpful. Previous studies have identified isolated aphasia as a risk factor for AF as the cause of the stroke. These studies, however, were performed with small population samples, in a retrospective setting or focused on a specific subtype of aphasia. The aim of this observational study is to prospectively evaluate whether there is a relation between isolated aphasia and AF as the cause of cerebrovascular ischemia. Methods: All patients admitted to the Atrium Medical Centre, Heerlen, the Netherlands, with cerebrovascular ischemia or transient ischemic attack in the period of August 2009 to March 2010 or October 2013 to January 2014 were included. The patients were evaluated by a neurologist and admitted to the Brain Care Unit for 24-48 h. Medical history, physical examination and diagnostic results were entered in a database. A diagnosis of isolated aphasia was assigned at admission using the National Institutes of Health Stroke Scale (NIHSS. Presence of AF was determined using a 12-lead electrocardiogram (ECG on admission and continuous ECG monitoring for 1-2 days. During admission, aphasia tests were done, notably the ScreeLing Test and the Boston Naming Test. Data were analyzed using Pearson's χ2 test, Fisher's exact test, the Mann-Whitney U test and univariate and multivariate logistic regression analyses. Results: A total of 347 patients were included, of which 115 (33.1% met the criteria for aphasia, with 26 (7.5% meeting the criteria

  10. International Genome-Wide Association Study Consortium Identifies Novel Loci Associated With Blood Pressure in Children and Adolescents

    Science.gov (United States)

    Parmar, Priyakumari Ganesh; Taal, H. Rob; Timpson, Nicholas J.; Howe, Laura D.; Verwoert, Germaine; Aalto, Ville; Uitterlinden, Andre G.; Briollais, Laurent; Evans, Dave M.; Wright, Margie J.; Newnham, John P.; Whitfield, John B.; Lyytikäinen, Leo-Pekka; Rivadeneira, Fernando; Boomsma, Dorrett I.; Viikari, Jorma; Gillman, Matthew W.; St Pourcain, Beate; Hottenga, Jouke-Jan; Montgomery, Grant W.; Hofman, Albert; Kähönen, Mika; Martin, Nicholas G.; Tobin, Martin D.; Raitakari, Ollie; Vioque, Jesus; Jaddoe, Vincent W.V.; Jarvelin, Marjo-Riita; Beilin, Lawrence J.; Heinrich, Joachim; van Duijn, Cornelia M.; Pennell, Craig E.; Lawlor, Debbie A.; Palmer, Lyle J.

    2017-01-01

    Background Our aim was to identify genetic variants associated with blood pressure (BP) in childhood and adolescence. Methods and Results Genome-wide association study data from participating European ancestry cohorts of the Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium was meta-analyzed across 3 epochs; prepuberty (4–7 years), puberty (8–12 years), and postpuberty (13–20 years). Two novel loci were identified as having genome-wide associations with systolic BP across specific age epochs: rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor chromatin immunoprecipitation and 5′-C-phosphate-G-3′ methylation site) during prepuberty (P=2.86×10–8) and rs872256 during puberty (P=8.67×10–9). Several single-nucleotide polymorphism clusters were also associated with childhood BP at P<5×10–3. Using a P value threshold of <5×10–3, we found some overlap in variants across the different age epochs within our study and between several single-nucleotide polymorphisms in any of the 3 epochs and adult BP-related single-nucleotide polymorphisms. Conclusions Our results suggest that genetic determinants of BP act from childhood, develop over the lifecourse, and show some evidence of age-specific effects. PMID:26969751

  11. Genome-wide association study identifies single-nucleotide polymorphism in KCNB1 associated with left ventricular mass in humans: The HyperGEN Study

    Directory of Open Access Journals (Sweden)

    Kraemer Rachel

    2009-05-01

    Full Text Available Abstract Background We conducted a genome-wide association study (GWAS and validation study for left ventricular (LV mass in the Family Blood Pressure Program – HyperGEN population. LV mass is a sensitive predictor of cardiovascular mortality and morbidity in all genders, races, and ages. Polymorphisms of candidate genes in diverse pathways have been associated with LV mass. However, subsequent studies have often failed to replicate these associations. Genome-wide association studies have unprecedented power to identify potential genes with modest effects on left LV mass. We describe here a GWAS for LV mass in Caucasians using the Affymetrix GeneChip Human Mapping 100 k Set. Cases (N = 101 and controls (N = 101 were selected from extreme tails of the LV mass index distribution from 906 individuals in the HyperGEN study. Eleven of 12 promising (Q Results Despite the relatively small sample, we identified 12 promising SNPs in the GWAS. Eleven SNPs were successfully genotyped in the validation study of 704 Caucasians and 1467 African Americans; 5 SNPs on chromosomes 5, 12, and 20 were significantly (P ≤ 0.05 associated with LV mass after correction for multiple testing. One SNP (rs756529 is intragenic within KCNB1, which is dephosphorylated by calcineurin, a previously reported candidate gene for LV hypertrophy within this population. Conclusion These findings suggest KCNB1 may be involved in the development of LV hypertrophy in humans.

  12. Replication of genome‐wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort

    OpenAIRE

    Gonzalez, Suzanne; Gupta, Jayanta; Villa, Erika; Mallawaarachchi, Indika; Rodriguez, Marco; Ramirez, Mercedes; Zavala, Juan; Armas, Regina; Dassori, Albana; Contreras, Javier; Flores, Deborah; Jerez, Alvaro; Ontiveros, Alfonso; Nicolini, Humberto; Escamilla, Michael

    2016-01-01

    Objectives Recent genome‐wide association studies (GWASs) have identified numerous putative genetic polymorphisms associated with bipolar disorder (BD) and/or schizophrenia (SC). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms (SNPs) in a sampl...

  13. [A study of otitis externa associated with Malassezia].

    Science.gov (United States)

    Shiota, Ryoko; Kaneko, Takamasa; Yano, Hiroaki; Takeshita, Kimiko; Nishioka, Keiko; Makimura, Koichi

    2009-01-01

    Malassezia-positive smears can be recognized from otitis externa, however, there are few references in the literature to the relation between Malassezia and otitis externa. Therefore, the bacterial and clinical characteristics of 72 cases (63 patients) with otitis externa were investigated at the Department of Otorhinolaryngology, Takinomiya General Hospital to analyze this. Thirty-seven cases were bacterial otitis externa, 20 cases were fungal otitis externa, and 15 cases were etiological agents unknown in this study. The causative organisms in fungal otitis externa were the genera Aspergillus (10 cases), Malassezia (5) and Candida (5), respectively. We suspected that 5 cases were caused by Malassezia because Malassezia cell counts were greater than 10 per field (x 400), and a large number of Malassezia were isolated from all cases. In these cases, many squamous epithelial cells were observed by direct examination, and cells from the middle or basal layer of the ear canal were also recognized in three cases. Therefore, accelerated turnover of epidermal cells of the ear canal was suggested. The main symptoms were itching and fullness in the ear, with observations of redness and erosion in objective deterioration, and we felt that these conditions were similar to seborrheic dermatitis (SD). In addition, these five cases were confirmed as fungus-related otitis externa by their improvement with antifungal agents.

  14. Association between physical and motor development in childhood: a longitudinal study of Japanese twins.

    Science.gov (United States)

    Silventoinen, Karri; Pitkäniemi, Janne; Latvala, Antti; Kaprio, Jaakko; Yokoyama, Yoshie

    2014-06-01

    Length and weight in infancy are associated with neurodevelopment, but less is known about growth in other anthropometric measures. In this study we analyzed how the development in length, weight, head circumference, and chest circumference over infancy is associated with motor development in early childhood, using a twin study design. Information on physical development over infancy and the age at achievement of eight developmental milestones over early childhood was collected for 370 Japanese twin pairs. Linear mixed models were used to analyze how physical development is associated with motor development between individual twins, as well as within twin pairs, adjusting the results for shared maternal and postnatal environmental factors. Delayed motor development was associated with smaller body size over infancy, and we also found some suggestive evidence that it was associated with catch-up growth as well. When studying the associations within twin pairs discordant for motor development, similar associations were found. However, chest circumference showed the most robust association within discordant twin pairs. Smaller body size and rapid catch-up growth are associated with delayed motor development. When studying these associations within twin pairs and thus adjusting the results for gestational age as well as many other maternal and postnatal environmental factors, chest circumference showed the most robust association. Chest circumference, rarely used in developed countries, can offer additional information on prenatal conditions relevant for further motor development not achieved by more traditional anthropometric measures.

  15. A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough.

    Science.gov (United States)

    Mosley, J D; Shaffer, C M; Van Driest, S L; Weeke, P E; Wells, Q S; Karnes, J H; Velez Edwards, D R; Wei, W-Q; Teixeira, P L; Bastarache, L; Crawford, D C; Li, R; Manolio, T A; Bottinger, E P; McCarty, C A; Linneman, J G; Brilliant, M H; Pacheco, J A; Thompson, W; Chisholm, R L; Jarvik, G P; Crosslin, D R; Carrell, D S; Baldwin, E; Ralston, J; Larson, E B; Grafton, J; Scrol, A; Jouni, H; Kullo, I J; Tromp, G; Borthwick, K M; Kuivaniemi, H; Carey, D J; Ritchie, M D; Bradford, Y; Verma, S S; Chute, C G; Veluchamy, A; Siddiqui, M K; Palmer, C N A; Doney, A; MahmoudPour, S H; Maitland-van der Zee, A H; Morris, A D; Denny, J C; Roden, D M

    2016-06-01

    The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency=0.33, odds ratio (OR)=1.3 (95% confidence interval (CI): 1.2-1.4), P=1.0 × 10(-8)). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n=926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n=4309). Replication was observed at rs7675300 (OR=1.32 (1.01-1.70), P=0.04) in eMERGE and at rs16870989 and rs1495509 (OR=1.15 (1.01-1.30), P=0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR=1.23 (1.15-1.32), P=1.9 × 10(-9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk.

  16. Genome-wide association study to identify common variants associated with brachial circumference: a meta-analysis of 14 cohorts.

    Directory of Open Access Journals (Sweden)

    Vesna Boraska

    Full Text Available Brachial circumference (BC, also known as upper arm or mid arm circumference, can be used as an indicator of muscle mass and fat tissue, which are distributed differently in men and women. Analysis of anthropometric measures of peripheral fat distribution such as BC could help in understanding the complex pathophysiology behind overweight and obesity. The purpose of this study is to identify genetic variants associated with BC through a large-scale genome-wide association scan (GWAS meta-analysis. We used fixed-effects meta-analysis to synthesise summary results across 14 GWAS discovery and 4 replication cohorts comprising overall 22,376 individuals (12,031 women and 10,345 men of European ancestry. Individual analyses were carried out for men, women, and combined across sexes using linear regression and an additive genetic model: adjusted for age and adjusted for age and BMI. We prioritised signals for follow-up in two-stages. We did not detect any signals reaching genome-wide significance. The FTO rs9939609 SNP showed nominal evidence for association (p<0.05 in the age-adjusted strata for men and across both sexes. In this first GWAS meta-analysis for BC to date, we have not identified any genome-wide significant signals and do not observe robust association of previously established obesity loci with BC. Large-scale collaborations will be necessary to achieve higher power to detect loci underlying BC.

  17. Polarographic Studies on Associations of Midecamycin and Chloroquine with Hydrogen Peroxide

    Institute of Scientific and Technical Information of China (English)

    LI Ning; SONG Jun-feng; XU Mao-tian; ZHANG Ya

    2005-01-01

    The associations of each of midecamycin and chloroquine phosphate to hydrogen peroxide were studied by using linear-potential scan polarography. In a 0.15 mol/L KH2PO4-NaOH(pH 7.4) buffer, the association ratio of the association complex of midecamycin to hydrogen peroxide is 1∶1, and the apparent association constant is 7.18. While in a 0.04 mol/L NH3·H2O-NH4Cl(pH 9.5) buffer, the association ratio and the apparent association constant of the association complex of chloroquine phosphate to hydrogen peroxide are 1∶1 and 45.4, respectively. The formation of the association complexes stabilizes H2O2 and results in the accumulation of H2O2, which is baneful to human body.

  18. A case-control study identifying chromosomal polymorphic variations as forms of epigenetic alterations associated with the infertility phenotype

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Athalye, Arundhati S; Madon, Prochi F

    2009-01-01

    To study the association of chromosomal polymorphic variations with infertility and subfertility.......To study the association of chromosomal polymorphic variations with infertility and subfertility....

  19. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

    NARCIS (Netherlands)

    Wain, Louise V; Verwoert, Germaine C; O'Reilly, Paul F; Shi, Gang; Johnson, Toby; Johnson, Andrew D; Bochud, Murielle; Rice, Kenneth M; Henneman, Peter; Smith, Albert V; Ehret, Georg B; Amin, Najaf; Larson, Martin G; Mooser, Vincent; Hadley, David; Dörr, Marcus; Bis, Joshua C; Aspelund, Thor; Esko, Tõnu; Janssens, A Cecile J W; Zhao, Jing Hua; Heath, Simon; Laan, Maris; Fu, Jingyuan; Pistis, Giorgio; Luan, Jian'an; Arora, Pankaj; Lucas, Gavin; Pirastu, Nicola; Pichler, Irene; Jackson, Anne U; Webster, Rebecca J; Zhang, Feng; Peden, John F; Schmidt, Helena; Tanaka, Toshiko; Campbell, Harry; Igl, Wilmar; Milaneschi, Yuri; Hottenga, Jouke-Jan; Vitart, Veronique; Chasman, Daniel I; Trompet, Stella; Bragg-Gresham, Jennifer L; Alizadeh, Behrooz Z; Chambers, John C; Guo, Xiuqing; Lehtimäki, Terho; Kühnel, Brigitte; Lopez, Lorna M; Polašek, Ozren; Boban, Mladen; Nelson, Christopher P; Morrison, Alanna C; Pihur, Vasyl; Ganesh, Santhi K; Hofman, Albert; Kundu, Suman; Mattace-Raso, Francesco U S; Rivadeneira, Fernando; Sijbrands, Eric J G; Uitterlinden, Andre G; Hwang, Shih-Jen; Vasan, Ramachandran S; Wang, Thomas J; Bergmann, Sven; Vollenweider, Peter; Waeber, Gérard; Laitinen, Jaana; Pouta, Anneli; Zitting, Paavo; McArdle, Wendy L; Kroemer, Heyo K; Völker, Uwe; Völzke, Henry; Glazer, Nicole L; Taylor, Kent D; Harris, Tamara B; Alavere, Helene; Haller, Toomas; Keis, Aime; Tammesoo, Mari-Liis; Aulchenko, Yurii; Barroso, Inês; Khaw, Kay-Tee; Galan, Pilar; Hercberg, Serge; Lathrop, Mark; Eyheramendy, Susana; Org, Elin; Sõber, Siim; Lu, Xiaowen; Nolte, Ilja M; Penninx, Brenda W; Corre, Tanguy; Masciullo, Corrado; Sala, Cinzia; Groop, Leif; Voight, Benjamin F; Melander, Olle; O'Donnell, Christopher J; Salomaa, Veikko; d'Adamo, Adamo Pio; Fabretto, Antonella; Faletra, Flavio; Ulivi, Sheila; Del Greco, Fabiola M; Facheris, Maurizio; Collins, Francis S; Bergman, Richard N; Beilby, John P; Hung, Joseph; Musk, A William; Mangino, Massimo; Shin, So-Youn; Soranzo, Nicole; Watkins, Hugh; Goel, Anuj; Hamsten, Anders; Gider, Pierre; Loitfelder, Marisa; Zeginigg, Marion; Hernandez, Dena; Najjar, Samer S; Navarro, Pau; Wild, Sarah H; Corsi, Anna Maria; Singleton, Andrew; de Geus, Eco J C; Willemsen, Gonneke; Parker, Alex N; Rose, Lynda M; Buckley, Brendan; Stott, David; Orru, Marco; Uda, Manuela; van der Klauw, Melanie M; Zhang, Weihua; Li, Xinzhong; Scott, James; Chen, Yii-Der Ida; Burke, Gregory L; Kähönen, Mika; Viikari, Jorma; Döring, Angela; Meitinger, Thomas; Davies, Gail; Starr, John M; Emilsson, Valur; Plump, Andrew; Lindeman, Jan H; Hoen, Peter A C 't; König, Inke R; Felix, Janine F; Clarke, Robert; Hopewell, Jemma C; Ongen, Halit; Breteler, Monique; Debette, Stéphanie; Destefano, Anita L; Fornage, Myriam; Mitchell, Gary F; Smith, Nicholas L; Holm, Hilma; Stefansson, Kari; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Samani, Nilesh J; Preuss, Michael; Rudan, Igor; Hayward, Caroline; Deary, Ian J; Wichmann, H-Erich; Raitakari, Olli T; Palmas, Walter; Kooner, Jaspal S; Stolk, Ronald P; Jukema, J Wouter; Wright, Alan F; Boomsma, Dorret I; Bandinelli, Stefania; Gyllensten, Ulf B; Wilson, James F; Ferrucci, Luigi; Schmidt, Reinhold; Farrall, Martin; Spector, Tim D; Palmer, Lyle J; Tuomilehto, Jaakko; Pfeufer, Arne; Gasparini, Paolo; Siscovick, David; Altshuler, David; Loos, Ruth J F; Toniolo, Daniela; Snieder, Harold; Gieger, Christian; Meneton, Pierre; Wareham, Nicholas J; Oostra, Ben A; Metspalu, Andres; Launer, Lenore; Rettig, Rainer; Strachan, David P; Beckmann, Jacques S; Witteman, Jacqueline C M; Erdmann, Jeanette; van Dijk, Ko Willems; Boerwinkle, Eric; Boehnke, Michael; Ridker, Paul M; Jarvelin, Marjo-Riitta; Chakravarti, Aravinda; Abecasis, Goncalo R; Gudnason, Vilmundur; Newton-Cheh, Christopher; Levy, Daniel; Munroe, Patricia B; Psaty, Bruce M; Caulfield, Mark J; Rao, Dabeeru C; Tobin, Martin D; Elliott, Paul; van Duijn, Cornelia M

    2011-01-01

    Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we ident

  20. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

    NARCIS (Netherlands)

    Wain, Louise V.; Verwoert, Germaine C.; O'Reilly, Paul F.; Shi, Gang; Johnson, Toby; Johnson, Andrew D.; Bochud, Murielle; Rice, Kenneth M.; Henneman, Peter; Smith, Albert V.; Ehret, Georg B.; Amin, Najaf; Larson, Martin G.; Mooser, Vincent; Hadley, David; Doerr, Marcus; Bis, Joshua C.; Aspelund, Thor; Esko, Tonu; Janssens, A. Cecile J. W.; Zhao, Jing Hua; Heath, Simon; Laan, Maris; Fu, Jingyuan; Pistis, Giorgio; Luan, Jian'an; Arora, Pankaj; Lucas, Gavin; Pirastu, Nicola; Pichler, Irene; Jackson, Anne U.; Webster, Rebecca J.; Zhang, Feng; Peden, John F.; Schmidt, Helena; Tanaka, Toshiko; Campbell, Harry; Igl, Wilmar; Milaneschi, Yuri; Hottenga, Jouke-Jan; Vitart, Veronique; Chasman, Daniel I.; Trompet, Stella; Bragg-Gresham, Jennifer L.; Alizadeh, Behrooz Z.; Chambers, John C.; Guo, Xiuqing; Lehtimaki, Terho; Kuehnel, Brigitte; Lopez, Lorna M.; Polasek, Ozren; Boban, Mladen; Nelson, Christopher P.; Morrison, Alanna C.; Pihur, Vasyl; Ganesh, Santhi K.; Hofman, Albert; Kundu, Suman; Mattace-Raso, Francesco U. S.; Rivadeneira, Fernando; Sijbrands, Eric J. G.; Uitterlinden, Andre G.; Hwang, Shih-Jen; Vasan, Ramachandran S.; Wang, Thomas J.; Bergmann, Sven; Vollenweider, Peter; Waeber, Gerard; Laitinen, Jaana; Pouta, Anneli; Zitting, Paavo; McArdle, Wendy L.; Kroemer, Heyo K.; Voelker, Uwe; Voelzke, Henry; Glazer, Nicole L.; Taylor, Kent D.; Harris, Tamara B.; Alavere, Helene; Haller, Toomas; Keis, Aime; Tammesoo, Mari-Liis; Aulchenko, Yurii; Barroso, Ines; Khaw, Kay-Tee; Galan, Pilar; Hercberg, Serge; Lathrop, Mark; Eyheramendy, Susana; Org, Elin; Sober, Siim; Lu, Xiaowen; Nolte, Ilja M.; Penninx, Brenda W.; Corre, Tanguy; Masciullo, Corrado; Sala, Cinzia; Groop, Leif; Voight, Benjamin F.; Melander, Olle; O'Donnell, Christopher J.; Salomaa, Veikko; d'Adamo, Adamo Pio; Fabretto, Antonella; Faletra, Flavio; Ulivi, Sheila; Del Greco, Fabiola M.; Facheris, Maurizio; Collins, Francis S.; Bergman, Richard N.; Beilby, John P.; Hung, Joseph; Musk, A. William; Mangino, Massimo; Shin, So-Youn; Soranzo, Nicole; Watkins, Hugh; Goel, Anuj; Hamsten, Anders; Gider, Pierre; Loitfelder, Marisa; Zeginigg, Marion; Hernandez, Dena; Najjar, Samer S.; Navarro, Pau; Wild, Sarah H.; Corsi, Anna Maria; Singleton, Andrew; de Geus, Eco J. C.; Willemsen, Gonneke; Parker, Alex N.; Rose, Lynda M.; Buckley, Brendan; Stott, David; Orru, Marco; Uda, Manuela; van der Klauw, Melanie M.; Zhang, Weihua; Li, Xinzhong; Scott, James; Chen, Yii-Der Ida; Burke, Gregory L.; Kahonen, Mika; Viikari, Jorma; Doering, Angela; Meitinger, Thomas; Davies, Gail; Starr, John M.; Emilsson, Valur; Plump, Andrew; Lindeman, Jan H.; 't Hoen, Peter A. C.; Koenig, Inke R.; Felix, Janine F.; Clarke, Robert; Hopewell, Jemma C.; Ongen, Halit; Breteler, Monique; Debette, Stephanie; DeStefano, Anita L.; Fornage, Myriam; Mitchell, Gary F.; Smith, Nicholas L.; Holm, Hilma; Stefansson, Kari; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Samani, Nilesh J.; Preuss, Michael; Rudan, Igor; Hayward, Caroline; Deary, Ian J.; Wichmann, H-Erich; Raitakari, Olli T.; Palmas, Walter; Kooner, Jaspal S.; Stolk, Ronald P.; Jukema, J. Wouter; Wright, Alan F.; Boomsma, Dorret I.; Bandinelli, Stefania; Gyllensten, Ulf B.; Wilson, James F.; Ferrucci, Luigi; Schmidt, Reinhold; Farrall, Martin; Spector, Tim D.; Palmer, Lyle J.; Tuomilehto, Jaakko; Pfeufer, Arne; Gasparini, Paolo; Siscovick, David; Altshuler, David; Loos, Ruth J. F.; Toniolo, Daniela; Snieder, Harold; Gieger, Christian; Meneton, Pierre; Wareham, Nicholas J.; Oostra, Ben A.; Metspalu, Andres; Launer, Lenore; Rettig, Rainer; Strachan, David P.; Beckmann, Jacques S.; Witteman, Jacqueline C. M.; Erdmann, Jeanette; van Dijk, Ko Willems; Boerwinkle, Eric; Boehnke, Michael; Ridker, Paul M.; Jarvelin, Marjo-Riitta; Chakravarti, Aravinda; Abecasis, Goncalo R.; Gudnason, Vilmundur; Newton-Cheh, Christopher; Levy, Daniel; Munroe, Patricia B.; Psaty, Bruce M.; Caulfield, Mark J.; Rao, Dabeeru C.; Tobin, Martin D.; Elliott, Paul; van Duijn, Cornelia M.

    2011-01-01

    Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we

  1. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

    NARCIS (Netherlands)

    L.V. Wain (Louise); G.C. Verwoert (Germaine); P.F. O'Reilly (Paul); G. Shi (Gang); T. Johnson (Toby); M. Bochud (Murielle); K. Rice (Kenneth); P. Henneman (Peter); A.V. Smith (Albert Vernon); G.B. Ehret (Georg); N. Amin (Najaf); M.G. Larson (Martin); V. Mooser (Vincent); D. Hadley (David); M. Dörr (Marcus); J.C. Bis (Joshua); T. Aspelund (Thor); T. Esko (Tõnu); A.C.J.W. Janssens (Cécile); J.H. Zhao; S.C. Heath (Simon); M. Laan (Maris); J. Fu (Jingyuan); G. Pistis (Giorgio); J. Luan; G. Lucas (Gavin); N. Pirastu (Nicola); I. Pichler (Irene); A.U. Jackson (Anne); R.J. Webster (Rebecca J.); F.F. Zhang; J. Peden (John); R. Schmidt (Reinhold); T. Tanaka (Toshiko); H. Campbell (Harry); W. Igl (Wilmar); Y. Milaneschi (Yuri); J.J. Hottenga (Jouke Jan); V. Vitart (Veronique); D.I. Chasman (Daniel); S. Trompet (Stella); J.L. Bragg-Gresham (Jennifer L.); B.Z. Alizadeh (Behrooz); J.C. Chambers (John); X. Guo (Xiuqing); T. Lehtimäki (Terho); B. Kuhnel (Brigitte); L.M. Lopez; O. Polasek (Ozren); M. Boban (Mladen); C.P. Nelson (Christopher P.); A.C. Morrison (Alanna); V. Pihur (Vasyl); S.K. Ganesh (Santhi); A. Hofman (Albert); S. Kundu (Suman); F.U.S. Mattace Raso (Francesco); F. Rivadeneira Ramirez (Fernando); E.J.G. Sijbrands (Eric); A.G. Uitterlinden (André); S.J. Hwang; R.S. Vasan (Ramachandran Srini); Y.A. Wang (Ying); S.M. Bergmann (Sven); P. Vollenweider (Peter); G. Waeber (Gérard); J. Laitinen (Jaana); A. Pouta (Anneli); P. Zitting (Paavo); W.L. McArdle (Wendy); H.K. Kroemer (Heyo); U. Völker (Uwe); H. Völzke (Henry); N.L. Glazer (Nicole); K.D. Taylor (Kent); T.B. Harris (Tamara); H. Alavere (Helene); T. Haller (Toomas); A. Keis (Aime); M.L. Tammesoo; Y.S. Aulchenko (Yurii); K-T. Khaw (Kay-Tee); P. Galan (Pilar); S. Hercberg (Serge); G.M. Lathrop (Mark); S. Eyheramendy (Susana); E. Org (Elin); S. Sõber (Siim); X. Lu (Xiaowen); I.M. Nolte (Ilja); B.W.J.H. Penninx (Brenda); T. Corre (Tanguy); C. Masciullo (Corrado); C. Sala (Cinzia); L. Groop (Leif); B.F. Voight (Benjamin); O. Melander (Olle); C.J. O'Donnell (Christopher); V. Salomaa (Veikko); P. d' Adamo (Pio); A. Fabretto (Antonella); F. Faletra (Flavio); S. Ulivi (Shelia); F. Del Greco M (Fabiola); M.F. Facheris (Maurizio); F.S. Collins (Francis); R.N. Bergman (Richard); J.P. Beilby (John); J. Hung (Judy); A.W. Musk (Arthur); M. Mangino (Massimo); S.Y. Shin (So Youn); N. Soranzo (Nicole); H. Watkins (Hugh); A. Goel (Anuj); A. Hamsten (Anders); P. Gider (Pierre); M. Loitfelder (Marisa); M. Zeginigg (Marion); D.G. Hernandez (Dena); S.S. Najjar (Samer); P. Navarro (Pau); S.H. Wild (Sarah); A.M. Corsi (Anna Maria); A. Singleton (Andrew); E.J.C. de Geus (Eco); G.A.H.M. Willemsen (Gonneke); A.N. Parker (Alex); L.M. Rose (Lynda); B.M. Buckley (Brendan M.); D.J. Stott (David. J.); M. Orrù (Marco); M. Uda (Manuela); M.M. van der Klauw (Melanie); X. Li (Xiaohui); J. Scott (James); Y.D.I. Chen (Yii-Der Ida); G.L. Burke (Greg); M. Kähönen (Mika); J. Viikari (Jorma); A. Döring (Angela); T. Meitinger (Thomas); G.S. Davis; J.M. Starr (John); V. Emilsson (Valur); A.S. Plump (Andrew); J.H. Lindeman (Jan H.); P.A.C. 't Hoen (Peter); I.R. König (Inke); J.F. Felix (Janine); R. Clarke; J. Hopewell; H. Ongen (Halit); M.M.B. Breteler (Monique); S. Debette (Stéphanie); A.L. DeStefano (Anita); M. Fornage (Myriam); G.F. Mitchell (Gary); H. Holm (Hilma); K. Stefansson (Kari); G. Thorleifsson (Gudmar); U. Thorsteinsdottir (Unnur); N.J. Samani (Nilesh); M. Preuss (Michael); I. Rudan (Igor); C. Hayward (Caroline); I.J. Deary (Ian); H.E. Wichmann (Heinz Erich); O. Raitakari (Olli); W. Palmas (Walter); J.S. Kooner (Jaspal); R.P. Stolk (Ronald); J.W. Jukema (Jan Wouter); A.F. Wright (Alan); D.I. Boomsma (Dorret); S. Bandinelli (Stefania); U. Gyllensten (Ulf); J.F. Wilson (James); L. Ferrucci (Luigi); M. Farrall (Martin); T.D. Spector (Timothy); L.J. Palmer; J. Tuomilehto (Jaakko); A. Pfeufer (Arne); P. Gasparini (Paolo); D.S. Siscovick (David); D. Altshuler (David); R.J.F. Loos (Ruth); D. Toniolo (Daniela); H. Snieder (Harold); C. Gieger (Christian); P. Meneton (Pierre); N.J. Wareham (Nick); B.A. Oostra (Ben); A. Metspalu (Andres); L.J. Launer (Lenore); R. Rettig (Rainer); D.P. Strachan (David); J.S. Beckmann (Jacques); J.C.M. Witteman (Jacqueline); J.A.P. Willems van Dijk (Ko); E.A. Boerwinkle (Eric); M. Boehnke (Michael); P.M. Ridker (Paul); M.R. Järvelin; A. Chakravarti (Aravinda); J. Erdmann (Jeanette); V. Gudnason (Vilmundur); C. Newton-Cheh (Christopher); D. Levy (Daniel); P. Arora (Pankaj); P. Munroe (Patricia); B.M. Psaty (Bruce); M. Caulfield (Mark); D.C. Rao (Dabeeru C.); P. Elliott (Paul); P. Tikka-Kleemola (Päivi); G.R. Abecasis (Gonçalo); I. Barroso (Inês)

    2011-01-01

    textabstractNumerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,60

  2. Lipoprotein-associated phospholipase A2 and coronary calcification - The Rotterdam coronary calcification study

    NARCIS (Netherlands)

    Kardys, Isabella; Oei, Hok-Hay S.; Hofman, Albert; Oudkerk, Matthijs; Witteman, Jacqueline C. M.

    2007-01-01

    Objectives: Although several studies have recently suggested that lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent predictor of coronary events, only one study has examined the association between Lp-PLA2 and coronary calcification, using young adults. We investigated the associat

  3. Impact of associated injuries in the Floating knee: A retrospective study

    Directory of Open Access Journals (Sweden)

    Yesupalan Rajam S

    2009-01-01

    Full Text Available Abstract Background Floating knee injuries are usually associated with other significant injuries. Do these injuries have implications on the management of the floating knee and the final outcome of patients? Our study aims to assess the implications of associated injuries in the management and final outcome of floating knee. Methods 29 patients with floating knees were assessed in our institution. A retrospective analysis of medical records and radiographs were done and all associated injuries were identified. The impact of associated injuries on delay in initial surgical management, delay in rehabilitation & final outcome of the floating knee were assessed. Results 38 associated injuries were noted. 7 were associated with ipsilateral knee injuries. Lower limb injuries were most commonly associated with the floating knee. Patients with some associated injuries had a delay in surgical management and others a delay in post-operative rehabilitation. Knee ligament and vascular injuries were associated with poor outcome. Conclusion The associated injuries were quite frequent with the floating knee. Some of the associated injuries caused a delay in surgical management and post-operative rehabilitation. In assessment of the final outcome, patients with associated knee and vascular injuries had a poor prognosis. Majority of the patients with associated injuries had a good or excellent outcome.

  4. Association of ADH4 genetic variants with alcohol dependence risk and related phenotypes: results from a larger multicenter association study.

    Science.gov (United States)

    Preuss, Ulrich W; Ridinger, Monika; Rujescu, Dan; Samochowiec, Jerzy; Fehr, Christoph; Wurst, Friedrich M; Koller, Gabriele; Bondy, Brigitta; Wodarz, Norbert; Debniak, Tadeusz; Grzywacz, Anna; Soyka, Michael; Zill, Peter

    2011-04-01

    Genetic variants of the alcohol-metabolizing enzyme ADH4, located on chromosome 4q22-4q23, have been related to alcohol dependence (AD) risk in previous research. The aim of this association study in a large multicenter sample of alcohol-dependent individuals and controls is to confirm ADH4 single nucleotide polymorphism (SNP) and haplotype association with AD and relevant related phenotypes. One thousand, six hundred and twenty-two (1622) inpatient subjects and 1469 control subjects with DSM-IV. AD from four addiction treatment centres were included. Characteristics of AD and related phenotypes including alcohol withdrawal, Cloninger's type I and II and first ages of drinking, regular drinking and AD onset were obtained using standardized structured interviews. After subjects were genotyped for 2 ADH4 polymorphisms, single SNP case-control and haplotype analyses were conducted. Both variants--rs1800759 and rs1042364--and the A-A and C-G haplotypes were significantly related to AD across samples. Furthermore, associations with AD-related phenotypes and subtypes revealed a potential protective influence of this haplotype. This study confirms the significant relationship of ADH4 variants with AD and related phenotypes. While the rs1800759 and rs1042364 A-A haplotype had a potential protective influence on the risk for several AD-related phenotypes, this effect is rather small compared to functional variants of other alcohol or acetaldehyde-metabolizing enzymes like ALDH2*2 or ADH1B*2.

  5. Magnesium intake is inversely associated with coronary artery calcification: the Framingham Heart Study

    Science.gov (United States)

    OBJECTIVES: The aim of this study was to examine whether magnesium intake is associated with coronary artery calcification (CAC) and abdominal aortic calcification (AAC). BACKGROUND: Animal and cell studies suggest that magnesium may prevent calcification within atherosclerotic plaques underlying c...

  6. Population-Specific Haplotype Association of the Postsynaptic Density Gene DLG4 with Schizophrenia, in Family-Based Association Studies

    Science.gov (United States)

    Balan, Shabeesh; Yamada, Kazuo; Hattori, Eiji; Iwayama, Yoshimi; Toyota, Tomoko; Ohnishi, Tetsuo; Maekawa, Motoko; Toyoshima, Manabu; Iwata, Yasuhide; Suzuki, Katsuaki; Kikuchi, Mitsuru; Yoshikawa, Takeo

    2013-01-01

    The post-synaptic density (PSD) of glutamatergic synapses harbors a multitude of proteins critical for maintaining synaptic dynamics. Alteration of protein expression levels in this matrix is a marked phenomenon of neuropsychiatric disorders including schizophrenia, where cognitive functions are impaired. To investigate the genetic relationship of genes expressed in the PSD with schizophrenia, a family-based association analysis of genetic variants in PSD genes such as DLG4, DLG1, PICK1 and MDM2, was performed, using Japanese samples (124 pedigrees, n = 376 subjects). Results showed a significant association of the rs17203281 variant from the DLG4 gene, with preferential transmission of the C allele (p = 0.02), although significance disappeared after correction for multiple testing. Replication analysis of this variant, found no association in a Chinese schizophrenia cohort (293 pedigrees, n = 1163 subjects) or in a Japanese case-control sample (n = 4182 subjects). The DLG4 expression levels between postmortem brain samples from schizophrenia patients showed no significant changes from controls. Interestingly, a five marker haplotype in DLG4, involving rs2242449, rs17203281, rs390200, rs222853 and rs222837, was enriched in a population specific manner, where the sequences A-C-C-C-A and G-C-C-C-A accumulated in Japanese (p = 0.0009) and Chinese (p = 0.0007) schizophrenia pedigree samples, respectively. However, this could not be replicated in case-control samples. None of the variants in other examined candidate genes showed any significant association in these samples. The current study highlights a putative role for DLG4 in schizophrenia pathogenesis, evidenced by haplotype association, and warrants further dense screening for variants within these haplotypes. PMID:23936182

  7. Epigenome-wide association study identifies TXNIP gene associated with type 2 diabetes mellitus and sustained hyperglycemia.

    Science.gov (United States)

    Soriano-Tárraga, Carolina; Jiménez-Conde, Jordi; Giralt-Steinhauer, Eva; Mola-Caminal, Marina; Vivanco-Hidalgo, Rosa M; Ois, Angel; Rodríguez-Campello, Ana; Cuadrado-Godia, Elisa; Sayols-Baixeras, Sergi; Elosua, Roberto; Roquer, Jaume

    2016-02-01

    Type 2 diabetes mellitus (DM) is an established risk factor for a wide range of vascular diseases, including ischemic stroke (IS). Glycated hemoglobin A1c (HbA1c), a marker for average blood glucose levels over the previous 12 weeks, is used as a measure of glycemic control and also as a diagnostic criterion for diabetes (HbA1c levels ≥ 6.5%). Epigenetic mechanisms, such as DNA methylation, may be associated with aging processes and with modulation of the risk of various pathologies, such as DM. Specifically, DNA methylation could be one of the mechanisms mediating the relation between DM and environmental exposures. Our goal was to identify new CpG methylation sites associated with DM. We performed a genome-wide methylation study in whole-blood DNA from an IS patient cohorts. Illumina HumanMethylation450 BeadChip array was used to measure DNA methylation in CpG sites. All statistical analyses were adjusted for sex, age, hyperlipidemia, body mass index (BMI), smoking habit and cell count. Findings were replicated in two independent cohorts, an IS cohort and a population-based cohort, using the same array. In the discovery phase (N = 355), we identified a CpG site, cg19693031 (located in the TXNIP gene) that was associated with DM (P = 1.17 × 10(-12)); this CpG was replicated in two independent cohorts (N = 167 and N = 645). Methylation of TXNIP was inversely and intensely associated with HbA1c levels (P = 7.3 × 10(-16)), specifically related to diabetic patients with poor control of glucose levels. We identified an association between the TXNIP gene and DM through epigenetic mechanisms, related to sustained hyperglycemia levels (HbA1c ≥ 7%).

  8. Population-specific haplotype association of the postsynaptic density gene DLG4 with schizophrenia, in family-based association studies.

    Directory of Open Access Journals (Sweden)

    Shabeesh Balan

    Full Text Available The post-synaptic density (PSD of glutamatergic synapses harbors a multitude of proteins critical for maintaining synaptic dynamics. Alteration of protein expression levels in this matrix is a marked phenomenon of neuropsychiatric disorders including schizophrenia, where cognitive functions are impaired. To investigate the genetic relationship of genes expressed in the PSD with schizophrenia, a family-based association analysis of genetic variants in PSD genes such as DLG4, DLG1, PICK1 and MDM2, was performed, using Japanese samples (124 pedigrees, n = 376 subjects. Results showed a significant association of the rs17203281 variant from the DLG4 gene, with preferential transmission of the C allele (p = 0.02, although significance disappeared after correction for multiple testing. Replication analysis of this variant, found no association in a Chinese schizophrenia cohort (293 pedigrees, n = 1163 subjects or in a Japanese case-control sample (n = 4182 subjects. The DLG4 expression levels between postmortem brain samples from schizophrenia patients showed no significant changes from controls. Interestingly, a five marker haplotype in DLG4, involving rs2242449, rs17203281, rs390200, rs222853 and rs222837, was enriched in a population specific manner, where the sequences A-C-C-C-A and G-C-C-C-A accumulated in Japanese (p = 0.0009 and Chinese (p = 0.0007 schizophrenia pedigree samples, respectively. However, this could not be replicated in case-control samples. None of the variants in other examined candidate genes showed any significant association in these samples. The current study highlights a putative role for DLG4 in schizophrenia pathogenesis, evidenced by haplotype association, and warrants further dense screening for variants within these haplotypes.

  9. Do intensive studies of a foreign language improve associative memory performance?

    Science.gov (United States)

    Mårtensson, Johan; Lövdén, Martin

    2011-01-01

    Formal education has been proposed to shape life-long cognitive development. Studies reporting that gains from cognitive training transfer to untrained tasks suggest direct effects of mental activity on cognitive processing efficiency. However, associative memory practice has not been known to produce transfer effects, which is odd considering that the key neural substrate of associative memory, the hippocampus, is known to be particularly plastic. We investigated whether extremely intensive studies of a foreign language, entailing demands on associative memory, cause improvements in associative memory performance. In a pretest-training-post-test design, military conscript interpreters and undergraduate students were measured on a battery of cognitive tasks. We found transfer from language studies to a face-name associative-memory task, but not to measures of working memory, strategy-sensitive episodic memory, or fluid intelligence. These findings provide initial evidence suggesting that associative memory performance can be improved in early adulthood, and that formal education can have such effects.

  10. A candidate gene association study of bone mineral density in an Iranian population.

    Directory of Open Access Journals (Sweden)

    Seyed Alireza Dastgheib

    2016-10-01

    Full Text Available The genetic epidemiology of variation in bone mineral density (BMD and osteoporosis is not well studied in Iranian populations and needs more research. We report a candidate gene association study of BMD variation in a healthy cross sectional study of 501 males and females sampled from the IMOS study Shiraz, Iran. We selected to study the association with 21 SNPs located in the 7 candidate genes LRP5, RANK, RANKL, OPG, P2RX7, VDR and ESR1. BMD was measured at the three sites L2-L4, neck of femur and total hip. Association between BMD and each SNP was assessed using multiple linear regression assuming an allele dose (additive effect on BMD (adjusted for age and sex. Statistically significant (at the unadjusted 5% level associations were seen with 7 SNPs in 5 of the candidate genes. Two SNPs showed statistically significant association with more than one BMD site. Significant association was seen between BMD at all three sites with the VDR SNP rs731246 (L2-L4 p=0.038; neck of femur p=0.001 and total hip p<0.001. The T allele was consistently associated with lower BMD than the C allele. Significant association was also seen for the P2RX7 SNP rs3751143 where the G allele was consistently associated with lower BMD than the T allele, (L2-L4 p=0.069; neck of femur p=0.024, total hip p=0.045.

  11. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer

    Science.gov (United States)

    Amundadottir, Laufey; Kraft, Peter; Stolzenberg-Solomon, Rachael Z.; Fuchs, Charles S.; Petersen, Gloria M.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gross, Myron; Helzlsouer, Kathy; Jacobs, Eric J.; LaCroix, Andrea; Zheng, Wei; Albanes, Demetrius; Bamlet, William; Berg, Christine D.; Berrino, Franco; Bingham, Sheila; Buring, Julie E.; Bracci, Paige M.; Canzian, Federico; Clavel-Chapelon, Françoise; Clipp, Sandra; Cotterchio, Michelle; de Andrade, Mariza; Duell, Eric J.; Fox, John W.; Gallinger, Steven; Gaziano, J. Michael; Giovannucci, Edward L.; Goggins, Michael; González, Carlos A.; Hallmans, Göran; Hankinson, Susan E.; Hassan, Manal; Holly, Elizabeth A.; Hunter, David J.; Hutchinson, Amy; Jackson, Rebecca; Jacobs, Kevin B.; Jenab, Mazda; Kaaks, Rudolf; Klein, Alison P.; Kooperberg, Charles; Kurtz, Robert C.; Li, Donghui; Lynch, Shannon M.; Mandelson, Margaret; McWilliams, Robert R.; Mendelsohn, Julie B.; Michaud, Dominique S.; Olson, Sara H.; Overvad, Kim; Patel, Alpa V.; Peeters, Petra H.M.; Rajkovic, Aleksandar; Riboli, Elio; Risch, Harvey A.; Shu, Xiao-Ou; Thomas, Gilles; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Van Den Eeden, Stephen K.; Virtamo, Jarmo; Wactawski-Wende, Jean; Wolpin, Brian M.; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Chanock, Stephen J.; Hartge, Patricia; Hoover, Robert N.

    2010-01-01

    We conducted a two-stage genome-wide association study (GWAS) of pancreatic cancer, a cancer with one of the poorest survival rates worldwide. Initially, we genotyped 558,542 single nucleotide polymorphisms in 1,896 incident cases and 1,939 controls drawn from twelve prospective cohorts plus one hospital-based case-control study. In a combined analysis adjusted for study, sex, ancestry and five principal components that included an additional 2,457 cases and 2,654 controls from eight case-control studies, we identified an association between a locus on 9q34 and pancreatic cancer marked by the single nucleotide polymorphism, rs505922 (combined P=5.37 × 10-8; multiplicative per-allele odds ratio (OR) 1.20; 95% CI 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B. PMID:19648918

  12. Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease

    Science.gov (United States)

    Paré, Peter D.; Rafaels, Nicholas; Sin, Don D.; Sandford, Andrew; Daley, Denise; Vergara, Candelaria; Huang, Lili; Elliott, W. Mark; Pascoe, Chris D.; Arsenault, Bryna A.; Postma, Dirkje S.; Boezen, H. Marike; Bossé, Yohan; van den Berge, Maarten; Hiemstra, Pieter S.; Cho, Michael H.; Litonjua, Augusto A.; Sparrow, David; Ober, Carole; Wise, Robert A.; Connett, John; Neptune, Enid R.; Beaty, Terri H.; Ruczinski, Ingo; Mathias, Rasika A.; Barnes, Kathleen C.

    2015-01-01

    Increased airway responsiveness is linked to lung function decline and mortality in subjects with chronic obstructive pulmonary disease (COPD); however, the genetic contribution to airway responsiveness remains largely unknown. A genome-wide association study (GWAS) was performed using the Illumina (San Diego, CA) Human660W-Quad BeadChip on European Americans with COPD from the Lung Health Study. Linear regression models with correlated meta-analyses, including data from baseline (n = 2,814) and Year 5 (n = 2,657), were used to test for common genetic variants associated with airway responsiveness. Genotypic imputation was performed using reference 1000 Genomes Project data. Expression quantitative trait loci (eQTL) analyses in lung tissues were assessed for the top 10 markers identified, and immunohistochemistry assays assessed protein staining for SGCD and MYH15. Four genes were identified within the top 10 associations with airway responsiveness. Markers on chromosome 9p21.2 flanked by LINGO2 met a predetermined threshold of genome-wide significance (P < 9.57 × 10−8). Markers on chromosomes 3q13.1 (flanked by MYH15), 5q33 (SGCD), and 6q21 (PDSS2) yielded suggestive evidence of association (9.57 × 10−8 < P ≤ 4.6 × 10−6). Gene expression studies in lung tissue showed single nucleotide polymorphisms on chromosomes 5 and 3 to act as eQTL for SGCD (P = 2.57 × 10−9) and MYH15 (P = 1.62 × 10−6), respectively. Immunohistochemistry confirmed localization of SGCD protein to airway smooth muscle and vessels and MYH15 to airway epithelium, vascular endothelium, and inflammatory cells. We identified novel loci associated with airway responsiveness in a GWAS among smokers with COPD. Risk alleles on chromosomes 5 and 3 acted as eQTLs for SGCD and MYH15 messenger RNA, and these proteins were expressed in lung cells relevant to the development of airway responsiveness. PMID:25514360

  13. Studies of metabolic phenotypic correlates of 15 obesity associated gene variants

    DEFF Research Database (Denmark)

    Sandholt, Camilla Helene; Vestmar, Marie Aare; Bille, Dorthe Sadowa;

    2011-01-01

    associate with type 2 diabetes and to elucidate potential underlying metabolic mechanisms. Methods: 15 gene variants in 14 loci including TMEM18 (rs7561317), SH2B1 (rs7498665), KCTD15 (rs29941), NEGR1 (rs2568958), ETV5 (rs7647305), BDNF (rs4923461, rs925946), SEC16B (rs10913469), FAIM2 (rs7138803), GNPDA2......Aims: Genome-wide association studies have identified novel BMI/obesity associated susceptibility loci. The purpose of this study is to determine associations with overweight, obesity, morbid obesity and/or general adiposity in a Danish population. Moreover, we want to investigate if these loci...

  14. Integrated analyses of gene expression and genetic association studies in a founder population

    Science.gov (United States)

    Cusanovich, Darren A.; Caliskan, Minal; Billstrand, Christine; Michelini, Katelyn; Chavarria, Claudia; De Leon, Sherryl; Mitrano, Amy; Lewellyn, Noah; Elias, Jack A.; Chupp, Geoffrey L.; Lang, Roberto M.; Shah, Sanjiv J.; Decara, Jeanne M.; Gilad, Yoav; Ober, Carole

    2016-01-01

    Genome-wide association studies (GWASs) have become a standard tool for dissecting genetic contributions to disease risk. However, these studies typically require extraordinarily large sample sizes to be adequately powered. Strategies that incorporate functional information alongside genetic associations have proved successful in increasing GWAS power. Following this paradigm, we present the results of 20 different genetic association studies for quantitative traits related to complex diseases, conducted in the Hutterites of South Dakota. To boost the power of these association studies, we collected RNA-sequencing data from lymphoblastoid cell lines for 431 Hutterite individuals. We then used Sherlock, a tool that integrates GWAS and expression quantitative trait locus (eQTL) data, to identify weak GWAS signals that are also supported by eQTL data. Using this approach, we found novel associations with quantitative phenotypes related to cardiovascular disease, including carotid intima-media thickness, left atrial volume index, monocyte count and serum YKL-40 levels. PMID:26931462

  15. Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer.

    Science.gov (United States)

    Rafnar, Thorunn; Sulem, Patrick; Thorleifsson, Gudmar; Vermeulen, Sita H; Helgason, Hannes; Saemundsdottir, Jona; Gudjonsson, Sigurjon A; Sigurdsson, Asgeir; Stacey, Simon N; Gudmundsson, Julius; Johannsdottir, Hrefna; Alexiusdottir, Kristin; Petursdottir, Vigdis; Nikulasson, Sigfus; Geirsson, Gudmundur; Jonsson, Thorvaldur; Aben, Katja K H; Grotenhuis, Anne J; Verhaegh, Gerald W; Dudek, Aleksandra M; Witjes, J Alfred; van der Heijden, Antoine G; Vrieling, Alina; Galesloot, Tessel E; De Juan, Ana; Panadero, Angeles; Rivera, Fernando; Hurst, Carolyn; Bishop, D Timothy; Sak, Sei C; Choudhury, Ananya; Teo, Mark T W; Arici, Cecilia; Carta, Angela; Toninelli, Elena; de Verdier, Petra; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; van der Keur, Kirstin A; Lurkin, Irene; Goossens, Mieke; Kellen, Eliane; Guarrera, Simonetta; Russo, Alessia; Critelli, Rossana; Sacerdote, Carlotta; Vineis, Paolo; Krucker, Clémentine; Zeegers, Maurice P; Gerullis, Holger; Ovsiannikov, Daniel; Volkert, Frank; Hengstler, Jan G; Selinski, Silvia; Magnusson, Olafur T; Masson, Gisli; Kong, Augustine; Gudbjartsson, Daniel; Lindblom, Annika; Zwarthoff, Ellen; Porru, Stefano; Golka, Klaus; Buntinx, Frank; Matullo, Giuseppe; Kumar, Rajiv; Mayordomo, José I; Steineck, D Gunnar; Kiltie, Anne E; Jonsson, Eirikur; Radvanyi, François; Knowles, Margaret A; Thorsteinsdottir, Unnur; Kiemeney, Lambertus A; Stefansson, Kari

    2014-10-15

    Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC cases and 10 456 controls. We tested a dataset containing 34.2 million variants, generated by imputation based on whole-genome sequencing of 2230 Icelanders. Several correlated variants at 20p12, represented by rs62185668, show genome-wide significant association with UBC after combining discovery and replication results (OR = 1.19, P = 1.5 × 10(-11) for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately 300 kb upstream from the JAG1 gene, an important component of the Notch signaling pathways that may be oncogenic or tumor suppressive in several forms of cancer. Our results add to the growing number of UBC risk variants discovered through GWAS.

  16. Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association retrospective study

    Science.gov (United States)

    Lazarovici, Julien; Dartigues, Peggy; Brice, Pauline; Obéric, Lucie; Gaillard, Isabelle; Hunault-Berger, Mathilde; Broussais-Guillaumot, Florence; Gyan, Emmanuel; Bologna, Serge; Nicolas-Virelizier, Emmanuelle; Touati, Mohamed; Casasnovas, Olivier; Delarue, Richard; Orsini-Piocelle, Frédérique; Stamatoullas, Aspasia; Gabarre, Jean; Fornecker, Luc-Matthieu; Gastinne, Thomas; Peyrade, Fréderic; Roland, Virginie; Bachy, Emmanuel; André, Marc; Mounier, Nicolas; Fermé, Christophe

    2015-01-01

    Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study Association centers. Progression-free survival (PFS) and overall survival (OS) were analyzed, and the competing risks formulation of a Cox regression model was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320–1.512], P=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234–0.643], P=0.0002). Early treatment appears more beneficial compared to watchful waiting in terms of progression-free survival, but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients, are the main options to treat adult patients with a curative intent. PMID:26430172

  17. Genome-wide association study identifies novel loci associated with serum level of vitamin B12 in Chinese men.

    Science.gov (United States)

    Lin, Xiaoling; Lu, Daru; Gao, Yong; Tao, Sha; Yang, Xiaobo; Feng, Junjie; Tan, Aihua; Zhang, Haiying; Hu, Yanling; Qin, Xue; Kim, Seong-Tae; Peng, Tao; Li, Li; Mo, Linjian; Zhang, Shijun; Trent, Jeffrey M; Mo, Zengnan; Zheng, S Lilly; Xu, Jianfeng; Sun, Jielin

    2012-06-01

    Vitamin B12 (VitB12 or cobalamin) is an essential cofactor in several metabolic pathways. Clinically, VitB12 deficiency is associated with pernicious anemia, neurodegenerative disorder, cardiovascular disease and gastrointestinal disease. Although previous genome-wide association studies (GWAS) identified several genes, including FUT2, CUBN, TCN1 and MUT, that may influence VitB12 levels in European populations, common genetic determinants of VitB12 remain largely unknown, especially in Asian populations. Here we performed a GWAS in 1999 healthy Chinese men and replicated the top findings in an independent Chinese sample with 1496 subjects. We identified four novel genomic loci that were significantly associated with serum level of VitB12 at a genome-wide significance level of 5.00 × 10(-8). These four loci were MS4A3 (11q12.1; rs2298585; P= 2.64 × 10(-15)), CLYBL (13q32; rs41281112; P= 9.23 × 10(-10)), FUT6 (19p13.3; rs3760776; P= 3.68 × 10(-13)) and 5q32 region (rs10515552; P= 3.94 × 10(-8)). In addition, we also confirmed the association with the serum level of VitB12 for the previously reported FUT2 gene and identified one novel non-synonymous single-nucleotide polymorphism in FUT2 gene in this Chinese population (19q13.33; rs1047781; P= 3.62 × 10(-36)). The new loci identified offer new insights into the biochemical pathways involved in determining the serum level of VitB12 and provide opportunities to better delineate the role of VitB12 in health and disease.

  18. The Association of Obesity with Walking Independent of Knee Pain: The Multicenter Osteoarthritis Study

    OpenAIRE

    White, Daniel K.; Tuhina Neogi; Yuqing Zhang; David Felson; Michael LaValley; Jingbo Niu; Michael Nevitt; Cora E Lewis; James Torner; K. Douglas Gross

    2012-01-01

    Practice guidelines recommend addressing obesity for people with knee OA, however, the association of obesity with walking independent of pain is not known. We investigated this association within the Multicenter Osteoarthritis Study, a cohort of older adults who have or are at high risk of knee OA. Subjects wore a StepWatch to record steps taken over 7 days. We measured knee pain from a visual analogue scale and obesity by BMI. We examined the association of obesity with walking using lin...

  19. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

    OpenAIRE

    Chambers, John C.; Zhang, Weihua; Sehmi, Joban; Li, Xinzhong; Wass, Mark N; Harst, Pim; Holm, Hilma; Sanna, Serena; Kavousi, Maryam; Baumeister, Sebastian E.; Coin, Lachlan J.; Deng, Guohong; Gieger, Christian; Heard-Costa, Nancy L.; Hottenga, Jouke-Jan

    2011-01-01

    Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, includi...

  20. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

    OpenAIRE

    Chambers, John C.; Zhang, Weihua; Sehmi, Joban; Li, Xinzhong; Wass, Mark N; Harst, Pim; Holm, Hilma; Sanna, Serena; Kavousi, Maryam; Baumeister, Sebastian E.; Coin, Lachlan J.; Deng, Guohong; Gieger, Christian; Heard-Costa, Nancy L.; Hottenga, Jouke-Jan

    2011-01-01

    Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10−8 to P = 10−190). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including g...

  1. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.

    OpenAIRE

    Chambers, John C.; Zhang, Weihua; Sehmi, Joban; Li, Xinzhong; Wass, Mark N; Harst, Pim; Holm, Hilma; Sanna, Serena; Kavousi, Maryam; Baumeister, Sebastian E.; Coin, Lachlan J.; Abecasis, Goncalo R.; Ahmadi, Kourosh R; Boomsma, Dorret I; Caulfield, Mark

    2011-01-01

    Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, includi...

  2. Genome wide association study identifies KCNMA1 contributing to human obesity

    DEFF Research Database (Denmark)

    Jiao, Hong; Arner, Peter; Hoffstedt, Johan;

    2011-01-01

    Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the total genetic variation expected to be present in the population....... Thus many genetic variants controlling obesity remain to be identified. The aim of this study was to use GWA followed by multiple stepwise validations to identify additional genes associated with obesity....

  3. Genome-wide pathway association studies of multiple correlated quantitative phenotypes using principle component analyses.

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    Full Text Available Genome-wide pathway association studies provide novel insight into the biological mechanism underlying complex diseases. Current pathway association studies primarily focus on single important disease phenotype, which is sometimes insufficient to characterize the clinical manifestations of complex diseases. We present a multi-phenotypes pathway association study(MPPAS approach using principle component analysis(PCA. In our approach, PCA is first applied to multiple correlated quantitative phenotypes for extracting a set of orthogonal phenotypic components. The extracted phenotypic components are then used for pathway association analysis instead of original quantitative phenotypes. Four statistics were proposed for PCA-based MPPAS in this study. Simulations using the real data from the HapMap project were conducted to evaluate the power and type I error rates of PCA-based MPPAS under various scenarios considering sample sizes, additive and interactive genetic effects. A real genome-wide association study data set of bone mineral density (BMD at hip and spine were also analyzed by PCA-based MPPAS. Simulation studies illustrated the performance of PCA-based MPPAS for identifying the causal pathways underlying complex diseases. Genome-wide MPPAS of BMD detected associations between BMD and KENNY_CTNNB1_TARGETS_UP as well as LONGEVITYPATHWAY pathways in this study. We aim to provide a applicable MPPAS approach, which may help to gain deep understanding the potential biological mechanism of association results for complex diseases.

  4. Association of periodontal and cardiovascular diseases: South-Asian studies 2001–2012

    OpenAIRE

    Syed Akhtar Hussain Bokhari; Ayyaz Ali Khan; Wai Keung Leung; Gohar Wajid

    2015-01-01

    Large proportion of Asian populations have moderate to severe periodontal disease and a substantial number are anticipated to be at high risk of cardiovascular diseases (CVD). This study reviews epidemiology and association of periodontal and CVDs from the South-Asian region. Observational studies and clinical trials published during January 2001–December 2012 focusing association between periodontitis and CVDs in South-Asian countries were retrieved from various databases and studied. Curren...

  5. Association between occupational physical activity and myocardial infarction : a prospective cohort study

    OpenAIRE

    Johnsen, Anna M; Alfredsson, Lars; Knutsson, Anders; Westerholm, Peter J M; Fransson, Eleonor I.

    2016-01-01

    Objective: Recommendations regarding physical activity typically include both leisure time and occupational physical activity. However, the results from previous studies on occupational physical activity and the association with myocardial infarction have been inconsistent. The aim of this study was to investigate if occupational physical activity is associated with the risk of myocardial infarction. Design: Prospective cohort study. Participants: Data from the Swedish Work, Lipids and Fibrin...

  6. The Potentiation of Associative Memory by Emotions: An Event-Related FMRI Study

    Directory of Open Access Journals (Sweden)

    David Luck

    2014-01-01

    Full Text Available Establishing associations between pieces of information is related to the medial temporal lobe (MTL. However, it remains unclear how emotions affect memory for associations and, consequently, MTL activity. Thus, this event-related fMRI study attempted to identify neural correlates of the influence of positive and negative emotions on associative memory. Twenty-five participants were instructed to memorize 90 pairs of standardized pictures during a scanned encoding phase. Each pair was composed of a scene and an unrelated object. Trials were neutral, positive, or negative as a function of the emotional valence of the scene. At the behavioral level, participants exhibited better memory retrieval for both emotional conditions relative to neutral trials. Within the right MTL, a functional dissociation was observed, with entorhinal activation elicited by emotional associations, posterior parahippocampal activation elicited by neutral associations, and hippocampal activation elicited by both emotional and neutral associations. In addition, emotional associations induced greater activation than neutral trials in the right amygdala. This fMRI study shows that emotions are associated with the performance improvement of associative memory, by enhancing activity in the right amygdala and the right entorhinal cortex. It also provides evidence for a rostrocaudal specialization within the MTL regarding the emotional valence of associations.

  7. Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk.

    Science.gov (United States)

    Lindström, Sara; Thompson, Deborah J; Paterson, Andrew D; Li, Jingmei; Gierach, Gretchen L; Scott, Christopher; Stone, Jennifer; Douglas, Julie A; dos-Santos-Silva, Isabel; Fernandez-Navarro, Pablo; Verghase, Jajini; Smith, Paula; Brown, Judith; Luben, Robert; Wareham, Nicholas J; Loos, Ruth J F; Heit, John A; Pankratz, V Shane; Norman, Aaron; Goode, Ellen L; Cunningham, Julie M; deAndrade, Mariza; Vierkant, Robert A; Czene, Kamila; Fasching, Peter A; Baglietto, Laura; Southey, Melissa C; Giles, Graham G; Shah, Kaanan P; Chan, Heang-Ping; Helvie, Mark A; Beck, Andrew H; Knoblauch, Nicholas W; Hazra, Aditi; Hunter, David J; Kraft, Peter; Pollan, Marina; Figueroa, Jonine D; Couch, Fergus J; Hopper, John L; Hall, Per; Easton, Douglas F; Boyd, Norman F; Vachon, Celine M; Tamimi, Rulla M

    2014-10-24

    Mammographic density reflects the amount of stromal and epithelial tissues in relation to adipose tissue in the breast and is a strong risk factor for breast cancer. Here we report the results from meta-analysis of genome-wide association studies (GWAS) of three mammographic density phenotypes: dense area, non-dense area and percent density in up to 7,916 women in stage 1 and an additional 10,379 women in stage 2. We identify genome-wide significant (P<5 × 10(-8)) loci for dense area (AREG, ESR1, ZNF365, LSP1/TNNT3, IGF1, TMEM184B and SGSM3/MKL1), non-dense area (8p11.23) and percent density (PRDM6, 8p11.23 and TMEM184B). Four of these regions are known breast cancer susceptibility loci, and four additional regions were found to be associated with breast cancer (P<0.05) in a large meta-analysis. These results provide further evidence of a shared genetic basis between mammographic density and breast cancer and illustrate the power of studying intermediate quantitative phenotypes to identify putative disease-susceptibility loci.

  8. A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22

    NARCIS (Netherlands)

    J.M. Kerkhof (Hanneke); R.J. Lories (Rik); I. Meulenbelt (Ingrid); I. Jonsdottir (Ingileif); A.M. Valdes (Ana Maria); P.P. Arp (Pascal); T. Ingvarsson (Torvaldur); M. Jhamai (Mila); H. Jonsson (Helgi); L. Stolk (Lisette); G. Thorleifsson (Gudmar); G. Zhai (Guangju); F. Zhang (Feng); Y. Zhu (Yicheng); R. van der Breggen (Ruud); M. Doherty (Michael); D. Felson; A. Gonzalez (Antonio); B.V. Halldorsson (Bjarni); D.J. Hart (Deborah); V.B. Hauksson (Valdimar); A. Hofman (Albert); J.P.A. Ioannidis (John); M. Kloppenburg (Margreet); N.E. Lane (Nancy); J. Loughlin (John); F.P. Luyten (Frank); M.C. Nevitt (Michael); N. Parimi (Neeta); H.A.P. Pols (Huib); F. Rivadeneira Ramirez (Fernando); E. Slagboom (Eline); U. Styrkarsdottir (Unnur); A. Tsezou (Aspasia); T. van de Putte (Tom); J. Zmuda (Joseph); T.D. Spector (Timothy); J-A. Zwart (John-Anker); A.G. Uitterlinden (André); J.B.J. van Meurs (Joyce); A.J. Carr (Andrew Jonathan)

    2010-01-01

    markdownabstract__Objective__ To identify novel genes involved in osteoarthritis (OA), by means of a genome-wide association study. Methods. We tested 500,510 single-nucleotide polymorphisms (SNPs) in 1,341 Dutch Caucasian OA cases and 3,496 Dutch Caucasian controls. SNPs associated with at least 2

  9. Genome-wide association studies in economics and entrepreneurship research: Promises and limitations

    NARCIS (Netherlands)

    Ph.D. Koellinger (Philipp); M.J.H.M. van der Loos (Matthijs); P.J.F. Groenen (Patrick); A.R. Thurik (Roy); F. Rivadeneira Ramirez (Fernando); F.J.A. van Rooij (Frank); A.G. Uitterlinden (André); A. Hofman (Albert)

    2010-01-01

    textabstractThe recently developed genome-wide association study (GWAS) design enables the identification of genes specifically associated with economic outcomes such as occupational and other choices. This is a promising new approach for economics research which we aim to apply to the choice for en

  10. Genome-wide association studies in economics and entrepreneurship research: promises and limitations

    NARCIS (Netherlands)

    Ph.D. Koellinger (Philipp); M.J.H.M. van der Loos (Matthijs); P.J.F. Groenen (Patrick); A.R. Thurik (Roy); F. Rivadeneira Ramirez (Fernando); F.J.A. van Rooij (Frank)

    2010-01-01

    textabstractThe recently developed genome-wide association study (GWAS) design enables the identification of genes specifically associated with economic outcomes such as occupational and other choices. This is a promising new approach for economics research which we aim to apply to the choice for en

  11. Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index

    DEFF Research Database (Denmark)

    Minster, Ryan L; Sanders, Jason L; Singh, Jatinder;

    2015-01-01

    BACKGROUND: The Healthy Aging Index (HAI) is a tool for measuring the extent of health and disease across multiple systems. METHODS: We conducted a genome-wide association study and a genome-wide linkage analysis to map quantitative trait loci associated with the HAI and a modified HAI weighted...

  12. An association study of suicide and candidate genes in the serotonergic system

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette N; Flint, Tracey J; Foldager, Leslie;

    2013-01-01

    Introduction: Strong evidence demonstrates a genetic susceptibility to suicidal behaviour and a relationship between suicide and mental disorders. The aim of this study was to test for association between suicide and five selected genetic variants, which had shown association with suicide in other...

  13. Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma

    NARCIS (Netherlands)

    Luykx, J. J.; Bakker, S. C.; Visser, W. F.; Verhoeven-Duif, N.; Buizer-Voskamp, J. E.; Den Heijer, J. M.; Boks, M. P. M.; Sul, J. H.; Eskin, E.; Ori, A. P.; Cantor, R. M.; Vorstman, J.; Strengman, E.; DeYoung, J.; Kappen, T. H.; Pariama, E.; van Dongen, E. P. A.; Borgdorff, P.; Bruins, P.; de Koning, T. J.; Kahn, R. S.; Ophoff, R. A.

    2015-01-01

    The N-methyl-D-aspartate receptor (NMDAR) coagonists glycine, D-serine and L-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and t

  14. Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma

    NARCIS (Netherlands)

    Luykx, J. J.; Bakker, S. C.; Visser, W. F.; Verhoeven-Duif, N.; Buizer-Voskamp, J. E.; den Heijer, J. M.; Boks, M. P M; Sul, J. H.; Eskin, E.; Ori, A. P.; Cantor, R. M.; Vorstman, J.; Strengman, E.; DeYoung, J.; Kappen, T. H.; Pariama, E.; van Dongen, E. P A; Borgdorff, P.; Bruins, P.; de Koning, T. J.; Kahn, R. S.; Ophoff, R. A.

    2015-01-01

    The N-methyl-d-aspartate receptor (NMDAR) coagonists glycine, d-serine and l-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and t

  15. Genome-wide association and functional studies identify a role for IGFBP3 in hip osteoarthritis

    NARCIS (Netherlands)

    D.S. Evans (Daniel); F. Cailotto (Frederic); N. Parimi (Neeta); A.M. Valdes (Ana Maria); M.C. Castaño Betancourt (Martha); Y. Liu (Youfang); R.C. Kaplan (Robert); M. Bidlingmaier (Martin); R.S. Vasan (Ramachandran Srini); A. Teumer (Alexander); G.J. Tranah (Gregory); M.C. Nevitt (Michael); S. Cummings; E.S. Orwoll (Eric); E. Barrett-Connor (Elizabeth); J.B. Renner (Jordan); J.M. Jordan (Joanne); M. Doherty (Michael); S. Doherty (Sally); A.G. Uitterlinden (André); J.B.J. van Meurs (Joyce); T.D. Spector (Timothy); R.J. Lories (Rik); N.E. Lane

    2014-01-01

    textabstractObjectives To identify genetic associations with hip osteoarthritis (HOA), we performed a meta-analysis of genome-wide association studies (GWAS) of HOA. Methods The GWAS meta-analysis included approximately 2.5 million imputed HapMap single nucleotide polymorphisms (SNPs). HOA cases and

  16. Unique associations among emotion dysregulation dimensions and aggressive tendencies : A multi-site study.

    NARCIS (Netherlands)

    Velotti, Patrizia; Casselman, Robert B.; Garofalo, C.; McKenzie, Melissa D.

    2017-01-01

    While problems with emotion regulation (ER) have long been associated with internalizing symptoms, only recently has an ER framework been applied to the study of aggression. Therefore, little is known about the unique and independent associations between specific domains of the ER construct and diff

  17. School, Neighborhood, and Family Factors Are Associated with Children's Bullying Involvement: A Nationally Representative Longitudinal Study

    Science.gov (United States)

    Bowes, Lucy; Arseneault, Louise; Maughan, Barbara; Taylor, Alan; Caspi, Ashalom; Moffitt, Terrie E.

    2009-01-01

    School size and problems with neighbors is associated with a greater risk of being a bullying victim while family factors such as maltreatment and domestic violence are associated with involvement in bullying. The findings are based on the Environmental Risk Longitudinal Twin Study that involves 2,232 children.

  18. Software engineering the mixed model for genome-wide association studies on large samples

    Science.gov (United States)

    Mixed models improve the ability to detect phenotype-genotype associations in the presence of population stratification and multiple levels of relatedness in genome-wide association studies (GWAS), but for large data sets the resource consumption becomes impractical. At the same time, the sample siz...

  19. Coffee consumption is inversely associated with cognitive decline in elderly European men: the FINE Study

    NARCIS (Netherlands)

    Gelder, van B.M.; Buijsse, B.; Tijhuis, M.J.; Kalmijn, S.; Giampaoli, S.; Nissinen, A.; Kromhout, D.

    2007-01-01

    Objective: To investigate whether coffee consumption is associated with 10-year cognitive decline in elderly men, as results of previous studies obtained hitherto have been controversial and prospective information on this association has been lacking. Design, subjects and setting: Six hundred and s

  20. Genome-wide association study of insect bite hypersensitivity in Dutch Shetland pony mares

    NARCIS (Netherlands)

    Schurink, A.; Ducro, B.J.; Bastiaansen, J.W.M.; Frankena, K.; Arendonk, van J.A.M.

    2013-01-01

    Insect bite hypersensitivity (IBH) is the most common allergic disease present in horses worldwide. It has been shown that IBH is under genetic control, but the knowledge of associated genes is limited. We conducted a genome-wide association study to identify and quantify genomic regions contributin

  1. Genome-Wide Association Study of Intelligence: Additive Effects of Novel Brain Expressed Genes

    Science.gov (United States)

    Loo, Sandra K.; Shtir, Corina; Doyle, Alysa E.; Mick, Eric; McGough, James J.; McCracken, James; Biederman, Joseph; Smalley, Susan L.; Cantor, Rita M.; Faraone, Stephen V.; Nelson, Stanley F.

    2012-01-01

    Objective: The purpose of the present study was to identify common genetic variants that are associated with human intelligence or general cognitive ability. Method: We performed a genome-wide association analysis with a dense set of 1 million single-nucleotide polymorphisms (SNPs) and quantitative intelligence scores within an ancestrally…

  2. Individual and Environmental Characteristics Associated with Cognitive Development in Down Syndrome: A Longitudinal Study

    Science.gov (United States)

    Couzens, Donna; Haynes, Michele; Cuskelly, Monica

    2012-01-01

    Background: Associations among cognitive development and intrapersonal and environmental characteristics were investigated for 89 longitudinal study participants with Down syndrome to understand developmental patterns associated with cognitive strengths and weaknesses. Materials and Methods: Subtest scores of the Stanford-Binet IV collected…

  3. The association between adolescents’ health and disparities in school career: a longitudinal cohort study.

    NARCIS (Netherlands)

    Uiters, E.; Maurits, E.; Droomers, M.; Zwaanswijk, M.; Verheij, R.A.; Lucht, F. van der

    2014-01-01

    Background: Literature suggests that children’s educational achievement is associated with their health status and the socioeconomic position of their parents. Few studies have investigated this association in adolescence, while this is an important period affecting future life trajectories. Our stu

  4. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    DEFF Research Database (Denmark)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ...

  5. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayes, Monica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; Blackwood, Douglas H. R.; Bloss, Cinnamon S.; Boehnke, Michael; Boomsma, Dorret I.; Breuer, Rene; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G.; Buitelaar, Jan K.; Bunney, William E.; Buxbaum, Joseph D.; Byerley, William F.; Byrne, Enda M.; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M.; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Mattheisen, Manuel; Cloninger, C. Robert; Collier, David A.; Cook, Edwin H.; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H.; Craig, David W.; Craig, Ian W.; Crosbie, Jennifer; Cuccaro, Michael L.; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J.; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J.; Doyle, Alysa E.; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P.; Edenberg, Howard J.; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E.; Ferrier, I. Nicol; Flicldnger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B.; Freitag, Christine M.; Friedl, Marion; Frisen, Louise; Gailagher, Louise; Gejman, Pablo V.; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Gill, Michael; Gordon, Scott D.; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grice, Dorothy E.; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L.; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P.; Hamshere, Marian L.; Hansen, Thomas F.; Hartmann, Annette M.; Hautzinger, Martin; Heath, Andrew C.; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hipolito, Maria; Hoefels, Susanne; Holsboer, Florian; Hoogendijk, Witte J.; Hottenga, Jouke-Jan; Hultman, Christina M.; Hus, Vanessa; Ingason, Andres; Ising, Marcus; Jamain, Stephane; Jones, Edward G.; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kaehler, Anna K.; Kahn, Rene S.; Kandaswamy, Radhika; Keller, Matthew C.; Kennedy, James L.; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K.; Klauck, Sabine M.; Klei, Lambertus; Knowles, James A.; Kohli, Martin A.; Koller, Daniel L.; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landen, Mikael; Laengstroem, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Ledbetter, David H.; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F.; Lewis, Cathryn M.; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A.; Lin, Dan-Yu; Linszen, Don H.; Liu, Chunyu; Lohoff, Falk W.; Loo, Sandra K.; Lord, Catherine; Lowe, Jennifer K.; Lucae, Susanne; MacIntyre, Donald J.; Madden, Pamela A. F.; Maestrini, Elena; Magnusson, Patrik K. E.; Mahon, Pamela B.; Maier, Wolfgang; Malhotra, Anil K.; Mane, Shrikant M.; Martin, Christa L.; Martin, Nicholas G.; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A.; McGhee, Kevin A.; McGough, James J.; McGrath, Patrick J.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McMahon, William M.; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E.; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M.; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P.; Montgomery, Grant W.; Moran, Jennifer L.; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W.; Morrow, Eric M.; Moskvina, Valentina; Muglia, Pierandrea; Muehleisen, Thomas W.; Muir, Walter J.; Mueller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M.; Myin-Germeys, Inez; Neale, Michael C.; Nelson, Stan F.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A.; Noethen, Markus M.; Nwulia, Evaristus A.; Nyholt, Dale R.; Oades, Robert D.; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A.; Osby, Urban; Owen, Michael J.; Palotie, Aarno; Parr, Jeremy R.; Paterson, Andrew D.; Pato, Carlos N.; Pato, Michele T.; Penninx, Brenda W.; Pergadia, Michele L.; Pericak-Vance, Margaret A.; Pickard, Benjamin S.; Pimm, Jonathan; Piven, Joseph; Potash, James B.; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J.; Quinn, Emma M.; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B.; Raychaudhuri, Soumya; Rehnstroem, Karola; Reif, Andreas; Ribases, Marta; Rice, John P.; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R.; Sanders, Stephan J.; Santangelo, Susan L.; Sergeant, Joseph A.; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F.; Scheftner, William A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Schork, Nicholas J.; Schulze, Thomas G.; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J.; Shi, Jianxin; Shilling, Paul D.; Shyn, Stanley I.; Silverman, Jeremy M.; Slager, Susan L.; Smalley, Susan L.; Smit, Johannes H.; Smith, Erin N.; Sonuga-Barke, Edmund J. S.; Cair, David St.; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S.; Strohmaier, Jana; Stroup, T. Scott; Sutdiffe, James S.; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C.; Todorov, Alexandre A.; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; Van den Oord, Edwin J. C. G.; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M.; Vieland, Veronica J.; Vincent, John B.; Visscher, Peter M.; Walsh, Christopher A.; Wassink, Thomas H.; Watson, Stanley J.; Weissman, Myrna M.; Werge, Thomas; Wienker, Thomas F.; Wijsman, Ellen M.; Willemsen, Gonneke; Williams, Nigel; Willsey, A. Jeremy; Witt, Stephanie H.; Xu, Wei; Young, Allan H.; Yu, Timothy W.; Zammit, Stanley; Zandi, Peter P.; Zhang, Peng; Zitman, Frans G.; Zoellner, Sebastian; Devlin, Bernie; Kelsoe, John R.; Sklar, Pamela; Daly, Mark J.; O'Donovan, Michael C.; Craddock, Nicholas; Kendler, Kenneth S.; Weiss, Lauren A.; Wray, Naomi R.; Zhao, Zhaoming; Geschwind, Daniel H.; Sullivan, Patrick F.; Smoller, Jordan W.; Holmans, Peter A.; Breen, Gerome

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ove

  6. Genome-wide association study of kidney function decline in individuals of European descent

    NARCIS (Netherlands)

    Gorski, Mathias; Tin, Adrienne; Garnaas, Maija; McMahon, Gearoid M.; Chu, Audrey Y.; Tayo, Bamidele O.; Pattaro, Cristian; Teumer, Alexander; Chasman, Daniel I.; Chalmers, John; Hamet, Pavel; Tremblay, Johanne; Woodward, Marc; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur; Harris, Tamara B.; Launer, Lenore J.; Smith, Albert V.; Mitchell, Braxton D.; O'Connell, Jeffrey R.; Shuldiner, Alan R.; Coresh, Josef; Li, Man; Freudenberger, Paul; Hofer, Edith; Schmidt, Helena; Schmidt, Reinhold; Holliday, Elizabeth G.; Mitchell, Paul; Wang, Jie Jin; de Boer, Ian H.; Li, Guo; Siscovick, David S.; Kutalik, Zoltan; Corre, Tanguy; Vollenweider, Peter; Waeber, Gerard; Gupta, Jayanta; Kanetsky, Peter A.; Hwang, Shih-Jen; Olden, Matthias; Yang, Qiong; de Andrade, Mariza; Atkinson, Elizabeth J.; Kardia, Sharon L. R.; Turner, Stephen T.; Stafford, Jeanette M.; Ding, Jingzhong; Liu, Yongmei; Barlassina, Cristina; Cusi, Daniele; Salvi, Erika; Staessen, Jan A.; Ridker, Paul M.; Grallert, Harald; Meisinger, Christa; Mueller-Nurasyid, Martina; Kraemer, Bernhard K.; Kramer, Holly; Rosas, Sylvia E.; Nolte, Ilja M.; Penninx, Brenda W.; Snieder, Harold; Del Greco, M. Fabiola; Franke, Andre; Noethlings, Ute; Lieb, Wolfgang; Bakker, Stephan J. L.; Gansevoort, Ron T.; van der Harst, Pim; Dehghan, Abbas; Franco, Oscar H.; Hofman, Albert; Rivadeneira, Fernando; Sedaghat, Sanaz; Uitterlinden, Andre G.; Coassin, Stefan; Haun, Margot; Kollerits, Barbara; Kronenberg, Florian; Paulweber, Bernhard; Aumann, Nicole; Endlich, Karlhans; Pietzner, Mike; Voelker, Uwe; Rettig, Rainer; Chouraki, Vincent; Helmer, Catherine; Lambert, Jean-Charles; Metzger, Marie; Stengel, Benedicte; Lehtimaki, Terho; Lyytikainen, Leo-Pekka; Raitakari, Olli; Johnson, Andrew; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Goessling, Wolfram; Kottgen, Anna; Kao, W. H. Linda; Fox, Caroline S.; Boeger, Carsten A.

    2015-01-01

    Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohor

  7. Genome-wide association study of kidney function decline in individuals of European descent

    NARCIS (Netherlands)

    M. Gorski (Mathias); A. Tin (Adrienne); M. Garnaas (Maija); G.M. McMahon (Gearoid M.); A.Y. Chu (Audrey Y.); B. Tayo (Bamidele); C. Pattaro (Cristian); A. Teumer (Alexander); D.I. Chasman (Daniel); J. Chalmers (John); P. Hamet (Pavel); J. Tremblay (Johanne); M. Woodward (Mark); T. Aspelund (Thor); G. Eiriksdottir (Gudny); V. Gudnason (Vilmundur); T.B. Harris (Tamara); L.J. Launer (Lenore); A.V. Smith (Albert V.); B.D. Mitchell (Braxton); J.R. O´Connell; A.R. Shuldiner (Alan); J. Coresh (Josef); M. Li (Man); P. Freudenberger (Paul); E. Hofer (Edith); R. Schmidt (Reinhold); R. Schmidt (Reinhold); E.G. Holliday (Elizabeth); P. Mitchell (Paul); J.J. Wang (Jie Jin); I.H. de Boer (Ian); G. Li (Guo); D.S. Siscovick (David); Z. Kutalik; T. Corre (Tanguy); P. Vollenweider (Peter); G. Waeber (Gérard); J. Gupta (Jayanta); P.P. Kanetsky (Peter P.); S.J. Hwang; M. Olden (Matthias); Q. Yang (Qiong Fang); M. de Andrade (Mariza); E.J. Atkinson (Elizabeth J.); S.L.R. Kardia (Sharon); S.T. Turner (Stephen); J.M. Stafford (Jeanette M.); J. Ding (Jinhui); Y. Liu; C. Barlassina (Christina); D. Cusi (Daniele); E. Salvi (Erika); J.A. Staessen (Jan); P.M. Ridker (Paul); H. Grallert (Harald); C. Meisinger (Christa); M. Müller-Nurasyid (Martina); B.K. Krämer (Bernhard K.); H. Kramer (Holly); S.E. Rosas (Sylvia E.); I.M. Nolte (Ilja M.); B.W.J.H. Penninx (Brenda); H. Snieder (Harold); M. Fabiola Del Greco; A. Franke (Andre); U. Nöthlings (Ute); W. Lieb (Wolfgang); S.J.L. Bakker (Stephan J L); R.T. Gansevoort (Ron); P. Van Der Harst (Pim); A. Dehghan (Abbas); O.H. Franco (Oscar); A. Hofman (Albert); F. Rivadeneira Ramirez (Fernando); S. Sedaghat (Sanaz); A.G. Uitterlinden (André); S. Coassin (Stefan); M. Haun (Margot); B. Kollerits (Barbara); F. Kronenberg (Florian); B. Paulweber (Bernhard); N. Aumann (Nicole); K. Endlich (Karlhans); M. Pietzner (Mike); U. Völker (Uwe); R. Rettig (Rainer); V. Chouraki (Vincent); C. Helmer (Catherine); J.-C. Lambert (Jean-Charles); M. Metzger (Marie); B. Stengel (Benedicte); T. Lehtimäki (Terho); L.-P. Lyytikäinen (Leo-Pekka); O. Raitakari (Olli); A.D. Johnson (Andrew); A. Parsa (Afshin); M. Bochud (Murielle); I.M. Heid (Iris); W. Goessling (Wolfram); A. K̈ttgen (Anna); W.H.L. Kao (Wen); C.S. Fox (Caroline S.); C.A. Böger (Carsten)

    2015-01-01

    textabstractGenome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially f

  8. Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia

    Science.gov (United States)

    Mansour, Hader A; Talkowski, Michael E; Wood, Joel; Chowdari, Kodavali V; McClain, Lora; Prasad, Konasale; Montrose, Debra; Fagiolini, Andrea; Friedman, Edward S; Allen, Michael H; Bowden, Charles L; Calabrese, Joseph; El-Mallakh, Rif S; Escamilla, Michael; Faraone, Stephen V; Fossey, Mark D; Gyulai, Laszlo; Loftis, Jennifer M; Hauser, Peter; Ketter, Terence A; Marangell, Lauren B; Miklowitz, David J; Nierenberg, Andrew A; Patel, Jayendra; Sachs, Gary S; Sklar, Pamela; Smoller, Jordan W; Laird, Nan; Keshavan, Matcheri; Thase, Michael E; Axelson, David; Birmaher, Boris; Lewis, David; Monk, Tim; Frank, Ellen; Kupfer, David J; Devlin, Bernie; Nimgaonkar, Vishwajit L

    2012-01-01

    Objective Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. Methods We assayed 276 publicly available ‘tag’ single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). Results Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. Conclusions Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results. PMID:19839995

  9. Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

    DEFF Research Database (Denmark)

    Song, H.; Koessler, T.; Ahmed, S.

    2008-01-01

    test of association was a comparison of genotype frequencies between cases and controls, and a test for trend stratified by study where appropriate. Genotype-specific odds ratios (OR) were estimated by logistic regression. SNP rs2660753 (chromosome 3p12) showed evidence of association with ovarian...... cancer [per minor allele OR, 1.19; 95% confidence interval (95% CI), 1.04-1.37; P(trend) = 0.012]. This association was stronger for the serous histologic subtype (OR, 1.29; 95% CI, 1.09-1.53; P = 0.003). SNP rs7931342 (chromosome 11q13) showed some evidence of association with breast cancer (per minor...

  10. Association of Hepatitis C Virus With Insulin Resistance: Evidences From Animal Studies and Clinical Studie

    Directory of Open Access Journals (Sweden)

    Sadaf Badar

    2012-01-01

    Full Text Available Context: HCV infection is strongly associated with development of insulin resistance and type-2 diabetes, however molecular mechanism of these associations is not known. The aim of this review was to conduct a comprehensive literature search to understand the nature of the association between hepatitis C virus (HCV infection and insulin resistance (IR. We also explored the role of HCV core protein and NS5a in modulating the course of the insulin-signaling pathway.Evidence Acquisitions: We searched Directory of Open Access Journals (DOAJ Google Scholar, Pubmed (NLM, LISTA (EBSCO, Web of Science (TS and PakMediNet.Results: Emerging evidence suggests an association between HCV infection and carotid/coronary vascular disease. IR appears to be a dominant underlying cause of accelerated atherosclerosis in patients with chronic hepatitis C (CHC. HCV can induce IR directly through the stimulation of SOCS3 and PPA2, and both of these molecules have been shown to inhibit interferon-α signaling. Improvement of insulin sensitivity may increase the response rate to antiviral treatment and prevent IR complications, including vascular diseases. The results of several clinical trials that have used insulin sensitizers (metformin and PPAR-γ agonists have been inconclusive.Conclusions: Beside the association between HCV and IR, the published data also have showed the possible association of HCV core and NS5A protein with IR.

  11. SIRT1 gene, schizophrenia and bipolar disorder in the Japanese population: an association study.

    Science.gov (United States)

    Kishi, T; Fukuo, Y; Kitajima, T; Okochi, T; Yamanouchi, Y; Kinoshita, Y; Kawashima, K; Inada, T; Kunugi, H; Kato, T; Yoshikawa, T; Ujike, H; Ozaki, N; Iwata, N

    2011-04-01

    Several lines of evidence suggest that alterations in circadian rhythms might be associated with the pathophysiology of psychiatric disorders such as schizophrenia and bipolar disorder (BP). A recent study reported that SIRT1 is a molecule that plays an important role in the circadian clock system. Therefore, to evaluate the association among the SIRT1 gene, schizophrenia and BP, we conducted a case-control study of Japanese population samples (1158 schizophrenia patients, 1008 BP patients and 2127 controls) with four tagging SNPs (rs12778366, rs2273773, rs4746720 and rs10997875) in the SIRT1 gene. Marker-trait association analysis was used to evaluate the allele and the genotype association with the χ(2) test, and haplotype association analysis was evaluated with a likelihood ratio test. We showed an association between rs4746720 in the SIRT1 gene and schizophrenia in the allele and the genotype analysis. However, the significance of these associations did not survive after Bonferroni's correction for multiple testing. On the other hand, the SIRT1 gene was associated with Japanese schizophrenia in a haplotype-wise analysis (global P(all markers) = 4.89 × 10(-15)). Also, four tagging SNPs in the SIRT1 gene were not associated with BP. In conclusion, the SIRT1 gene may play an important role in the pathophysiology of schizophrenia in the Japanese population.

  12. Genome-wide population-based association study of extremely overweight young adults--the GOYA study.

    Directory of Open Access Journals (Sweden)

    Lavinia Paternoster

    Full Text Available Thirty-two common variants associated with body mass index (BMI have been identified in genome-wide association studies, explaining ∼1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight individuals. We aimed to identify new loci associated with BMI and to ascertain whether using an extreme sampling design would identify the variants known to be associated with BMI in general populations.From two large Danish cohorts we selected all extremely overweight young men and women (n = 2,633, and equal numbers of population-based controls (n = 2,740, drawn randomly from the same populations as the extremes, representing ∼212,000 individuals. We followed up novel (at the time of the study association signals (p<0.001 from the discovery cohort in a genome-wide study of 5,846 Europeans, before attempting to replicate the most strongly associated 28 SNPs in an independent sample of Danish individuals (n = 20,917 and a population-based cohort of 15-year-old British adolescents (n = 2,418. Our discovery analysis identified SNPs at three loci known to be associated with BMI with genome-wide confidence (P<5×10(-8; FTO, MC4R and FAIM2. We also found strong evidence of association at the known TMEM18, GNPDA2, SEC16B, TFAP2B, SH2B1 and KCTD15 loci (p<0.001, and nominal association (p<0.05 at a further 8 loci known to be associated with BMI. However, meta-analyses of our discovery and replication cohorts identified no novel associations.Our results indicate that the detectable genetic variation associated with extreme overweight is very similar to that previously found for general BMI. This suggests that population-based study designs with enriched sampling of individuals with the extreme phenotype may be an efficient method for identifying common variants that influence quantitative traits and a valid alternative to genotyping all

  13. A small-sample multivariate kernel machine test for microbiome association studies.

    Science.gov (United States)

    Zhan, Xiang; Tong, Xingwei; Zhao, Ni; Maity, Arnab; Wu, Michael C; Chen, Jun

    2017-04-01

    High-throughput sequencing technologies have enabled large-scale studies of the role of the human microbiome in health conditions and diseases. Microbial community level association test, as a critical step to establish the connection between overall microbiome composition and an outcome of interest, has now been routinely performed in many studies. However, current microbiome association tests all focus on a single outcome. It has become increasingly common for a microbiome study to collect multiple, possibly related, outcomes to maximize the power of discovery. As these outcomes may share common mechanisms, jointly analyzing these outcomes can amplify the association signal and improve statistical power to detect potential associations. We propose the multivariate microbiome regression-based kernel association test (MMiRKAT) for testing association between multiple continuous outcomes and overall microbiome composition, where the kernel used in MMiRKAT is based on Bray-Curtis or UniFrac distance. MMiRKAT directly regresses all outcomes on the microbiome profiles via a semiparametric kernel machine regression framework, which allows for covariate adjustment and evaluates the association via a variance-component score test. Because most of the current microbiome studies have small sample sizes, a novel small-sample correction procedure is implemented in MMiRKAT to correct for the conservativeness of the association test when the sample size is small or moderate. The proposed method is assessed via simulation studies and an application to a real data set examining the association between host gene expression and mucosal microbiome composition. We demonstrate that MMiRKAT is more powerful than large sample based multivariate kernel association test, while controlling the type I error. A free implementation of MMiRKAT in R language is available at http://research.fhcrc.org/wu/en.html.

  14. Power assessment for genetic association study of human longevity using offspring of long-lived subjects.

    Science.gov (United States)

    Tan, Qihua; Zhao, Jing Hua; Li, Shuxia; Kruse, Torben A; Christensen, Kaare

    2010-07-01

    Recently, an indirect genetic association approach that compares genotype frequencies in offspring of long-lived subjects and offspring from random families has been introduced to study gene-longevity associations. Although the indirect genetic association has certain advantages over the direct association approach that compares genotype frequency between centenarians and young controls, the power has been of concern. This paper reports a power study performed on the indirect approach using computer simulation. We perform our simulation study by introducing the current Danish population life table and the proportional hazard model for generating individual lifespan. Family genotype data is generated using a genetic linkage program for given SNP allele frequency. Power is estimated by setting the type I error rate at 0.05 and by calculating the Armitage's chi-squared test statistic for 200 replicate samples for each setting of the specified allele risk and frequency parameters under different modes of inheritance and for different sample sizes. The indirect genetic association analysis is a valid approach for studying gene-longevity association, but the sample size requirement is about 3-4 time larger than the direct approach. It also has low power in detecting non-additive effect genes. Indirect genetic association using offspring from families with both parents as nonagenarians is nearly as powerful as using offspring from families with one centenarian parent. In conclusion, the indirect design can be a good choice for studying longevity in comparison with other alternatives, when relatively large sample size is available.

  15. Non-replication study of a genome-wide association study for hypertension and blood pressure in African Americans

    Directory of Open Access Journals (Sweden)

    Kidambi Srividya

    2012-04-01

    Full Text Available Abstract Background A recent genome wide association study in 1017 African Americans identified several single nucleotide polymorphisms that reached genome-wide significance for systolic blood pressure. We attempted to replicate these findings in an independent sample of 2474 unrelated African Americans in the Milwaukee metropolitan area; 53% were women and 47% were hypertensives. Methods We evaluated sixteen top associated SNPs from the above genome wide association study for hypertension as a binary trait or blood pressure as a continuous trait. In addition, we evaluated eight single nucleotide polymorphisms located in two genes (STK-39 and CDH-13 found to be associated with systolic and diastolic blood pressures by other genome wide association studies in European and Amish populations. TaqMan MGB-based chemistry with fluorescent probes was used for genotyping. We had an adequate sample size (80% power to detect an effect size of 1.2-2.0 for all the single nucleotide polymorphisms for hypertension as a binary trait, and 1% variance in blood pressure as a continuous trait. Quantitative trait analyses were performed both by excluding and also by including subjects on anti-hypertensive therapy (after adjustments were made for anti-hypertensive medications. Results For all 24 SNPs, no statistically significant differences were noted in the minor allele frequencies between cases and controls. One SNP (rs2146204 showed borderline association (p = 0.006 with hypertension status using recessive model and systolic blood pressure (p = 0.02, but was not significant after adjusting for multiple comparisons. In quantitative trait analyses, among normotensives only, rs12748299 was associated with SBP (p = 0.002. In addition, several nominally significant associations were noted with SBP and DBP among normotensives but none were statistically significant. Conclusions This study highlights the importance of replication to confirm the validity of genome wide

  16. The GOALS Study: The association between physical activity, cognitive performance, and academic achievement in adolescents

    NARCIS (Netherlands)

    Van Dijk, Martin; De Groot, Renate; Kirschner, Paul A.

    2011-01-01

    Van Dijk, M. L., De Groot, R. H. M., & Kirschner, P. A. (2011, 26 April). The GOALS Study: The association between physical activity, cognitive performance, and academic achievement in adolescents. Presentation at the Learning & Cognition meeting, Heerlen, The Netherlands.

  17. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies

    DEFF Research Database (Denmark)

    Bulik-Sullivan, Brendan K.; Loh, Po-Ru; Finucane, Hilary K.

    2015-01-01

    Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from...

  18. Born to Lead? A Twin Design and Genetic Association Study of Leadership Role Occupancy.

    Science.gov (United States)

    De Neve, Jan-Emmanuel; Mikhaylov, Slava; Dawes, Christopher T; Christakis, Nicholas A; Fowler, James H

    2013-02-01

    We address leadership emergence and the possibility that there is a partially innate predisposition to occupy a leadership role. Employing twin design methods on data from the National Longitudinal Study of Adolescent Health, we estimate the heritability of leadership role occupancy at 24%. Twin studies do not point to specific genes or neurological processes that might be involved. We therefore also conduct association analysis on the available genetic markers. The results show that leadership role occupancy is associated with rs4950, a single nucleotide polymorphism (SNP) residing on a neuronal acetylcholine receptor gene (CHRNB3). We replicate this family-based genetic association result on an independent sample in the Framingham Heart Study. This is the first study to identify a specific genotype associated with the tendency to occupy a leadership position. The results suggest that what determines whether an individual occupies a leadership position is the complex product of genetic and environmental influences; with a particular role for rs4950.

  19. Genome-Wide Association Study of Suicide Attempts in Mood Disorder Patients

    NARCIS (Netherlands)

    Perlis, Roy H.; Huang, Jie; Purcell, Shaun; Fava, Maurizio; Rush, A. John; Sullivan, Patrick F.; Hamilton, Steven P.; McMahon, Francis J.; Schulze, Thomas; Potash, James B.; Zandi, Peter P.; Willour, Virginia L.; Penninx, Brenda W.; Boomsma, Dorret I.; Vogelzangs, Nicole; Middeldorp, Christel M.; Rietschel, Marcella; Noethen, Markus; Cichon, Sven; Gurling, Hugh; Bass, Nick; McQuillin, Andrew; Hamshere, Marian; Craddock, Nick; Sklar, Pamela; Smoller, Jordan W.

    2010-01-01

    Objective: Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. Method: The authors analyzed data on lifetime

  20. A twin and molecular genetics study of sleep paralysis and associated factors.

    Science.gov (United States)

    Denis, Dan; French, Christopher C; Rowe, Richard; Zavos, Helena M S; Nolan, Patrick M; Parsons, Michael J; Gregory, Alice M

    2015-08-01

    Sleep paralysis is a relatively common but under-researched phenomenon. In this paper we examine prevalence in a UK sample and associations with candidate risk factors. This is the first study to investigate the heritability of sleep paralysis in a twin sample and to explore genetic associations between sleep paralysis and a number of circadian expressed single nucleotide polymorphisms. Analyses are based on data from the Genesis1219 twin/sibling study, a community sample of twins/siblings from England and Wales. In total, data from 862 participants aged 22-32 years (34% male) were used in the study. This sample consisted of monozygotic and dizygotic twins and siblings. It was found that self-reports of general sleep quality, anxiety symptoms and exposure to threatening events were all associated independently with sleep paralysis. There was moderate genetic influence on sleep paralysis (53%). Polymorphisms in the PER2 gene were associated with sleep paralysis in additive and dominant models of inheritance-although significance was not reached once a Bonferroni correction was applied. It is concluded that factors associated with disrupted sleep cycles appear to be associated with sleep paralysis. In this sample of young adults, sleep paralysis was moderately heritable. Future work should examine specific polymorphisms associated with differences in circadian rhythms and sleep homeostasis further in association with sleep paralysis.

  1. Autism and genetics: Clinical approach and association study with two markers of HRAS gene

    Energy Technology Data Exchange (ETDEWEB)

    Herault, J.; Petit, E.; Cherpi, C. [Laboratoire de Biochimie Medicale, Tours (France)] [and others

    1995-08-14

    Twin studies and familial aggregation studies indicate that genetic factors could play a role in infantile autism. In an earlier study, we identified a possible positive association between autism and a c-Harvey-ras (HRAS) oncogene marker at the 3{prime} end of the coding region. In an attempt to confirm this finding, we studied a larger population, well-characterized clinically and genetically. We report a positive association between autism and two HRAS markers, the 3{prime} marker used in the initial study and an additional marker in exon 1. 46 refs., 1 fig., 2 tabs.

  2. Power assessment for genetic association study of human longevity using offspring of long-lived subjects

    DEFF Research Database (Denmark)

    Tan, Qihua; Zhao, Jing Hua; Li, Shuxia;

    2010-01-01

    Recently, an indirect genetic association approach that compares genotype frequencies in offspring of long-lived subjects and offspring from random families has been introduced to study gene-longevity associations. Although the indirect genetic association has certain advantages over the direct...... and the proportional hazard model for generating individual lifespan. Family genotype data is generated using a genetic linkage program for given SNP allele frequency. Power is estimated by setting the type I error rate at 0.05 and by calculating the Armitage's chi-squared test statistic for 200 replicate samples...... for each setting of the specified allele risk and frequency parameters under different modes of inheritance and for different sample sizes. The indirect genetic association analysis is a valid approach for studying gene-longevity association, but the sample size requirement is about 3-4 time larger than...

  3. A twin and molecular genetics study of sleep paralysis and associated factors.

    OpenAIRE

    Denis, Dan; French, Christopher C.; Rowe, Richard; Zavos, Helena M S; Nolan, Patrick M.; Parsons, Michael J.; Gregory, Alice M

    2015-01-01

    Sleep paralysis is a relatively common but under-researched phenomenon. In this paper we examine prevalence in a UK sample and associations with candidate risk factors. This is the first study to investigate the heritability of sleep paralysis in a twin sample and to explore genetic associations between sleep paralysis and a number of circadian expressed single nucleotide polymorphisms. Analyses are based on data from the Genesis1219 twin/sibling study, a community sample of twins/siblings fr...

  4. Principal components analysis corrects for stratification in genome-wide association studies.

    Science.gov (United States)

    Price, Alkes L; Patterson, Nick J; Plenge, Robert M; Weinblatt, Michael E; Shadick, Nancy A; Reich, David

    2006-08-01

    Population stratification--allele frequency differences between cases and controls due to systematic ancestry differences-can cause spurious associations in disease studies. We describe a method that enables explicit detection and correction of population stratification on a genome-wide scale. Our method uses principal components analysis to explicitly model ancestry differences between cases and controls. The resulting correction is specific to a candidate marker's variation in frequency across ancestral populations, minimizing spurious associations while maximizing power to detect true associations. Our simple, efficient approach can easily be applied to disease studies with hundreds of thousands of markers.

  5. An information-gain approach to detecting three-way epistatic interactions in genetic association studies

    DEFF Research Database (Denmark)

    Hu, Ting; Chen, Yuanzhu; Kiralis, Jeff W;

    2013-01-01

    Background Epistasis has been historically used to describe the phenomenon that the effect of a given gene on a phenotype can be dependent on one or more other genes, and is an essential element for understanding the association between genetic and phenotypic variations. Quantifying epistasis....... In the tuberculosis data, we found a statistically significant pure three-way epistatic interaction effect that was stronger than any lower-order associations. Conclusion Our study provides a methodological basis for detecting and characterizing high-order gene-gene interactions in genetic association studies....

  6. Imputation-based analysis of association studies: candidate regions and quantitative traits.

    Directory of Open Access Journals (Sweden)

    Bertrand Servin

    2007-07-01

    Full Text Available We introduce a new framework for the analysis of association studies, designed to allow untyped variants to be more effectively and directly tested for association with a phenotype. The idea is to combine knowledge on patterns of correlation among SNPs (e.g., from the International HapMap project or resequencing data in a candidate region of interest with genotype data at tag SNPs collected on a phenotyped study sample, to estimate ("impute" unmeasured genotypes, and then assess association between the phenotype and these estimated genotypes. Compared with standard single-SNP tests, this approach results in increased power to detect association, even in cases in which the causal variant is typed, with the greatest gain occurring when multiple causal variants are present. It also provides more interpretable explanations for observed associations, including assessing, for each SNP, the strength of the evidence that it (rather than another correlated SNP is causal. Although we focus on association studies with quantitative phenotype and a relatively restricted region (e.g., a candidate gene, the framework is applicable and computationally practical for whole genome association studies. Methods described here are implemented in a software package, Bim-Bam, available from the Stephens Lab website http://stephenslab.uchicago.edu/software.html.

  7. Associations between Dietary Patterns and Impaired Fasting Glucose in Chinese Men: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Meilin Zhang

    2015-09-01

    Full Text Available Few studies have examined the association between Asian dietary pattern and prediabetes, in particular, the Chinese diet. We conducted a cross-sectional study to identify dietary patterns associated with impaired fasting glucose (IFG which considered a state of prediabetes in Chinese men. The study included 1495 Chinese men aged 20 to 75 years. Information about diet was obtained using an 81-item food frequency questionnaire (FFQ, and 21 predefined food groups were considered in a factor analysis. Three dietary patterns were generated by factor analysis: (1 a vegetables-fruits pattern; (2 an animal offal-dessert pattern; and (3 a white rice-red meat pattern. The multivariate-adjusted odds ratio (OR of IFG for the highest tertile of the animal offal-dessert pattern in comparison with the lowest tertile was 3.15 (95% confidence intervals (CI: 1.87–5.30. The vegetables-fruits dietary pattern was negatively associated with the risk of IFG, but a significant association was observed only in the third tertile. There was no significant association between IFG and the white rice-red meat pattern. Our findings indicated that the vegetables-fruits dietary pattern was inversely associated with IFG, whereas the animal offal-dessert pattern was associated with an increased risk of IFG in Chinese men. Further prospective studies are needed to elucidate the diet-prediabetes relationships.

  8. Associations between Dietary Patterns and Impaired Fasting Glucose in Chinese Men: A Cross-Sectional Study.

    Science.gov (United States)

    Zhang, Meilin; Zhu, Yufeng; Li, Ping; Chang, Hong; Wang, Xuan; Liu, Weiqiao; Zhang, Yuwen; Huang, Guowei

    2015-09-21

    Few studies have examined the association between Asian dietary pattern and prediabetes, in particular, the Chinese diet. We conducted a cross-sectional study to identify dietary patterns associated with impaired fasting glucose (IFG) which considered a state of prediabetes in Chinese men. The study included 1495 Chinese men aged 20 to 75 years. Information about diet was obtained using an 81-item food frequency questionnaire (FFQ), and 21 predefined food groups were considered in a factor analysis. Three dietary patterns were generated by factor analysis: (1) a vegetables-fruits pattern; (2) an animal offal-dessert pattern; and (3) a white rice-red meat pattern. The multivariate-adjusted odds ratio (OR) of IFG for the highest tertile of the animal offal-dessert pattern in comparison with the lowest tertile was 3.15 (95% confidence intervals (CI): 1.87-5.30). The vegetables-fruits dietary pattern was negatively associated with the risk of IFG, but a significant association was observed only in the third tertile. There was no significant association between IFG and the white rice-red meat pattern. Our findings indicated that the vegetables-fruits dietary pattern was inversely associated with IFG, whereas the animal offal-dessert pattern was associated with an increased risk of IFG in Chinese men. Further prospective studies are needed to elucidate the diet-prediabetes relationships.

  9. Comparison of population-based association study methods correcting for population stratification.

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    Full Text Available Population stratification can cause spurious associations in population-based association studies. Several statistical methods have been proposed to reduce the impact of population stratification on population-based association studies. We simulated a set of stratified populations based on the real haplotype data from the HapMap ENCODE project, and compared the relative power, type I error rates, accuracy and positive prediction value of four prevailing population-based association study methods: traditional case-control tests, structured association (SA, genomic control (GC and principal components analysis (PCA under various population stratification levels. Additionally, we evaluated the effects of sample sizes and frequencies of disease susceptible allele on the performance of the four analytical methods in the presence of population stratification. We found that the performance of PCA was very stable under various scenarios. Our comparison results suggest that SA and PCA have comparable performance, if sufficient ancestral informative markers are used in SA analysis. GC appeared to be strongly conservative in significantly stratified populations. It may be better to apply GC in the stratified populations with low stratification level. Our study intends to provide a practical guideline for researchers to select proper study methods and make appropriate inference of the results in population-based association studies.

  10. Associations between Dopamine and Serotonin Genes and Job Satisfaction: Preliminary Evidence from the Add Health Study

    Science.gov (United States)

    Song, Zhaoli; Li, Wendong; Arvey, Richard D.

    2011-01-01

    Previous behavioral genetic studies have found that job satisfaction is partially heritable. We went a step further to examine particular genetic markers that may be associated with job satisfaction. Using an oversample from the National Adolescent Longitudinal Study (Add Health Study), we found 2 genetic markers, dopamine receptor gene DRD4 VNTR…

  11. Association Between the Mediterranean Diet and Cancer Risk: A Review of Observational Studies

    NARCIS (Netherlands)

    Verberne, L.D.M.; Bach-Faig, A.; Buckland, G.; Serra-Majem, L.

    2010-01-01

    The aim of this article was to summarize the evidence concerning the association between Mediterranean dietary pattern and cancer risk in observational epidemiological studies. All the studies that met the following criteria were reviewed: human cohort and case-control studies that examined the effe

  12. Dietary patterns associated with male lung cancer risk in the Netherlands Cohort Study

    NARCIS (Netherlands)

    Balder, H.F.; Goldbohm, R.A.; Brandt, P.A. van den

    2005-01-01

    The objective of this article was to study the association between dietary patterns and lung cancer incidence in the Netherlands Cohort Study on Diet and Cancer. The baseline measurement of this prospective case cohort study that was completed by 58,279 men in 1986 included a self-administered quest

  13. Testing for direct genetic effects using a screening step in family-based association studies

    Directory of Open Access Journals (Sweden)

    Sharon M Lutz

    2013-11-01

    Full Text Available In genome wide association studies (GWAS, families based studies tend to have less power to detect genetic associations than population based studies, such as case-control studies. This can be an issue when testing if genes in a family based GWAS have a direct effect on the phenotype of interest or if the genes act indirectly through a secondary phenotype. When multiple SNPs are tested for a direct effect in the family based study, a screening step can be used to minimize the burden of multiple comparisons in the causal analysis. We propose a 2-stage screening step that can be incorporated into the family based association test (FBAT approach similar to the conditional mean model approach in the VanSteen-algorithm [1]. Simulations demonstrate that the type 1 error is preserved and this method is advantageous when multiple markers are tested. This method is illustrated by an application to the Framingham Heart Study.

  14. Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies

    Science.gov (United States)

    Grallert, Harald; Dupuis, Josée; Bis, Joshua C.; Dehghan, Abbas; Barbalic, Maja; Baumert, Jens; Lu, Chen; Smith, Nicholas L.; Uitterlinden, André G.; Roberts, Robert; Khuseyinova, Natalie; Schnabel, Renate B.; Rice, Kenneth M.; Rivadeneira, Fernando; Hoogeveen, Ron C.; Fontes, João Daniel; Meisinger, Christa; Keaney, John F.; Lemaitre, Rozenn; Aulchenko, Yurii S.; Vasan, Ramachandran S.; Ellis, Stephen; Hazen, Stanley L.; van Duijn, Cornelia M.; Nelson, Jeanenne J.; März, Winfried; Schunkert, Heribert; McPherson, Ruth M.; Stirnadel-Farrant, Heide A.; Psaty, Bruce M.; Gieger, Christian; Siscovick, David; Hofman, Albert; Illig, Thomas; Cushman, Mary; Yamamoto, Jennifer F.; Rotter, Jerome I.; Larson, Martin G.; Stewart, Alexandre F.R.; Boerwinkle, Eric; Witteman, Jacqueline C.M.; Tracy, Russell P.; Koenig, Wolfgang; Benjamin, Emelia J.; Ballantyne, Christie M.

    2012-01-01

    Aims Lipoprotein-associated phospholipase A2 (Lp-PLA2) generates proinflammatory and proatherogenic compounds in the arterial vascular wall and is a potential therapeutic target in coronary heart disease (CHD). We searched for genetic loci related to Lp-PLA2 mass or activity by a genome-wide association study as part of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Methods and results In meta-analyses of findings from five population-based studies, comprising 13 664 subjects, variants at two loci (PLA2G7, CETP) were associated with Lp-PLA2 mass. The strongest signal was at rs1805017 in PLA2G7 [P = 2.4 × 10−23, log Lp-PLA2 difference per allele (beta): 0.043]. Variants at six loci were associated with Lp-PLA2 activity (PLA2G7, APOC1, CELSR2, LDL, ZNF259, SCARB1), among which the strongest signals were at rs4420638, near the APOE–APOC1–APOC4–APOC2 cluster [P = 4.9 × 10−30; log Lp-PLA2 difference per allele (beta): −0.054]. There were no significant gene–environment interactions between these eight polymorphisms associated with Lp-PLA2 mass or activity and age, sex, body mass index, or smoking status. Four of the polymorphisms (in APOC1, CELSR2, SCARB1, ZNF259), but not PLA2G7, were significantly associated with CHD in a second study. Conclusion Levels of Lp-PLA2 mass and activity were associated with PLA2G7, the gene coding for this protein. Lipoprotein-associated phospholipase A2 activity was also strongly associated with genetic variants related to low-density lipoprotein cholesterol levels. PMID:22003152

  15. P-value based analysis for shared controls design in genome-wide association studies.

    Science.gov (United States)

    Zaykin, Dmitri V; Kozbur, Damian O

    2010-11-01

    An appealing genome-wide association study design compares one large control group against several disease samples. A pioneering study by the Wellcome Trust Case Control Consortium that employed such a design has identified multiple susceptibility regions, many of which have been independently replicated. While reusing a control sample provides effective utilization of data, it also creates correlation between association statistics across diseases. An observation of a large association statistic for one of the diseases may greatly increase chances of observing a spuriously large association for a different disease. Accounting for the correlation is also particularly important when screening for SNPs that might be involved in a set of diseases with overlapping etiology. We describe methods that correct association statistics for dependency due to shared controls, and we describe ways to obtain a measure of overall evidence and to combine association signals across multiple diseases. The methods we describe require no access to individual subject data, instead, they efficiently utilize information contained in P-values for association reported for individual diseases. P-value based combined tests for association are flexible and essentially as powerful as the approach based on aggregating the individual subject data.

  16. Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes

    Science.gov (United States)

    Matsuo, Hirotaka; Yamamoto, Ken; Nakaoka, Hirofumi; Nakayama, Akiyoshi; Sakiyama, Masayuki; Chiba, Toshinori; Takahashi, Atsushi; Nakamura, Takahiro; Nakashima, Hiroshi; Takada, Yuzo; Danjoh, Inaho; Shimizu, Seiko; Abe, Junko; Kawamura, Yusuke; Terashige, Sho; Ogata, Hiraku; Tatsukawa, Seishiro; Yin, Guang; Okada, Rieko; Morita, Emi; Naito, Mariko; Tokumasu, Atsumi; Onoue, Hiroyuki; Iwaya, Keiichi; Ito, Toshimitsu; Takada, Tappei; Inoue, Katsuhisa; Kato, Yukio; Nakamura, Yukio; Sakurai, Yutaka; Suzuki, Hiroshi; Kanai, Yoshikatsu; Hosoya, Tatsuo; Hamajima, Nobuyuki; Inoue, Ituro; Kubo, Michiaki; Ichida, Kimiyoshi; Ooyama, Hiroshi; Shimizu, Toru; Shinomiya, Nariyoshi

    2016-01-01

    Objective Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. Methods A GWAS was conducted with 945 patients with clinically defined gout and 1213 controls in a Japanese male population, followed by replication study of 1048 clinically defined cases and 1334 controls. Results Five gout susceptibility loci were identified at the genome-wide significance level (p<5.0×10−8), which contained well-known urate transporter genes (ABCG2 and SLC2A9) and additional genes: rs1260326 (p=1.9×10−12; OR=1.36) of GCKR (a gene for glucose and lipid metabolism), rs2188380 (p=1.6×10−23; OR=1.75) of MYL2-CUX2 (genes associated with cholesterol and diabetes mellitus) and rs4073582 (p=6.4×10−9; OR=1.66) of CNIH-2 (a gene for regulation of glutamate signalling). The latter two are identified as novel gout loci. Furthermore, among the identified single-nucleotide polymorphisms (SNPs), we demonstrated that the SNPs of ABCG2 and SLC2A9 were differentially associated with types of gout and clinical parameters underlying specific subtypes (renal underexcretion type and renal overload type). The effect of the risk allele of each SNP on clinical parameters showed significant linear relationships with the ratio of the case–control ORs for two distinct types of gout (r=0.96 [p=4.8×10−4] for urate clearance and r=0.96 [p=5.0×10−4] for urinary urate excretion). Conclusions Our findings provide clues to better understand the pathogenesis of gout and will be useful for development of companion diagnostics. PMID:25646370

  17. Hyperhomocysteinemia is independently associated with albuminuria in the population-based CoLaus study

    Directory of Open Access Journals (Sweden)

    Paccaud Fred

    2011-09-01

    Full Text Available Abstract Background Increased serum levels of homocysteine and uric acid have each been associated with cardiovascular risk. We analyzed whether homocysteine and uric acid were associated with glomerular filtration rate (GFR and albuminuria independently of each other. We also investigated the association of MTHFR polymorphisms related to homocysteine with albuminuria to get further insight into causality. Methods This was a cross-sectional population-based study in Caucasians (n = 5913. Hyperhomocysteinemia was defined as total serum homocysteine ≥ 15 μmol/L. Albuminuria was defined as urinary albumin-to-creatinine ratio > 30 mg/g. Results Uric acid was associated positively with homocysteine (r = 0.246 in men and r = 0.287 in women, P P for trend P P = 0.004 were significantly associated with albuminuria, independently of hypertension and type 2 diabetes. The 2-fold higher risk of albuminuria associated with hyperhomocysteinemia was similar to the risk associated with hypertension or diabetes. MTHFR alleles related to higher homocysteine were associated with increased risk of albuminuria. Conclusions In the general adult population, elevated serum homocysteine and uric acid were associated with albuminuria independently of each other and of renal function.

  18. Association Between Antioxidant Intake/Status and Obesity: a Systematic Review of Observational Studies.

    Science.gov (United States)

    Hosseini, Banafshe; Saedisomeolia, Ahmad; Allman-Farinelli, Margaret

    2017-02-01

    The global prevalence of obesity has doubled in recent decades. Compelling evidences indicated that obesity was associated with lower concentrations of specific antioxidants which may play a role in the development of obesity-related diseases such as cardiovascular disease. The present review aimed to synthesize the evidence from studies on the association between obesity and antioxidant micronutrients in a systematic manner. Data bases including MEDLINE, Science Direct, and Cochrane were searched from inception to October 2015. Thirty-one articles were reviewed using the MOOSE checklist. Lower concentrations of antioxidants have been reported in obese individuals among age groups worldwide. Circulatory levels of carotenoids, vitamins E and C, as well as zinc, magnesium, and selenium were inversely correlated with obesity and body fat mass. However, studies demonstrated inconsistencies in findings. Lower status of carotenoids, vitamins E and C, zinc, magnesium, and selenium appears to be associated with adiposity. Intervention studies may be needed to establish the causality of these associations.

  19. Genome wide association studies for body conformation traits in the Chinese Holstein cattle population

    DEFF Research Database (Denmark)

    Wu, Xiaoping; Fang, Ming; Liu, Lin;

    2013-01-01

    Background: Genome-wide association study (GWAS) is a powerful tool for revealing the genetic basis of quantitative traits. However, studies using GWAS for conformation traits of cattle is comparatively less. This study aims to use GWAS to find the candidates genes for body conformation traits.......Results: The Illumina BovineSNP50 BeadChip was used to identify single nucleotide polymorphisms (SNPs) that are associated with body conformation traits. A least absolute shrinkage and selection operator (LASSO) was applied to detect multiple SNPs simultaneously for 29 body conformation traits with 1,314 Chinese...... Holstein cattle and 52,166 SNPs. Totally, 59 genome-wide significant SNPs associated with 26 conformation traits were detected by genome-wide association analysis; five SNPs were within previously reported QTL regions (Animal Quantitative Trait Loci (QTL) database) and 11 were very close to the reported...

  20. More heritability probably captured by psoriasis genome-wide association study in Han Chinese.

    Science.gov (United States)

    Jiang, Long; Liu, Lu; Cheng, Yuyan; Lin, Yan; Shen, Changbing; Zhu, Caihong; Yang, Sen; Yin, Xianyong; Zhang, Xuejun

    2015-11-15

    Missing heritability is a common problem in genome-wide association studies in complex diseases/traits. To quantify the unbiased heritability estimate, we applied the phenotype correlation-genotype correlation regression in psoriasis genome-wide association data in Han Chinese which comprises 1139 cases and 1132 controls. We estimated that 45.7% heritability of psoriasis in Han Chinese were captured by common variants (s.e.=12.5%), which reinforced that the majority of psoriasis heritability can be covered by common variants in genome-wide association data (68.2%). The results provided evidence that the heritability covered by psoriasis genome-wide genotyping data was probably underestimated in previous restricted maximum likelihood method. Our study highlights the broad role of common variants in the etiology of psoriasis and sheds light on the possibility to identify more common variants of small effect by increasing the sample size in psoriasis genome-wide association studies.

  1. Study on fluorescence spectra of molecular association of acetic acid-water

    Institute of Scientific and Technical Information of China (English)

    Caiqin Han; Ying Liu; Yang Yang; Xiaowu Ni; Jian Lu; Xiaosen Luo

    2009-01-01

    Fluorescence spectra of acetic acid-water solution excited by ultraviolet (UV) light are studied, and the relationship between fluorescence spectra and molecular association of acetic acid is discussed. The results indicate that when the exciting light wavelength is longer than 246 nm, there are two fluorescence peaks located at 305 and 334 nm, respectively. By measuring the excitation spectra, the optimal wavelengths of the two fluorescence peaks are obtained, which are 258 and 284 nm, respectively. Fluorescence spectra of acetic acid-water solution change with concentrations, which is primarily attributed to changes of molecular association of acetic acid in aqueous solution. Through theoretical analysis, three variations of molecular association have been obtained in acetic acid-water solution, which are the hydrated monomers, the linear dimers, and the water separated dimers. This research can provide references to studies of molecular association of acetic acid-water, especially studies of hydrogen bonds.

  2. Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study

    Science.gov (United States)

    Orozco, Gisela; Eyre, Steve; Hinks, Anne; Ke, Xiayi; Wilson, Anthony G; Bax, Deborah E; Morgan, Ann W; Emery, Paul; Steer, Sophia; Hocking, Lynne; Reid, David M; Wordsworth, Paul; Harrison, Pille; Thomson, Wendy; Barton, Anne; Worthington, Jane

    2010-01-01

    Objective A recent meta-analysis of published genome-wide association studies (GWAS) in populations of European descent reported novel associations of markers mapping to the CD40, CCL21 and CDK6 genes with rheumatoid arthritis (RA) susceptibility while a large-scale, case-control association study in a Japanese population identified association with multiple single nucleotide polymorphisms (SNPs) in the CD244 gene. The aim of the current study was to validate these potential RA susceptibility markers in a UK population. Methods A total of 4 SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3962 UK patients with RA and 3531 healthy controls using the Sequenom iPlex platform. Genotype counts in patients and controls were analysed with the χ2 test using Stata. Results Association to the CD40 gene was robustly replicated (p=2×10−4, OR 0.86, 95% CI 0.79 to 0.93) and modest evidence was found for association with the CCL21 locus (p=0.04, OR 1.08, 95% CI 1.01 to 1.16). However, there was no evidence for association of rs42041 (CDK6) and rs6682654 (CD244) with RA susceptibility in this UK population. Following a meta-analysis including the original data, association to CD40 was confirmed (p=7.8×10−8, OR 0.87 (95% CI 0.83 to 0.92). Conclusion In this large UK cohort, strong association of the CD40 gene with susceptibility to RA was found, and weaker evidence for association with RA in the CCL21 locus. PMID:19435719

  3. A validation of the first genome-wide association study of calcaneus ultrasound parameters in the European Male Ageing Study

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    Han Thang S

    2011-01-01

    Full Text Available Abstract Background A number of single nucleotide polymorphisms (SNPs have been associated with broadband ultrasound attenuation (BUA and speed of sound (SOS as measured by quantitative ultrasound (QUS at the calcaneus in the Framingham 100K genome-wide association study (GWAS but have not been validated in independent studies. The aim of this analysis was to determine if these SNPs are associated with QUS measurements assessed in a large independent population of European middle-aged and elderly men. The association between these SNPs and bone mineral density (BMD measured using dual-energy X-ray absorptiometry (DXA was also tested. Methods Men aged 40-79 years (N = 2960 were recruited from population registers in seven European centres for participation in an observational study of male ageing, the European Male Ageing Study (EMAS. QUS at the calcaneus was measured in all subjects and blood was taken for genetic analysis. Lumbar spine (LS, femoral neck (FN and total hip (TH BMD were measured by DXA in a subsample of 620 men in two centres. SNPs associated with BUA or SOS in the Framingham study with p -4 were selected and genotyped using SEQUENOM technology. Linear regression was used to test for the association between SNPs and standardised (SD bone outcomes under an additive genetic model adjusting for centre. The same direction of effect and p Results Thirty-four of 38 selected SNPs were successfully genotyped in 2377 men. Suggestive evidence of replication was observed for a single SNP, rs3754032, which was associated with a higher SOS (β(SD = 0.07, p = 0.032 but not BUA (β(SD = 0.02, p = 0.505 and is located in the 3'UTR of WDR77 (WD repeat domain 77 also known as androgen receptor cofactor p44. A single SNP, rs238358, was associated with BMD at the LS (β(SD = -0.22, p = 0.014, FN (β(SD = -0.31,p = 0.001 and TH (β(SD = -0.36, p = 0.002 in a locus previously associated with LS BMD in large-scale GWAS, incorporating AKAP11 and RANKL

  4. Genome wide association study of fetal hemoglobin in sickle cell anemia in Tanzania.

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    Siana Nkya Mtatiro

    Full Text Available BACKGROUND: Fetal hemoglobin (HbF is an important modulator of sickle cell disease (SCD. HbF has previously been shown to be affected by variants at three loci on chromosomes 2, 6 and 11, but it is likely that additional loci remain to be discovered. METHODS AND FINDINGS: We conducted a genome-wide association study (GWAS in 1,213 SCA (HbSS/HbSβ0 patients in Tanzania. Genotyping was done with Illumina Omni2.5 array and imputation using 1000 Genomes Phase I release data. Association with HbF was analysed using a linear mixed model to control for complex population structure within our study. We successfully replicated known associations for HbF near BCL11A and the HBS1L-MYB intergenic polymorphisms (HMIP, including multiple independent effects near BCL11A, consistent with previous reports. We observed eight additional associations with P<10(-6. These associations could not be replicated in a SCA population in the UK. CONCLUSIONS: This is the largest GWAS study in SCA in Africa. We have confirmed known associations and identified new genetic associations with HbF that require further replication in SCA populations in Africa.

  5. The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study

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    Poulton Joanna

    2009-04-01

    Full Text Available Abstract Background The mitochondrial DNA (mtDNA T16189C polymorphism, with a homopolymeric C-tract of 10–12 cytosines, is a putative genetic risk factor for idiopathic dilated cardiomyopathy in the African and British populations. We hypothesized that this variant may predispose to dilated cardiomyopathy in people who are infected with the human immunodeficiency virus (HIV. Methods A case-control study of 30 HIV-positive cases with dilated cardiomyopathy and 37 HIV-positive controls without dilated cardiomyopathy was conducted. The study was confined to persons of black African ancestry to minimize confounding of results by population admixture. HIV-positive patients with an echocardiographically confirmed diagnosis of dilated cardiomyopathy and HIV-positive controls with echocardiographically normal hearts were studied. Patients with secondary causes of cardiomyopathy (such as hypertension, diabetes, pregnancy, alcoholism, valvular heart disease, and opportunistic infection were excluded from the study. DNA samples were sequenced for the mtDNA T16189C polymorphism with a homopolymeric C-tract in the forward and reverse directions on an ABI3100 sequencer. Results The cases and controls were well matched for age (median 35 years versus 34 years, P = 0.93, gender (males 60% vs 53%, P = 0.54, and stage of HIV disease (mean CD4 T cell count 260.7/μL vs. 176/μL, P = 0.21. The mtDNA T16189C variant with a homopolymeric C-tract was detected at a frequency of 26.7% (8/30 in the HIV-associated cardiomyopathy cases and 13.5% (5/37 in the HIV-positive controls. There was no significant difference between cases and controls (Odds Ratio 2.33, 95% Confidence Interval 0.67–8.06, p = 0.11. Conclusion The mtDNA T16189C variant with a homopolymeric C-tract is not associated with dilated cardiomyopathy in black African people infected with HIV.

  6. The HapMap and genome-wide association studies in diagnosis and therapy.

    Science.gov (United States)

    Manolio, Teri A; Collins, Francis S

    2009-01-01

    The International HapMap Project produced a genome-wide database of human genetic variation for use in genetic association studies of common diseases. The initial output of these studies has been overwhelming, with over 150 risk loci identified in studies of more than 60 common diseases and traits. These associations have suggested previously unsuspected etiologic pathways for common diseases that will be of use in identifying new therapeutic targets and developing targeted interventions based on genetically defined risk. Here we examine the development and application of the HapMap to genome-wide association (GWA) studies; present and future technologies for GWA research; current major efforts in GWA studies; successes and limitations of the GWA approach in identifying polymorphisms related to complex diseases; data release and privacy polices; use of these findings by clinicians, the public, and academic physicians; and sources of ongoing authoritative information on this rapidly evolving field.

  7. Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies.

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    Roman Pfister

    2011-10-01

    Full Text Available BACKGROUND: Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP levels in blood and risk of type 2 diabetes (T2D, but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded. METHODS AND FINDINGS: We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36% decreased risk of incident T2D per one standard deviation (SD higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97 was similar to that expected (0.96, 0.93-0.98 based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90 and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29 per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders. CONCLUSIONS: Our results provide evidence for a potential causal role of the BNP

  8. Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study.

    Science.gov (United States)

    Shea, M Kyla; Booth, Sarah L; Massaro, Joseph M; Jacques, Paul F; D'Agostino, Ralph B; Dawson-Hughes, Bess; Ordovas, José M; O'Donnell, Christopher J; Kathiresan, Sekar; Keaney, John F; Vasan, Ramachandran S; Benjamin, Emelia J

    2008-02-01

    In vitro data suggest protective roles for vitamins K and D in inflammation. To examine associations between vitamins K and D and inflammation in vivo, the authors used multiple linear regression analyses, adjusted for age, sex, body mass index, triglyceride concentrations, use of aspirin, use of lipid-lowering medication, season, menopausal status, and hormone replacement therapy. Participants were from the Framingham Offspring Study (1997-2001; n = 1,381; mean age = 59 years; 52% women). Vitamin K status, measured by plasma phylloquinone concentration and phylloquinone intake, was inversely associated with circulating inflammatory markers as a group and with several individual inflammatory biomarkers (p vitamin K status, was not associated with overall inflammation but was associated with C-reactive protein (p vitamin D status and inflammation were inconsistent. The observation that high vitamin K status was associated with lower concentrations of inflammatory markers suggests that a possible protective role for vitamin K in inflammation merits further investigation.

  9. Association of Adaptive and Maladaptive Narcissism with Personal Burnout: findings from a cross-sectional study.

    Science.gov (United States)

    Känel, Roland VON; Herr, Raphael M; Vianen, Annelies E M VAN; Schmidt, Burkhard

    2017-01-25

    Burnout is associated with poor mental and physical functioning and high costs for societies. Personality attributes may critically increase the risk of personal burnout. We specifically examined whether narcissism associates with personal burnout in a working population. We studied n=1461employees (mean age 41.3±9.4 years, 52% men) drawn from a random sample of a pharmaceutical company in Germany. All participants completed the personal burnout subscale of the Copenhagen Burnout Inventory and the Narcissistic Personality Inventory to assess maladaptive (entitlement/exploitativeness) and adaptive (leadership/authority) narcissism. In linear regression analysis, when mutually adjusting for the maladaptive and adaptive narcissism scales, higher adaptive narcissism was associated with lower burnout scores (ß=-0.04, pvalues personality attributes may play an important role in personal burnout. While maladaptive narcissism was associated with increased levels of burnout symptoms, adaptive narcissism was associated with fewer burnout symptoms.

  10. ALOUD psychological: Adult Learning Open University Determinants StudyAssociation between psychological factors and study success in formal lifelong learners

    NARCIS (Netherlands)

    Neroni, Joyce; De Groot, Renate; Kirschner, Paul A.

    2012-01-01

    Neroni, J., De Groot, R. H. M., & Kirschner, P. A. (2012, 12 April). ALOUD psychological: Adult Learning Open University Determinants StudyAssociation between psychological factors and study success in formal lifelong learners. Presentation given at the plenary meeting of Learning & Cognition, He

  11. ALOUD biological: Adult Learning Open University Determinants study - Association of biological determinants with study success in formal lifelong learners

    NARCIS (Netherlands)

    Gijselaers, Jérôme; De Groot, Renate; Kirschner, Paul A.

    2012-01-01

    Gijselaers, H. J. M., De Groot, R. H. M., & Kirschner, P. A. (2012, 15 March). ALOUD biological: Adult Learning Open University Determinants study - Association of biological determinants with study success in formal lifelong learners. Presentation given at the plenary meeting of Learning & Cognitio

  12. Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI's Framingham Heart Study

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    Hwang Shih-Jen

    2007-09-01

    Full Text Available Abstract Introduction Subclinical atherosclerosis (SCA measures in multiple arterial beds are heritable phenotypes that are associated with increased incidence of cardiovascular disease. We conducted a genome-wide association study (GWAS for SCA measurements in the community-based Framingham Heart Study. Methods Over 100,000 single nucleotide polymorphisms (SNPs were genotyped (Human 100K GeneChip, Affymetrix in 1345 subjects from 310 families. We calculated sex-specific age-adjusted and multivariable-adjusted residuals in subjects tested for quantitative SCA phenotypes, including ankle-brachial index, coronary artery calcification and abdominal aortic calcification using multi-detector computed tomography, and carotid intimal medial thickness (IMT using carotid ultrasonography. We evaluated associations of these phenotypes with 70,987 autosomal SNPs with minor allele frequency ≥ 0.10, call rate ≥ 80%, and Hardy-Weinberg p-value ≥ 0.001 in samples ranging from 673 to 984 subjects, using linear regression with generalized estimating equations (GEE methodology and family-based association testing (FBAT. Variance components LOD scores were also calculated. Results There was no association result meeting criteria for genome-wide significance, but our methods identified 11 SNPs with p -5 by GEE and five SNPs with p -5 by FBAT for multivariable-adjusted phenotypes. Among the associated variants were SNPs in or near genes that may be considered candidates for further study, such as rs1376877 (GEE p ABI2 for maximum internal carotid artery IMT and rs4814615 (FBAT p = 0.000003, located in PCSK2 for maximum common carotid artery IMT. Modest significant associations were noted with various SCA phenotypes for variants in previously reported atherosclerosis candidate genes, including NOS3 and ESR1. Associations were also noted of a region on chromosome 9p21 with CAC phenotypes that confirm associations with coronary heart disease and CAC in two

  13. Genome Wide Association Study:Searching for Genes Underlying Body Mass Index in the Chinese

    Institute of Scientific and Technical Information of China (English)

    YANG Fang; CHEN Xiang Ding; TAN Li Jun; SHEN Jie; LI Ding You; ZHANG Fang; SHA Bao Yong; DENG Hong Wen

    2014-01-01

    Objective Obesity is becoming a worldwide health problem. The genome wide association (GWA) study particularly for body mass index (BMI) has not been successfully conducted in the Chinese. In order to identify novel genes for BMI variation in the Chinese, an initial GWA study and a follow up replication study were performed. Methods Affymetrix 500K SNPs were genotyped for initial GWA of 597 Northern Chinese. After quality control, 281 533 SNPs were included in the association analysis. Three SNPs were genotyped in a Southern Chinese replication sample containing 2 955 Chinese Han subjects. Association analyses were performed by Plink software. Results Eight SNPs were significantly associated with BMI variation after false discovery rate (FDR) correction (P=5.45×10-7-7.26×10-6, FDR q=0.033-0.048). Two adjacent SNPs (rs4432245 &rs711906) in the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) gene were significantly associated with BMI (P=6.38×10-6&4.39×10-6, FDR q=0.048). In the follow-up replication study, we confirmed the associations between BMI and rs4432245, rs711906 in the EIF2AKE gene (P=0.03&0.01, respectively). Conclusion Our study suggests novel mechanisms for BMI, where EIF2AK4 has exerted a profound effect on the synthesis and storage of triglycerides and may impact on overall energy homeostasis associated with obesity. The minor allele frequencies for the two SNPs in the EIF2AK4 gene have marked ethnic differences between Caucasians and the Chinese. The association of the EIF2AK4 gene with BMI is suggested to be‘ethnic specific’ in the Chinese.

  14. Loci associated with N-glycosylation of human IgG are not associated with rheumatoid arthritis: a Mendelian randomisation study

    Science.gov (United States)

    Yarwood, Annie; Okada, Yukinori; Plenge, Robert; Yamamoto, Kazuhiko; Barton, Anne; Symmons, Deborah; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter; Worthington, Jane; Eyre, Steve

    2016-01-01

    Objectives A recent study identified 16 genetic variants associated with N-glycosylation of human IgG. Several of the genomic regions where these single nucleotide polymorphisms (SNPs) reside have also been associated with autoimmune disease (AID) susceptibility, suggesting there may be pleiotropy (genetic sharing) between loci controlling both N-glycosylation and AIDs. We investigated this by testing variants associated with levels of IgG N-glycosylation for association with rheumatoid arthritis (RA) susceptibility using a Mendelian randomisation study, and testing a subset of these variants in a less well-powered study of treatment response and severity. Methods SNPs showing association with IgG N-glycosylation were analysed for association with RA susceptibility in 14 361 RA cases and 43 923 controls. Five SNPs were tested for association with response to anti-tumour necrosis factor (TNF) therapy in 1081 RA patient samples and for association with radiological disease severity in 342 patients. Results Only one SNP (rs9296009) associated with N-glycosylation showed an association (p=6.92×10–266) with RA susceptibility, although this was due to linkage disequilibrium with causal human leukocyte antigen (HLA) variants. Four regions of the genome harboured SNPs associated with both traits (shared loci); although statistical analysis indicated that the associations observed for the two traits are independent. No SNPs showed association with response to anti-TNF therapy. One SNP rs12342831 was modestly associated with Larsen score (p=0.05). Conclusions In a large, well-powered cohort of RA patients, we show SNPs driving levels of N-glycosylation have no association with RA susceptibility, indicating colocalisation of associated SNPs are not necessarily indicative of a shared genetic background or a role for glycosylation in disease susceptibility. PMID:26386125

  15. Sedentary behaviours and its association with bone mass in adolescents: the HELENA cross-sectional study

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    Gracia-Marco Luis

    2012-11-01

    Full Text Available Abstract Background We aimed to examine whether time spent on different sedentary behaviours is associated with bone mineral content (BMC in adolescents, after controlling for relevant confounders such as lean mass and objectively measured physical activity (PA, and if so, whether extra-curricular participation in osteogenic sports could have a role in this association. Methods Participants were 359 Spanish adolescents (12.5-17.5 yr, 178 boys, from the HELENA-CSS (2006–07. Relationships of sedentary behaviours with bone variables were analysed by linear regression. The prevalence of low BMC (at least 1SD below the mean and time spent on sedentary behaviours according to extracurricular sport participation was analysed by Chi-square tests. Results In boys, the use of internet for non-study was negatively associated with whole body BMC after adjustment for lean mass and moderate to vigorous PA (MVPA. In girls, the time spent studying was negatively associated with femoral neck BMC. Additional adjustment for lean mass slightly reduced the negative association between time spent studying and femoral neck BMC. The additional adjustment for MVPA did not change the results at this site. The percentage of girls having low femoral neck BMC was significantly smaller in those participating in osteogenic sports (≥ 3 h/week than in the rest, independently of the cut-off selected for the time spent studying. Conclusions The use of internet for non-study (in boys and the time spent studying (in girls are negatively associated with whole body and femoral neck BMC, respectively. In addition, at least 3 h/week of extra-curricular osteogenic sports may help to counteract the negative association of time spent studying on bone health in girls.

  16. Common FLG mutation K4671X not associated with atopic dermatitis in Han Chinese in a family association study.

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    Ruhong Cheng

    Full Text Available BACKGROUND: Filaggrin gene (FLG mutations have been identified as the cause of ichthyosis vulgaris (IV and major predisposing factors for atopic dermatitis (AD. The relationship among AD, IV and FLG mutations has not been clarified yet. Mutations 3321delA and K4671X, two of the most common mutations in Chinese patients, were both statistically associated with AD in case-control studies. MATERIALS AND METHODS: A group of 100 family trios (a total of 300 members with one affected AD proband and both parents were recruited and screened for three filaggrin null mutations (3222del4, 3321delA and K4671X. The subjects' manifestations of AD and IV were assessed by two experienced dermatologists and recorded in detail. The relationship of common mutations to AD were assessed using both case-control and family-based tests of association. Filaggrin expression was measured in skin of 3 subjects with K4671X heterozygote and the normal control using quantitative real-time RT-PCR and immunohistochemistry. RESULTS: Of 100 probands for AD, 22 were carriers for common FLG mutations and only 2 of them were from 40 none-IV family trios (5.00%, consistent with that of the healthy control group (3.99%, P>0.05. Significant statistical associations were revealed between AD and 3321delA (P<0.001, odds ratio 12.28, 95% confidence interval 3.35-44.98 as well as K4671X (P = 0.002, odds ratio 4.53, 95% confidence interval 1.77-11.60. The family-based approach revealed that 3321delA was over-transmitted to AD offspring from parents (T:U = 12∶1, P = 0.003 but failed to demonstrate transmission disequilibrium between K4671X and AD (T:U = 10∶8, P = 0.815. Moreover, compared to the normal control, filaggrin expression at both mRNA and protein levels in epidermis of subjects with K4671X(heter was not reduced. CONCLUSIONS: AD patients from none-IV family trios have low probability of carrying FLG mutations. The present family samples confirmed the

  17. Association of periodontal and cardiovascular diseases: South-Asian studies 2001–2012

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    Syed Akhtar Hussain Bokhari

    2015-01-01

    Full Text Available Large proportion of Asian populations have moderate to severe periodontal disease and a substantial number are anticipated to be at high risk of cardiovascular diseases (CVD. This study reviews epidemiology and association of periodontal and CVDs from the South-Asian region. Observational studies and clinical trials published during January 2001–December 2012 focusing association between periodontitis and CVDs in South-Asian countries were retrieved from various databases and studied. Current evidence suggests that both periodontal and CVDs are globally prevalent and show an increasing trend in developing countries. Global data on epidemiology and association of periodontal and CVDs are predominantly from the developed world; whereas Asia with 60% of the world's population lacks substantial scientific data on the link between periodontal and CVDs. During the search period, 14 studies (5 clinical trials, 9 case–controls were reported in literature from South-Asia; 100% of clinical trials and 77% case–control studies have reported a significant association between the oral/periodontal parameters and CVD. Epidemiological and clinical studies from South-Asia validate the global evidence on association of periodontal disease with CVDs. However, there is a need for meticulous research for public health and scientific perspective of the Periodontal and CVDs from South-Asia.

  18. Factors accounting for the association between anxiety and depression, and eczema: the Hordaland health study (HUSK

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    Gotestam Karl

    2010-04-01

    Full Text Available Abstract Background The association between anxiety and depression, and eczema is well known in the literature, but factors underlying this association remain unclear. Low levels of omega-3 fatty acids and female gender have been found to be associated with both depression and eczema. Somatization and health anxiety are known to be associated with anxiety and depression, further, somatization symptoms and health anxiety have also been found in several dermatological conditions. Accordingly, omega-3 fatty acid supplement, female gender, somatization and health anxiety are possible contributing factors in the association between anxiety and depression, and eczema. The aim of the study is to examine the relevance of proposed contributing factors for the association between anxiety and depression, and eczema, including, omega-3 fatty acid supplement, female gender, health anxiety and somatization. Methods Anxiety and depression was measured in the general population (n = 15715 employing the Hospital Anxiety and Depression Scale (HADS. Information on eczema, female gender, omega-3 fatty acid supplement, health anxiety and somatization was obtained by self-report. Results Somatization and health anxiety accounted for more than half of the association between anxiety/depression, and eczema, while the other factors examined were of minor relevance for the association of interest. Conclusions We found no support for female gender and omega-3 fatty acid supplement as contributing factors in the association between anxiety/depression, and eczema. Somatization and health anxiety accounted for about half of the association between anxiety/depression, and eczema, somatization contributed most. The association between anxiety/depression, and eczema was insignificant after adjustment for somatization and health anxiety. Biological mechanisms underlying the mediating effect of somatization are yet to be revealed.

  19. Genome-wide association study of smoking behaviours in patients with COPD.

    Science.gov (United States)

    Siedlinski, Mateusz; Cho, Michael H; Bakke, Per; Gulsvik, Amund; Lomas, David A; Anderson, Wayne; Kong, Xiangyang; Rennard, Stephen I; Beaty, Terri H; Hokanson, John E; Crapo, James D; Silverman, Edwin K

    2011-10-01

    Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a dopamine beta-hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in patients with COPD. Methods GWAS were conducted in four independent cohorts encompassing 3441 ever-smoking patients with COPD (Global Initiative for Obstructive Lung Disease stage II or higher). Untyped SNPs were imputed using the HapMap (phase II) panel. Results from all cohorts were meta-analysed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2×10(-7). No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p<10(-6). Nominally significant associations with candidate SNPs within cholinergic receptors, nicotinic, alpha 3/5 (CHRNA3/CHRNA5; eg, p=0.00011 for SNP rs1051730) and cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6; eg, p=2.78×10(-5) for a non-synonymous SNP rs1801272) regions were observed for lifetime average CPD, however only CYP2A6 showed evidence of significant association with current CPD. A candidate SNP (rs3025343) in DBH was significantly (p=0.015) associated with smoking cessation. Conclusion The authors identified two candidate regions associated with age at smoking initiation in patients with COPD. Associations of CHRNA3/CHRNA5 and CYP2A6 loci with CPD and DBH with smoking cessation are also likely of importance in the smoking behaviours of patients with COPD.

  20. Toll-like receptor gene polymorphisms are associated with allergic rhinitis: a case control study

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    Nilsson Daniel

    2012-08-01

    Full Text Available Abstract Background The Toll-like receptor proteins are important in host defense and initiation of the innate and adaptive immune responses. A number of studies have identified associations between genetic variation in the Toll-like receptor genes and allergic disorders such as asthma and allergic rhinitis. The present study aim to search for genetic variation associated with allergic rhinitis in the Toll-like receptor genes. Methods A first association analysis genotyped 73 SNPs in 182 cases and 378 controls from a Swedish population. Based on these results an additional 24 SNPs were analyzed in one Swedish population with 352 cases and 709 controls and one Chinese population with 948 cases and 580 controls. Results The first association analysis identified 4 allergic rhinitis-associated SNPs in the TLR7-TLR8 gene region. Subsequent analysis of 24 SNPs from this region identified 7 and 5 significant SNPs from the Swedish and Chinese populations, respectively. The corresponding risk-associated haplotypes are significant after Bonferroni correction and are the most common haplotypes in both populations. The associations are primarily detected in females in the Swedish population, whereas it is seen in males in the Chinese population. Further independent support for the involvement of this region in allergic rhinitis was obtained from quantitative skin prick test data generated in both populations. Conclusions Haplotypes in the TLR7-TLR8 gene region were associated with allergic rhinitis in one Swedish and one Chinese population. Since this region has earlier been associated with asthma and allergic rhinitis in a Danish linkage study this speaks strongly in favour of this region being truly involved in the development of this disease.

  1. Association of traumatic police event exposure with sleep quality and quantity in the BCOPS Study cohort.

    Science.gov (United States)

    Bond, Jonathan; Hartley, Tara A; Sarkisian, Khachatur; Andrew, Michael E; Charles, Luenda E; Violanti, John M; Burchfiel, Cecil M

    2013-01-01

    Police officers are exposed to traumatic and life-threatening events, which may lead to sleep problems. Prior studies of police officers have found them to have poor sleep quality and reduced sleep time. This study examined associations between traumatic events and sleep quality. Participants were 372 police officers from the Buffalo Cardio-metabolic Occupational Police Stress (BCOPS) Study. Police incidents were measured by the Police Incident Survey; sleep quality and quantity were derived from the Pittsburgh Sleep Quality Index (PSQI). Analysis of covariance (ANCOVA) was used to examine mean PSQI scores across categories of traumatic event frequency. Models were adjusted for age, education and ethnicity and stratified by sex and workload. In men, significant associations were found for the 'shooting of another officer' and sleep quality (p-value = 0.024) and sleep disturbances (p-value = 0.022). In women, seeing more 'abused children' was associated with poorer sleep quality (p-value = 0.050); increasing frequency of 'seeing victims of a serious traffic accident' was associated with shorter sleep duration (p-value = 0.032). Increased frequency of 'seeing dead bodies' was associated with poorer sleep quality (p-value = 0.040) and shorter sleep duration (p-value = 0.048). Among women with a high workload, a significant inverse association was found between 'seeing serious traffic accident victims' and global sleep quality (p-value = 0.031). In conclusion, a significant inverse association between frequency of select traumatic events and sleep quality was found in male and female police officers. The significant events differed by sex. Future research could examine longitudinal associations between career-long traumatic event exposures and sleep quality and how these associations differ by sex.

  2. Differentially Methylated DNA Regions in Monozygotic Twin Pairs Discordant for Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Svendsen, Anders J; Gervin, Kristina; Lyle, Robert;

    2016-01-01

    OBJECTIVES: In an explorative epigenome-wide association study (EWAS) to search for gene independent, differentially methylated DNA positions and regions (DMRs) associated with rheumatoid arthritis (RA) by studying monozygotic (MZ) twin pairs discordant for RA. METHODS: Genomic DNA was isolated......: We identified several differentially methylated regions associated with RA, which may represent environmental effects or consequences of the disease and plausible biological pathways pertinent to the pathogenesis of RA....

  3. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

    DEFF Research Database (Denmark)

    Lundby, Alicia; Rossin, Elizabeth J.; Steffensen, Annette B.;

    2014-01-01

    Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes...... involved in the Mendelian disorder long QT syndrome (LOTS). We integrated the LOTS network with GWAS loci from the corresponding common complex trait, QT-interval variation, to identify candidate genes that were subsequently confirmed in Xenopus laevis oocytes and zebrafish. We used the LOTS protein...... to propose candidates in GWAS loci for functional studies and to systematically filter subtle association signals using tissue-specific quantitative interaction proteomics....

  4. Associations of low grade inflammation and endothelial dysfunction with depression - The Maastricht Study

    DEFF Research Database (Denmark)

    van Dooren, Fleur E P; Schram, Miranda T; Schalkwijk, Casper G

    2016-01-01

    in this association. METHODS: In The Maastricht Study, a population-based cohort study (n=852, 55% men, m=59.8±8.5years), depressive symptoms were assessed with the Patient Health Questionnaire-9 and (major and minor) depressive disorder with the Mini-International Neuropsychiatric Interview. Plasma biomarkers......BACKGROUND: The pathogenesis of depression may involve low-grade inflammation and endothelial dysfunction. We aimed to evaluate the independent associations of inflammation and endothelial dysfunction with depressive symptoms and depressive disorder, and the role of lifestyle factors......E-Selectin) were univariately associated with depressive symptoms and depressive disorder. The sum scores of inflammation and endothelial dysfunction were associated with depressive disorder after adjustment for age, sex, type 2 diabetes, kidney function and prior cardiovascular disease (OR 1.54, p=0.001 and 1...

  5. Curvature Dependence of Interfacial Properties for Associating Lennard-Jones Fluids: A Density Functional Study

    Institute of Scientific and Technical Information of China (English)

    SUN Zong-Li; KANG Yan-Shuang

    2011-01-01

    Classical density functional theory is used to study the associating Lennard Jones fluids in contact with spherical hard wall of different curvature radii. The interfacial properties including contact density and fluid-solid interfacial tension are investigated. The influences of associating energy, curvature of hard wall and the bulk density of Huids on these properties are analyzed in detail. The results may provide helpful clues to understand the interfacial properties of other complex fluids.%@@ Classical density functional theory is used to study the associating Lennard Jones fluids in contact with spherical hard wall of different curvature radii.The interfacial properties including contact density and fluid-solid intcrfacial tension are investigated.The influences of associating energy, curvature of hard wall and the hulk density of fluids on these properties are analyzed in detail.The results may provide helpful clues to understand the interfacial properties of other complex fluids.

  6. Using hybrid associative classifier with translation (HACT for studying imbalanced data sets

    Directory of Open Access Journals (Sweden)

    Laura Cleofas Sánchez

    2012-04-01

    Full Text Available Class imbalance may reduce the classifier performance in several recognition pattern problems. Such negative effect is more notable with least represented class (minority class Patterns. A strategy for handling this problem consisted of treating the classes included in this problem separately (majority and minority classes to balance the data sets (DS. This paper has studied high sensitivity to class imbalance shown by an associative model of classification: hybrid associative classifier with translation (HACT; imbalanced DS impact on associative model performance was studied. The convenience of using sub-sampling methods for decreasing imbalanced negative effects on associative memories was analysed. This proposal’s feasibility was based on experimental results obtained from eleven real-world datasets.

  7. Replication of a Genome-Wide Association Study of Birth Weight in Preterm Neonates

    Science.gov (United States)

    Ryckman, Kelli K; Feenstra, Bjarke; Shaffer, John R.; Bream, Elise NA; Geller, Frank; Feingold, Eleanor; Weeks, Daniel E; Gadow, Enrique; Cosentino, Viviana; Saleme, Cesar; Simhan, Hyagriv N; Merrill, David; Fong, Chin-To; Busch, Tamara; Berends, Susan K; Comas, Belen; Camelo, Jorge L; Boyd, Heather; Laurie, Cathy; Crosslin, David; Zhang, Qi; Doheny, Kim F; Pugh, Elizabeth; Melbye, Mads; Marazita, Mary L; Dagle, John M; Murray, Jeffrey C

    2011-01-01

    Objective To examine associations in a preterm population between rs9883204 in ADCY5 and rs900400 near LEKR1 and CCNL1 with birth weight. Both markers were associated with birth weight in a term population in a recent genome-wide association (GWA) study by Freathy et al. Study design A meta-analysis of mother and infant samples was performed for associations of rs900400 and rs9883204 with birth weight in 393 families from the U.S., 265 families from Argentina and 735 mother-infant pairs from Denmark. Z scores adjusted for infant sex and gestational age were generated for each population separately and regressed on allele counts. Association evidence was combined across sites by inverse-variance weighted meta-analysis. Results Each additional C allele of rs900400 (LEKR1/CCNL1) in infants was marginally associated with a 0.069 standard deviation (SD) lower birth weight (95% CI = −0.159 – 0.022, P = 0.068). This result was slightly more pronounced after adjusting for smoking (P = 0.036). There were no significant associations identified with rs9883204 or in maternal samples. Conclusions These results indicate the potential importance of this marker on birth weight irrespective of gestational age. PMID:21885063

  8. Genome-wide Association Study Identifies New Loci for Resistance to Leptosphaeria maculans in Canola

    Directory of Open Access Journals (Sweden)

    Harsh Raman

    2016-10-01

    Full Text Available Blackleg, caused by Leptosphaeria maculans, is a significant disease which affects the sustainable production of canola. This study reports a genome-wide association study based on 18,804 polymorphic SNPs to identify loci associated with qualitative and quantitative resistance to L. maculans. Genomic regions delimited with 503 significant SNP markers, that are associated with resistance evaluated using 12 single spore isolates and pathotypes from four canola stubble were identified. Several significant associations were detected at known disease resistance loci including in the vicinity of recently cloned Rlm2/LepR3 genes, and at new loci on chromosomes A01/C01, A02/C02, A03/C03, A05/C05, A06, A08, and A09. In addition, we validated statistically significant associations on A01, A07 and A10 in four genetic mapping populations, demonstrating that GWAS marker loci are indeed associated with resistance to L. maculans. One of the novel loci identified for the first time, Rlm12, conveys adult plant resistance and mapped within 13.2 kb from Arabidopsis R gene of TIR-NBS class. We showed that resistance loci are located in the vicinity of R genes of A. thaliana and B. napus on the sequenced genome of B. napus cv. Darmor-bzh. Significantly associated SNP markers provide a valuable tool to enrich germplasm for favorable alleles in order to improve the level of resistance to L. maculans in canola.

  9. The study of association Phyllitidi-Fagetum in Codru-Moma Mountains (North-Western Romania

    Directory of Open Access Journals (Sweden)

    Călin-Gheorghe PĂŞCUŢ

    2010-11-01

    Full Text Available In the present study we aimed to analyse the phytocoenoses that take part in the association Phyllitidi-Fagetum Vida (1959 1963, in the area of the Codru-Moma Mountains.The phytocoenoses of association Phyllitidi-Fagetum Vida (1959 1963 were analyzed from the point of view of floristic diversity, of the life forms spectrum, of the floristic elements spectrum and the diagram of the ecological indices. The presence of this association in Codru-Moma Mountains was signaled following 10 phytocoenological relevées done during the period 2008-2010.

  10. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

    DEFF Research Database (Denmark)

    Hor, Hyun; Kutalik, Zoltán; Dauvilliers, Yves;

    2010-01-01

    Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing...... narcolepsy. To further define the genetic basis of narcolepsy risk, we performed a genome-wide association study (GWAS) in 562 European individuals with narcolepsy (cases) and 702 ethnically matched controls, with independent replication in 370 cases and 495 controls, all heterozygous for DRB1*1501-DQB1...... ratio = 0.02; P narcolepsy susceptibility....

  11. Microbiome-wide association studies link dynamic microbial consortia to disease.

    Science.gov (United States)

    Gilbert, Jack A; Quinn, Robert A; Debelius, Justine; Xu, Zhenjiang Z; Morton, James; Garg, Neha; Jansson, Janet K; Dorrestein, Pieter C; Knight, Rob

    2016-07-06

    Rapid advances in DNA sequencing, metabolomics, proteomics and computational tools are dramatically increasing access to the microbiome and identification of its links with disease. In particular, time-series studies and multiple molecular perspectives are facilitating microbiome-wide association studies, which are analogous to genome-wide association studies. Early findings point to actionable outcomes of microbiome-wide association studies, although their clinical application has yet to be approved. An appreciation of the complexity of interactions among the microbiome and the host's diet, chemistry and health, as well as determining the frequency of observations that are needed to capture and integrate this dynamic interface, is paramount for developing precision diagnostics and therapies that are based on the microbiome.

  12. Replication of association between ELAVL4 and Parkinson disease: the GenePD study

    Science.gov (United States)

    DeStefano, Anita L.; Latourelle, Jeanne; Lew, Mark F.; Suchowersky, Oksana; Klein, Christine; Golbe, Lawrence I.; Mark, Margery H.; Growdon, John H.; Wooten, G. Fredrick; Watts, Ray; Guttman, Mark; Racette, Brad A.; Perlmutter, Joel S.; Marlor, Lynn; Shill, Holly A.; Singer, Carlos; Goldwurm, Stefano; Pezzoli, Gianni; Saint-Hilaire, Marie H.; Hendricks, Audrey E.; Gower, Adam; Williamson, Sally; Nagle, Michael W.; Wilk, Jemma B.; Massood, Tiffany; Huskey, Karen W.; Baker, Kenneth B.; Itin, Ilia; Litvan, Irene; Nicholson, Garth; Corbett, Alastair; Nance, Martha; Drasby, Edward; Isaacson, Stuart; Burn, David J.; Chinnery, Patrick F.; Pramstaller, Peter P.; Al-hinti, Jomana; Moller, Anette T.; Ostergaard, Karen; Sherman, Scott J.; Roxburgh, Richard; Snow, Barry; Slevin, John T.; Cambi, Franca; Gusella, James F.; Myers, Richard H.

    2009-01-01

    Genetic variants in embryonic lethal, abnormal vision, Drosophila-like 4 (ELAVL4) have been reported to be associated with onset age of Parkinson disease (PD) or risk for PD affection in Caucasian populations. In the current study we genotyped three single nucleotide polymorphisms in ELAVL4 in a Caucasian study sample consisting of 712 PD patients and 312 unrelated controls from the GenePD study. The minor allele of rs967582 was associated with increased risk of PD (odds ratio = 1.46, nominal P value = 0.011) in the GenePD population. The minor allele of rs967582 was also the risk allele for PD affection or earlier onset age in the previously studied populations. This replication of association with rs967582 in a third cohort further implicates ELAVL4 as a PD susceptibility gene. PMID:18587682

  13. A genome-wide association study of neuroticism in a population-based sample.

    Science.gov (United States)

    Calboli, Federico C F; Tozzi, Federica; Galwey, Nicholas W; Antoniades, Athos; Mooser, Vincent; Preisig, Martin; Vollenweider, Peter; Waterworth, Dawn; Waeber, Gerard; Johnson, Michael R; Muglia, Pierandrea; Balding, David J

    2010-07-09

    Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 million SNPs imputed with high quality from the Hap Map CEU samples. We found a very small effect of population stratification, corrected using one principal component, and some cryptic kinship that required no correction. NKAIN2 showed suggestive evidence of association with neuroticism as a main effect (p neuroticism. Our study was powered to detect almost all SNPs explaining at least 2% of heritability, and so our results effectively exclude the existence of loci having a major effect on neuroticism.

  14. A genome-wide association study of heparin-induced thrombocytopenia using an electronic medical record

    DEFF Research Database (Denmark)

    Karnes, Jason H; Cronin, Robert M; Rollin, Jerome

    2015-01-01

    . Here, we performed a genome-wide association study (GWAS) and candidate gene study using HIT cases and controls identified using electronic medical records (EMRs) coupled to a DNA biobank and attempted to replicate GWAS associations in an independent cohort. We subsequently investigated influences......-heparin treated patients (OR 3.09; 1.14-8.13; p=0.02). In the candidate gene study, SNPs at HLA-DRA were nominally associated with HIT (OR 0.25; 0.15-0.44; p=2.06×10(-6)). Further study of TDAG8 and HLA-DRA SNPs is warranted to assess their influence on the risk of developing HIT....

  15. Association between alcohol consumption and amyotrophic lateral sclerosis: a meta-analysis of five observational studies.

    Science.gov (United States)

    E, Meng; Yu, Sufang; Dou, Jianrui; Jin, Wu; Cai, Xiang; Mao, Yiyang; Zhu, Daojian; Yang, Rumei

    2016-08-01

    The purpose of this study is to examine the association between alcohol consumption and amyotrophic lateral sclerosis. Published literature on the association between alcohol consumption and amyotrophic lateral sclerosis was retrieved from the PubMed and Embase databases. Two authors independently extracted the data. The quality of the identified studies was evaluated according to the Newcastle-Ottawa scale. Subgroup and sensitivity analyses were performed and publication bias was assessed. Five articles, including one cohort study and seven case-control studies, and a total of 431,943 participants, were identified. The odds ratio for the association between alcohol consumption and amyotrophic lateral sclerosis was 0.57 (95 % confidence interval 0.51-0.64). Subgroup and sensitivity analyses confirmed the result. Evidence for publication bias was detected. Alcohol consumption reduced the risk of developing amyotrophic lateral sclerosis compared with non-drinking. Alcohol, therefore, has a potentially neuroprotective effect on the development of amyotrophic lateral sclerosis.

  16. Microbiome-wide association studies link dynamic microbial consortia to disease

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, Jack A.; Quinn, Robert A.; Debelius, Justine; Xu, Zhenjiang Z.; Morton, James; Garg, Neha; Jansson, Janet K.; Dorrestein, Pieter C.; Knight, Rob

    2016-07-06

    Rapid advances in DNA sequencing, metabolomics, proteomics and computation dramatically increase accessibility of microbiome studies and identify links between the microbiome and disease. Microbial time-series and multiple molecular perspectives enable Microbiome-Wide Association Studies (MWAS), analogous to Genome-Wide Association Studies (GWAS). Rapid research advances point towards actionable results, although approved clinical tests based on MWAS are still in the future. Appreciating the complexity of interactions between diet, chemistry, health and the microbiome, and determining the frequency of observations needed to capture and integrate this dynamic interface, is paramount for addressing the need for personalized and precision microbiome-based diagnostics and therapies.

  17. On family-based genome-wide association studies with large pedigrees: observations and recommendations

    OpenAIRE

    Fardo, David W.; Zhang, Xue; Ding, Lili; He, Hua; Kurowski, Brad; Alexander, Eileen S.; Mersha, Tesfaye B.; Pilipenko, Valentina; Kottyan, Leah; Nandakumar, Kannabiran; Martin, Lisa

    2014-01-01

    Family based association studies are employed less often than case-control designs in the search for disease-predisposing genes. The optimal statistical genetic approach for complex pedigrees is unclear when evaluating both common and rare variants. We examined the empirical power and type I error rates of 2 common approaches, the measured genotype approach and family-based association testing, through simulations from a set of multigenerational pedigrees. Overall, these results suggest that ...

  18. The association between vitamin B12, albuminuria and reduced kidney function: an observational cohort study

    OpenAIRE

    McMahon, Gearoid M.; Hwang, Shih-Jen; Rikki M Tanner; Jacques, Paul F.; Selhub, Jacob; Muntner, Paul; Fox, Caroline S.

    2015-01-01

    Background: Variants in CUBN, the gene encoding cubilin, a proximal tubular transport protein, have been associated with albuminuria and vitamin B12 (B12) deficiency. We hypothesized that low levels of B12 would be associated with albuminuria in a population-based cohort. Methods: We analyzed participants from the Framingham Heart Study (n = 2965, mean age 58 years, 53% female) who provided samples for plasma B12. Logistic regression models adjusted for covariates including homocysteine were ...

  19. Associations between fruit and vegetable consumption and psychological distress: results from a population-based study

    OpenAIRE

    Richard, A.; Rohrmann, S; Vandeleur, C.L.; Mohler-Kuo, M.; Eichholzer, M

    2015-01-01

    BACKGROUND: Several studies observed associations of various aspects of diet with mental health, but little is known about the relationship between following the 5-a-day recommendation for fruit and vegetables consumption and mental health. Thus, we examined the associations of the Swiss daily recommended fruit and vegetable intake with psychological distress. METHODS: Data from 20,220 individuals aged 15+ years from the 2012 Swiss Health Survey were analyzed. The recommended portions of f...

  20. Whole-genome association studies of alcoholism with loci linked to schizophrenia susceptibility

    OpenAIRE

    Kim Youngchul; Namkung Junghyun; Park Taesung

    2005-01-01

    Abstract Background Alcoholism is a complex disease. There have been many reports on significant comorbidity between alcoholism and schizophrenia. For the genetic study of complex diseases, association analysis has been recommended because of its higher power than that of the linkage analysis for detecting genes with modest effects on disease. Results To identify alcoholism susceptibility loci, we performed genome-wide single-nucleotide polymorphisms (SNP) association tests, which yielded 489...

  1. Chronic neck pain : An epidemiological, psychological and SPECT study with emphasis on whiplash-associated disorders

    OpenAIRE

    2006-01-01

    Chronic neck pain, a common cause of disability, seems to be the result of several interacting mechanisms. In addition to degenerative and inflammatory changes and trauma, psychological and psychosocial factors are also involved. One common type of trauma associated with chronic neck pain is whiplash injury; this sometimes results in whiplash-associated disorder (WAD), a controversial condition with largely unknown pathogenetic mechanisms. We studied the prevalence of chronic neck pain of tra...

  2. Community-based case-control study of childhood stroke risk associated with congenital heart disease

    OpenAIRE

    Fox, CK; Sidney, S.; Fullerton, HJ

    2015-01-01

    © 2015 American Heart Association, Inc. BACKGROUND AND PURPOSE - : A better understanding of the stroke risk factors in children with congenital heart disease (CHD) could inform stroke prevention strategies. We analyzed pediatric stroke associated with CHD in a large community-based case-control study. METHODS - : From 2.5 million children (aged 30-fold (odds ratio, 31; confidence interval 4-241) increased risk of stroke in children with CHD when compared with controls. After excluding periop...

  3. Behavioral Outcomes of Supervisory Education in the Association for Clinical Pastoral Education: A Qualitative Research Study.

    Science.gov (United States)

    Ragsdale, Judith R; Orme-Rogers, Charles; Bush, Johnny C; Stowman, Sheryl Lyndes; Seeger, Rodney W

    2016-03-01

    This study advances the work of developing a theory for educating Clinical Pastoral Education (CPE) Supervisors by describing the behaviors which result from the successful completion of CPE supervisory education. Twenty-eight Association for Clinical Pastoral Education (ACPE) Certification Commissioners were interviewed to identify the behaviors demonstrated by Supervisory Education Students (Candidates) which influenced the decision to certify them at the level of Associate Supervisor. Specific behavioral descriptors are listed for each ACPE supervisory competency.

  4. False Recognition in DRM Lists with Low Association: A Normative Study

    Science.gov (United States)

    Cadavid, Sara; Beato, María Soledad

    2017-01-01

    A wide array of studies have explored memory distortions with the Deese/Roediger-McDermott (DRM) paradigm, where participants study lists of words (e.g., "door," "glass," "pane," "shade," "ledge," etc.) that are associated to another nonpresented critical word (e.g., WINDOW). On a subsequent memory…

  5. Association between alcohol consumption and diabetic retinopathy and visual acuity-the AdRem Study

    NARCIS (Netherlands)

    Lee, C. C.; Stolk, R. P.; Adler, A. I.; Patel, A.; Chalmers, J.; Neal, B.; Poulter, N.; Harrap, S.; Woodward, M.; Marre, M.; Grobbee, D. E.; Beulens, J. W.

    2010-01-01

    Aims We investigated the association between alcohol consumption and diabetic retinopathy and deterioration of visual acuity in individuals with Type 2 diabetes. Methods We conducted a cohort analysis of 1239 participants with Type 2 diabetes aged 55-81 years enrolled in the AdRem study, a sub-study

  6. Bidirectional Prospective Associations Between Physical Activity and Depressive Symptoms. The TRAILS Study

    NARCIS (Netherlands)

    Stavrakakis, Nikolaos; de Jonge, Peter; Ormel, Johan; Oldehinkel, Albertine J.

    2012-01-01

    Purpose: Low levels of physical activity (PA) have been shown to be associated with depression in adults. The few studies that focused on adolescents yielded mixed and inconsistent results. Efforts to examine the direction of this relationship have been inconclusive up to now. The aims of this study

  7. Association between BDNF-rs6265 and obesity in the Boston Puerto Rican Health Study

    Science.gov (United States)

    The objective of this study is to examine a functional variant (rs6265) in the BDNF gene interacting with dietary intake modulate obesity traits in the Boston Puerto Rican Health Study population. BDNF rs6265 was genotyped in 1147 Puerto Ricans (aged 45-75 years), and examined for association with o...

  8. Case-Control Genome-Wide Association Study of Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Neale, Benjamin M.; Medland, Sarah; Ripke, Stephan; Anney, Richard J. L.; Asherson, Philip; Buitelaar, Jan; Franke, Barbara; Gill, Michael; Kent, Lindsey; Holmans, Peter; Middleton, Frank; Thapar, Anita; Lesch, Klaus-Peter; Faraone, Stephen V.; Daly, Mark; Nguyen, Thuy Trang; Schafer, Helmut; Steinhausen, Hans-Christoph; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Warnke, Andreas; Walitza, Susanne; Freitag, Christine; Meyer, Jobst; Palmason, Haukur; Rothenberger, Aribert; Hawi, Ziarih; Sergeant, Joseph; Roeyers, Herbert; Mick, Eric; Biederman, Joseph

    2010-01-01

    Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genome-wide association studies (GWAS) are needed. Method: We used case-control analyses of 896 cases…

  9. Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Neale, Benjamin M.; Medland, Sarah E.; Ripke, Stephan; Asherson, Philip; Franke, Barbara; Lesch, Klaus-Peter; Faraone, Stephen V.; Nguyen, Thuy Trang; Schafer, Helmut; Holmans, Peter; Daly, Mark; Steinhausen, Hans-Christoph; Freitag, Christine; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Walitza, Susanne; Warnke, Andreas; Meyer, Jobst; Palmason, Haukur; Buitelaar, Jan; Vasquez, Alejandro Arias; Lambregts-Rommelse, Nanda; Gill, Michael; Anney, Richard J. L.; Langely, Kate; O'Donovan, Michael; Williams, Nigel; Owen, Michael; Thapar, Anita; Kent, Lindsey; Sergeant, Joseph; Roeyers, Herbert; Mick, Eric; Biederman, Joseph; Doyle, Alysa; Smalley, Susan; Loo, Sandra; Hakonarson, Hakon; Elia, Josephine; Todorov, Alexandre; Miranda, Ana; Mulas, Fernando; Ebstein, Richard P.; Rothenberger, Aribert; Banaschewski, Tobias; Oades, Robert D.; Sonuga-Barke, Edmund; McGough, James; Nisenbaum, Laura; Middleton, Frank; Hu, Xiaolan; Nelson, Stan

    2010-01-01

    Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of…

  10. A Longitudinal Study of the Association between Violent Video Game Play and Aggression among Adolescents

    Science.gov (United States)

    Willoughby, Teena; Adachi, Paul J. C.; Good, Marie

    2012-01-01

    In the past 2 decades, correlational and experimental studies have found a positive association between violent video game play and aggression. There is less evidence, however, to support a long-term relation between these behaviors. This study examined sustained violent video game play and adolescent aggressive behavior across the high school…

  11. Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

    DEFF Research Database (Denmark)

    Mitchell, Jonathan S; Li, Ni; Weinhold, Niels;

    2016-01-01

    Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a ...

  12. The association of effort-reward imbalance and asthma: findings from two cross-sectional studies

    NARCIS (Netherlands)

    A. Loerbroks; R.M. Herr; J. Li; J.A. Bosch; M. Seegel; M. Schneider; P. Angerer; B. Schmidt

    2014-01-01

    Purpose: There is evidence to suggest that work stress is positively associated with the occurrence of asthma. A limitation is that the small number of prior studies utilized unestablished work stress measures, thus constraining interpretation and generalizability. The present study re-examined this

  13. Is higher dairy consumption associated with lower body weight and fewer metabolic disturbances? The Hoorn Study

    NARCIS (Netherlands)

    Snijder, M.B.; Heijden, van der A.A.; Dam, van R.M.; Stehouwer, C.D.A.; Hiddink, G.J.; Nijpels, Giel; Heine, R.J.; Bouter, L.M.; Dekker, J.M.

    2007-01-01

    Objective:The aim of this study was to evaluate the associations of dairy consumption with body weight and other components of the metabolic syndrome. Design:We used cross-sectional data for 2064 men and women aged 50¿75 y who participated in the Hoorn Study. The metabolic syndrome was defined accor

  14. Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder.

    NARCIS (Netherlands)

    Neale, B.M.; Medland, S.E.; Ripke, S.; Asherson, P.; Franke, B.; Lesch, K.P.; Faraone, S.V.; Nguyen, T.T.; Schafer, H.; Holmans, P.; Daly, M.; Steinhausen, H.C.; Freitag, C.; Reif, A.; Renner, T.J.; Romanos, M.; Romanos, J.; Walitza, S.; Warnke, A.; Meyer, J.; Palmason, H.; Buitelaar, J.K.; Vasquez, A.A.; Lambregts-Rommelse, N.N.J.; Gill, M.; Anney, R.J.; Langely, K.; O'Donovan, M.; Williams, N.; Owen, M.; Thapar, A.; Kent, L.; Sergeant, J.A.; Roeyers, H.; Mick, E.; Biederman, J.; Doyle, A.; Smalley, S.; Loo, S.; Hakonarson, H.; Elia, J.; Todorov, A.; Miranda, A.; Mulas, F.; Ebstein, R.P.; Rothenberger, A.; Banaschewski, T.; Oades, R.D.; Sonuga-Barke, E.; McGough, J.; Nisenbaum, L.; Middleton, F.; Hu, X.; Nelson, S.

    2010-01-01

    OBJECTIVE: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded signifi

  15. From disease association to risk assessment: an optimistic view from genome-wide association studies on type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Zhi Wei

    2009-10-01

    Full Text Available Genome-wide association studies (GWAS have been fruitful in identifying disease susceptibility loci for common and complex diseases. A remaining question is whether we can quantify individual disease risk based on genotype data, in order to facilitate personalized prevention and treatment for complex diseases. Previous studies have typically failed to achieve satisfactory performance, primarily due to the use of only a limited number of confirmed susceptibility loci. Here we propose that sophisticated machine-learning approaches with a large ensemble of markers may improve the performance of disease risk assessment. We applied a Support Vector Machine (SVM algorithm on a GWAS dataset generated on the Affymetrix genotyping platform for type 1 diabetes (T1D and optimized a risk assessment model with hundreds of markers. We subsequently tested this model on an independent Illumina-genotyped dataset with imputed genotypes (1,008 cases and 1,000 controls, as well as a separate Affymetrix-genotyped dataset (1,529 cases and 1,458 controls, resulting in area under ROC curve (AUC of approximately 0.84 in both datasets. In contrast, poor performance was achieved when limited to dozens of known susceptibility loci in the SVM model or logistic regression model. Our study suggests that improved disease risk assessment can be achieved by using algorithms that take into account interactions between a large ensemble of markers. We are optimistic that genotype-based disease risk assessment may be feasible for diseases where a notable proportion of the risk has already been captured by SNP arrays.

  16. Iris color and associated pathological ocular complications: a review of epidemiologic studies

    Institute of Scientific and Technical Information of China (English)

    Hong-Peng; Sun; Yi; Lin; Chen-Wei; Pan

    2014-01-01

    AIM:To elucidate the associations of iris color with major eye diseases.· METHODS:A systematic search on Medline with coverage up to August 2013 was conducted. Assessment of the quality of studies based on their levels of evidence was in accordance with the Centre for Evidence-Based Medicine, Oxford, United Kingdom.RESULTS:A relationship between darker iris color and an increased risk of age-related cataract has been reported from cross-sectional studies and prospective cohort studies. There was no consistent evidence supporting a major role of iris color in the development or progression of age-related macular degeneration. The association of iris color with ocular uveal melanoma has been confirmed by a meta-analysis of observational studies previously. The etiologic synergism between light iris color and environmental exposure such as UV the exposure of UV radiation was found. There were no studies evaluating the refractive associations with iris color but there may be a possible link between iris color and myopia.CONCLUSION:Darker iris color is associated with an increased risk of cataract and a reduced risk of ocular uveal melanoma. The association of iris color with agerelated macular degeneration is not confirmed.Ophthalmologists should be aware that the risk of ocular disorders appears to vary by differences in iris color.

  17. HLA alleles associated with the adaptive immune response to smallpox vaccine: a replication study.

    Science.gov (United States)

    Ovsyannikova, Inna G; Pankratz, V Shane; Salk, Hannah M; Kennedy, Richard B; Poland, Gregory A

    2014-09-01

    We previously reported HLA allelic associations with vaccinia virus (VACV)-induced adaptive immune responses in a cohort of healthy individuals (n = 1,071 subjects) after a single dose of the licensed smallpox (Dryvax) vaccine. This study demonstrated that specific HLA alleles were significantly associated with VACV-induced neutralizing antibody (NA) titers (HLA-B*13:02, *38:02, *44:03, *48:01, and HLA-DQB1*03:02, *06:04) and cytokine (HLA-DRB1*01:03, *03:01, *10:01, *13:01, *15:01) immune responses. We undertook an independent study of 1,053 healthy individuals and examined associations between HLA alleles and measures of adaptive immunity after a single dose of Dryvax-derived ACAM2000 vaccine to evaluate previously discovered HLA allelic associations from the Dryvax study and determine if these associations are replicated with ACAM2000. Females had significantly higher NA titers than male subjects in both study cohorts [median ID50 discovery cohort 159 (93, 256) vs. 125 (75, 186), p smallpox vaccine-induced adaptive immune responses are significantly influenced by HLA gene polymorphisms. These data provide information for functional studies and design of novel candidate smallpox vaccines.

  18. Incorporating biological pathways via a Markov random field model in genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Min Chen

    2011-04-01

    Full Text Available Genome-wide association studies (GWAS examine a large number of markers across the genome to identify associations between genetic variants and disease. Most published studies examine only single markers, which may be less informative than considering multiple markers and multiple genes jointly because genes may interact with each other to affect disease risk. Much knowledge has been accumulated in the literature on biological pathways and interactions. It is conceivable that appropriate incorporation of such prior knowledge may improve the likelihood of making genuine discoveries. Although a number of methods have been developed recently to prioritize genes using prior biological knowledge, such as pathways, most methods treat genes in a specific pathway as an exchangeable set without considering the topological structure of a pathway. However, how genes are related with each other in a pathway may be very informative to identify association signals. To make use of the connectivity information among genes in a pathway in GWAS analysis, we propose a Markov Random Field (MRF model to incorporate pathway topology for association analysis. We show that the conditional distribution of our MRF model takes on a simple logistic regression form, and we propose an iterated conditional modes algorithm as well as a decision theoretic approach for statistical inference of each gene's association with disease. Simulation studies show that our proposed framework is more effective to identify genes associated with disease than a single gene-based method. We also illustrate the usefulness of our approach through its applications to a real data example.

  19. Studies of metabolic phenotypic correlates of 15 obesity associated gene variants.

    Directory of Open Access Journals (Sweden)

    Camilla Helene Sandholt

    Full Text Available AIMS: Genome-wide association studies have identified novel BMI/obesity associated susceptibility loci. The purpose of this study is to determine associations with overweight, obesity, morbid obesity and/or general adiposity in a Danish population. Moreover, we want to investigate if these loci associate with type 2 diabetes and to elucidate potential underlying metabolic mechanisms. METHODS: 15 gene variants in 14 loci including TMEM18 (rs7561317, SH2B1 (rs7498665, KCTD15 (rs29941, NEGR1 (rs2568958, ETV5 (rs7647305, BDNF (rs4923461, rs925946, SEC16B (rs10913469, FAIM2 (rs7138803, GNPDA2 (rs10938397, MTCH2 (rs10838738, BAT2 (rs2260000, NPC1 (rs1805081, MAF (rs1424233, and PTER (rs10508503 were genotyped in 18,014 middle-aged Danes. RESULTS: Five of the 15 gene variants associated with overweight, obesity and/or morbid obesity. Per allele ORs ranged from 1.15-1.20 for overweight, 1.10-1.25 for obesity, and 1.41-1.46 for morbid obesity. Five of the 15 variants moreover associated with increased measures of adiposity. BDNF rs4923461 displayed a borderline BMI-dependent protective effect on type 2 diabetes (0.87 (0.78-0.96, p = 0.008, whereas SH2B1 rs7498665 associated with nominally BMI-independent increased risk of type 2 diabetes (1.16 (1.07-1.27, p = 7.8×10(-4. CONCLUSIONS: Associations with overweight and/or obesity and measures of obesity were confirmed for seven out of the 15 gene variants. The obesity risk allele of BDNF rs4923461 protected against type 2 diabetes, which could suggest neuronal and peripheral distinctive ways of actions for the protein. SH2B1 rs7498665 associated with type 2 diabetes independently of BMI.

  20. Genome-wide association study of serum minerals levels in children of different ethnic background.

    Directory of Open Access Journals (Sweden)

    Xiao Chang

    Full Text Available Calcium, magnesium, potassium, sodium, chloride and phosphorus are the major dietary minerals involved in various biological functions and are commonly measured in the blood serum. Sufficient mineral intake is especially important for children due to their rapid growth. Currently, the genetic mechanisms influencing serum mineral levels are poorly understood, especially for children. We carried out a genome-wide association (GWA study on 5,602 European-American children and 4,706 African-American children who had mineral measures available in their electronic medical records (EMR. While no locus met the criteria for genome-wide significant association, our results demonstrated a nominal association of total serum calcium levels with a missense variant in the calcium -sensing receptor (CASR gene on 3q13 (rs1801725, P = 1.96 × 10(-3 in the African-American pediatric cohort, a locus previously reported in Caucasians. We also confirmed the association result in our pediatric European-American cohort (P = 1.38 × 10(-4. We further replicated two other loci associated with serum calcium levels in the European-American cohort (rs780094, GCKR, P = 4.26 × 10(-3; rs10491003, GATA3, P = 0.02. In addition, we replicated a previously reported locus on 1q21, demonstrating association of serum magnesium levels with MUC1 (rs4072037, P = 2.04 × 10(-6. Moreover, in an extended gene-based association analysis we uncovered evidence for association of calcium levels with the previously reported gene locus DGKD in both European-American children and African-American children. Taken together, our results support a role for CASR and DGKD mediated calcium regulation in both African-American and European-American children, and corroborate the association of calcium levels with GCKR and GATA3, and the association of magnesium levels with MUC1 in the European-American children.

  1. Exome-wide association study of endometrial cancer in a multiethnic population.

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    Maxine M Chen

    Full Text Available Endometrial cancer (EC contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome-wide association studies (GWAS have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2. No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC.

  2. Association of childhood trauma with cognitive function in healthy adults: a pilot study

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    Lin Jin-Mann S

    2010-07-01

    Full Text Available Abstract Background Animal and human studies suggest that stress experienced early in life has detrimental consequences on brain development, including brain regions involved in cognitive function. Cognitive changes are cardinal features of depression and posttraumatic stress disorder. Early-life trauma is a major risk factor for these disorders. Only few studies have measured the long-term consequences of childhood trauma on cognitive function in healthy adults. Methods In this pilot study, we investigated the relationship between childhood trauma exposure and cognitive function in 47 healthy adults, who were identified as part of a larger study from the general population in Wichita, KS. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB and the Wide-Range-Achievement-Test (WRAT-3 to examine cognitive function and individual achievement. Type and severity of childhood trauma was assessed by the Childhood Trauma Questionnaire (CTQ. Data were analyzed using multiple linear regression on CANTAB measures with primary predictors (CTQ scales and potential confounders (age, sex, education, income. Results Specific CTQ scales were significantly associated with measures of cognitive function. Emotional abuse was associated with impaired spatial working memory performance. Physical neglect correlated with impaired spatial working memory and pattern recognition memory. Sexual abuse and physical neglect were negatively associated with WRAT-3 scores. However, the association did not reach the significance level of p Conclusions Our results suggest that physical neglect and emotional abuse might be associated with memory deficits in adulthood, which in turn might pose a risk factor for the development of psychopathology.

  3. Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

    DEFF Research Database (Denmark)

    Song, Honglin; Ramus, Susan J; Kjaer, Susanne Krüger;

    2009-01-01

    , three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend ....01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast...... cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function....

  4. Socioeconomic Indicators Are Independently Associated with Nutrient Intake in French Adults: A DEDIPAC Study

    Directory of Open Access Journals (Sweden)

    Wendy Si Hassen

    2016-03-01

    Full Text Available Studies have suggested differential associations of specific indicators of socioeconomic position (SEP with nutrient intake and a cumulative effect of these indicators on diet. We investigated the independent association of SEP indicators (education, income, occupation with nutrient intake and their effect modification. This cross-sectional analysis included 91,900 French adults from the NutriNet-Santé cohort. Nutrient intake was estimated using three 24-h records. We investigated associations between the three SEP factors and nutrient intake using sex-stratified analysis of covariance, adjusted for age and energy intake, and associations between income and nutrient intake stratified by education and occupation. Low educated participants had higher protein and cholesterol intakes and lower fibre, vitamin C and beta-carotene intakes. Low income individuals had higher complex carbohydrate intakes, and lower magnesium, potassium, folate and vitamin C intakes. Intakes of vitamin D and alcohol were lower in low occupation individuals. Higher income was associated with higher intakes of fibre, protein, magnesium, potassium, beta-carotene, and folate among low educated persons only, highlighting effect modification. Lower SEP, particularly low education, was associated with lower intakes of nutrients required for a healthy diet. Each SEP indicator was associated with specific differences in nutrient intake suggesting that they underpin different social processes.

  5. Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy

    Science.gov (United States)

    Kouri, Naomi; Ross, Owen A.; Dombroski, Beth; Younkin, Curtis S.; Serie, Daniel J.; Soto-Ortolaza, Alexandra; Baker, Matthew; Finch, Ni Cole A.; Yoon, Hyejin; Kim, Jungsu; Fujioka, Shinsuke; McLean, Catriona A.; Ghetti, Bernardino; Spina, Salvatore; Cantwell, Laura B.; Farlow, Martin R.; Grafman, Jordan; Huey, Edward D.; Ryung Han, Mi; Beecher, Sherry; Geller, Evan T.; Kretzschmar, Hans A.; Roeber, Sigrun; Gearing, Marla; Juncos, Jorge L.; Vonsattel, Jean Paul G.; Van Deerlin, Vivianna M.; Grossman, Murray; Hurtig, Howard I.; Gross, Rachel G.; Arnold, Steven E.; Trojanowski, John Q.; Lee, Virginia M.; Wenning, Gregor K.; White, Charles L.; Höglinger, Günter U.; Müller, Ulrich; Devlin, Bernie; Golbe, Lawrence I.; Crook, Julia; Parisi, Joseph E.; Boeve, Bradley F.; Josephs, Keith A.; Wszolek, Zbigniew K.; Uitti, Ryan J.; Graff-Radford, Neill R.; Litvan, Irene; Younkin, Steven G.; Wang, Li-San; Ertekin-Taner, Nilüfer; Rademakers, Rosa; Hakonarsen, Hakon; Schellenberg, Gerard D.; Dickson, Dennis W.

    2015-01-01

    Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.42 × 10−12), 8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472; P=3.41 × 10−8), and 2p22 at SOS1 (rs963731; P=1.76 × 10−7). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22; rs1768208; P=2.07 × 10−7) and MAPT H1c (17q21; rs242557; P=7.91 × 10−6). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein). PMID:26077951

  6. Socioeconomic Indicators Are Independently Associated with Nutrient Intake in French Adults: A DEDIPAC Study

    Science.gov (United States)

    Si Hassen, Wendy; Castetbon, Katia; Cardon, Philippe; Enaux, Christophe; Nicolaou, Mary; Lien, Nanna; Terragni, Laura; Holdsworth, Michelle; Stronks, Karien; Hercberg, Serge; Méjean, Caroline

    2016-01-01

    Studies have suggested differential associations of specific indicators of socioeconomic position (SEP) with nutrient intake and a cumulative effect of these indicators on diet. We investigated the independent association of SEP indicators (education, income, occupation) with nutrient intake and their effect modification. This cross-sectional analysis included 91,900 French adults from the NutriNet-Santé cohort. Nutrient intake was estimated using three 24-h records. We investigated associations between the three SEP factors and nutrient intake using sex-stratified analysis of covariance, adjusted for age and energy intake, and associations between income and nutrient intake stratified by education and occupation. Low educated participants had higher protein and cholesterol intakes and lower fibre, vitamin C and beta-carotene intakes. Low income individuals had higher complex carbohydrate intakes, and lower magnesium, potassium, folate and vitamin C intakes. Intakes of vitamin D and alcohol were lower in low occupation individuals. Higher income was associated with higher intakes of fibre, protein, magnesium, potassium, beta-carotene, and folate among low educated persons only, highlighting effect modification. Lower SEP, particularly low education, was associated with lower intakes of nutrients required for a healthy diet. Each SEP indicator was associated with specific differences in nutrient intake suggesting that they underpin different social processes. PMID:26978393

  7. An ASMT variant associated with bipolar disorder influences sleep and circadian rhythms: a pilot study.

    Science.gov (United States)

    Geoffroy, P A; Boudebesse, C; Henrion, A; Jamain, S; Henry, C; Leboyer, M; Bellivier, F; Etain, B

    2014-03-01

    Patients with bipolar disorder (BD) experience persistent circadian rhythm and sleep abnormalities during periods of remission, and biological studies have shown that these patients have abnormal melatonin secretion profiles or reactivity to light. We previously reported the association with BD of a common polymorphism (rs4446909) of the promoter of the acetylserotonin O-methyltransferase (ASMT) gene, encoding one of the two enzymes involved in melatonin biosynthesis. This variant was associated with weaker transcription and lower levels of ASMT activity in lymphoblastoid cell lines. Actigraphy, based on the use of a mobile portable device for the analysis of sleep/wake cycles in natural conditions, may be useful for studies of carriers of the at-risk allele. We studied the association between the ASMT rs4446909 variant and sleep/activity, as assessed with the Pittsburgh Sleep Quality Index (PSQI) and by actigraphy, in 53 subjects (25 patients with BD in remission and 28 healthy controls). The two groups were similar for age, sex ratio, current mood symptoms, body mass index and risk of sleep apnea syndrome. In the total sample, the GG at-risk genotype was associated with longer sleep duration (P = 0.03), greater activity in active periods of sleep (P = 0.015) and greater interday stability (P = 0.003). These associations remained significant when disease status was included in the model. Only the association with interday stability remained significant after correction for multiple testing. This pilot study thus shows that a BD-associated functional variant involved in the melatonin synthesis pathway influences sleep and circadian rhythms in bipolar patients in remission and controls.

  8. A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.

    Science.gov (United States)

    Ikeda, M; Takahashi, A; Kamatani, Y; Okahisa, Y; Kunugi, H; Mori, N; Sasaki, T; Ohmori, T; Okamoto, Y; Kawasaki, H; Shimodera, S; Kato, T; Yoneda, H; Yoshimura, R; Iyo, M; Matsuda, K; Akiyama, M; Ashikawa, K; Kashiwase, K; Tokunaga, K; Kondo, K; Saito, T; Shimasaki, A; Kawase, K; Kitajima, T; Matsuo, K; Itokawa, M; Someya, T; Inada, T; Hashimoto, R; Inoue, T; Akiyama, K; Tanii, H; Arai, H; Kanba, S; Ozaki, N; Kusumi, I; Yoshikawa, T; Kubo, M; Iwata, N

    2017-01-24

    Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10(-9)), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10(-10)), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10(-9)), TRANK1 (Pbest=2.1 × 10(-9)) and ODZ4 (Pbest=3.3 × 10(-9)). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', Pbest~10(-29), R(2)~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' Pbest~10(-13), R(2)~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.Molecular Psychiatry advance online publication, 24 January 2017; doi:10.1038/mp.2016.259.

  9. Associations between vertebral fractures, increased thoracic kyphosis, a flexed posture and falls in older adults : a prospective cohort study

    NARCIS (Netherlands)

    van der Jagt-Willems, Hanna C.; de Groot, Maartje H.; van Campen, Jos P. C. M.; Lamoth, Claudine J. C.; Lems, Willem F.

    2015-01-01

    Background: Vertebral fractures, an increased thoracic kyphosis and a flexed posture are associated with falls. However, this was not confirmed in prospective studies. We performed a prospective cohort study to investigate the association between vertebral fractures, increased thoracic kyphosis and/

  10. The Genetic and Environmental Contributions to Internet Use and Associations With Psychopathology: A Twin Study.

    Science.gov (United States)

    Long, Elizabeth C; Verhulst, Brad; Neale, Michael C; Lind, Penelope A; Hickie, Ian B; Martin, Nicholas G; Gillespie, Nathan A

    2016-02-01

    Excessive internet use has been linked to psychopathology. Therefore, understanding the genetic and environmental risks underpinning internet use and their relation to psychopathology is important. This study aims to explore the genetic and environmental etiology of internet use measures and their associations with internalizing disorders and substance use disorders. The sample included 2,059 monozygotic (MZ) and dizygotic (DZ) young adult twins from the Brisbane Longitudinal Twin Study (BLTS). Younger participants reported more frequent internet use, while women were more likely to use the internet for interpersonal communication. Familial aggregation in 'frequency of internet use' was entirely explained by additive genetic factors accounting for 41% of the variance. Familial aggregation in 'frequency of use after 11 pm', 'using the internet to contact peers', and 'using the internet primarily to access social networking sites' was attributable to varying combinations of additive genetic and shared environmental factors. In terms of psychopathology, there were no significant associations between internet use measures and major depression (MD), but there were positive significant associations between 'frequency of internet use' and 'frequency of use after 11 pm' with social phobia (SP). 'Using the internet to contact peers' was positively associated with alcohol abuse, whereas 'using the internet to contact peers' and 'using the internet primarily to access social networking sites' were negatively associated with cannabis use disorders and nicotine symptoms. Individual differences in internet use can be attributable to varying degrees of genetic and environmental risks. Despite some significant associations of small effect, variation in internet use appears mostly unrelated to psychopathology.

  11. Association Between Geographic Elevation, Bone Status, and Exercise Habits: The Shimane CoHRE Study

    Directory of Open Access Journals (Sweden)

    Miwako Takeda

    2015-06-01

    Full Text Available In recent years, there has been growing interest in the association between the residential environment and health. The association between residential environment (i.e., geographic elevation and bone status is unknown. Furthermore, these associations could differ by exercise habits due to the chronically greater daily activity caused by steep slopes in mountainous areas. The aim of this study was to test whether the association between bone status of elderly people measured using quantitative ultrasound (QUS and elevation varied according to the exercise habits in a mountainous area population. Data were collected from a cross-sectional study conducted during 2012–2013. QUS value was expressed as a proportion of the young adult mean (%YAM, with higher scores donating better bone status. After excluding subjects with missing data, we analyzed the data for 321 men and 500 women. Our results indicate that %YAM was not associated with elevation among men, or among women with exercise habits. However, elevation was associated with %YAM among women without exercise habits. Our results highlight the importance of considering residential environment and exercise habits when establishing promotion strategies to maintain bone status of the elderly people who live in rural mountainous areas.

  12. Heart rate is associated with markers of fatty acid desaturation: the GOCADAN study

    Directory of Open Access Journals (Sweden)

    Sven O.E. Ebbesson

    2012-03-01

    Full Text Available Objectives: To determine if heart rate (HR is associated with desaturation indexes as HR is associated with arrhythmia and sudden death. Study design: A community based cross-sectional study of 1214 Alaskan Inuit. Methods: Data of FA concentrations from plasma and red blood cell membranes from those ≥35 years of age (n = 819 were compared to basal HR at the time of examination. Multiple linear regression with backward stepwise selection was employed to analyze the effect of the desaturase indexes on HR, after adjustment for relevant covariates. Results: The Δ5 desaturase index (Δ5-DI measured in serum has recently been associated with a protective role for cardiovascular disease. This index measured here in plasma and red blood cells showed a negative correlation with HR. The plasma stearoyl-CoA-desaturase (SCD index, previously determined to be related to cardiovascular disease (CVD mortality, on the other hand, was positively associated with HR, while the Δ6 desaturase index (Δ6-DI had no significant effect on HR. Conclusion: Endogenous FA desaturation is associated with HR and thereby, in the case of SCD, possibly with arrhythmia and sudden death, which would at least partially explain the previously observed association between cardiovascular mortality and desaturase activity.

  13. Genome-wide association study of hepatitis C virus- and cryoglobulin-related vasculitis.

    Science.gov (United States)

    Zignego, A L; Wojcik, G L; Cacoub, P; Visentini, M; Casato, M; Mangia, A; Latanich, R; Charles, E D; Gragnani, L; Terrier, B; Piazzola, V; Dustin, L B; Khakoo, S I; Busch, M P; Lauer, G M; Kim, A Y; Alric, L; Thomas, D L; Duggal, P

    2014-10-01

    The host genetic basis of mixed cryoglobulin vasculitis is not well understood and has not been studied in large cohorts. A genome-wide association study was conducted among 356 hepatitis C virus (HCV) RNA-positive individuals with cryoglobulin-related vasculitis and 447 ethnically matched, HCV RNA-positive controls. All cases had both serum cryoglobulins and a vasculitis syndrome. A total of 899 641 markers from the Illumina HumanOmni1-Quad chip were analyzed using logistic regression adjusted for sex, as well as genetically determined ancestry. Replication of select single-nucleotide polymorphisms (SNPs) was conducted using 91 cases and 180 controls, adjusting for sex and country of origin. The most significant associations were identified on chromosome 6 near the NOTCH4 and MHC class II genes. A genome-wide significant association was detected on chromosome 6 at SNP rs9461776 (odds ratio=2.16, P=1.16E-07) between HLA-DRB1 and DQA1: this association was further replicated in additional independent samples (meta-analysis P=7.1 × 10(-9)). A genome-wide significant association with cryoglobulin-related vasculitis was identified with SNPs near NOTCH4 and MHC Class II genes. The two regions are correlated and it is difficult to disentangle which gene is responsible for the association with mixed cryoglobulinemia vasculitis in this extended major histocompatibility complex region.

  14. Reproductive factors associated with mammographic density: a Korean co-twin control study.

    Science.gov (United States)

    Sung, Joohon; Song, Yun-Mi; Stone, Jennifer; Lee, Kayoung; Lee, Donghun

    2011-07-01

    To determine the mechanism by which menstrual and reproductive factors are associated with the risk of breast cancer, we examined the relationships between mammographic density and known menstrual and reproductive risk factors for breast cancer. A co-twin control study was conducted with 122 pairs of monozygotic Korean female twins selected from the Healthy Twin study. Mammographic density was measured from digital mammograms using a computer-assisted method. Information on selected menstrual and reproductive factors was collected through a self-administered questionnaire. Within-pair differences for each mammographic measure were regressed against within-pair differences for each menstrual and reproductive risk factor with an adjustment for body mass index and other menstrual and reproductive factors. The percent dense area was inversely associated with the age at the first full-term childbirth (FFTB) and the number of live births, although the associations were marginally significant with an adjustment for BMI and other reproductive factors. The non-dense area was positively associated with the age at the FFTB and the number of live births. The absolute dense area was positively associated with the duration of breast feeding. The age at menarche was not associated with any component of the mammographic measures. This finding suggests that mammographic density can mediate the protective effect of greater parity against breast cancer, at least in part while age at menarche, age at the FFTB, and breast feeding do not exert their effects through mammographic density.

  15. The Associations between Ethical Organizational Culture, Burnout, and Engagement: A Multilevel Study

    OpenAIRE

    Huhtala, Mari; Tolvanen, Asko; Mauno, Saija; Feldt, Taru

    2015-01-01

    Purpose – Ethical culture is a specific form of organizational culture (including values and systems that can promote ethical behavior), and as such a socially constructed phenomenon. However, no previous studies have investigated the degree to which employees’ perceptions of their organization’s ethical culture are shared within work units (departments), which was the first aim of this study. In addition, we studied the associations between ethical culture and occupational wel...

  16. Study of the associated production of Higgs boson with a single top quark

    CERN Document Server

    Das, Pallabi

    2017-01-01

    The study of the production of single top quark in association with the Higgs boson at LHC with CMS experiment is presented. Characteristics of the signal and major backgrounds are studied in the multi-leptonic final state, specifically, same-sign dimuon channel. Discrimination between the signal and background processes is done using the multi-variate analysis technique in ROOT framework. Results from preliminary simulation studies at proton-proton collision energy of 13 TeV are discussed briefly.

  17. Study of Association of Psychological Stress and Depression among Undergraduate Medical Students in Pondicherry

    OpenAIRE

    Devi Kittu, Rohan Patil

    2013-01-01

    Background: Medical education across the globe is perceived as being inherently stressful. Studies on psychological problems such as stress, depression and anxiety among medical students have found that these disorders are under diagnosed and under treated. In this background the present study was undertaken with the objectives to assess the magni-tude of depression and its association with stress among medical students. Methods: A Cross sectional study was undertaken among 235 medical st...

  18. VCA-DVC VMware certified associate on vSphere study guide VCAD-510

    CERN Document Server

    Schmidt, Robert

    2015-01-01

    Use this expert guide to prepare for the VCA-DCV exam VCA-DCV VMware Certified Associate on vSphere Study Guide: VCAD-510 is a comprehensive study guide for the VMware Certified Associate - Data Center Virtualization exam. Hands-on examples, real-world scenarios, and expert review questions cover the full exam blueprint, and the companion website offers a suite of tools to help you prepare for the exam including practice exams, electronic flashcards, and a glossary of key terms. In addition, the website includes videos that demonstrate how to complete the more challenging tasks. Focused on p

  19. Ocular myasis and associated mucopurulent conjuctivitis acquired occupationally: A case study

    Directory of Open Access Journals (Sweden)

    Jayaprakash K

    2008-01-01

    Full Text Available Ocular myasis and associated mucopurulent conjunctivitis in human eyes is a rare phenomenon. However, if the sheep bot fly abounds and poor hygienic environment prevails, the Oestrous ovis deposits its larvae in the conjunctival eye sac of human. The present paper reports a case study of ocular myasis among sheep farm workers caused by Oestrous ovis . The ocular myasis and the associated mucopurulent conjunctivitis are occupationally acquired in these cases. This study also suggests the treatment of patients and the recovery of the larvae.

  20. Reporting of Human Genome Epidemiology (HuGE association studies: An empirical assessment

    Directory of Open Access Journals (Sweden)

    Gwinn Marta

    2008-05-01

    Full Text Available Abstract Background Several thousand human genome epidemiology association studies are published every year investigating the relationship between common genetic variants and diverse phenotypes. Transparent reporting of study methods and results allows readers to better assess the validity of study findings. Here, we document reporting practices of human genome epidemiology studies. Methods Articles were randomly selected from a continuously updated database of human genome epidemiology association studies to be representative of genetic epidemiology literature. The main analysis evaluated 315 articles published in 2001–2003. For a comparative update, we evaluated 28 more recent articles published in 2006, focusing on issues that were poorly reported in 2001–2003. Results During both time periods, most studies comprised relatively small study populations and examined one or more genetic variants within a single gene. Articles were inconsistent in reporting the data needed to assess selection bias and the methods used to minimize misclassification (of the genotype, outcome, and environmental exposure or to identify population stratification. Statistical power, the use of unrelated study participants, and the use of replicate samples were reported more often in articles published during 2006 when compared with the earlier sample. Conclusion We conclude that many items needed to assess error and bias in human genome epidemiology association studies are not consistently reported. Although some improvements were seen over time, reporting guidelines and online supplemental material may help enhance the transparency of this literature.

  1. Genome-wide association study of autistic-like traits in a general population study of young adults

    Directory of Open Access Journals (Sweden)

    Rachel Maree Jones

    2013-10-01

    Full Text Available Research has proposed that autistic-like traits in the general population lie on a continuum, with clinical Autism Spectrum Disorder (ASD representing the extreme end of this distribution. Inherent in this proposal is that biological mechanisms associated with clinical ASD may also underpin variation in autistic-like traits within the general population. A genome-wide association study using 2,462,046 single nucleotide polymorphisms (SNPs was undertaken for ASD in 965 individuals from the Western Australian Pregnancy Cohort (Raine Study. No SNP associations reached genome-wide significance (p < 5.0 x 10-8. However, investigations into nominal observed SNP associations (p < 1.0 x 10-5 add support to two positional candidate genes previously implicated in ASD aetiology, PRKCB1 and CBLN1.The rs198198 SNP (p = 9.587 x 10-6, is located within an intron of the protein kinase C, beta 1 (PRKCB1 gene on chromosome 16p11. The PRKCB1 gene has been previously reported in linkage and association studies for ASD, and its mRNA expression has been shown to be significantly down regulated in ASD cases compared with controls. The rs16946931 SNP (p = 1.78 x 10-6 is located in a region flanking the Cerebellin 1 (CBLN1 gene on chromosome 16q12.1. The CBLN1 gene is involved with synaptogenesis and is part of a gene family previously implicated in ASD. This GWA study is only the second to examine SNPs associated with autistic-like traits in the general population, and provides evidence to support roles for the PRKCB1 and CBLN1 genes in risk of clinical ASD.

  2. Genome-wide association study of retinopathy in individuals without diabetes.

    Directory of Open Access Journals (Sweden)

    Richard A Jensen

    Full Text Available BACKGROUND: Mild retinopathy (microaneurysms or dot-blot hemorrhages is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS of mild retinopathy in persons without diabetes. METHODS: A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy. RESULTS: No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9 on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, -1.3±0.23 (beta ± standard error, p = 6.6×10(-9. Evidence suggests this was a false positive finding. The minor allele frequency was low (∼2%, the quality of the imputation was moderate (r(2 ∼0.7, and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension. CONCLUSIONS: This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.

  3. Exploratory Cohort Study of Associations between Serum C - Reactive Protein and Fatigue after Stroke.

    Directory of Open Access Journals (Sweden)

    Simiao Wu

    Full Text Available Post-stroke fatigue is a common and distressing problem but little is known about its biological mechanisms. This cohort study was to investigate associations between C-reactive protein (CRP and fatigue after stroke.Patients were assessed at one, six and 12 months after their stroke onset, with the Fatigue Assessment Scale, a case definition of post-stroke fatigue, Hospital Anxiety and Depression Scale, and daily step counts. Blood samples were collected at each assessment and the CRP level was determined by a standard CRP immunoassay. Cross-sectional associations between CRP and fatigue at each time point were determined by Pearson correlation coefficient and independent-samples t-test. Whether CRP levels at one month predict fatigue scores at six and 12 months was explored by multiple linear regression, with anxiety, depression, and daily step counts as covariates.Sixty-five patients (mean age 67 years, 65% men were included: 61 at one month, 49 at six months, and 41 at 12 months. CRP levels and fatigue scores were not associated at one month (p = 0.88 or 12 months (p = 0.56, but weakly associated at six months (r = 0.27, p = 0.04; however, this association was no longer significant (p = 0.14 after controlling for the effects of covariates. The CRP level was not associated with the fulfilment of case definition of post-stroke fatigue at any time points (all p > 0.05. The CRP level at one month was not a significant predictor for fatigue levels at either six months (p = 0.93 or 12 months (p = 0.78.There is insufficient evidence for the association between CRP and PSF in stroke patients. Future studies with larger sample sizes and controlling for potential confounders are needed to investigate whether this association exists.

  4. Exploratory Cohort Study of Associations between Serum C - Reactive Protein and Fatigue after Stroke

    Science.gov (United States)

    Wu, Simiao; Duncan, Fiona; Anderson, Niall H.; Kuppuswamy, Annapoorna; Macloed, Malcolm R.; Mead, Gillian E.

    2015-01-01

    Background and Aim Post-stroke fatigue is a common and distressing problem but little is known about its biological mechanisms. This cohort study was to investigate associations between C-reactive protein (CRP) and fatigue after stroke. Methods Patients were assessed at one, six and 12 months after their stroke onset, with the Fatigue Assessment Scale, a case definition of post-stroke fatigue, Hospital Anxiety and Depression Scale, and daily step counts. Blood samples were collected at each assessment and the CRP level was determined by a standard CRP immunoassay. Cross-sectional associations between CRP and fatigue at each time point were determined by Pearson correlation coefficient and independent-samples t-test. Whether CRP levels at one month predict fatigue scores at six and 12 months was explored by multiple linear regression, with anxiety, depression, and daily step counts as covariates. Results Sixty-five patients (mean age 67 years, 65% men) were included: 61 at one month, 49 at six months, and 41 at 12 months. CRP levels and fatigue scores were not associated at one month (p = 0.88) or 12 months (p = 0.56), but weakly associated at six months (r = 0.27, p = 0.04); however, this association was no longer significant (p = 0.14) after controlling for the effects of covariates. The CRP level was not associated with the fulfilment of case definition of post-stroke fatigue at any time points (all p > 0.05). The CRP level at one month was not a significant predictor for fatigue levels at either six months (p = 0.93) or 12 months (p = 0.78). Conclusions There is insufficient evidence for the association between CRP and PSF in stroke patients. Future studies with larger sample sizes and controlling for potential confounders are needed to investigate whether this association exists. PMID:26599129

  5. Bacterial Factors Associated with Lethal Outcome of Enteropathogenic Escherichia coli Infection: Genomic Case-Control Studies.

    Directory of Open Access Journals (Sweden)

    Michael S Donnenberg

    2015-05-01

    Full Text Available Typical enteropathogenic Escherichia coli (tEPEC strains were associated with mortality in the Global Enteric Multicenter Study (GEMS. Genetic differences in tEPEC strains could underlie some of the variability in clinical outcome.We produced draft genome sequences of all available tEPEC strains from GEMS lethal infections (LIs and of closely matched EPEC strains from GEMS subjects with non-lethal symptomatic infections (NSIs and asymptomatic infections (AIs to identify gene clusters (potential protein encoding sequences sharing ≥90% nucleotide sequence identity associated with lethality.Among 14,412 gene clusters identified, the presence or absence of 392 was associated with clinical outcome. As expected, more gene clusters were associated with LI versus AI than LI versus NSI. The gene clusters more prevalent in strains from LI than those from NSI and AI included those encoding proteins involved in O-antigen biogenesis, while clusters encoding type 3 secretion effectors EspJ and OspB were among those more prevalent in strains from non-lethal infections. One gene cluster encoding a variant of an NleG ubiquitin ligase was associated with LI versus AI, while two other nleG clusters had the opposite association. Similar associations were found for two nleG gene clusters in an additional, larger sample of NSI and AI GEMS strains.Particular genes are associated with lethal tEPEC infections. Further study of these factors holds potential to unravel the mechanisms underlying severe disease and to prevent adverse outcomes.

  6. A genome-wide association study of emotion dysregulation: Evidence for interleukin 2 receptor alpha.

    Science.gov (United States)

    Powers, Abigail; Almli, Lynn; Smith, Alicia; Lori, Adriana; Leveille, Jen; Ressler, Kerry J; Jovanovic, Tanja; Bradley, Bekh

    2016-12-01

    Emotion dysregulation has been implicated as a risk factor for many psychiatric conditions. Therefore, examining genetic risk associated with emotion dysregulation could help inform cross-disorder risk more generally. A genome-wide association study (GWAS) of emotion dysregulation using single nucleotide polymorphism (SNP) array technology was conducted in a highly traumatized, minority, urban sample (N = 2600, males = 774). Post-hoc analyses examined associations between SNPs identified in the GWAS and current depression, posttraumatic stress disorder (PTSD), and history of suicide attempt. Methylation quantitative trait loci were identified and gene set enrichment analyses were used to broadly determine biological processes involved with these SNPs. Among males, SNP rs6602398, located within the interleukin receptor 2A gene, IL2RA, was significantly associated with emotion dysregulation (p = 1.1 × 10(-8)). Logistic regression analyses revealed this SNP was significantly associated with depression (Exp(B) = 2.67, p < 0.001) and PTSD (Exp(B) = 2.07, p < 0.01). This SNP was associated with differential DNA methylation (p < 0.05) suggesting it may be functionally active. Finally, through gene set enrichment analyses, ten psychiatric disease pathways (adjusted p < 0.01) and the calcium signaling pathway (adjusted p = 0.008) were significantly associated with emotion dysregulation. We found initial evidence for an association between emotion dysregulation and genetic risk loci that have already been implicated in medical disorders that have high comorbidity with psychiatric disorders. Our results provide further evidence that emotion dysregulation can be understood as a potential psychiatric cross-disorder risk factor, and that sex differences across these phenotypes may be critical. Continued research into genetic and biological risk associated with emotion dysregulation is needed.

  7. Item familiarity and controlled associative retrieval in Alzheimer's disease: an fMRI study.

    Science.gov (United States)

    Genon, Sarah; Collette, Fabienne; Feyers, Dorothée; Phillips, Christophe; Salmon, Eric; Bastin, Christine

    2013-06-01

    Typical Alzheimer's disease (AD) is characterized by an impaired form of associative memory, recollection, that includes the controlled retrieval of associations. In contrast, familiarity-based memory for individual items may sometimes be preserved in the early stages of the disease. This is the first study that directly examines whole-brain regional activity during one core aspect of the recollection function: associative controlled episodic retrieval (CER), contrasted to item familiarity in AD patients. Cerebral activity related to associative CER and item familiarity in AD patients and healthy controls (HCs) was measured with functional magnetic resonance imaging during a word-pair recognition task to which the process dissociation procedure was applied. Some patients had null CER estimates (AD-), whereas others did show some CER abilities (AD+), although significantly less than HC. In contrast, familiarity estimates were equivalent in the three groups. In AD+, as in controls, associative CER activated the inferior precuneus/posterior cingulate cortex (PCC). When performing group comparisons, no region was found to be significantly more activated during CER in HC than AD+ and vice versa. However, during associative CER, functional connectivity between this region and the hippocampus, the inferior parietal and dorsolateral prefrontal cortex (DLPFC) was significantly higher in HC than in AD+. In all three groups, item familiarity was related to activation along the intraparietal sulcus (IPS). In conclusion, whereas the preserved automatic detection of an old item (without retrieval of accurate word association) is related to parietal activation centred on the IPS, the inferior precuneus/PCC supports associative CER ability in AD patients, as in HC. However, AD patients have deficient functional connectivity during associative CER, suggesting that the residual recollection function in these patients might be impoverished by the lack of some recollection

  8. Utilization of Positive and Negative Controls to Examine Comorbid Associations in Observational Database Studies

    Science.gov (United States)

    Hyde, Craig L.; Kabadi, Shaum; St Louis, Matthew; Bonato, Vinicius; Katrina Loomis, A.; Galaznik, Aaron; Berger, Marc L.

    2017-01-01

    Background: Opportunities to leverage observational data for precision medicine research are hampered by underlying sources of bias and paucity of methods to handle resulting uncertainty. We outline an approach to account for bias in identifying comorbid associations between 2 rare genetic disorders and type 2 diabetes (T2D) by applying a positive and negative control disease paradigm. Research Design: Association between 10 common and 2 rare genetic disorders [Hereditary Fructose Intolerance (HFI) and α-1 antitrypsin deficiency] and T2D was compared with the association between T2D and 7 negative control diseases with no established relationship with T2D in 4 observational databases. Negative controls were used to estimate how much bias and variance existed in datasets when no effect should be observed. Results: Unadjusted association for common and rare genetic disorders and T2D was positive and variable in magnitude and distribution in all 4 databases. However, association between negative controls and T2D was 200% greater than expected indicating the magnitude and confidence intervals for comorbid associations are sensitive to systematic bias. A meta-analysis using this method demonstrated a significant association between HFI and T2D but not for α-1 antitrypsin deficiency. Conclusions: For observational studies, when covariate data are limited or ambiguous, positive and negative controls provide a method to account for the broadest level of systematic bias, heterogeneity, and uncertainty. This provides greater confidence in assessing associations between diseases and comorbidities. Using this approach we were able to demonstrate an association between HFI and T2D. Leveraging real-world databases is a promising approach to identify and corroborate potential targets for precision medicine therapies. PMID:27787351

  9. Association study of FOXO3A SNPs and aging phenotypes in Danish oldest-old individuals.

    Science.gov (United States)

    Soerensen, Mette; Nygaard, Marianne; Dato, Serena; Stevnsner, Tinna; Bohr, Vilhelm A; Christensen, Kaare; Christiansen, Lene

    2015-02-01

    FOXO3A variation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether FOXO3A variation also associates with aging-related traits. Here, we investigate the association of 15 FOXO3A tagging single nucleotide polymorphisms (SNPs) in 1088 oldest-old Danes (age 92-93) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self-rated health. Based on previous studies in humans and foxo animal models, we also explore self-reported diabetes, cancer, cardiovascular disease, osteoporosis, and bone (femur/spine/hip/wrist) fracture. Gene-based testing revealed significant associations of FOXO3A variation with ADL (P = 0.044) and bone fracture (P = 0.006). The single-SNP statistics behind the gene-based analysis indicated increased ADL (decreased disability) and reduced bone fracture risk for carriers of the minor alleles of 8 and 10 SNPs, respectively. These positive directions of effects are in agreement with the positive effects on longevity previously reported for these SNPs. However, when correcting for the test of 9 phenotypes by Bonferroni correction, bone fracture showed borderline significance (P = 0.054), while ADL did not (P = 0.396). Although the single-SNP associations did not formally replicate in another study population of oldest-old Danes (n = 1279, age 94-100), the estimates were of similar direction of effect as observed in the Discovery sample. A pooled analysis of both study populations displayed similar or decreased sized P-values for most associations, hereby supporting the initial findings. Nevertheless, confirmation in additional study populations is needed.

  10. Association between Allergic Rhinitis and Asthma Control in Peruvian School Children: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Justo Padilla

    2013-01-01

    Full Text Available Background. Asthma and allergic rhinitis are highly prevalent conditions that cause major illness worldwide. This study aimed to assess the association between allergic rhinitis and asthma control in Peruvian school children. Methods. A cross-sectional study was conducted among 256 children with asthma recruited in 5 schools from Lima and Callao cities. The outcome was asthma control assessed by the asthma control test. A score test for trend of odds was used to evaluate the association between allergic rhinitis severity and the prevalence of inadequate asthma control. A generalized linear regression model was used to estimate the adjusted prevalence ratios of inadequate asthma control. Results. Allergic rhinitis was present in 66.4% of the population with asthma. The trend analysis showed a positive association between allergic rhinitis and the probability of inadequate asthma control (. It was associated with an increased prevalence of inadequate asthma control, with adjusted prevalence ratios of 1.53 (95% confidence interval: 1.19−1.98. Conclusion. This study indicates that allergic rhinitis is associated with an inadequate level of asthma control, giving support to the recommendation of evaluating rhinitis to improve asthma control in children.

  11. Impaired Fertility Associated with Subclinical Hypothyroidism and Thyroid Autoimmunity: The Danish General Suburban Population Study

    Directory of Open Access Journals (Sweden)

    Anne-Dorthe Feldthusen

    2015-01-01

    Full Text Available Introduction. The aim of this study was to estimate the significance of TSH, thyroid peroxidase antibody (TPOAb, and mild (subclinical hypothyroidism in women from The Danish General Suburban Population Study (GESUS on the number of children born, the number of pregnancies, and the number of spontaneous abortions. Methods. Retrospective cross sectional study of 11254 women participating in GESUS. Data included biochemical measurements and a self-administrated questionnaire. Results. 6.7% had mild (subclinical hypothyroidism and 9.4% prevalent hypothyroidism. In women with mild hypothyroidism TPOAb was significantly elevated and age at first child was older compared to controls. TSH and TPOAb were negatively linearly associated with the number of children born and the number of pregnancies in the full cohort in age-adjusted and multiadjusted models. TSH or TPOAb was not associated with spontaneous abortions. Mild (subclinical hypothyroidism was associated with a risk of not having children and a risk of not getting pregnant in age-adjusted and multiadjusted models. Prevalent hypothyroidism was not associated with the number of children born, the number of pregnancies, or spontaneous abortions. Conclusion. Impaired fertility is associated with TSH, TPOAb, and mild (subclinical hypothyroidism in a Danish population of women.

  12. Association of variants in the PCSK1 gene with obesity in the EPIC-Norfolk study

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas; Bingham, Sheila A; Khaw, Kay-Tee;

    2009-01-01

    , BMI or waist circumference under the additive genetic model (P > 0.05). However, we observed an interaction between rs6232 and age on the level of BMI (P = 0.010) and risk of obesity (P = 0.020). The rs6232 SNP was associated with BMI (P = 0.021) and obesity (P = 0.022) in the younger individuals......Recently, the rs6232 (N221D) and rs6235 (S690T) SNPs in the PCSK1 gene were associated with obesity in a meta-analysis comprising more than 13 000 individuals of European ancestry. Each additional minor allele of rs6232 or rs6235 was associated with a 1.34- or 1.22-fold increase in the risk...... of obesity, respectively. So far, only one relatively small study has aimed to replicate these findings, but could not confirm the association of the rs6235 SNP and did not study the rs6232 variant. In the present study, we examined the associations of the rs6232 and rs6235 SNPs with obesity in a population...

  13. A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

    Science.gov (United States)

    Rothman, Nathaniel; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Malats, Nuria; Wu, Xifeng; Figueroa, Jonine; Real, Francisco X; Van Den Berg, David; Matullo, Giuseppe; Baris, Dalsu; Thun, Michael; Kiemeney, Lambertus A; Vineis, Paolo; De Vivo, Immaculata; Albanes, Demetrius; Purdue, Mark P; Rafnar, Thorunn; Hildebrandt, Michelle A T; Kiltie, Anne E; Cussenot, Olivier; Golka, Klaus; Kumar, Rajiv; Taylor, Jack A; Mayordomo, Jose I; Jacobs, Kevin B; Kogevinas, Manolis; Hutchinson, Amy; Wang, Zhaoming; Fu, Yi-Ping; Prokunina-Olsson, Ludmila; Burdette, Laurie; Yeager, Meredith; Wheeler, William; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Johnson, Alison; Schwenn, Molly; Karagas, Margaret R; Schned, Alan; Andriole, Gerald; Grubb, Robert; Black, Amanda; Jacobs, Eric J; Diver, W Ryan; Gapstur, Susan M; Weinstein, Stephanie J; Virtamo, Jarmo; Cortessis, Victoria K; Gago-Dominguez, Manuela; Pike, Malcolm C; Stern, Mariana C; Yuan, Jian-Min; Hunter, David; McGrath, Monica; Dinney, Colin P; Czerniak, Bogdan; Chen, Meng; Yang, Hushan; Vermeulen, Sita H; Aben, Katja K; Witjes, J Alfred; Makkinje, Remco R; Sulem, Patrick; Besenbacher, Soren; Stefansson, Kari; Riboli, Elio; Brennan, Paul; Panico, Salvatore; Navarro, Carmen; Allen, Naomi E; Bueno-de-Mesquita, H Bas; Trichopoulos, Dimitrios; Caporaso, Neil; Landi, Maria Teresa; Canzian, Federico; Ljungberg, Borje; Tjonneland, Anne; Clavel-Chapelon, Francoise; Bishop, David T; Teo, Mark T W; Knowles, Margaret A; Guarrera, Simonetta; Polidoro, Silvia; Ricceri, Fulvio; Sacerdote, Carlotta; Allione, Alessandra; Cancel-Tassin, Geraldine; Selinski, Silvia; Hengstler, Jan G; Dietrich, Holger; Fletcher, Tony; Rudnai, Peter; Gurzau, Eugen; Koppova, Kvetoslava; Bolick, Sophia C E; Godfrey, Ashley; Xu, Zongli; Sanz-Velez, José I; García-Prats, María D; Sanchez, Manuel; Valdivia, Gabriel; Porru, Stefano; Benhamou, Simone; Hoover, Robert N; Fraumeni, Joseph F; Silverman, Debra T; Chanock, Stephen J

    2010-01-01

    We conducted a multi-stage, genome-wide association study (GWAS) of bladder cancer with a primary scan of 589,299 single nucleotide polymorphisms (SNPs) in 3,532 cases and 5,120 controls of European descent (5 studies) followed by a replication strategy, which included 8,381 cases and 48,275 controls (16 studies). In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1; rs1014971, (P=8×10−12) maps to a non-genic region of chromosome 22q13.1; rs8102137 (P=2×10−11) on 19q12 maps to CCNE1; and rs11892031 (P=1×10−7) maps to the UGT1A cluster on 2q37.1. We confirmed four previous GWAS associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P=4×10−11) and a tag SNP for NAT2 acetylation status (P=4×10−11), as well as demonstrated smoking interactions with both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into mechanisms of carcinogenesis. PMID:20972438

  14. Association study between OCTN1 functional haplotypes and Crohn's disease in a Korean population

    Science.gov (United States)

    Jung, Eun Suk; Park, Hyo Jin; Kong, Kyoung Ae

    2017-01-01

    Crohn's disease (CD) is a chronic inflammatory bowel disease with multifactorial causes including environmental and genetic factors. Several studies have demonstrated that the organic cation/carnitine transporter 1 (OCTN1) non-synonymous variant L503F is associated with susceptibility to CD. However, it was reported that L503F is absent in Asian populations. Previously, we identified and functionally characterized genetic variants of the OCTN1 promoter region in Koreans. In that study, four variants demonstrated significant changes in promoter activity. In the present study, we determined whether four functional variants of the OCTN1 promoter play a role in the susceptibility to or clinical course of CD in Koreans. To examine it, the frequencies of the four variants of the OCTN1 promoter were determined by genotyping using DNA samples from 194 patients with CD and 287 healthy controls. Then, associations between genetic variants and the susceptibility to CD or clinical course of CD were evaluated. We found that susceptibility to CD was not associated with OCTN1 functional promoter variants or haplotypes showing altered promoter activities in in vitro assays. However, OCTN1 functional promoter haplotypes showing decreased promoter activities were significantly associated with a penetrating behavior in CD patients (HR=2.428, p=0.009). Our results suggest that the OCTN1 functional promoter haplotypes can influence the CD phenotype, although these might not be associated with susceptibility to this disease. PMID:28066136

  15. Association of glycosylated hemoglobin with the gene encoding CDKAL1 in the Korean Association Resource (KARE) study.

    Science.gov (United States)

    Ryu, Jihye; Lee, Chaeyoung

    2012-04-01

    Genome-wide associations with glycosylated hemoglobin, which reflects the long-term glycemia, were examined using two independent cohorts of the Korea Association Resource (KARE) consortium. We first identified sequence variants within a linkage disequilibrium block (r(2) > 0.98) in the intron 5 of cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) gene using 4,275 normoglycemic subjects of Cohort 1 (P glycosylated hemoglobin by affecting 1 h glucose level. Ultimately, accumulated effects on the glycosylated hemoglobin level by the genetic variation of CDKAL1 might affect susceptibility to type 2 diabetes mellitus.

  16. An Updated Study to Determine Association between Gadolinium-Based Contrast Agents and Nephrogenic Systemic Fibrosis.

    Directory of Open Access Journals (Sweden)

    Bin Zhang

    Full Text Available Nephrogenic systemic fibrosis (NSF is a rare but serious disorder disease affecting patients with advanced renal disease. Although multiple studies have indicated an association between gadolinium-based contrast agents (GBCAs and NSF, some studies published after 2007 found no association. We therefore performed a meta-analysis to evaluate the association and analyze related (cofactors.Studies for analysis were identified by searching PubMed, Embase, and the Cochrane Central Register of Controlled Trials through December 2014. Pooled odds ratios (OR with 95% confidence intervals (CI were calculated using the fixed-effects model. Statistical heterogeneity was assessed by Q statistics and the I2 test. Publication bias was evaluated using Begg's test, Egger's test, funnel plot, and classic fail-safe N. Study quality was assessed using the Newcastle-Ottawa Scale. We also conducted sensitivity analyses, subgroup analyses and a cumulative meta-analysis. All statistical analyses were performed using Comprehensive Meta-Analysis 2.0.A total of 14 studies (6,398 patients met the inclusion criteria, but 3 were excluded since they reported no NSF events. Meta-analysis of controlled trials indicated a significant association between GBCAs and NSF development (OR = 16.504; 95% CI: 7.455-36.533; P < 0.001 and between gadodiamide and NSF (OR = 20.037; 95% CI: 3.725-107.784; P < 0.001. No statistical heterogeneity was observed across studies (P = 0.819, I2 = 0%; P = 0.874, I2 = 0%, respectively. Cumulative analysis demonstrated that the pooled ORs for association between GBCAs and NSF decreased post-2007 compared to pre-2007 (OR = 26.708; 95% CI: 10.273-69.436; P<0.001.Although this updated meta-analysis found a significant association between GBCAs and the incidence of NSF in patients with advanced renal disease, the association decreased after 2007. More studies, especially randomized controlled trials, are warranted to examine the potential association

  17. An Updated Study to Determine Association between Gadolinium-Based Contrast Agents and Nephrogenic Systemic Fibrosis

    Science.gov (United States)

    Zhang, Bin; Liang, Long; Chen, Wenbo; Liang, Changhong; Zhang, Shuixing

    2015-01-01

    Background Nephrogenic systemic fibrosis (NSF) is a rare but serious disorder disease affecting patients with advanced renal disease. Although multiple studies have indicated an association between gadolinium-based contrast agents (GBCAs) and NSF, some studies published after 2007 found no association. We therefore performed a meta-analysis to evaluate the association and analyze related (co)factors. Methods Studies for analysis were identified by searching PubMed, Embase, and the Cochrane Central Register of Controlled Trials through December 2014. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using the fixed-effects model. Statistical heterogeneity was assessed by Q statistics and the I2 test. Publication bias was evaluated using Begg’s test, Egger’s test, funnel plot, and classic fail-safe N. Study quality was assessed using the Newcastle-Ottawa Scale. We also conducted sensitivity analyses, subgroup analyses and a cumulative meta-analysis. All statistical analyses were performed using Comprehensive Meta-Analysis 2.0. Results A total of 14 studies (6,398 patients) met the inclusion criteria, but 3 were excluded since they reported no NSF events. Meta-analysis of controlled trials indicated a significant association between GBCAs and NSF development (OR = 16.504; 95% CI: 7.455–36.533; P < 0.001) and between gadodiamide and NSF (OR =