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. Sparse PCA corrects for cell type heterogeneity in epigenome-wide association studies.

    Science.gov (United States)

    Rahmani, Elior; Zaitlen, Noah; Baran, Yael; Eng, Celeste; Hu, Donglei; Galanter, Joshua; Oh, Sam; Burchard, Esteban G; Eskin, Eleazar; Zou, James; Halperin, Eran

    2016-05-01

    In epigenome-wide association studies (EWAS), different methylation profiles of distinct cell types may lead to false discoveries. We introduce ReFACTor, a method based on principal component analysis (PCA) and designed for the correction of cell type heterogeneity in EWAS. ReFACTor does not require knowledge of cell counts, and it provides improved estimates of cell type composition, resulting in improved power and control for false positives in EWAS. Corresponding software is available at http://www.cs.tau.ac.il/~heran/cozygene/software/refactor.html. PMID:27018579

  4. A Super-Resolution Method with EWA

    Institute of Scientific and Technical Information of China (English)

    JIANG ZhongDing (姜忠鼎); LIN Hai (林海); BAO HuJun (鲍虎军); MA LiZhuang (马利庄)

    2003-01-01

    This paper introduces a practical algorithm for super-resolution, the process of reconstructing a high-resolution image from low-resolution input ones. The emphasis of the work is to super-resolve frames from real-world image/video sequences which may contain significant object occlusion or scene changes. As the quality of super-resolved images highly relies on the correctness of image alignment between consecutive frames, the robust optical flow method is used to accurately estimate motion between the image pair. An efficient and reliable scheme is devised to detect and discard incorrect matchings which may degrade the output quality. The usage of elliptical weighted average (EWA) filter is also introduced to model the point spread function (PSF) of acquisition system in order to improve accuracy of the model. A number of complex video sequences are tested to demonstrate the applicability and reliability of the proposed algorithm.

  5. Epigenome-Wide Association Studies for common human diseases

    OpenAIRE

    Rakyan, Vardhman K; Down, Thomas A; Balding, David J.; Beck, Stephan

    2011-01-01

    Despite the success of genome-wide association studies (GWAS) in identifying loci associated with common diseases, a significant proportion of the causality remains unexplained. Recent advances in genomic technologies have placed us in a position to initiate large-scale studies of human disease-associated epigenetic variation, specifically variation in DNA methylation (DNAm). Such Epigenome-Wide Association Studies (EWAS) present novel opportunities but also create new challenges that are not...

  6. 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.

  7. 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...

  8. 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...

  9. Epigenome-wide association of liver methylation patterns and complex metabolic traits in mice

    OpenAIRE

    Orozco, Luz D; Morselli, Marco; Rubbi, Liudmilla; Guo, Weilong; Go, James; Shi, Huwenbo; Lopez, David; Furlotte, Nicholas A; Bennett, Brian J.; Farber, Charles R; Ghazalpour, Anatole; Zhang, Michael Q; Bahous, Renata; Rozen, Rima; Lusis, Aldons J.

    2015-01-01

    Heritable epigenetic factors can contribute to complex disease etiology. Here we examine the contribution of DNA methylation to complex traits that are precursors to heart disease, diabetes and osteoporosis. We profiled DNA methylation in the liver using bisulfite sequencing in 90 mouse inbred strains, genome-wide expression levels, proteomics, metabolomics and sixty-eight clinical traits, and performed epigenome-wide association studies (EWAS). We found associations with numerous clinical tr...

  10. Environment-Wide Association Study of Blood Pressure in the National Health and Nutrition Examination Survey (1999–2012)

    Science.gov (United States)

    McGinnis, Denise P.; Brownstein, John S.; Patel, Chirag J.

    2016-01-01

    Identifying environmental exposures associated with blood pressure is a priority. Recently, we proposed the environment-wide association study to search for and replicate environmental factors associated with phenotypes. We conducted the environment-wide association study (EWAS) using the National Health and Nutrition Examination Surveys (1999–2012) which evaluated a total of 71,916 participants to prioritize environmental factors associated with systolic and diastolic blood pressure. We searched for factors on participants from survey years 1999–2006 and tentatively replicated findings in participants from years 2007–2012. Finally, we estimated the overall association and performed a second meta-analysis using all survey years (1999–2012). For systolic blood pressure, self-reported alcohol consumption emerged as our top finding (a 0.04 increase in mmHg of systolic blood pressure for 1 standard deviation increase in self-reported alcohol), though the effect size is small. For diastolic blood pressure, urinary cesium was tentatively replicated; however, this factor demonstrated high heterogeneity between populations (I2 = 51%). The lack of associations across this wide of an analysis raises the call for a broader search for environmental factors in blood pressure. PMID:27457472

  11. 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/).

  12. 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.

  13. 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

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

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    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.

  15. 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....

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

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    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.

  17. 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.

  18. 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

  19. 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.

  20. Functional analysis of variance for association studies.

    Science.gov (United States)

    Vsevolozhskaya, Olga A; Zaykin, Dmitri V; Greenwood, Mark C; Wei, Changshuai; Lu, Qing

    2014-01-01

    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. PMID:25244256

  1. 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].

  2. Microorganisms associated particulate matter: a preliminary study.

    Science.gov (United States)

    Alghamdi, Mansour A; Shamy, Magdy; Redal, Maria Ana; Khoder, Mamdouh; Awad, Abdel Hameed; Elserougy, Safaa

    2014-05-01

    This study aims to determine the microbiological quality of particulate matter (PM) in an urban area in Jeddah, Saudi Arabia, during December 2012 to April 2013. This was achieved by the determination of airborne bacteria, fungi, and actinobacteria associated PM10 and PM2.5, as well as their relationships with gaseous pollutants, O3, SO2 and NO2, and meteorological factors (T°C, RH% and Ws). High volume samplers with PM10 and PM2.5 selective sizes, and glass fiber filters were used to collect PM10 and PM2.5, respectively. The filters were suspended in buffer phosphate and aliquots were spread plated onto the surfaces of trypticase soy agar, malt extract agar, and starch casein agar media for counting of bacteria, fungi and actinobacteria-associated PM, respectively. PM10 and PM2.5 concentrations averaged 159.9 μg/m(3) and 60 μg/m(3), respectively, with the ratio of PM2.5/PM10 averaged ~0.4. The concentrations of O3, SO2 and NO2 averaged 35.73 μg/m(3), 38.1μg/m(3) and 52.5 μg/m(3), respectively. Fungi and actinobacteria associated PM were found in lower concentrations than bacteria. The sum of microbial loads was higher in PM10 than PM2.5, however a significant correlation (r=0.57, P ≤ 0.05) was found between the sum of microbial loads associated PM10 and PM2.5. Aspergillus fumigatus and Aspergillus niger were the common fungal types associated PM. Temperature significantly correlated with both PM10 (r=0.44), and PM2.5 (r=0.5). Significant negative correlations were found between O3 and PM2.5 (r=-0.47), and between SO2 with PM10 (r=-0.48). Wind speed positively correlated with airborne microorganisms associated PM. The regression model showed that the inverse PM2.5 concentration (1/PM2.5) was a significant determinant of fungal count associated PM. Chemical processes and environmental factors could affect properties of PM and in turn its biological quality.

  3. 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.

  4. 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

  5. '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.

  6. 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.

  7. 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....

  8. 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....

  9. 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)....

  10. Association between arterial stiffness and atherosclerosis: the Rotterdam Study

    NARCIS (Netherlands)

    N.M-L. van Popele (Nicole); D.E. Grobbee (Diederick); M.L. Bots (Michiel); R. Asmar (Roland); J. Topouchian; R.S. Reneman; A.P.G. Hoeks; D.A. van der Kuip (Deirdre); J.C.M. Witteman (Jacqueline); A. Hofman (Albert)

    2001-01-01

    textabstractBACKGROUND AND PURPOSE: Studies of the association between arterial stiffness and atherosclerosis are contradictory. We studied stiffness of the aorta and the common carotid artery in relation to several indicators of atherosclerosis. METHODS: This study was conducted w

  11. 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

  12. 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...

  13. 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......, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs)....

  14. 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 ...

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

    OpenAIRE

    Bhavana Gupta; Attiuddin Siddique

    2013-01-01

    Background: To study the association between dental health status and pregnancy in rural India. Methods: The cohort study was carried out in the department of Obstetrics and Gynecology at Integral Institute of Medical Sciences and Research, Lucknow from March 2012 to April 2013, for the period of 1year. The dental health statuses of 600 antenatal cases were studied. The prevalence of gingivitis, dental caries and periodontal disease were studied. The association between poor oral hygiene, ...

  16. Combination of mouse models and genomewide association studies highlights novel genes associated with human kidney function.

    Science.gov (United States)

    Jing, Jiaojiao; Pattaro, Cristian; Hoppmann, Anselm; Okada, Yukinori; Fox, Caroline S; Köttgen, Anna

    2016-10-01

    Genomewide association studies have identified numerous chronic kidney disease-associated genetic variants, but often do not pinpoint causal genes. This limitation was addressed by combining Mouse Genome Informatics with human genomewide association studies of kidney function. Genes for which mouse models showed abnormal renal physiology, morphology, glomerular filtration rate (GFR), or urinary albumin-to-creatinine ratio were identified from Mouse Genome Informatics. The corresponding human orthologs were then evaluated for GFR-associated single-nucleotide polymorphisms in 133,814 individuals and urinary albumin-to-creatinine ratio-associated SNPs in 54,451 individuals in genome-wide association studies meta-analysis of the CKDGen Consortium. After multiple testing corrections, significant associations with estimated GFR in humans were identified for single-nucleotide polymorphisms in 2, 7, and 17 genes causing abnormal GFR, abnormal physiology, and abnormal morphology in mice, respectively. Genes identified for abnormal kidney morphology showed significant enrichment for estimated GFR-associated single-nucleotide polymorphisms. In total, 19 genes contained variants associated with estimated GFR or the urinary albumin-to-creatinine ratio of which 16 mapped into previously reported genomewide significant loci. CYP26A1 and BMP4 emerged as novel signals subsequently validated in a large, independent study. An additional gene, CYP24A1, was discovered after conditioning on a published nearby association signal. Thus, our novel approach to combine comprehensive mouse phenotype information with human genomewide association studies data resulted in the identification of candidate genes for kidney disease pathogenesis. PMID:27263491

  17. 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.

  18. Australian and South Pacific External Studies Association: Odlaa's Regional Predecessor

    Science.gov (United States)

    Bewley, Donald

    2008-01-01

    The Australian and South Pacific External Studies Association (ASPESA)-- the predecessor of the Open and Distance Learning Association of Australia, Inc. (ODLAA)--was founded in 1973. From the outset, ASPESA adopted a broader-than-Australia focus for open and distance learning that included New Zealand, Papua New Guinea, and the member countries…

  19. 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....

  20. 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.

  1. Genome-wide association study identifies three novel genetic markers associated with elite endurance performance

    DEFF Research Database (Denmark)

    Ahmetov, Ii; Kulemin, Na; Popov, Dv;

    2015-01-01

    To investigate the association between multiple single-nucleotide polymorphisms (SNPs), aerobic performance and elite endurance athlete status in Russians. By using GWAS approach, we examined the association between 1,140,419 SNPs and relative maximal oxygen consumption rate ([Formula: see text]O2...... Russian controls, 1367 European controls, and 230 Russian power athletes). Initially, six 'endurance alleles' were identified showing discrete associations with [Formula: see text]O2max both in males and females. Next, case-control studies resulted in remaining three SNPs (NFIA-AS2 rs1572312, TSHR rs......7144481, RBFOX1 rs7191721) associated with endurance athlete status. The C allele of the most significant SNP, rs1572312, was associated with high values of [Formula: see text]O2max (males: P = 0.0051; females: P = 0.0005). Furthermore, the frequency of the rs1572312 C allele was significantly higher...

  2. A Genomewide Association Study of DSM-IV Cannabis Dependence

    OpenAIRE

    Agrawal, Arpana; Lynskey, Michael T.; Hinrichs, Anthony; Grucza, Richard; Saccone, Scott F; Krueger, Robert; Neuman, Rosalind; Howells, William; Fisher, Sherri; Fox, Louis; Cloninger, Robert,; Dick, Danielle M; Doheny, Kimberly F.; Edenberg, Howard J.; Goate, Alison M.

    2010-01-01

    Despite twin studies showing that 50–70% of variation in DSM-IV cannabis dependence is attributable to heritable influences, little is known of specific genotypes that influence vulnerability to cannabis dependence. We conducted a genomewide association study of DSM-IV cannabis dependence. Association analyses of 708 DSM-IV cannabis dependent cases with 2,346 cannabis exposed nondependent controls was conducted using logistic regression in PLINK. None of the 948,142 SNPs met genomewide signif...

  3. Families or Unrelated: The Evolving Debate in Genetic Association Studies

    OpenAIRE

    Fardo, David W.; Charnigo, Richard; Epstein, Michael P.

    2012-01-01

    To help uncover the genetic determinants of complex disease, a scientist often designs an association study using either unrelated subjects or family members within pedigrees. But which of these two subject recruitment paradigms is preferable? This editorial addresses the debate over the relative merits of family- and population-based genetic association studies. We begin by briefly recounting the evolution of genetic epidemiology and the rich crossroads of statistics and genetics. We then de...

  4. A genome wide association study identifies common variants associated with lipid levels in the Chinese population.

    Directory of Open Access Journals (Sweden)

    Li Zhou

    Full Text Available Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC, triglycerides (TG, low-density lipoprotein cholesterol (LDL and high-density lipoprotein cholesterol (HDL in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52 × 10(-16, 1.38 × 10(-6 and 5.59 × 10(-9, respectively. These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population.

  5. 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.

  6. 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

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

    Science.gov (United States)

    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; Lehtimäki, 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; Fülöp, T; Gehrman, P R; Goodloe, R; Harris, T B; Heath, A C; Hernandez, D; Hofman, A; Hottenga, J-J; Hunter, D J; Jensen, M K; Johnson, A D; Kähönen, 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; Räikkönen, K; Völzke, H; Mignot, E; Tiemeier, H

    2015-10-01

    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 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- to 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 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS 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

  8. 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.

  9. A Genome Wide Association Study Identifies Common Variants Associated with Lipid Levels in the Chinese Population

    OpenAIRE

    Zhou, Li; He, Meian; Mo, Zengnan; Wu, Chen; Handong YANG; Yu, Dianke; Yang, Xiaobo; Zhang, Xiaomin; Wang, Yiqin; Sun, Jielin; Gao, Yong; Tan, Aihua; He, Yunfeng; Zhang, Haiying; Qin, Xue

    2013-01-01

    Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS) have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome w...

  10. 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.

  11. 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.

  12. Sialolithiasis is associated with nephrolithiasis: a case-control study.

    Science.gov (United States)

    Wu, Chuan-Chang; Hung, Shih-Han; Lin, Herng-Ching; Lee, Cha-Ze; Lee, Hsin-Chien; Chung, Shiu-Dong

    2016-05-01

    Conclusions This study demonstrates an association between sialolithiasis and nephrolithiasis. The results call for more awareness of this association among physicians and patients with nephrolithiasis. Objective Very few empirical studies have been conducted to explore the potential association between sialolithiasis and nephrolithiasis. As such, the association between sialolithiasis and nephrolithiasis still remains unclear. This study aimed to explore the possible association between sialolithiasis and nephrolithiasis using a population-based dataset. Methods Using data from the Taiwan Longitudinal Health Insurance Database 2005, this case-control study identified 966 patients with sialolithiasis as cases and 2898 sex- and age-matched subjects without sialolithiasis as controls. Conditional logistic regressions were conducted to examine the association of sialolithiasis with previously diagnosed nephrolithiasis. Results Out of 3864 sampled patients, 165 (4.27%) had prior nephrolithiasis. Using Chi-square test, it was found that there was a significant difference in the prevalence of prior nephrolithiasis between the cases and controls (10.25% vs 2.28%, p nephrolithiasis for cases was 4.74 (95% CI = 3.41-6.58, p < 0.001) when compared to controls after adjusting for monthly income, geographic location, urbanization level of residence, diabetes, hypertension, heart failure, chronic renal disease, and tobacco use. PMID:26808906

  13. Joint Analysis of Multiple Traits in Rare Variant Association Studies.

    Science.gov (United States)

    Wang, Zhenchuan; Wang, Xuexia; Sha, Qiuying; Zhang, Shuanglin

    2016-05-01

    The joint analysis of multiple traits has recently become popular since it can increase statistical power to detect genetic variants and there is increasing evidence showing that pleiotropy is a widespread phenomenon in complex diseases. Currently, the majority of existing methods for the joint analysis of multiple traits test association between one common variant and multiple traits. However, the variant-by-variant methods for common variant association studies may not be optimal for rare variant association studies due to the allelic heterogeneity as well as the extreme rarity of individual variants. Current statistical methods for rare variant association studies are for one single trait only. In this paper, we propose an adaptive weighting reverse regression (AWRR) method to test association between multiple traits and rare variants in a genomic region. AWRR is robust to the directions of effects of causal variants and is also robust to the directions of association of traits. Using extensive simulation studies, we compare the performance of AWRR with canonical correlation analysis (CCA), Single-TOW, and the weighted sum reverse regression (WSRR). Our results show that, in all of the simulation scenarios, AWRR is consistently more powerful than CCA. In most scenarios, AWRR is more powerful than Single-TOW and WSRR. PMID:26990300

  14. Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study.

    Science.gov (United States)

    Du, Yeting; Ter-Minassian, Monica; Brais, Lauren; Brooks, Nichole; Waldron, Amanda; Chan, Jennifer A; Lin, Xihong; Kraft, Peter; Christiani, David C; Kulke, Matthew H

    2016-08-01

    The etiology of neuroendocrine tumors remains poorly defined. Although neuroendocrine tumors are in some cases associated with inherited genetic syndromes, such syndromes are rare. The majority of neuroendocrine tumors are thought to be sporadic. We performed a genome-wide association study (GWAS) to identify potential genetic risk factors for sporadic neuroendocrine tumors. Using germline DNA from blood specimens, we genotyped 909,622 SNPs using the Affymetrix 6.0 GeneChip, in a cohort comprising 832 neuroendocrine tumor cases from Dana-Farber Cancer Institute and Massachusetts General Hospital and 4542 controls from the Harvard School of Public Health. An additional 241 controls from Dana-Farber Cancer Institute were used for quality control. We assessed risk associations in the overall cohort, and in neuroendocrine tumor subgroups. We identified no potential risk associations in the cohort overall. In the small intestine neuroendocrine tumor subgroup, comprising 293 cases, we identified risk associations with three SNPs on chromosome 12, all in strong LD. The three SNPs are located upstream of ELK3, a transcription factor implicated in angiogenesis. We did not identify clear risk associations in the bronchial or pancreatic neuroendocrine subgroups. This large-scale study provides initial evidence that presumed sporadic small intestine neuroendocrine tumors may have a genetic etiology. Our results provide a basis for further exploring the role of genes implicated in this analysis, and for replication studies to confirm the observed associations. Additional studies to evaluate potential genetic risk factors for sporadic pancreatic and bronchial neuroendocrine tumors are warranted. PMID:27492634

  15. 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.

  16. 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

  17. 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

  18. 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.

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

    Science.gov (United States)

    Davenport, Emily R; Cusanovich, Darren A; Michelini, Katelyn; Barreiro, Luis B; Ober, Carole; Gilad, Yoav

    2015-01-01

    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. PMID:26528553

  20. Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma.

    Science.gov (United States)

    Chahal, Harvind S; Wu, Wenting; Ransohoff, Katherine J; Yang, Lingyao; Hedlin, Haley; Desai, Manisha; Lin, Yuan; Dai, Hong-Ji; Qureshi, Abrar A; Li, Wen-Qing; Kraft, Peter; Hinds, David A; Tang, Jean Y; Han, Jiali; Sarin, Kavita Y

    2016-01-01

    Basal cell carcinoma (BCC) is the most common cancer worldwide with an annual incidence of 2.8 million cases in the United States alone. Previous studies have demonstrated an association between 21 distinct genetic loci and BCC risk. Here, we report the results of a two-stage genome-wide association study of BCC, totalling 17,187 cases and 287,054 controls. We confirm 17 previously reported loci and identify 14 new susceptibility loci reaching genome-wide significance (P<5 × 10(-8), logistic regression). These newly associated SNPs lie within predicted keratinocyte regulatory elements and in expression quantitative trait loci; furthermore, we identify candidate genes and non-coding RNAs involved in telomere maintenance, immune regulation and tumour progression, providing deeper insight into the pathogenesis of BCC. PMID:27539887

  1. 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

  2. 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, ...

  3. 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

  4. 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

  5. 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

  6. 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

  7. Metagenome-wide association studies: fine-mining the microbiome.

    Science.gov (United States)

    Wang, Jun; Jia, Huijue

    2016-08-01

    Metagenome-wide association studies (MWAS) have enabled the high-resolution investigation of associations between the human microbiome and several complex diseases, including type 2 diabetes, obesity, liver cirrhosis, colorectal cancer and rheumatoid arthritis. The associations that can be identified by MWAS are not limited to the identification of taxa that are more or less abundant, as is the case with taxonomic approaches, but additionally include the identification of microbial functions that are enriched or depleted. In this Review, we summarize recent findings from MWAS and discuss how these findings might inform the prevention, diagnosis and treatment of human disease in the future. Furthermore, we highlight the need to better characterize the biology of many of the bacteria that are found in the human microbiota as an essential step in understanding how bacterial strains that have been identified by MWAS are associated with disease. PMID:27396567

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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...

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. SNPTrack™ : an integrated bioinformatics system for genetic association studies.

    Science.gov (United States)

    Xu, Joshua; Kelly, Reagan; Zhou, Guangxu; Turner, Steven A; Ding, Don; Harris, Stephen C; Hong, Huixiao; Fang, Hong; Tong, Weida

    2012-01-01

    A genetic association study is a complicated process that involves collecting phenotypic data, generating genotypic data, analyzing associations between genotypic and phenotypic data, and interpreting genetic biomarkers identified. SNPTrack is an integrated bioinformatics system developed by the US Food and Drug Administration (FDA) to support the review and analysis of pharmacogenetics data resulting from FDA research or submitted by sponsors. The system integrates data management, analysis, and interpretation in a single platform for genetic association studies. Specifically, it stores genotyping data and single-nucleotide polymorphism (SNP) annotations along with study design data in an Oracle database. It also integrates popular genetic analysis tools, such as PLINK and Haploview. SNPTrack provides genetic analysis capabilities and captures analysis results in its database as SNP lists that can be cross-linked for biological interpretation to gene/protein annotations, Gene Ontology, and pathway analysis data. With SNPTrack, users can do the entire stream of bioinformatics jobs for genetic association studies. SNPTrack is freely available to the public at http://www.fda.gov/ScienceResearch/BioinformaticsTools/SNPTrack/default.htm. PMID:23245293

  18. Academic Over- and Underachievement and Residence Patterns: An Associative Study.

    Science.gov (United States)

    Weislogel, Louis F.

    The purpose of this study was to examine the impact of various types of living accommodations on the academic performance of college freshmen at West Chester State College (Pennsylvania). Three types of housing were defined: single-sex dormitories, coeducational dormitories, and commuter living accommodations. The association of housing…

  19. 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...

  20. 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

  1. 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...

  2. 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.

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

    Science.gov (United States)

    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; Pina Concas, Maria; 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; deLeeuw, 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; 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; 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; Evans, 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; Bültmann, 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; Davey Smith, George; 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

    2016-05-26

    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. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-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 development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment 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 diseases. PMID:27225129

  4. 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

  5. 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.

  6. Logistic regression protects against population structure in genetic association studies

    OpenAIRE

    Setakis, Efrosini; Stirnadel, Heide; Balding, David J.

    2006-01-01

    We conduct an extensive simulation study to compare the merits of several methods for using null (unlinked) markers to protect against false positives due to cryptic substructure in population-based genetic association studies. The more sophisticated “structured association” methods perform well but are computationally demanding and rely on estimating the correct number of subpopulations. The simple and fast “genomic control” approach can lose power in certain scenarios. We find that procedur...

  7. Population Structure and Cryptic Relatedness in Genetic Association Studies

    OpenAIRE

    Astle, William; Balding, David J.

    2010-01-01

    We review the problem of confounding in genetic association studies, which arises principally because of population structure and cryptic relatedness. Many treatments of the problem consider only a simple ``island'' model of population structure. We take a broader approach, which views population structure and cryptic relatedness as different aspects of a single confounder: the unobserved pedigree defining the (often distant) relationships among the study subjects. Kinship is therefore a cent...

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

    OpenAIRE

    Bozcali, Evin; 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 co...

  9. Automated quality control for genome wide association studies

    Science.gov (United States)

    Ellingson, Sally R.; Fardo, David W.

    2016-01-01

    This paper provides details on the necessary steps to assess and control data in genome wide association studies (GWAS) using genotype information on a large number of genetic markers for large number of individuals. Due to varied study designs and genotyping platforms between multiple sites/projects as well as potential genotyping errors, it is important to ensure high quality data. Scripts and directions are provided to facilitate others in this process.

  10. A STUDY ON CO MORBIDITIES ASSOCIATED WITH PSORIASIS

    OpenAIRE

    Remya Reghu; Roshni PR; Meenu Vijayan; Emmanuel James

    2013-01-01

    Psoriasis is a chronic, disfiguring inflammatory and proliferative condition of the skin. The present study focused on the comorbidities associated with psoriasis patients and also the medications used for the treatment of the same. It was a Non experimental (Observational) prospective and cross sectional study and done in the department of dermatology, Amrita Institute of Medical Sciences, (a tertiary care referral and teaching hospital, in Kochi). A total of 100 cases of psoriasis were iden...

  11. Genome-wide association study of circulating retinol levels

    OpenAIRE

    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

    2011-01-01

    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-nucl...

  12. Genetics, Genome-Wide Association Studies, and Menarche.

    Science.gov (United States)

    Witchel, Selma Feldman

    2016-07-01

    Puberty is characterized by maturation of the hypothalamic-pituitary-gonadal axis, development of secondary sexual features, increased linear growth velocity, maturation of the epiphyses limiting additional growth, and achievement of menarche. The age at menarche appears to have a significant genetic component. With the advent of genome-wide association studies (GWASs), the genome has been interrogated to find associations between specific loci and age at menarche. It is apparent that multiple genetic loci, epigenetic mechanisms, and environmental factors modulate this biological event crucial for reproductive competence. PMID:27513021

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

    OpenAIRE

    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; St. Clair, David; Corvin, Aiden; Gurling, Hugh

    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 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 ...

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

    OpenAIRE

    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; St. Clair, David; Corvin, Aiden; Gurling, Hugh

    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 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 ...

  15. Genome-Wide Association Study Reveals Multiple Loci Associated with Primary Tooth Development during Infancy

    OpenAIRE

    Pillas, D.; Hoggart, C. J.; Evans, D. M.; O'Reilly, P. F.; Sipila, K.; Lahdesmaki, R.; Millwood, I. Y.; Kaakinen, M; Netuveli, G.; Blane, D; Charoen, P.; Sovio, U; Pouta, A.; Freimer, N; Hartikainen, A. L.

    2010-01-01

    Tooth development is a highly heritable process which relates to other growth and developmental processes, and which interacts with the development of the entire craniofacial complex. Abnormalities of tooth development are common, with tooth agenesis being the most common developmental anomaly in humans. We performed a genome-wide association study of time to first tooth eruption and number of teeth at one year in 4,564 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966) and 1,...

  16. Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study

    OpenAIRE

    Matullo, Giuseppe; Guarrera, Simonetta; Betti, Marta; Fiorito, Giovanni; Ferrante, Daniela; Voglino, Floriana; Cadby, Gemma; Di Gaetano, Cornelia; De Rosa, Fabio; Russo, Alessia; Hirvonen, Ari; Casalone, Elisabetta; Tunesi, Sara; Padoan, Marina; Giordano, Mara

    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 complet...

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Genome-wide association studies in pharmacogenetics research debate

    Science.gov (United States)

    Bailey, Kent R; Cheng, Cheng

    2016-01-01

    Will genome-wide association studies (GWAS) ‘work’ for pharmacogenetics research? This question was the topic of a staged debate, with pro and con sides, aimed to bring out the strengths and weaknesses of GWAS for pharmacogenetics studies. After a full day of seminars at the Fifth Statistical Analysis Workshop of the Pharmacogenetics Research Network, the lively debate was held – appropriately – at Goonies Comedy Club in Rochester (MN, USA). The pro side emphasized that the many GWAS successes for identifying genetic variants associated with disease risk show that it works; that the current genotyping platforms are efficient, with good imputation methods to fill in missing data; that its global assessment is always a success even if no significant associations are detected; and that genetic effects are likely to be large because humans have not evolved in a drug-therapy environment. By contrast, the con side emphasized that we have limited knowledge of the complexity of the genome; limited clinical phenotypes compromise studies; the likely multifactorial nature of drug response clouding the small genetic effects; and limitations of sample size and replication studies in pharmacogenetic studies. Lively and insightful discussions emphasized further research efforts that might benefit GWAS in pharmacogenetics. PMID:20235786

  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. 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.

  4. 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. PMID:19961302

  5. Brain expression genome-wide association study (eGWAS identifies human disease-associated variants.

    Directory of Open Access Journals (Sweden)

    Fanggeng Zou

    Full Text Available Genetic variants that modify brain gene expression may also influence risk for human diseases. We measured expression levels of 24,526 transcripts in brain samples from the cerebellum and temporal cortex of autopsied subjects with Alzheimer's disease (AD, cerebellar n=197, temporal cortex n=202 and with other brain pathologies (non-AD, cerebellar n=177, temporal cortex n=197. We conducted an expression genome-wide association study (eGWAS using 213,528 cisSNPs within ± 100 kb of the tested transcripts. We identified 2,980 cerebellar cisSNP/transcript level associations (2,596 unique cisSNPs significant in both ADs and non-ADs (q<0.05, p=7.70 × 10(-5-1.67 × 10(-82. Of these, 2,089 were also significant in the temporal cortex (p=1.85 × 10(-5-1.70 × 10(-141. The top cerebellar cisSNPs had 2.4-fold enrichment for human disease-associated variants (p<10(-6. We identified novel cisSNP/transcript associations for human disease-associated variants, including progressive supranuclear palsy SLCO1A2/rs11568563, Parkinson's disease (PD MMRN1/rs6532197, Paget's disease OPTN/rs1561570; and we confirmed others, including PD MAPT/rs242557, systemic lupus erythematosus and ulcerative colitis IRF5/rs4728142, and type 1 diabetes mellitus RPS26/rs1701704. In our eGWAS, there was 2.9-3.3 fold enrichment (p<10(-6 of significant cisSNPs with suggestive AD-risk association (p<10(-3 in the Alzheimer's Disease Genetics Consortium GWAS. These results demonstrate the significant contributions of genetic factors to human brain gene expression, which are reliably detected across different brain regions and pathologies. The significant enrichment of brain cisSNPs among disease-associated variants advocates gene expression changes as a mechanism for many central nervous system (CNS and non-CNS diseases. Combined assessment of expression and disease GWAS may provide complementary information in discovery of human disease variants with functional implications. Our findings

  6. Genome-Wide Association Studies for Polycystic Ovary Syndrome.

    Science.gov (United States)

    Liu, Hongbin; Zhao, Han; Chen, Zi-Jiang

    2016-07-01

    Over the past several years, the field of reproductive medicine has witnessed great advances in genome-wide association studies (GWASs) of polycystic ovary syndrome (PCOS), leading to identification of several promising genes involved in hormone action, type 2 diabetes, and cell proliferation. This review summarizes the key findings and discusses their potential implications with regard to genetic mechanisms of PCOS. Limitations of GWAS are evaluated, emphasizing the understanding of the reasons for variability in results between individual studies. Root causes of misinterpretations of GWASs are also addressed. Finally, the impact of GWAS on future directions of multi- and interdisciplinary studies is discussed. PMID:27513023

  7. Multiple Comparisons in Genetic Association Studies: A Hierarchical Modeling Approach

    Science.gov (United States)

    Yi, Nengjun; Xu, Shizhong; Lou, Xiang-Yang; Mallick, Himel

    2016-01-01

    Multiple comparisons or multiple testing has been viewed as a thorny issue in genetic association studies aiming to detect disease-associated genetic variants from a large number of genotyped variants. We alleviate the problem of multiple comparisons by proposing a hierarchical modeling approach that is fundamentally different from the existing methods. The proposed hierarchical models simultaneously fit as many variables as possible and shrink unimportant effects towards zero. Thus, the hierarchical models yield more efficient estimates of parameters than the traditional methods that analyze genetic variants separately, and also coherently address the multiple comparisons problem due to largely reducing the effective number of genetic effects and the number of statistically ‘significant’ effects. We develop a method for computing the effective number of genetic effects in hierarchical generalized linear models, and propose a new adjustment for multiple comparisons, the hierarchical Bonferroni correction, based on the effective number of genetic effects. Our approach not only increases the power to detect disease-associated variants but also controls the Type I error. We illustrate and evaluate our method with real and simulated data sets from genetic association studies. The method has been implemented in our freely available R package BhGLM (http://www.ssg.uab.edu/bhglm/). PMID:24259248

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Genetic association- and linkage studies in colorectal cancer

    OpenAIRE

    Holst, Susanna von

    2014-01-01

    Colorectal cancer (CRC) is the third most common cancer type in the Western world. Over one million patients are diagnosed worldwide yearly. A family history of CRC is a major risk factor for CRC. The total genetic contribution to disease development is estimated to be 35%. High-risk syndromes caused by known genes such as familial adenomatous polyposis (FAP) and Lynch Syndrome (LS) explain less than 5% of that number. Recently, several genome-wide association studies (GWAS) ha...

  13. Genome-Wide Association Study of Proneness to Anger

    OpenAIRE

    Mick, Eric; Mcgough, James,; Deutsch, Curtis K.; Jean A. Frazier; Kennedy, David; Goldberg, Robert J.

    2014-01-01

    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 S...

  14. 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...

  15. Associative learning on imbalanced environments: An empirical study

    OpenAIRE

    Cleofas Sánchez, Laura; Sánchez Garreta, José Salvador; García, V.; Valdovinos, R.M.

    2015-01-01

    Associative memories have emerged as a powerful computational neural network model for several pattern classification problems. Like most traditional classifiers, these models assume that the classes share similar prior probabilities. However, in many real-life applications the ratios of prior probabilities between classes are extremely skewed. Although the literature has provided numerous studies that examine the performance degradation of renowned classifiers on different imbalanced scenari...

  16. Genome-Wide Association Study of Antiphospholipid Antibodies

    Directory of Open Access Journals (Sweden)

    M. Ilyas Kamboh

    2013-01-01

    Full Text Available Background. The persistent presence of antiphospholipid antibodies (APA may lead to the development of primary or secondary antiphospholipid syndrome. Although the genetic basis of APA has been suggested, the identity of the underlying genes is largely unknown. In this study, we have performed a genome-wide association study (GWAS in an effort to identify susceptibility loci/genes for three main APA: anticardiolipin antibodies (ACL, lupus anticoagulant (LAC, and anti-β2 glycoprotein I antibodies (anti-β2GPI. Methods. DNA samples were genotyped using the Affymetrix 6.0 array containing 906,600 single-nucleotide polymorphisms (SNPs. Association of SNPs with the antibody status (positive/negative was tested using logistic regression under the additive model. Results. We have identified a number of suggestive novel loci with Passociations of HLA genes and APOH with APA but these were not the top loci. Conclusions. We have identified a number of suggestive novel loci for APA that will stimulate follow-up studies in independent and larger samples to replicate our findings.

  17. 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.

  18. 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.

  19. 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. PMID:26176695

  20. Genome-wide association study of aggressive behaviour in chicken

    Science.gov (United States)

    Li, Zhenhui; Zheng, Ming; Abdalla, Bahareldin Ali; Zhang, Zhe; Xu, Zhenqiang; Ye, Qiao; Xu, Haiping; Luo, Wei; Nie, Qinghua; Zhang, Xiquan

    2016-01-01

    In the poultry industry, aggressive behaviour is a large animal welfare issue all over the world. To date, little is known about the underlying genetics of the aggressive behaviour. Here, we performed a genome-wide association study (GWAS) to explore the genetic mechanism associated with aggressive behaviour in chickens. The GWAS results showed that a total of 33 SNPs were associated with aggressive behaviour traits (P < 4.6E-6). rs312463697 on chromosome 4 was significantly associated with aggression (P = 2.10905E-07), and it was in the intron region of the sortilin-related VPS10 domain containing receptor 2 (SORCS2) gene. In addition, biological function analysis of the nearest 26 genes around the significant SNPs was performed with Ingenuity Pathway Analysis. An interaction network contained 17 genes was obtained and SORCS2 was involved in this network, interacted with nerve growth factor (NGF), nerve growth factor receptor (NGFR), dopa decarboxylase (L-dopa) and dopamine. After knockdown of SORCS2, the mRNA levels of NGF, L-dopa and dopamine receptor genes DRD1, DRD2, DRD3 and DRD4 were significantly decreased (P < 0.05). In summary, our data indicated that SORCS2 might play an important role in chicken aggressive behaviour through the regulation of dopaminergic pathways and NGF. PMID:27485826

  1. [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.

  2. 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.

  3. 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.

  4. Automated quality control for genome wide association studies.

    Science.gov (United States)

    Ellingson, Sally R; Fardo, David W

    2016-01-01

    This paper provides details on the necessary steps to assess and control data in genome wide association studies (GWAS) using genotype information on a large number of genetic markers for large number of individuals. Due to varied study designs and genotyping platforms between multiple sites/projects as well as potential genotyping errors, it is important to ensure high quality data. Scripts and directions are provided to facilitate others in this process. PMID:27635224

  5. [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. PMID:27013625

  6. [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.

  7. 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

  8. 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. PMID:23626673

  9. 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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

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

    Directory of Open Access Journals (Sweden)

    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

  13. 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

  14. An efficient empirical Bayes method for genomewide association studies.

    Science.gov (United States)

    Wang, Q; Wei, J; Pan, Y; Xu, S

    2016-08-01

    Linear mixed model (LMM) is one of the most popular methods for genomewide association studies (GWAS). Numerous forms of LMM have been developed; however, there are two major issues in GWAS that have not been fully addressed before. The two issues are (i) the genomic background noise and (ii) low statistical power after Bonferroni correction. We proposed an empirical Bayes (EB) method by assigning each marker effect a normal prior distribution, resulting in shrinkage estimates of marker effects. We found that such a shrinkage approach can selectively shrink marker effects and reduce the noise level to zero for majority of non-associated markers. In the meantime, the EB method allows us to use an 'effective number of tests' to perform Bonferroni correction for multiple tests. Simulation studies for both human and pig data showed that EB method can significantly increase statistical power compared with the widely used exact GWAS methods, such as GEMMA and FaST-LMM-Select. Real data analyses in human breast cancer identified improved detection signals for markers previously known to be associated with breast cancer. We therefore believe that EB method is a valuable tool for identifying the genetic basis of complex traits. PMID:26582716

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

    2016-03-01

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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....

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. Multicentric Genome-Wide Association Study for Primary Spontaneous Pneumothorax.

    Science.gov (United States)

    Sousa, Inês; Abrantes, Patrícia; Francisco, Vânia; Teixeira, Gilberto; Monteiro, Marta; Neves, João; Norte, Ana; Robalo Cordeiro, Carlos; Moura E Sá, João; Reis, Ernestina; Santos, Patrícia; Oliveira, Manuela; Sousa, Susana; Fradinho, Marta; Malheiro, Filipa; Negrão, Luís; Feijó, Salvato; Oliveira, Sofia A

    2016-01-01

    Despite elevated incidence and recurrence rates for Primary Spontaneous Pneumothorax (PSP), little is known about its etiology, and the genetics of idiopathic PSP remains unexplored. To identify genetic variants contributing to sporadic PSP risk, we conducted the first PSP genome-wide association study. Two replicate pools of 92 Portuguese PSP cases and of 129 age- and sex-matched controls were allelotyped in triplicate on the Affymetrix Human SNP Array 6.0 arrays. Markers passing quality control were ranked by relative allele score difference between cases and controls (|RASdiff|), by a novel cluster method and by a combined Z-test. 101 single nucleotide polymorphisms (SNPs) were selected using these three approaches for technical validation by individual genotyping in the discovery dataset. 87 out of 94 successfully tested SNPs were nominally associated in the discovery dataset. Replication of the 87 technically validated SNPs was then carried out in an independent replication dataset of 100 Portuguese cases and 425 controls. The intergenic rs4733649 SNP in chromosome 8 (between LINC00824 and LINC00977) was associated with PSP in the discovery (P = 4.07E-03, ORC[95% CI] = 1.88[1.22-2.89]), replication (P = 1.50E-02, ORC[95% CI] = 1.50[1.08-2.09]) and combined datasets (P = 8.61E-05, ORC[95% CI] = 1.65[1.29-2.13]). This study identified for the first time one genetic risk factor for sporadic PSP, but future studies are warranted to further confirm this finding in other populations and uncover its functional role in PSP pathogenesis. PMID:27203581

  3. 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.

  4. Modelling BMI trajectories in children for genetic association studies.

    Directory of Open Access Journals (Sweden)

    Nicole M Warrington

    Full Text Available BACKGROUND: The timing of associations between common genetic variants and changes in growth patterns over childhood may provide insight into the development of obesity in later life. To address this question, it is important to define appropriate statistical models to allow for the detection of genetic effects influencing longitudinal childhood growth. METHODS AND RESULTS: Children from The Western Australian Pregnancy Cohort (Raine; n=1,506 Study were genotyped at 17 genetic loci shown to be associated with childhood obesity (FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, ETV5, SEC16B, LYPLAL1, TFAP2B, MTCH2, BCDIN3D, NRXN3, SH2B1, MRSA and an obesity-risk-allele-score was calculated as the total number of 'risk alleles' possessed by each individual. To determine the statistical method that fits these data and has the ability to detect genetic differences in BMI growth profile, four methods were investigated: linear mixed effects model, linear mixed effects model with skew-t random errors, semi-parametric linear mixed models and a non-linear mixed effects model. Of the four methods, the semi-parametric linear mixed model method was the most efficient for modelling childhood growth to detect modest genetic effects in this cohort. Using this method, three of the 17 loci were significantly associated with BMI intercept or trajectory in females and four in males. Additionally, the obesity-risk-allele score was associated with increased average BMI (female: β=0.0049, P=0.0181; male: β=0.0071, P=0.0001 and rate of growth (female: β=0.0012, P=0.0006; male: β=0.0008, P=0.0068 throughout childhood. CONCLUSIONS: Using statistical models appropriate to detect genetic variants, variations in adult obesity genes were associated with childhood growth. There were also differences between males and females. This study provides evidence of genetic effects that may identify individuals early in life that are more likely to rapidly increase their BMI

  5. Association between androgenetic alopecia and hyperlipidemia: a comparative study

    Directory of Open Access Journals (Sweden)

    Ramin Taheri

    2013-12-01

    Full Text Available Background: Androgenetic alopecia (AGA is the most common type of progressive balding that appears with early loss of hair, chiefly from the vertex. There has been significant relationship between AGA with coronary artery disease and related risk factors, such as hypertension in some studies. The aim of this study is to investigate the association between androgenetic alopecia with hyperlipidemia.Methods: This cross-sectional study was performed on 112 patients with vertex type AGA (in male grade 3 or higher Hamilton- Norwood scale, and in female grade 2 or higher Ludwig scale (study group and 115 persons age and sex matched, with normal hair status (Normal group. None of participants had diabetes mellitus, hypothyroidism, liver disease, kidney disease and none of them had history of smoking and using drugs with effect on serum lipids. They were 20-35 years old and their body mass index were 20-30. Blood samples were obtained following 12 hours fasting status and serum levels of triglyceride (TG, cholesterol, high-density lipoprotein (HDL and low-density lipoprotein (LDL were determined using standard laboratory methods. Total cholesterol greater than 240 or TG greater than 200 or LDL greater than 160 or HDL less than 40 in men or HDL less than 50 in women were considered hyperlipidemia.Results: In androgenetic alopecia group 46.4% and 47% of normal group were female. Mean (±SE of total cholesterol (172.4±3.1, 148.8±3.1, P 0.05.Conclusion: The findings showed that there is no relationship between AGA and hyperlipidemia. Regarding to high levels of total cholesterol, LDL and triglyceride in AGA patients, it seems that, AGA increases risk of coronary heart disease. To determine a definite association between AGA and hyperlipidemia more studies are recommended.

  6. 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.

  7. 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

  8. 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

    Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasiv...

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Case-control association studies with matching and genomic controlling.

    Science.gov (United States)

    Lee, Wen-Chung

    2004-07-01

    Family-based association studies have gained in popularity for mapping disease-susceptibility gene(s) of complex diseases. However, recruiting family controls is often more difficult than recruiting unrelated controls. The author proposes a case-control study, where the possible biases due to population stratification are controlled by matching in the design stage and by genomic controlling in the data-analytic stage. The matching is based on a set of "stratum-delineating variables," such as, race, ethnicity, nationality, ancestry, and birthplace; and the genomic controlling is based on typing a number of null markers across the genome and applying the principle of multiplicative scaling of chi-square distribution. It pays to match carefully to have a higher proportion of correctly matched sets, as computer simulation showed that this would increase the power of the study. If matching is crude, one loses power but still has the correct type I error rate after genomic controlling. Power studies showed that the numbers of affected subjects required for the pair-matched study are comparable to those required by the case-parents design, if the study was conducted in a homogeneous population. As the (control-to-case) matching ratio increases, the number of affected subjects required decreases. With matching ratio tending toward infinity, the number required shrinks roughly by half. The case-control study with matching and genomic controlling frees us from family bondage, and the genetic problem as complicated as mapping genes can now be studied using simple epidemiologic methods. PMID:15185398

  14. 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.

  15. 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.

  16. Association studies in okra (Abelmoschus esculentus (L. Moench

    Directory of Open Access Journals (Sweden)

    Sateesh Adiger, G. Shanthkumar, P. I. Gangashetty* and P. M. Salimath

    2011-12-01

    Full Text Available The present study was undertaken on 163 genotypes including 43 parents and 120 crosses of okra to determine the geneticvariability, nature of association among different yield attributes and their direct and indirect contribution towards yield. Fromthe analysis of variance, it was observed that mean squares due to genotypes were significant for all the traits, indicating thepresence of genetic variability in the experimental material. The values of PCV were higher than that of GCV values for all theten characters indicating influence of environmental effects in the expression of these characters. The GCV, heritability andgenetic advance as percentage of mean were higher for plant height, fruit yield per plant, fruit weight and days to 50 per centflowering which might be attributed to additive gene action of inheritance. The Fruit yield has significantly positive correlationwith plant height, number of branches per plant, inter nodal length, fruit length, fruit weight and number of fruits per plant at bothgenotypic and phenotypic level, indicating mutual association of these traits. Path coefficient analysis revealed that fruit weighthad maximum direct contribution (0.884 towards fruit yield followed by number of fruits per plant (0.852, plant height (0.024and number of branches per plant (0.020. However, days to 50 per cent flowering exhibited highest negative direct effect (-0.013 followed by test weight (-0.009 and fruit diameter (-0.003. These important traits may be viewed in selection programmefor the further improvement of okra.

  17. 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.

  18. 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)).

  19. 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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  2. A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity

    International Nuclear Information System (INIS)

    Background and purpose: This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity 2 years after radiotherapy. Materials and methods: A genome wide association study was performed in 1850 patients from the RAPPER study: 1217 received adjuvant breast radiotherapy and 633 had radical prostate radiotherapy. Genotype associations with both overall and individual endpoints of toxicity were tested via univariable and multivariable regression. Replication of potentially associated SNPs was carried out in three independent patient cohorts who had radiotherapy for prostate (516 RADIOGEN and 862 Gene-PARE) or breast (355 LeND) cancer. Results: Quantile–quantile plots show more associations at the P < 5 × 10−7 level than expected by chance (164 vs. 9 for the prostate cases and 29 vs. 4 for breast cases), providing evidence that common genetic variants are associated with risk of toxicity. Strongest associations were for individual endpoints rather than an overall measure of toxicity in all patients. However, in general, significant associations were not validated at a nominal 0.05 level in the replication cohorts. Conclusions: This largest GWAS to date provides evidence of true association between common genetic variants and toxicity. Associations with toxicity appeared to be tumour site-specific. Future GWAS require higher statistical power, in particular in the validation stage, to test clinically relevant effect sizes of SNP associations with individual endpoints, but the required sample sizes are achievable

  3. 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

  4. 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.

  5. 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....

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

  13. 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

  14. A study of association of obesity with maternal complications

    International Nuclear Information System (INIS)

    To determine the association of obesity with maternal complications. Methodology: A prospective cohort study was conducted at Gynae Unit lll Jinnah Hospital Lahore, from 21st May 2011 to 20th Nov.2011 All women fulfilling the inclusion were included in this study. Two groups were made, Group l was allotted to obese pregnant women and Group ll was allotted to non-obese pregnant women. Demographic data included age, parity, duration of pregnancy and maternal complications i-e urinary tract infection , instrumental vaginal delivery and post-partum haemorrhage were recorded and analyzed by SPSS -version 13. Results: The results of this study revealed that demographics like age parity and duration of pregnancy were almost similar in both groups , common age was 25.21 +- 2.73 in group-A and 26.34 +- 3.56 years in group -B . Comparison of maternal complications revealed that 22.23 % in group-A and 10.70% in group -B had urinary tract infection, relative risk was 2.087, instrumental delivery in group -A was 14.42% and in group-B was 4.19% relative risk was 3.44 while post-partum haemorrhage was 9.77% in group -A and 3.26% in group -B , relative risk was 3.00. Conclusion: The frequency of maternal complications is higher among obese pregnant women so it is recommended that every pregnant woman who presents with increased BMI should be sort out for maternal complications. (author)

  15. 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

  16. 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...... development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals...

  17. Statistical Analysis of Genetic Data in Twin Studies and Association Studies

    OpenAIRE

    Setiawan, A.

    2007-01-01

    In studies in human genetics we want to answer questions such as: how important are genetic effects on a phenotype; what kind of action and interaction exists between gene products in the pathways between genotypes and phenotype; are the genetic effects on a phenotype consistent across sexes; do some genes have particularly outstanding effects when compared to others; what are the locations of the genes involved in the phenotype of interest ? Twin studies and association studies as described ...

  18. 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.

  19. 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.

  20. Genome-wide association studies and infectious disease.

    Science.gov (United States)

    Bowcock, Anne M

    2010-01-01

    The identification of genetic variants predisposing to complex diseases and phenotypes represent a challenge for geneticists in the early part of the 21st century. These are not simple Mendelian disorders caused by single mutations, such as cystic fibrosis or Huntington's disease, but common diseases that are usually polygenic in origin. The predisposing genes can be susceptibility factors or protective factors. One example of such a complex disease is the inflammatory skin disease psoriasis. However, another example could be protection from an infectious disease. Both of these phenotypes are due in part to the presence of low-risk variants in the host. Moreover, all of these complex phenotypes require environmental triggers as well and, in the case of infectious diseases, these are pathogens. In the case of other common diseases such as cardiovascular disease the triggers are often lifestyle-related issues such as diet or exercise. Genome-wide association studies are now identifying some of these genetic susceptibility factors. PMID:20370638

  1. Power analysis of principal components regression in genetic association studies

    Institute of Scientific and Technical Information of China (English)

    Yan-feng SHEN; Jun ZHU

    2009-01-01

    Association analysis provides an opportunity to find genetic variants underlying complex traits. A principal com-ponents regression (PCR)-based approach was shown to outperform some competing approaches. However, a limitation of this method is that the principal components (PCs) selected from single nucleotide polymorphisms (SNPs) may be unrelated to the phenotype. In this article, we investigate the theoretical properties of such a method in more detail. We first derive the exact power function of the test based on PCR, and hence clarify the relationship between the test power and the degrees of freedom (DF). Next, we extend the PCR test to a general weighted PCs test, which provides a unified framework for understanding the properties of some related statistics. We then compare the performance of these tests. We also introduce several data-driven adaptive alterna-tives to overcome difficulties in the PCR approach. Finally, we illustrate our results using simulations based on real genotype data. Simulation study shows the risk of using the unsupervised rule to determine the number of PCs, and demonstrates that there is no single uniformly powerful method for detecting genetic variants.

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

    NARCIS (Netherlands)

    A.E. Dijkstra (Akkelies); J. Smolonska (Joanna); M. van den Berge (Maarten); C. Wijmenga (Ciska); P. Zanen (Pieter); M.A. Luinge (Marjan); I. Platteel (Inge); J.-W.J. Lammers (Jan-Willem); M. Dahlback (Magnus); K. Tosh (Kerrie); P.S. Hiemstra (Pieter); P.J. Sterk (Peter); M.E. Spira (Micha); J. Vestbo (Jorgen); B.G. Nordestgaard (Børge); M. Benn (Marianne); S.F. Nielsen (Sune); M. Dahl (Morten); W.M.M. Verschuren (W. M. Monique); H.S.J. Picavet (Susan); H.A. Smit (Henriëtte); M. Owsijewitsch (Michael); H.U. Kauczor (Hans); H.J. de Koning (Harry); E. Nizankowska-Mogilnicka (Eva); F. Mejza (Filip); P. Nastalek (Pawel); C.C. van Diemen (Cleo); M.H. Cho (Michael); E.K. Silverman (Edwin); R.O. Crapo (Robert); T.H. Beaty (Terri); D.J. Lomas (David John); A.B. Bakke (Arnold B.); A. Gulsvik (Amund); Y. Bossé (Yohan); M. Obeidat; D.W. Loth (Daan); L. Lahousse (Lies); F. Rivadeneira Ramirez (Fernando); A.G. Uitterlinden (André); A. Hofman (Albert); B.H.Ch. Stricker (Bruno); G.G. Brusselle (Guy); C.M. van Duijn (Cock); U. Brouwer (Uilke); G.H. Koppelman (Gerard); J.M. Vonk (Judith); M.C. Nawijn (Martijn); H.J.M. Groen (Henk); W. Timens (Wim); H.M. Boezen (H. Marike); D.S. Postma (Dirkje); B.Z. Alizadeh (Behrooz); R.A. de Boer; M. Bruinenberg (M.); L. Franke (Lude); P. van der Harst (Pim); H.L. Hillege (Hans); M.M. van der Klauw (Melanie); G. Navis (Gerjan); J. Ormel (Johan); J. Rosmalen (Jgm); J.P.J. Slaets (Joris); H. Snieder (Harold); R.P. Stolk (Ronald); B. Wolffenbuttel (Bhr)

    2014-01-01

    textabstractBackground: 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 minor

  3. A whole genome association study on meat palatability in hanwoo.

    Science.gov (United States)

    Hyeong, K-E; Lee, Y-M; Kim, Y-S; Nam, K C; Jo, C; Lee, K-H; Lee, J-E; Kim, J-J

    2014-09-01

    A whole genome association (WGA) study was carried out to find quantitative trait loci (QTL) for sensory evaluation traits in Hanwoo. Carcass samples of 250 Hanwoo steers were collected from National Agricultural Cooperative Livestock Research Institute, Ansung, Gyeonggi province, Korea, between 2011 and 2012 and genotyped with the Affymetrix Bovine Axiom Array 640K single nucleotide polymorphism (SNP) chip. Among the SNPs in the chip, a total of 322,160 SNPs were chosen after quality control tests. After adjusting for the effects of age, slaughter-year-season, and polygenic effects using genome relationship matrix, the corrected phenotypes for the sensory evaluation measurements were regressed on each SNP using a simple linear regression additive based model. A total of 1,631 SNPs were detected for color, aroma, tenderness, juiciness and palatability at 0.1% comparison-wise level. Among the significant SNPs, the best set of 52 SNP markers were chosen using a forward regression procedure at 0.05 level, among which the sets of 8, 14, 11, 10, and 9 SNPs were determined for the respectively sensory evaluation traits. The sets of significant SNPs explained 18% to 31% of phenotypic variance. Three SNPs were pleiotropic, i.e. AX-26703353 and AX-26742891 that were located at 101 and 110 Mb of BTA6, respectively, influencing tenderness, juiciness and palatability, while AX-18624743 at 3 Mb of BTA10 affected tenderness and palatability. Our results suggest that some QTL for sensory measures are segregating in a Hanwoo steer population. Additional WGA studies on fatty acid and nutritional components as well as the sensory panels are in process to characterize genetic architecture of meat quality and palatability in Hanwoo. PMID:25178363

  4. 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

  5. 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 ...

  6. 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

  7. 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.

  8. Fatalities associated with farm tractor injuries: an epidemiologic study.

    OpenAIRE

    Goodman, R A; Smith, J. D.; Sikes, R K; Rogers, D L; Mickey, J L

    1985-01-01

    Death certificates were used as a source of information to characterize fatalities associated with farm tractor injuries in Georgia for the period 1971-81. In this period, 202 tractor-associated fatalities occurred among residents of Georgia; 198 of these persons were males. The annual tractor-associated fatality rate for males based on the population of male farm residents was 23.6 per 100,000; rates of fatal injury increased with age for this population. Persons whose primary occupation was...

  9. 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).

  10. 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

  11. Clinical and molecular studies in ANCA associated vasculitis

    OpenAIRE

    Wendt, Mårten

    2014-01-01

    ANCA associated vasculitis (AAV) is a heterogeneous group of diseases characterised by sterile pauci-immune systemic small vessel inflammation and closely associated with the presence of anti-neutrophil cytoplasmatic antibodies (ANCA). Although AAV can affect any organ, the kidney, skin, lungs and upper and lower airways are most commonly involved. In some patients there is granuloma formation and in some asthma and eosinophilia, and based on this patients can be further classi...

  12. Systematic study of the thermal diffusion in associated mixtures

    OpenAIRE

    Polyakov, P.; Wiegand, S.

    2008-01-01

    We performed systematic temperature and concentration dependent measurements of the Soret coefficient in different associated binary mixtures of water, deuterated water, dimethyl sulfoxide (DMSO), methanol, ethanol, acetone, methanol, 1-propanol, 2-propanol, and propionaldehyde using the so-called thermal diffusion forced Rayleigh scattering method. For some of the associating binary mixtures such as ethanol/water, acetone/water, and DMSO/water, the concentration xw+/- at which the Soret coef...

  13. 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...

  14. 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

  15. 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

  16. Factors associated with adolescent cigarette smoking in Greece: Results from a cross sectional study (GYTS Study

    Directory of Open Access Journals (Sweden)

    Gourgoulianis Konstantinos

    2008-09-01

    Full Text Available Abstract Background Data about the predictors of smoking among adolescents in Greece are sparse. We tried to identify factors associated with current cigarette smoking among in-school adolescents in Greece in the context of GYTS study. Methods A secondary analysis of data from a questionnaire study using the Global Youth Tobacco Survey methodology was conducted to identify factors associated with smoking among adolescents in Greece. Data were collected in 2004–2005. The outcome variable was cigarette smoking within the past 30 days preceding the survey while independent variables included age, gender, parental educational status, parental smoking, perception of harmfulness of smoking, and the amount of pocket money at the adolescent's disposal. Results 6141 adolescents (51.5% males and 48.5% females participated in the study. In multivariate analysis, cigarette smoking was associated with male gender (OR: 1.62; 95% CI: 1, 08–3.08, parental smoking (OR: 2.59; 95% CI: 1.45–5.89, and having pocket money ≥ 16 Euros (OR: 2.64; 95% CI: 1.19–5.98. Conclusion Male gender, parental smoking, and having pocket-money ≥ 16 Euros were independently associated with current smoking among Greek students. These findings could be taken into account in order to formulate a comprehensive anti-smoking strategy in Greece.

  17. Narcissism is associated with weakened frontostriatal connectivity: a DTI study.

    Science.gov (United States)

    Chester, David S; Lynam, Donald R; Powell, David K; DeWall, C Nathan

    2016-07-01

    Narcissism is characterized by the search for affirmation and admiration from others. Might this motivation to find external sources of acclaim exist to compensate for neurostructural deficits that link the self with reward? Greater structural connectivity between brain areas that process self-relevant stimuli (i.e. the medial prefrontal cortex) and reward (i.e. the ventral striatum) is associated with fundamentally positive self-views. We predicted that narcissism would be associated with less integrity of this frontostriatal pathway. We used diffusion tensor imaging to assess the frontostriatal structural connectivity among 50 healthy undergraduates (32 females, 18 males) who also completed a measure of grandiose narcissism. White matter integrity in the frontostriatal pathway was negatively associated with narcissism. Our findings, while purely correlational, suggest that narcissism arises, in part, from a neural disconnect between the self and reward. The exhibitionism and immodesty of narcissists may then be a regulatory strategy to compensate for this neural deficit. PMID:26048178

  18. 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.

  19. Association studies for asthma and atopic diseases: a comprehensive review of the literature

    Directory of Open Access Journals (Sweden)

    Nicolae Dan

    2003-12-01

    Full Text Available Abstract Hundreds of genetic association studies on asthma-related phenotypes have been conducted in different populations. To date, variants in 64 genes have been reported to be associated with asthma or related traits in at least one study. Of these, 33 associations were replicated in a second study, 9 associations were not replicated either in a second study or a second sample in the same study, and 22 associations were reported in just a single published study. These results suggest the potential for a great amount of heterogeneity underlying asthma. However, many of these studies are methodologically limited and their interpretation hampered by small sample sizes.

  20. Imputation Aware Meta-Analysis of Genome-Wide Association Studies

    OpenAIRE

    Zaitlen, Noah; Eskin, Eleazar

    2010-01-01

    Genome-wide association studies have recently identified many new loci associated with human complex diseases. These newly discovered variants typically have weak effects requiring studies with large numbers of individuals to achieve the statistical power necessary to identify them. Likely, there exist even more associated variants, which remain to be found if even larger association studies can be assembled. Meta-analysis provides a straightforward means of increasing study sample sizes with...

  1. 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

  2. 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.

  3. Microscopic study and modeling of thermodiffusion in binary associating mixtures.

    Science.gov (United States)

    Eslamian, Morteza; Saghir, M Ziad

    2009-12-01

    Thermodiffusion in associating mixtures is a complex phenomenon, owing to the strong dependence of the molecular structure of such mixtures on concentration. In this paper, we attempt to elucidate this phenomenon and propose a qualitative mechanism for the separation of species in binary associating mixtures. A correlation between the sign change in the thermal diffusion factor and a change in the molecular structure, mixture viscosity, and the excess entropy of mixing in such mixtures is established. To quantify this correlation, we modify our recently developed dynamic model based on the Drickamer nonequilibrium thermodynamic approach [M. Eslamian and M. Z. Saghir, Phys. Rev. E 80, 011201 (2009)] and propose expressions for the estimation of thermal diffusion factor in binary associating mixtures. The prediction power of the proposed expressions, as well as other widely used models, are examined against the experimental data. The proposed theoretical expressions are self-contained and only rely on the viscosity data as input and predict a sign change in the thermal diffusion factor in associating mixtures. PMID:20365155

  4. 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

  5. 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…

  6. 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

  7. 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.

  8. Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

    DEFF Research Database (Denmark)

    Fatemifar, Ghazaleh; Hoggart, Clive J; Paternoster, Lavinia;

    2013-01-01

    Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption, we performed a population-based genome-wide association study of 'age at first tooth' and 'number of tee...... for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development....

  9. Multivariate Meta-Analysis of Genetic Association Studies: A Simulation Study.

    Directory of Open Access Journals (Sweden)

    Binod Neupane

    Full Text Available In a meta-analysis with multiple end points of interests that are correlated between or within studies, multivariate approach to meta-analysis has a potential to produce more precise estimates of effects by exploiting the correlation structure between end points. However, under random-effects assumption the multivariate estimation is more complex (as it involves estimation of more parameters simultaneously than univariate estimation, and sometimes can produce unrealistic parameter estimates. Usefulness of multivariate approach to meta-analysis of the effects of a genetic variant on two or more correlated traits is not well understood in the area of genetic association studies. In such studies, genetic variants are expected to roughly maintain Hardy-Weinberg equilibrium within studies, and also their effects on complex traits are generally very small to modest and could be heterogeneous across studies for genuine reasons. We carried out extensive simulation to explore the comparative performance of multivariate approach with most commonly used univariate inverse-variance weighted approach under random-effects assumption in various realistic meta-analytic scenarios of genetic association studies of correlated end points. We evaluated the performance with respect to relative mean bias percentage, and root mean square error (RMSE of the estimate and coverage probability of corresponding 95% confidence interval of the effect for each end point. Our simulation results suggest that multivariate approach performs similarly or better than univariate method when correlations between end points within or between studies are at least moderate and between-study variation is similar or larger than average within-study variation for meta-analyses of 10 or more genetic studies. Multivariate approach produces estimates with smaller bias and RMSE especially for the end point that has randomly or informatively missing summary data in some individual studies, when

  10. 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...

  11. Worrying Affects Associative Fear Learning: A Startle Fear Conditioning Study

    OpenAIRE

    Gazendam, F.J.; Kindt, M

    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 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. W...

  12. Enrichment of statistical power for genome-wide association studies

    OpenAIRE

    Li, Meng; Liu, Xiaolei; Bradbury, Peter; Yu, Jianming; Zhang, Yuan-Ming; Todhunter, Rory J.; Buckler, Edward S; Zhang, Zhiwu

    2014-01-01

    Background The inheritance of most human diseases and agriculturally important traits is controlled by many genes with small effects. Identifying these genes, while simultaneously controlling false positives, is challenging. Among available statistical methods, the mixed linear model (MLM) has been the most flexible and powerful for controlling population structure and individual unequal relatedness (kinship), the two common causes of spurious associations. The introduction of the compressed ...

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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...

  19. 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…

  20. 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.

  1. 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.

  2. 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.

  3. Smart Commute Association : commuter attitudes study 2005 : final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-08-01

    The Smart Commute Association is a Greater Toronto Area (GTA)-wide joint municipal undertaking that has developed a range of transportation demand management strategies. This paper discussed the results of a survey conducted to gather baseline information on commuter behaviour and attitudes relating to modes of transportation and awareness of Smart Commute Association programs. Information on telecommuters was also presented. The survey consisted of telephone interviews conducted with 1000 GTA and Hamilton residents. Nearly all the survey participants commuted to work, school or places where they were volunteers. Most commuters were under the age of 45, were employed full-time and lived in households without children. Most had household incomes of under $100,000 per year, and travelled 5 days a week on a standard Monday to Friday schedule, commuting an average of 1 hour and 10 minutes a day. The 2 most popular modes of commuting were driving alone and using public transit. Commuters recognized transportation in and around the GTA and Hamilton as an important issue. Congestion, delay, and gridlock were the main problems encountered on a daily basis. Transportation by motorized vehicle was perceived to be the ideal commuting method. Motorized vehicles were considered to be the most convenient, efficient, and affordable means of travel. Commuters were satisfied with their current commute arrangement and cited the lack of alternative viable transportation options as the primary reason for not wanting to switch commuting methods. There was a significant lack of awareness of the Smart Commute program, but it was viewed as a good idea. Strategies of the Smart Commute program include ride matching for carpooling and a guaranteed ride home service; program modules such as employer vanpools; and a regional marketing and education campaign. 20 figs.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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...

  9. 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

  10. 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.

  11. 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

  12. EPR spin probe study of polymer associative systems

    Science.gov (United States)

    Wasserman, A. M.; Yasina, L. L.; Motyakin, M. V.; Aliev, I. I.; Churochkina, N. A.; Rogovina, L. Z.; Lysenko, E. A.; Baranovsky, V. Yu.

    2008-05-01

    Molecular dynamics of polyacrilamide gels, polymeric micelles and hydrogel of polyacrylic acid and macrodiisocyanate was investigated by the ESR spectroscopy of spin probes. The local mobility in network junction of polyacrylamide gels is found to be essentially slower than that in the micelles created by the low molecular weight detergents and does not depend on the amount and length of hydrophobic groups (C9 or C12) in the polymer chain. The immersion of 10-30 mol.% of ionic monomers into the polymer chain (sodium acrylate) influences insufficiently on the local mobility of network junctions. In aqueous solutions, polystyrene-block-poly-( N-ethyl-4-vinylpyridinium bromide) block copolymers create polymeric micelles. The local mobility in the polystyrene core of the micelles is about twice as much as that in the solid polystyrene. Partially swellable polymer network in aqueous solutions was synthesized from polyacrylic acid and macrodiisocyanate. The local mobility in hydrophobic regions of the gel is substantially lower than that in the hydrophilic regions. It was concluded that the hydrophobic and hydrophilic regions and the local dynamics of them dictate practical application of the polymer associative systems.

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

    OpenAIRE

    Evangelou, Evangelos; Kerkhof, Hanneke J.; Styrkarsdottir, Unnur; Ntzani, Evangelia E; Bos, Steffan D.; Esko, Tonu; Evans, Daniel S.; Metrustry, Sarah; Panoutsopoulou, Kalliope; Ramos, Yolande F M; Thorleifsson, Gudmar; Tsilidis, Konstantinos K.; ,; Arden, Nigel; Aslam, Nadim

    2013-01-01

    Objectives 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 on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for ‘in silico’ or ‘de novo’ replication. Besides the main analysis, a stratified by sex a...

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

    OpenAIRE

    Evangelou, Evangelos; Kerkhof, Hanneke; Styrkarsdottir, Unnur; Ntzani, Evangelia; Bos, Steffan; Esko, Tõnu; Evans, Daniel; Metrustry, Sarah; Panoutsopoulou, Kalliope; Ramos, Yolande; Thorleifsson, Gudmar; Tsilidis, Konstantinos; Arden, Nigel; Aslam, Nadim; Bellamy, Nicholas

    2014-01-01

    Objectives 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 on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a str...

  15. 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

  16. 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

  17. Studies on methanogenic consortia associated with mangrove sediments of Ennore.

    Digital Repository Service at National Institute of Oceanography (India)

    Ahila, N.K.; Kannapiran, E.; Ravindran, J.; Ramkumar, V.S.

    and stored at 4 °C for further study. Culture enrichment : To enrich the methanogenic culture, 1 g of sediment samples were inoculated in 14 ml of anaerobic media (bicarbonate-buffered media - Boone et al., 1989, filter-sterilized trace vitamin solution...

  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. Study of an association of gout and metabolic syndrome

    OpenAIRE

    I I Pol'skaya; Irina Mikhaylovna Marusenko; I I Polskaya; : Mikhailovna Marusenko

    2011-01-01

    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

  20. 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

  1. 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 possible. This paper summarizes the rich literature dealing with the various aspects of the influence of genes on individual survival. Common phenomena affecting the development of disease and longevity are discussed. The major methodological difficulty one is confronted with when studying the epidemiology...... of longevity involves the complexity of the phenomenon, which arises from the polygenic nature of life span and historical mortality change. We discuss this issue and suggest new methodological approaches....

  2. 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

  3. Study of an association of gout and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    I I Pol'skaya

    2011-01-01

    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

  4. 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…

  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; Kuehnel, 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.; Doering, 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; Hyppoenen, Elina; Janssen, Harry L. A.; Johnson, Toby; Kangas, Antti J.; Kema, Ido P.; Kuehn, 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; Wuertz, 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; Pietilainen, Kirsi H.; Schumann, Gunter; Snieder, Harold; Sternberg, Michael J. E.; Stolk, Ronald P.; Thomas, Howard C.; Thorsteinsdottir, Unnur; Uda, Manuela; Waeber, Gerard; 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; Voelzke, Henry; Schadt, Eric E.; Scott, James; Jarvelin, 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. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer

    OpenAIRE

    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

    2009-01-01

    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-con...

  9. 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.

  10. Becoming a young parent: a longitudinal study of associated factors.

    Science.gov (United States)

    Kiernan, K E

    1997-09-01

    Teenage fertility rates in the UK are amongst the highest in Europe and have not altered significantly in the last 15 years, but the proportion of births outside marriage has risen rapidly. In this study we used longitudinal data from the National Child Development Study (NCDS) to investigate the social, economic and educational backgrounds of young parents. The analysis showed there to be striking variations in the probabilities of becoming young parents but not with respect to whether the child was born within or outside marriage. Young mothers and fathers were more likely to come from economically disadvantaged families and to have lower educational attainment. Teenage mothers were more likely to have mothers who had a child in her teens and were more likely to have exhibited higher levels of emotional problems particularly in adolescence. Young women whose educational attainment scores deteriorated between childhood and adolescence had particularly high probabilities of becoming young mothers. For some teenage motherhood was unintended and the result of unprotected intercourse whilst other men and women who subsequently become young parents had expressed a preference for early parenthood whilst still at school. PMID:9372635

  11. 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

  12. Association between the Education and Thalassaemia: A Statistical Study

    Directory of Open Access Journals (Sweden)

    Qamruz Zaman

    2006-07-01

    Full Text Available This article comprises the questionnaire/interview survey of 320 patients and their parent’s conducted in Peshawar, Pakistan to study the literacy of thalassaemia among parents and the severity of thalassaemia on different social aspects. Parent’s educations were strongly linked to cure that disease specially the test (during pregnancy. The majority of parent’s were illiterate and were also against the family planning. Inter family marriages was also one of the main reason of the disease among these patient’s. 56.9% of the patient parents were first cousins while only 1.3% of the patients were matriculate. In the social factors, their average family income was very less as compared to the family members and the expenditure of the treatment. It was also found that the disease was more common in positive blood groups. To coup with the situation, efforts to increase the literacy rate and awareness of the disease are urgently required.

  13. 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.

  14. Genome-wide association study identifies novel loci association with fasting insulin and insulin resistance in African Americans.

    Science.gov (United States)

    Chen, Guanjie; Bentley, Amy; Adeyemo, Adebowale; Shriner, Daniel; Zhou, Jie; Doumatey, Ayo; Huang, Hanxia; Ramos, Edward; Erdos, Michael; Gerry, Norman; Herbert, Alan; Christman, Michael; Rotimi, Charles

    2012-10-15

    Insulin resistance (IR) is a key determinant of type 2 diabetes (T2D) and other metabolic disorders. This genome-wide association study (GWAS) was designed to shed light on the genetic basis of fasting insulin (FI) and IR in 927 non-diabetic African Americans. 5 396 838 single-nucleotide polymorphisms (SNPs) were tested for associations with FI or IR with adjustments for age, sex, body mass index, hypertension status and first two principal components. Genotyped SNPs (n = 12) with P KLF14 and PPARG) which exert their action via IR. In summary, variants in/near SC4MOL, and TCERG1L were associated with FI and IR in this cohort of African Americans and were replicated in West Africans. SC4MOL is under-expressed in an animal model of T2D and plays a key role in lipid biosynthesis, with implications for the regulation of energy metabolism, obesity and dyslipidemia. TCERG1L is associated with plasma adiponectin, a key modulator of obesity, inflammation, IR and diabetes. PMID:22791750

  15. Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies

    OpenAIRE

    2014-01-01

    Summary Background The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilep...

  16. Toll-like receptor gene polymorphisms are associated with allergic rhinitis: a case control study

    OpenAIRE

    Nilsson Daniel; Andiappan Anand; Halldén Christer; Yun Wang; Säll Torbjörn; Tim Chew; Cardell Lars-Olaf

    2012-01-01

    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 case...

  17. 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....

  18. 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); A.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; 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

  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; 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

  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; 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

  1. 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

  2. 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.

  3. 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%). PMID:26643952

  4. 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...

  5. [Future direction of pharmacogenomics: identification of genes associated with risk of adverse drug reactions using genome-wide association study].

    Science.gov (United States)

    Mushiroda, Taisei

    2014-01-01

    Drug-induced skin rash characterized by an acute inflammatory reaction of skin and mucous membranes is dose-independent, unpredictable, and sometimes life-threatening. In recent years, the U.S. Food and Drug Administration (FDA) has recommended genotyping of polymorphisms in the human leukocyte antigen (HLA) prior to drug administration for the avoidance of severe skin rash induced by drugs, such as abacavir and carbamazepine. A genome-wide association study (GWAS) is useful for the identification of genomic biomarkers that can predict the efficacy or risk of toxicity of various drugs. We identified novel susceptibility loci associated with the risk of a skin rash induced by nevirapine and carbamazepine in Thai and Japanese populations, respectively, through case-control GWAS with high-throughput single-nucleotide polymorphism (SNP) genotyping technology. In order to apply the genomic biomarkers to clinical therapeutics, prospective clinical trials will be necessary for the evaluation of an intervention based on genetic tests. PMID:24724431

  6. Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures.

    Science.gov (United States)

    Wang, Xinchen; Tucker, Nathan R; Rizki, Gizem; Mills, Robert; Krijger, Peter Hl; de Wit, Elzo; Subramanian, Vidya; Bartell, Eric; Nguyen, Xinh-Xinh; Ye, Jiangchuan; Leyton-Mange, Jordan; Dolmatova, Elena V; van der Harst, Pim; de Laat, Wouter; Ellinor, Patrick T; Newton-Cheh, Christopher; Milan, David J; Kellis, Manolis; Boyer, Laurie A

    2016-01-01

    Genetic variants identified by genome-wide association studies explain only a modest proportion of heritability, suggesting that meaningful associations lie 'hidden' below current thresholds. Here, we integrate information from association studies with epigenomic maps to demonstrate that enhancers significantly overlap known loci associated with the cardiac QT interval and QRS duration. We apply functional criteria to identify loci associated with QT interval that do not meet genome-wide significance and are missed by existing studies. We demonstrate that these 'sub-threshold' signals represent novel loci, and that epigenomic maps are effective at discriminating true biological signals from noise. We experimentally validate the molecular, gene-regulatory, cellular and organismal phenotypes of these sub-threshold loci, demonstrating that most sub-threshold loci have regulatory consequences and that genetic perturbation of nearby genes causes cardiac phenotypes in mouse. Our work provides a general approach for improving the detection of novel loci associated with complex human traits. PMID:27162171

  7. Validation study of candidate single nucleotide polymorphisms associated with left ventricular hypertrophy in the Korean population

    OpenAIRE

    Park, Jin-Kyu; Kim, Mi Kyung; Choi, Bo Youl; Jung, Yusun; Song, Kyuyoung; Kim, Yu Mi; Shin, Jinho

    2015-01-01

    Background Left ventricular hypertrophy (LVH) is a valid predictor for cardiovascular mortality and morbidity regardless of age, gender, and race. The HyperGEN study conducted a genome-wide association study and identified twelve single nucleotide polymorphisms (SNPs) associated with LVH. The aim of this study was to validate these candidate SNPs in the Korean population. Methods Among 1637 individuals from the Korean Multi-Rural Communities Cohort Study (MRCohort) of the Korean Genome Epidem...

  8. Association of Open-Angle Glaucoma Loci With Incident Glaucoma in the Blue Mountains Eye Study

    OpenAIRE

    Kathryn P Burdon; Mitchell, Paul; Lee, Anne; Healey, Paul R.; White, Andrew J R; Rochtchina, Elena; Thomas, Peter B.M.; Wang, Jie Jin; Craig, Jamie E

    2015-01-01

    Purpose To determine if open-angle glaucoma (OAG)-associated single nucleotide polymorphisms (SNPs) are associated with incident glaucoma and if such genetic information is useful in OAG risk prediction. Design Case-control from within a population-based longitudinal study. Methods study population : Individuals aged over 49 years of age living in the Blue Mountains region west of Sydney and enrolled in the Blue Mountains Eye Study. observation : Cases for this sub-study (n = 67) developed in...

  9. 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

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

    Science.gov (United States)

    Hansel, Nadia N; 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

    2015-08-01

    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

  11. 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

  12. 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...

  13. Can social psychological attitude measures be used to study language attitudes? - A case study exploring the Personalized Implicit Association Test

    OpenAIRE

    Rosseel, Laura; Speelman, Dirk; Geeraerts, Dirk

    2015-01-01

    In the field of social psychology, a wide range of implicit attitude measures have recently been developed. These measures have hardly been used in linguistic attitude research so far. This paper presents a case study exploring the potential of one of these social psychological measures, the Personalized Implicit Association Test, in order to find out whether it can be useful for the study of language attitudes. In the case study, the Personalized Implicit Association Test is applied to measu...

  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. Genome-wide association study identifies multiple novel loci associated with disease progression in subjects with mild cognitive impairment.

    Science.gov (United States)

    Hu, X; Pickering, E H; Hall, S K; Naik, S; Liu, Y C; Soares, H; Katz, E; Paciga, S A; Liu, W; Aisen, P S; Bales, K R; Samad, T A; John, S L

    2011-01-01

    Alzheimer's disease (AD) is the leading cause of dementia among the elderly population; however, knowledge about genetic risk factors involved in disease progression is limited. We conducted a genome-wide association study (GWAS) using clinical decline as measured by changes in the Clinical Dementia Rating-sum of boxes as a quantitative trait to test for single-nucleotide polymorphisms (SNPs) that were associated with the rate of progression in 822 Caucasian subjects of amnestic mild cognitive impairment (MCI). There was no significant association with disease progress for any of the recently identified disease susceptibility variants in CLU, CR1, PICALM, BIN1, EPHA1, MS4A6A, MS4A4E or CD33 following multiple testing correction. We did, however, identify multiple novel loci that reached genome-wide significance at the 0.01 level. These top variants (rs7840202 at chr8 in UBR5: P=4.27 × 10(-14); rs11637611 with a cluster of SNPs at chr15q23 close to the Tay-Sachs disease locus: P=1.07 × 10(-15); and rs12752888 at chr1: P=3.08 × 10(-11)) were also associated with a significant decline in cognition as well as the conversion of subjects with MCI to a diagnosis of AD. Taken together, these variants define approximately 16.6% of the MCI sub-population with a faster rate of decline independent of the other known disease risk factors. In addition to providing new insights into protein pathways that may be involved with the progress to AD in MCI subjects, these variants if further validated may enable the identification of a more homogeneous population of subjects at an earlier stage of disease for testing novel hypotheses and/or therapies in the clinical setting. PMID:22833209

  17. 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

    2016-01-01

    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 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. PMID:26169577

  18. The Genetics of POAG in Black South Africans: A Candidate Gene Association Study

    OpenAIRE

    Williams, Susan E. I.; Carmichael, Trevor R.; Allingham, R. Rand; Hauser, Michael; Ramsay, Michele

    2015-01-01

    Multiple loci have been associated with either primary open angle glaucoma (POAG) or heritable ocular quantitative traits associated with this condition. This study examined the association of these loci with POAG, with central corneal thickness (CCT), vertical cup-to-disc ratio (VCDR) and with diabetes mellitus in a group of black South Africans (215 POAG cases and 214 controls). The population was homogeneous and distinct from other African and European populations. Single SNPs in the MYOC,...

  19. Re-mining item associations: methodology and a case study in apparel retailing

    OpenAIRE

    Demiriz, Ayhan; Ertek, Gürdal; Ertek, Gurdal; Atan, Tankut; Kula, Ufuk

    2011-01-01

    Association mining is the conventional data mining technique for analyzing market basket data and it reveals the positive and negative associations between items. While being an integral part of transaction data, pricing and time information have not been integrated into market basket analysis in earlier studies. This paper proposes a new approach to mine price, time and domain related attributes through re-mining of association mining results. The underlying factors behind positive and negat...

  20. Genetic variants associated with lung function: the long life family study

    OpenAIRE

    Thyagarajan, Bharat; Wojczynski, Mary; Minster, Ryan L.; Sanders, Jason; Barral, Sandra; Christiansen, Lene; Barr, R Graham; ,; Newman, Anne

    2014-01-01

    Background Reduced forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) are strong predictors of mortality and lung function is higher among individuals with exceptional longevity. However, genetic factors associated with lung function in individuals with exceptional longevity have not been identified. Method We conducted a genome wide association study (GWAS) to identify novel genetic variants associated with lung function in the Long Life Family S...

  1. 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....

  2. Association study between brain-derived neurotrophic factor gene polymorphisms and methamphetamine abusers in Japan

    OpenAIRE

    Itoh, Kanako; Hashimoto, Kenji; Shimizu, Eiji; Sekine, Yoshimoto; Ozaki, Norio; Inada, Toshiya; Harano, Mutsuo; Iwata, Nakao; Komiyama, Tokutaro; Yamada, Mitsuhiko; Sora,Ichiro; Nakata, Kenji; Ujike, Hiroshi; Iyo, Masaomi

    2005-01-01

    Several lines of evidence suggest that genetic factors might contribute to drug abuse vulnerability. Recent genomic scans for association demonstrated that the brain-derived neurotrophic factor (BDNF) gene was associated with drug abuse vulnerability. In this study, we analyzed association of two BDNF gene single nucleotide polymorphisms (SNPs), 132C>T (C270T named formerly) in the noncoding region of exon V and 196G >A (val66met) in the coding region of exon XIIIA, with methamphetamine (MAP)...

  3. A General Framework for Association Tests With Multivariate Traits in Large-Scale Genomics Studies

    OpenAIRE

    He, Qianchuan; Avery, Christy L; Lin, Dan-Yu

    2013-01-01

    Genetic association studies often collect data on multiple traits that are correlated. Discovery of genetic variants influencing multiple traits can lead to better understanding of the etiology of complex human diseases. Conventional univariate association tests may miss variants that have weak or moderate effects on individual traits. We propose several multivariate test statistics to complement univariate tests. Our framework covers both studies of unrelated individuals and family studies a...

  4. A Genome-Wide Association Study of Neuroticism in a Population-Based Sample

    OpenAIRE

    Calboli, F. C. F.; Tozzi, F.; Galwey, N. W.; Antoniades, A.; Mooser, V.; Preisig, M.; Vollenweider, P; Waterworth, D.; Waeber, G.; Johnson, M. R.; Muglia, P; Balding, D. J.

    2010-01-01

    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 mi...

  5. A STUDY OF ASSOCIATION OF BODY MASS INDEX WITH SEVERITY OF BRONCHIAL ASTHMA IN 132 PATIENTS

    OpenAIRE

    Vijaykumar; Mahavir; Dattatray; Rakhi

    2014-01-01

    As the prevalence of both obesity and severity of asthma are in increasing trend, we study association between body mass index (BMI) and asthma severity in cross sectional study. OBJECTIVE: To study association between Body mass index and Asthma severity METHODOLOGY- We included adults (age >13yrs), who are diagnosed as patients of asthma by Pulmonologist and who are non -smoker, without any other lung pathology, are not on long term systemic steroids. Total of 132 patient...

  6. A genome-wide association study of body mass index across early life and childhood

    OpenAIRE

    Nicole M Warrington; Howe, Laura D; Paternoster, Lavinia; Kaakinen, Marika; Herrala, Sauli; Huikari, Ville; Wu, Yan Yan; Kemp, John P.; Timpson, Nicholas J.; Pourcain, Beate St; Davey Smith, George; Tilling, Kate; Jarvelin, Marjo-Riitta; Pennell, Craig E.; Evans, David M.

    2015-01-01

    Background: Several studies have investigated the effect of known adult body mass index (BMI) associated single nucleotide polymorphisms (SNPs) on BMI in childhood. There has been no genome-wide association study (GWAS) of BMI trajectories over childhood. Methods: We conducted a GWAS meta-analysis of BMI trajectories from 1 to 17 years of age in 9377 children (77 967 measurements) from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Western Australian Pregnancy Cohort (Ra...

  7. A genome-wide association study of body mass index across early life and childhood

    OpenAIRE

    Warrington, N.; Howe, L; Paternoster, L.; Kaakinen, M.; Herrala, S. (Sauli); Huikari, V.; Wu, Y.; Kemp, J.; Timpson, N.; St Pourcain, B.; Smith, G.; Tilling, K; Jarvelin, M; Pennell, C; Evans, D

    2015-01-01

    Background: Several studies have investigated the effect of known adult body mass index (BMI) associated single nucleotide polymorphisms (SNPs) on BMI in childhood. There has been no genome-wide association study (GWAS) of BMI trajectories over childhood. Methods: We conducted a GWAS meta-analysis of BMI trajectories from 1 to 17 years of age in 9377 children (77 967 measurements) from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Western Australian Pregnancy Cohort (Ra...

  8. Systematic review and metaanalysis of genetic association studies of urinary symptoms and prolapse in women

    OpenAIRE

    Cartwright, Rufus; Kirby, Anna C.; Tikkinen, Kari A O; Mangera, Altaf; Thiagamoorthy, Gans; Rajan, Prabhakar; Pesonen, Jori; Ambrose, Chris; Gonzalez-Maffe, Juan; Bennett, Phillip; Palmer, Tom; Walley, Andrew; Järvelin, Marjo-Riitta; Chapple, Chris; Khullar, Vik

    2015-01-01

    Objective Family studies and twin studies demonstrate that lower urinary tract symptoms and pelvic organ prolapse are heritable. This review aimed to identify genetic polymorphisms tested for an association with lower urinary tract symptoms or prolapse, and to assess the strength, consistency, and risk of bias among reported associations. Study Design PubMed and HuGE Navigator were searched up to May 1, 2014, using a combination of genetic and phenotype key words, including “nocturi...

  9. The genetics of POAG in black South Africans: a candidate gene association study.

    Science.gov (United States)

    Williams, Susan E I; Carmichael, Trevor R; Allingham, R Rand; Hauser, Michael; Ramsay, Michele

    2015-01-01

    Multiple loci have been associated with either primary open angle glaucoma (POAG) or heritable ocular quantitative traits associated with this condition. This study examined the association of these loci with POAG, with central corneal thickness (CCT), vertical cup-to-disc ratio (VCDR) and with diabetes mellitus in a group of black South Africans (215 POAG cases and 214 controls). The population was homogeneous and distinct from other African and European populations. Single SNPs in the MYOC, COL8A2, COL1A1 and ZNF469 gene regions showed marginal associations with POAG. No association with POAG was identified with tagging SNPs in TMCO1, CAV1/CAV2, CYP1B1, COL1A2, COL5A1, CDKN2B/CDKN2BAS-1, SIX1/SIX6 or the chromosome 2p16 regions and there were no associations with CCT or VCDR. However, SNP rs12522383 in WDR36 was associated with diabetes mellitus (p = 0.00008). This first POAG genetic association study in black South Africans has therefore identified associations that require additional investigation in this and other populations to determine their significance. This highlights the need for larger studies in this population if we are to achieve the goal of facilitating early POAG detection and ultimately preventing irreversible blindness from this condition. PMID:25669751

  10. A Review of Genome-Wide Association Studies of Stimulant and Opioid Use Disorders.

    Science.gov (United States)

    Jensen, Kevin P

    2016-05-01

    Substance use disorders (SUD) are a major contributor to disability and disease burden worldwide. Risk for developing SUDs is influenced by variation in the genome. Identifying the genetic variants that influence SUD risk may help us to understand the biological mechanisms for the disorders and improve treatments. Genome-wide association studies (GWAS) have been successful in identifying many regions of the genome associated with common human disorders. Here, findings from recent GWAS of SUDs that involve illicit substances will be reviewed. Several GWAS have been reported, including studies on opioid and stimulant use disorder (cocaine and methamphetamine). Several of these GWAS report associations that are biologically interesting and statistically robust. Replication of the associations in independent samples and functional studies to understand the basis for the statistical associations will be important next steps. PMID:27606319

  11. 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.

    2015-01-01

    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, SGSM3/MKL1), non-dense area (8p11.23) and percent density (PRDM6, 8p11.23, 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. PMID:25342443

  12. Association between Lifestyle and School Attendance in Japanese Medical Students: A Pilot Study

    Science.gov (United States)

    Tanaka, Masaaki; Watanabe, Yasuyoshi

    2012-01-01

    Objective: Lifestyle factors are thought to be associated with students' academic performance. Whether lifestyle factors were associated with medical students' school attendance was determined. Design: Cross-sectional design. Setting: The study group consisted of 157 healthy second-year medical students attending Osaka City University Graduate…

  13. 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

  14. 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...

  15. 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

  16. 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...

  17. 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 ...

  18. 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

  19. 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.

  20. 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

  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. Preliminary study on regulatory limits of coal mines associated with radionuclides in Xinjiang

    International Nuclear Information System (INIS)

    In this paper, limits of radon concentration and gamma radiation dose rate of coal mines associated with radionuclide in Xinjiang were studied to provide theoretical bases in developing scientific and practical regulatory standards of radiation protection for coal mines associated with radionuclides. It is meaningful in strengthening the supervision to coal mines associated with radionuclides, boosting their development of exploitation and utilization, as well as the protection to the health of worker and public and the environment. It may also provide references in defining the limits of regulatory standards for NORMs associated mining and processing of ore resources. (authors)

  3. Genome Wide Association Study and Follow-Up Analysis of Adiposity Traits in Hispanic-Americans: the IRAS Family Study

    OpenAIRE

    Norris, Jill M.; Langefeld, Carl D.; Talbert, Matthew E.; Wing, Maria R; Haritunians, Talin; Fingerlin, Tasha E.; Hanley, Anthony J. G.; Ziegler, Julie T.; Taylor, Kent D.; Haffner, Steven M.; Chen, Yii-Der I.; Donald W Bowden; Wagenknecht, Lynne E.

    2009-01-01

    We investigated candidate genomic regions associated with computed tomography (CT)-derived measures of adiposity in Hispanic from the IRAS Family Study. In 1190 Hispanic individuals from 92 families from the San Luis Valley, CO and San Antonio, TX, we measured CT-derived visceral adipose tissue (VAT); subcutaneous adipose tissue (SAT); and visceral: subcutaneous ratio (VSR). A genome-wide association study (GWAS) was completed using the Illumina HumanHap 300 BeadChip (~317K single nucleotide ...

  4. 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.

  5. The Newcastle 85+ study: biological, clinical and psychosocial factors associated with healthy ageing: study protocol

    Directory of Open Access Journals (Sweden)

    Martin-Ruiz Carmen

    2007-06-01

    Full Text Available Abstract Background The UK, like other developed countries, is experiencing a marked change in the age structure of its population characterised by increasing life expectancy and continuing growth in the older fraction of the population. There is remarkably little up-to-date information about the health of the oldest old (over 85 years, demographically the fastest growing section of the population. There is a need, from both a policy and scientific perspective, to describe in detail the health status of this population and the factors that influence individual health trajectories. For a very large proportion of medical conditions, age is the single largest risk factor. Gaining new knowledge about why aged cells and tissues are more vulnerable to pathology is likely to catalyse radical new insights and opportunities to intervene. The aims of the Newcastle 85+ Study are to expose the spectrum of health within an inception cohort of 800 85 year-olds; to examine health trajectories and outcomes as the cohort ages and their associations with underlying biological, medical and social factors; and to advance understanding of the biological nature of ageing. Methods A cohort of 800 85 year olds from Newcastle and North Tyneside will be recruited at baseline and followed until the last participant has died. Eligible individuals will be all those who turn 85 during the year 2006 (i.e. born in 1921 and who are registered with a Newcastle or North Tyneside general practice. Participants will be visited in their current residence (own home or institution by a research nurse at baseline, 18 months and 36 months. The assessment protocol entails a detailed multi-dimensional health assessment together with review of general practice medical records. Participants will be flagged with the NHS Central Register to provide details of the date and cause of death. Discussion The Newcastle 85+ Study will address key questions about health and health-maintenance in the

  6. Abdominal adiposity largely explains associations between insulin resistance, hyperglycemia and subclinical atherosclerosis: the NEO study

    NARCIS (Netherlands)

    Gast, K.B.; Smit, J.W.A.; Heijer, M. den; Middeldorp, S.; Rippe, R.C.; Cessie, S. le; Koning, E.J. de; Jukema, J.W.; Rabelink, T.J.; Roos, A. de; Rosendaal, F.R.; Mutsert, R. de; Assendelft, P.

    2013-01-01

    OBJECTIVE: The relative importance of insulin resistance and hyperglycemia to the development of atherosclerosis remains unclear. Furthermore, adiposity may be responsible for observed associations. Our aim was to study the relative contributions of adiposity, insulin resistance and hyperglycemia to

  7. 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

  8. 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. PMID:23459689

  9. 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.

  10. 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.

  11. 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...

  12. Studies on the associates and parasites of zooplankton from southwest and southeast coasts of India

    Digital Repository Service at National Institute of Oceanography (India)

    Santhakumari, V.

    Associates and parasites of zooplankton from southwest and southeast coasts of India were studied. Among the epizoic forms two species of ciliates infesting copepods were new records from Indian waters. Eight species of suctorians were found epizoic...

  13. 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.

  14. Personality traits and association with depression in the elderly: The AGES-Reykjavík Study

    OpenAIRE

    Elísabet Þórðardóttir 1965

    2015-01-01

    Background: Personality is associated with various mental disorders. The personality factor of neuroticism is a risk factor for developing depression; extraversion and conscientiousness can also have an impact on depression. Few studies have looked at the elderly population in relation to personality and depression. The aim of this study was to examine the association between the Big Five personality factors of neuroticism, extroversion and conscientiousness and symptoms of depression and dep...

  15. Association between Allergic Rhinitis and Asthma Control in Peruvian School Children: A Cross-Sectional Study

    OpenAIRE

    Justo Padilla; Mónica Uceda; Otto Ziegler; Felipe Lindo; Eder Herrera-Pérez; Luis Huicho

    2013-01-01

    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 betwe...

  16. Association between Diet and Lifestyle Habits and Irritable Bowel Syndrome: A Case-Control Study

    OpenAIRE

    Guo, Yu-Bin; Zhuang, Kang-Min; Kuang, Lei; Zhan, Qiang; Wang, Xian-fei; Liu, Si-De

    2014-01-01

    Background/Aims Recent papers have highlighted the role of diet and lifestyle habits in irritable bowel syndrome (IBS), but very few population-based studies have evaluated this association in developing countries. The aim of this study was to evaluate the association between diet and lifestyle habits and IBS. Methods A food frequency and lifestyle habits questionnaire was used to record the diet and lifestyle habits of 78 IBS subjects and 79 healthy subjects. Cross-tabulation analysis and lo...

  17. Association between Vitamin D Status and Risk of Peripheral Arterial Disease: The Dong-gu Study

    Science.gov (United States)

    Oh, Su-Hyun; Kweon, Sun-Seog; Choi, Jin-Su; Rhee, Jung-Ae; Lee, Young-Hoon; Nam, Hae-Sung; Jeong, Seul-Ki; Park, Kyeong-Soo; Ryu, So-Yeon; Choi, Seong-Woo

    2016-01-01

    Low levels of vitamin D have been associated with increased cardiovascular disease risk. However, few studies have evaluated the association between vitamin D status and peripheral arterial disease (PAD). We therefore aimed to investigate whether low 25-hydroxyvitamin D (25(OH)D) levels were associated with increased risk of PAD in the Korean population. This cross-sectional study was conducted among 8,960 subjects aged 50 years or older without known myocardial infarction or stroke. PAD was defined by an ankle brachial blood pressure index vitamin D levels may contribute to PAD in the Korean population.

  18. 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 of...... 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....

  19. Association between Vitamin D Status and Risk of Peripheral Arterial Disease: The Dong-gu Study.

    Science.gov (United States)

    Oh, Su-Hyun; Kweon, Sun-Seog; Choi, Jin-Su; Rhee, Jung-Ae; Lee, Young-Hoon; Nam, Hae-Sung; Jeong, Seul-Ki; Park, Kyeong-Soo; Ryu, So-Yeon; Choi, Seong-Woo; Shin, Min-Ho

    2016-09-01

    Low levels of vitamin D have been associated with increased cardiovascular disease risk. However, few studies have evaluated the association between vitamin D status and peripheral arterial disease (PAD). We therefore aimed to investigate whether low 25-hydroxyvitamin D (25(OH)D) levels were associated with increased risk of PAD in the Korean population. This cross-sectional study was conducted among 8,960 subjects aged 50 years or older without known myocardial infarction or stroke. PAD was defined by an ankle brachial blood pressure index vitamin D levels may contribute to PAD in the Korean population. PMID:27689032

  20. 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.

  1. 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.

  2. Association between Herpesviruses and Chronic Periodontitis: A Meta-Analysis Based on Case-Control Studies

    Science.gov (United States)

    Wong, May. Chun. Mei; Feng, Xi-Ping; Lu, Hai-Xia; Xu, Wei

    2015-01-01

    Objective Numerous studies have investigated the associations between herpesviruses and chronic periodontitis; however, the results remain controversial. To derive a more precise estimation, a meta-analysis on all available studies was performed to identify the association between herpesviruses and chronic periodontitis. Methods A computerized literature search was conducted in December 2014 to identify eligible case-control studies from the PUBMED and EMBASE databases according to inclusion and exclusion criteria. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were used to assess the association between herpesviruses and risk of chronic periodontitis. A fixed or random effects model was determined based on a heterogeneity test. Sensitivity analysis was conducted to investigate stability and reliability. Publication bias was investigated using the Begg rank correlation test and Egger's funnel plot. Results Ten eligible studies were included to investigate the association between Epstein–Barr virus (EBV) and chronic periodontitis. The results showed that EBV has a significant association with chronic periodontitis compared with periodontally healthy group (OR = 5.74, 95% CI = 2.53–13.00, Pherpesvirus 7 (HHV-7) and chronic periodontitis risk (OR = 1.00, 95% CI = 0.21–4.86). Conclusion The findings of this meta-analysis suggest that two members of the herpesvirus family, EBV and HCMV, are significantly associated with chronic periodontitis. There is insufficient evidence to support associations between HSV, HHV-7 and chronic periodontitis. PMID:26666412

  3. 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…

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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...

  10. 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.

  11. 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

  12. Whole-genome association study identifies STK39 as a hypertension susceptibility gene

    Science.gov (United States)

    Wang, Ying; O'Connell, Jeffrey R.; McArdle, Patrick F.; Wade, James B.; Dorff, Sarah E.; Shah, Sanjiv J.; Shi, Xiaolian; Pan, Lin; Rampersaud, Evadnie; Shen, Haiqing; Kim, James D.; Subramanya, Arohan R.; Steinle, Nanette I.; Parsa, Afshin; Ober, Carole C.; Welling, Paul A.; Chakravarti, Aravinda; Weder, Alan B.; Cooper, Richard S.; Mitchell, Braxton D.; Shuldiner, Alan R.; Chang, Yen-Pei C.

    2009-01-01

    Hypertension places a major burden on individual and public health, but the genetic basis of this complex disorder is poorly understood. We conducted a genome-wide association study of systolic and diastolic blood pressure (SBP and DBP) in Amish subjects and found strong association signals with common variants in a serine/threonine kinase gene, STK39. We confirmed this association in an independent Amish and 4 non-Amish Caucasian samples including the Diabetes Genetics Initiative, Framingham Heart Study, GenNet, and Hutterites (meta-analysis combining all studies: n = 7,125, P 0.09 and were associated with increases of 3.3/1.3 mm Hg in SBP/DBP, respectively, in the Amish subjects and with smaller but consistent effects across the non-Amish studies. Cell-based functional studies showed that STK39 interacts with WNK kinases and cation-chloride cotransporters, mutations in which cause monogenic forms of BP dysregulation. We demonstrate that in vivo, STK39 is expressed in the distal nephron, where it may interact with these proteins. Although none of the associated SNPs alter protein structure, we identified and experimentally confirmed a highly conserved intronic element with allele-specific in vitro transcription activity as a functional candidate for this association. Thus, variants in STK39 may influence BP by increasing STK39 expression and consequently altering renal Na+ excretion, thus unifying rare and common BP-regulating alleles in the same physiological pathway. PMID:19114657

  13. Prevalence of anemia and associated factors in older adults: evidence from the SABE Study

    OpenAIRE

    Ligiana Pires Corona; Yeda Aparecida de Oliveira Duarte; Maria Lucia Lebrão

    2014-01-01

    OBJECTIVE To assess the prevalence of anemia and associated factors in older adults. METHODS The prevalence and factors associated with anemia in older adults were studied on the basis of the results of the Saúde, Bem-Estar e Envelhecimento (SABE – Health, Welfare and Aging) study. A group of 1,256 individuals were interviewed during the third wave of the SABE study performed in Sao Paulo, SP, in 2010. The study included 60.4% females; the mean age of the participants was 70.4 years, and ...

  14. A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study

    Science.gov (United States)

    Abstract Background: Blood lipid levels including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are highly heritable. Genome-wide association is a promising approach to map genetic loci related to these heritable phenotypes. Metho...

  15. The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study

    Directory of Open Access Journals (Sweden)

    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.

  16. Genome wide association study of fetal hemoglobin in sickle cell anemia in Tanzania.

    Directory of Open Access Journals (Sweden)

    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.

  17. A validation of the first genome-wide association study of calcaneus ultrasound parameters in the European Male Ageing Study

    Directory of Open Access Journals (Sweden)

    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

  18. Genome-wide and candidate gene association study of cigarette smoking behaviors.

    Directory of Open Access Journals (Sweden)

    Neil Caporaso

    Full Text Available The contribution of common genetic variation to one or more established smoking behaviors was investigated in a joint analysis of two genome wide association studies (GWAS performed as part of the Cancer Genetic Markers of Susceptibility (CGEMS project in 2,329 men from the Prostate, Lung, Colon and Ovarian (PLCO Trial, and 2,282 women from the Nurses' Health Study (NHS. We analyzed seven measures of smoking behavior, four continuous (cigarettes per day [CPD], age at initiation of smoking, duration of smoking, and pack years, and three binary (ever versus never smoking, 10 cigarettes per day [CPDBI], and current versus former smoking. Association testing for each single nucleotide polymorphism (SNP was conducted by study and adjusted for age, cohabitation/marital status, education, site, and principal components of population substructure. None of the SNPs achieved genome-wide significance (p<10(-7 in any combined analysis pooling evidence for association across the two studies; we observed between two and seven SNPs with p<10(-5 for each of the seven measures. In the chr15q25.1 region spanning the nicotinic receptors CHRNA3 and CHRNA5, we identified multiple SNPs associated with CPD (p<10(-3, including rs1051730, which has been associated with nicotine dependence, smoking intensity and lung cancer risk. In parallel, we selected 11,199 SNPs drawn from 359 a priori candidate genes and performed individual-gene and gene-group analyses. After adjusting for multiple tests conducted within each gene, we identified between two and five genes associated with each measure of smoking behavior. Besides CHRNA3 and CHRNA5, MAOA was associated with CPDBI (gene-level p<5.4x10(-5, our analysis provides independent replication of the association between the chr15q25.1 region and smoking intensity and data for multiple other loci associated with smoking behavior that merit further follow-up.

  19. Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies.

    Directory of Open Access Journals (Sweden)

    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

  20. 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

  1. 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

  2. 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

  3. 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.

  4. Common FLG mutation K4671X not associated with atopic dermatitis in Han Chinese in a family association study.

    Directory of Open Access Journals (Sweden)

    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

  5. Genome-Wide Association Study Identifies Novel Susceptibility Genes Associated with Coronary Artery Aneurysm Formation in Kawasaki Disease

    Science.gov (United States)

    Guo, Mindy Ming-Huey; Huang, Ying-Hsien; Yu, Hong-Ren; Huang, Fu-Chen; Jiao, Fuyong; Kuo, Hsing-Chun; Andrade, Jorge

    2016-01-01

    Kawasaki disease (KD) or Kawasaki syndrome is known as a vasculitis of small to medium-sized vessels, and coronary arteries are predominantly involved in childhood. Generally, 20–25% of untreated with IVIG and 3–5% of treated KD patients have been developed coronary artery lesions (CALs), such as dilatation and aneurysm. Understanding how coronary artery aneurysms (CAAs) are established and maintained in KD patients is therefore of great importance. Upon our previous genotyping data of 157 valid KD subjects, a genome-wide association study (GWAS) has been conducted among 11 (7%) CAA-developed KD patients to reveal five significant genetic variants passed pre-defined thresholds and resulted in two novel susceptibility protein-coding genes, which are NEBL (rs16921209 (P = 7.44 × 10−9; OR = 32.22) and rs7922552 (P = 8.43 × 10−9; OR = 32.0)) and TUBA3C (rs17076896 (P = 8.04 × 10−9; OR = 21.03)). Their known functions have been reported to associate with cardiac muscle and tubulin, respectively. As a result, this might imply their putative roles of establishing CAAs during KD progression. Additionally, various model analyses have been utilized to determine dominant and recessive inheritance patterns of identified susceptibility mutations. Finally, all susceptibility genes hit by significant genetic variants were further investigated and the top three representative gene-ontology (GO) clusters were regulation of cell projection organization, neuron recognition, and peptidyl-threonine phosphorylation. Our results help to depict the potential routes of the pathogenesis of CAAs in KD patients and will facilitate researchers to improve the diagnosis and prognosis of KD in personalized medicine. PMID:27171184

  6. Factors accounting for the association between anxiety and depression, and eczema: the Hordaland health study (HUSK

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. Toll-like receptor gene polymorphisms are associated with allergic rhinitis: a case control study

    Directory of Open Access Journals (Sweden)

    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.

  9. Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study

    OpenAIRE

    Newton-Cheh, Christopher; Guo, Chao-Yu; Wang, Thomas J.; O'Donnell, Christopher J.; Levy, Daniel; Larson, Martin G.

    2007-01-01

    Background Heritable electrocardiographic (ECG) and heart rate variability (HRV) measures, reflecting pacemaking, conduction, repolarization and autonomic function in the heart have been associated with risks for cardiac arrhythmias. Whereas several rare monogenic conditions with extreme phenotypes have been noted, few common genetic factors contributing to interindividual variability in ECG and HRV measures have been identified. We report the results of a community-based genomewide associati...

  10. Replication of Prostate Cancer Risk Variants in a Danish Case-Control Association Study

    DEFF Research Database (Denmark)

    Bentzon, Diem Nguyen; Nyegaard, Mette; Børglum, Anders;

    2012-01-01

    Background: Prostate cancer is one of the main causes for cancer morbidity and mortality in Western countries. Recently, several single nucleotide polymorphisms (SNPs) associated with prostate cancer have been identified in genome-wide association studies and multiple variant models have been...... developed to predict prostate cancer risk. The association between genetic markers and clinico-pathological tumor variables has, however, been inconsistent. Methods and Materials: A total of 32 previously identified prostate cancer-associated risk SNPs were genotyped in 648 prostate cancer cases and 526 age......-matched controls. Family history was obtained by questionnaire. Age at diagnosis, clinical tumor variables including pre- and postoperative PSA, Gleason score, and T stage were obtained from prospectively collected clinical data (Aarhus Prostate Cancer Study). The SNPs were genotyped using Sequenom and Taqman...

  11. 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.

  12. 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....

  13. A genome-wide association study for age-related hearing impairment in the Saami

    OpenAIRE

    Van Camp, Guy; Van Laer, Lut; Huyghe, Jeroen; Hannula, Samuli; Van Eyken, Els; Stephan, Dietrich; Mäki-Torkko, Elina; Aikio, Pekka; Lysholm-Bernacchi, Alana; Sorri, Martti; Huentelman, Matthew J; Fransen, Erik

    2010-01-01

    International audience This study aimed to contribute to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genome-wide association study (GWAS) in the Finnish Saami, a small ancient genetically isolated population without evidence of demographic expansion. The choice of this study population was motivated by its anticipated higher exten...

  14. A genome-wide association study for age-related hearing impairment in the Saami

    OpenAIRE

    Van Laer, Lut; Huyghe, Jeroen R; Hannula, Samuli; Van Eyken, Els; Stephan, Dietrich A.; Mäki-Torkko, Elina; Aikio, Pekka; Fransen, Erik; Lysholm-Bernacchi, Alana; Sorri, Martti; Huentelman, Matthew J; Van Camp, Guy

    2010-01-01

    This study aimed at contributing to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genome-wide association study (GWAS) in the Finnish Saami, a small, ancient, genetically isolated population without evidence of demographic expansion. The choice of this study population was motivated by its anticipated higher extent of LD, potentially o...

  15. A genome-wide association study identifies multiple loci for variation in human ear morphology

    OpenAIRE

    Adhikari, K.; Reales, G.; Smith, A. J.; Konka, E.; Palmen, J.; Quinto-Sanchez, M.; Acuña-Alonzo, V.; Jaramillo, C; Arias, W.; Fuentes, M; Pizarro, M.; Barquera Lozano, R.; Macín Pérez, G.; Gómez-Valdés, J.; Villamil-Ramírez, H.

    2015-01-01

    Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10(-8) to 3 × 10(-14)). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage devel...

  16. A genome-wide association study identifies multiple loci for variation in human ear morphology

    OpenAIRE

    Adhikari, Kaustubh; Reales, Guillermo; Smith, Andrew J. P.; Konka, Esra; Palmen, Jutta; Quinto-Sanchez, Mirsha; Acuña-Alonzo, Victor; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Barquera Lozano, Rodrigo; Macín Pérez, Gastón; Gómez-Valdés, Jorge; Villamil-Ramírez, Hugo

    2015-01-01

    Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10−8 to 3 × 10−14). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage developme...

  17. An efficient weighted tag SNP-set analytical method in genome-wide association studies

    OpenAIRE

    Yan, Bin; Wang, Shudong; Jia, Huaqian; Liu, Xing; Wang, Xinzeng

    2015-01-01

    Background Single-nucleotide polymorphism (SNP)-set analysis in Genome-wide association studies (GWAS) has emerged as a research hotspot for identifying genetic variants associated with disease susceptibility. But most existing methods of SNP-set analysis are affected by the quality of SNP-set, and poor quality of SNP-set can lead to low power in GWAS. Results In this research, we propose an efficient weighted tag-SNP-set analytical method to detect the disease associations. In our method, we...

  18. 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.

  19. Preliminary Study on Coral Reef and Its Associated Biota in Qatari Waters, Arabian Gulf

    OpenAIRE

    Al Ansi, Mohsin A. [محسن عبد الله العنسي; AL-KHAYAT, Jassim A.

    1999-01-01

    Coral reef grounds and their associated biota m Qatari waters were investigated by Scuba diving. Four selected reef-sites were studied. Coral was presented by 17 species. Descriptive notes of each site and an initial list of associated fauna and flora were presented. The associated biota composed mainly of Algae 23 sp, Porifera 5 sp, Bryozoa 4 sp, Polychaeta 17 sp, Echinodermata 21 sp, Mollusca 102 sp, Chordata 4 sp, and Crustacea 15 sp. Mollusca was the predominant group in all visited sites...

  20. The association between alcohol consumption and contact sensitization in Danish adults: the Glostrup Allergy Study

    DEFF Research Database (Denmark)

    Thyssen, Jacob Pontoppidan; Nielsen, N.H.; Linneberg, A.

    2008-01-01

    Background Population-based epidemiological studies have indicated that alcohol consumption is associated with IgE-mediated immune diseases (i.e. allergic rhinitis, asthma and urticaria). These studies have been strongly supported by several immunological studies. Furthermore, an inhibitory effect...... of alcohol consumption on the development of delayed-type hypersensitivity has been shown in healthy controls. However, a possible association between contact sensitization and alcohol consumption in a general population has never been reported. Objectives To investigate whether alcohol consumption...... is associated with contact sensitization in a general population. Methods In 1990, self-reported consumption of alcohol and patch testing results were assessed in 1112 subjects, aged 15-69 years, participating in a population-based cross-sectional study in Glostrup, Denmark. In 1998, they were invited...

  1. 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.

  2. 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

    2016-07-01

    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. PMID:27383984

  3. Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS.

    Science.gov (United States)

    Mattheisen, M; Samuels, J F; Wang, Y; Greenberg, B D; Fyer, A J; McCracken, J T; Geller, D A; Murphy, D L; Knowles, J A; Grados, M A; Riddle, M A; Rasmussen, S A; McLaughlin, N C; Nurmi, E L; Askland, K D; Qin, H-D; Cullen, B A; Piacentini, J; Pauls, D L; Bienvenu, O J; Stewart, S E; Liang, K-Y; Goes, F S; Maher, B; Pulver, A E; Shugart, Y Y; Valle, D; Lange, C; Nestadt, G

    2015-03-01

    Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10(-)(7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P<1 × 10(-)(6), experiment-wide significant), as well as OFCC1 (P=6.29 × 10(-)(5)). The suggestive findings in this study await replication in larger samples. PMID:24821223

  4. Association between -T786C NOS3 polymorphism and resistant hypertension: a prospective cohort study

    OpenAIRE

    Martín-Luengo Cándido; Sánchez-Rodríguez Angel; Sánchez-Ledesma María; Corral Esther; Cruz-González Ignacio; González-Sarmiento Rogelio

    2009-01-01

    Abstract Background It is estimated that 5% of the hypertensive patients are resistant to conventional antihypertensive therapy. Polymorphisms in the endothelial nitric oxide synthase (NOS3) gene have been associated with high blood pressure levels, but not with resistant hypertension. The aim of the present study was to investigate if the -786T>C and G894T (Glu298Asp) polymorphisms of the NOS3 gene were associated with resistant hypertension. Methods A prospective case-control observational ...

  5. Multiple SNP-sets Analysis for Genome-wide Association Studies through Bayesian Latent Variable Selection

    OpenAIRE

    Lu, Zhaohua; Zhu, Hongtu; Knickmeyer, Rebecca C.; Sullivan, Patrick F.; Stephanie, Williams N.; Zou, Fei

    2015-01-01

    The power of genome-wide association studies (GWAS) for mapping complex traits with single SNP analysis may be undermined by modest SNP effect sizes, unobserved causal SNPs, correlation among adjacent SNPs, and SNP-SNP interactions. Alternative approaches for testing the association between a single SNP-set and individual phenotypes have been shown to be promising for improving the power of GWAS. We propose a Bayesian latent variable selection (BLVS) method to simultaneously model the joint a...

  6. Admixture Mapping Identifies a Quantitative Trait Locus Associated with FEV1/FVC in the COPDGene Study

    OpenAIRE

    Parker, Margaret M.; Foreman, Marilyn G; Abel, Haley J.; Rasika A Mathias; Hetmanksi, Jacqueline B.; Crapo, James D.; Silverman, Edwin K.; Terri H Beaty

    2014-01-01

    African Americans are admixed with genetic contributions from European and African ancestral populations. Admixture mapping leverages this information to map genes influencing differential disease risk across populations. We performed admixture and association mapping in 3300 African American current or former smokers from the COPDGene Study. We analyzed estimated local ancestry and SNP genotype information to identify regions associated with FEV1/FVC, the ratio of forced expiratory volume in...

  7. Paradoxical effects of brain death and associated trauma on rat mesenteric microcirculation: an intravital microscopic study

    OpenAIRE

    Rafael Simas; Paulina Sannomiya; José Walber M. C Cruz; Cristiano de Jesus Correia; Fernando Luiz Zanoni; Maurício Kase; Laura Menegat; Isaac Azevedo Silva; Moreira, Luiz Felipe P.

    2012-01-01

    OBJECTIVE: Experimental findings support clinical evidence that brain death impairs the viability of organs for transplantation, triggering hemodynamic, hormonal, and inflammatory responses. However, several of these events could be consequences of brain death–associated trauma. This study investigated microcirculatory alterations and systemic inflammatory markers in brain-dead rats and the influence of the associated trauma. METHOD: Brain death was induced using intracranial balloon inflatio...

  8. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci

    OpenAIRE

    Reveille, John D.; Sims, Anne-Marie; Danoy, Patrick; Evans, David M; Leo, Paul; Pointon, Jennifer J.; Jin, Rui; Zhou, Xiaodong; Bradbury, Linda A.; Appleton, Louise H; Davis, John C.; Diekman, Laura; Doan, Tracey; Dowling, Alison; Duan, Ran

    2010-01-01

    To identify susceptibility loci for ankylosing spondylitis, we undertook a genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent and 5,140 ethnically matched controls, with replication in an independent cohort of 898 ankylosing spondylitis cases and 1,518 controls. Cases were genotyped with Illumina HumHap370 genotyping chips. In addition to strong association with the major histocompatibility complex (MHC; P < 10−800), we found associa...

  9. Association Study of TRPC4 as a Candidate Gene for Generalized Epilepsy with Photosensitivity

    OpenAIRE

    von Spiczak, S.; Muhle, H; Helbig, I.; de Kovel, C; Hampe, J; Gaus, V.; Koeleman, B.; Lindhout, D; Schreiber, S; Sander, T; Stephani, U

    2010-01-01

    Photoparoxysmal response (PPR) is characterized by abnormal visual sensitivity of the brain to photic stimulation. Frequently associated with idiopathic generalized epilepsies (IGEs), it might be an endophenotype for cortical excitability. Transient receptor potential cation (TRPC) channels are involved in the generation of epileptiform discharges, and TRPC4 constitutes the main TRPC channel in the central nervous system. The present study investigated an association of PPR with sequence vari...

  10. 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 ...

  11. 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...

  12. Association of headache with childhood adversity and mental disorder: cross-national study

    OpenAIRE

    Lee, Sing; Tsang, Adley; Von Korff, Michael; De Graaf, Ron; Benjet, Corina; Haro, Josep Maria; Angermeyer, Matthias; Demyttenaere, Koen; de Girolamo, Giovanni; Gasquet, Isabelle; Merikangas, Kathleen; Posada-Villa, José; Takeshima, Tadashi; Ronald C. Kessler

    2009-01-01

    BACKGROUND: Community studies about the association of headache with both childhood family adversities and depression/anxiety disorders are limited. AIMS: To assess the independent and joint associations of childhood family adversities and early-onset depression and anxiety disorders with risks of adult-onset headache. METHOD: Data were pooled from cross-sectional community surveys conducted in ten Latin and North American, European and Asian countries (n=18 303) by using standardised instrum...

  13. Association Between Pulmonary Function and Nonalcoholic Fatty Liver Disease in the NHANES III Study

    OpenAIRE

    Peng, Tao-Chun; Kao, Tung-Wei; Wu, Li-Wei; Chen, Ying-Jen; Chang, Yaw-Wen; Wang, Chung-Ching; Tsao, Yu-Tzu; Chen, Wei-liang

    2015-01-01

    Abstract Emerging evidence indicates that nonalcoholic fatty liver disease (NAFLD) is associated with a wide variety of extrahepatic complications. However, the potential association between impaired pulmonary function and NAFLD has been less investigated. This study examined the relationship between pulmonary function and hepatic steatosis in 9976 adults participating in a cross-sectional analysis of the Third National Health and Nutrition Examination Survey (NHANES III). NAFLD was defined a...

  14. Association of UV radiation with Parkinson's disease incidence: A nationwide French ecologic study

    OpenAIRE

    Elbaz, A; Sofiane, K; Wald, Lucien; Dugravot, A.; Singh-Manoux, A.; Moisan, F.; Kravietz, A

    2016-01-01

    International audience Meeting: 20th International Congress Abstract Number: 467 Objective: Using ultraviolet B (UV-B) as a surrogate for vitamin D levels, we conducted a nationwide ecologic study in France in order to examine the association of UV-B exposure with Parkinson's disease (PD) incidence. Background: In addition to regulating calcium homeostasis and bone metabolism, vitamin D is involved in multiple biological pathways. Lower vitamin D is associated with increased mortality, in ...

  15. Cinnarizine for the prophylaxis of migraine associated vertigo: a retrospective study

    OpenAIRE

    Taghdiri, Foad; Togha, Mansoureh; Razeghi Jahromi, Soodeh; Refaeian, Farshid

    2014-01-01

    Objective To assess the efficacy and safety of cinnarizine for the prophylaxis of migraine associated vertigo in the vestibular migraine and migraine with brainstem aura. Background Vestibular migraine and migraine with brainstem aura are two principal clinical syndromes that frequently are associated with vertigo. Since cinnarizine is a well-tolerated calcium channel blocker which has acceptable effect on both vertigo and migraine headache, we carried out this study to evaluate the efficacy ...

  16. 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.

  17. 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

  18. Breast cancer risk associated with different HRT formulations: a register-based case-control study

    OpenAIRE

    Thai Do; Möhner Sabine; Heinemann Lothar AJ; Dinger Juergen C; Assmann Anita

    2006-01-01

    Abstract Background Previous epidemiological studies have inconsistently shown a modestly increased breast cancer risk associated with hormone replacement therapy (HRT). Limited information is available about different formulations – particularly concerning different progestins. Methods A case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched breast cancer cases. Conditional logistic regression analysis...

  19. 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

  20. Retrospective analysis of main and interaction effects in genetic association studies of human complex traits

    DEFF Research Database (Denmark)

    Tan, Qihua; Christiansen, Lene; Brasch-Andersen, Charlotte;

    2007-01-01

    with that of the case-only model. RESULTS: Results from our simulation study indicate that our retrospective model exhibits high power in capturing even relatively small effect with reasonable sample sizes. Application of our method to data from an association study on the catalase -262C/T promoter polymorphism...

  1. Genome-wide association study for claw disorders and trimming status in dairy cattle

    NARCIS (Netherlands)

    Spek, van der D.; Arendonk, van J.A.M.; Bovenhuis, H.

    2015-01-01

    Performing a genome-wide association study (GWAS) might add to a better understanding of the development of claw disorders and the need for trimming. Therefore, the aim of the current study was to perform a GWAS on claw disorders and trimming status and to validate the results for claw disorders bas

  2. Case-control genome-wide association study of attention-deficit/hyperactivity disorder.

    NARCIS (Netherlands)

    Neale, B.M.; Medland, S.; Ripke, S.; Anney, R.J.; Asherson, P.; Buitelaar, J.K.; Franke, B.; Gill, M.; Kent, L.; Holmans, P.; Middleton, F.; Thapar, A.; Lesch, K.P.; Faraone, S.V.; Daly, M.; Nguyen, T.T.; Schafer, H.; Steinhausen, H.C.; Reif, A.; Renner, T.J.; Romanos, M.; Romanos, J.; Warnke, A.; Walitza, S.; Freitag, C.; Meyer, J.; Palmason, H.; Rothenberger, A.; Hawi, Z.; Sergeant, J.A.; Roeyers, H.; Mick, E.; Biederman, J.

    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 genomewide association studies (GWAS) are needed. METHOD

  3. 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

  4. Sickness benefit claims due to mental disorders in Brazil : associations in a population-based study

    NARCIS (Netherlands)

    Barbosa-Branco, Anadergh; Bultmann, Ute; Steenstra, Ivan

    2012-01-01

    This study aims to determine the prevalence and duration of sickness benefit claims due to mental disorders and their association with economic activity, sex, age, work-relatedness and income replacement using a population-based study of sickness benefit claims (> 15 days) due to mental disorders in

  5. 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

  6. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

    NARCIS (Netherlands)

    A.D. Børglum; D. Demontis; J. Grove (Jakob); J. Pallesen (J.); M.V. Hollegaard (Mads V); C.B. Pedersen (C.); A. Hedemand (A.); M. Mattheisen (Manuel); A.G. Uitterlinden (André); M. Nyegaard (M.); T.F. Orntoft (Torben); C. Wiuf (Carsten); M. Didriksen (Michael); M. Nordentoft (M.); M.M. Nö then (M.); M. Rietschel (M.); R.A. Ophoff (Roel); S. Cichon (Sven); R.H. Yolken (Robert); D.M. Hougaard (David); P.B. Mortensen; O. Mors

    2014-01-01

    textabstractGenetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all indi

  7. 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…

  8. 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...

  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. 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…

  11. Genome-wide association study reveals a set of genes associated with resistance to the Mediterranean corn borer (Sesamia nonagrioides L.) in a maize diversity panel

    Science.gov (United States)

    Corn borers are the primary maize pest in many environments; their feeding on the pith of the stem results in yield losses because stem damage interferes with assimilate movement to developing kernels. In this study, we performed genome-wide association study (GWAS) to identify SNPs associated with ...

  12. 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.

  13. Dietary Patterns are Associated with Helicobacter Pylori Infection in Chinese Adults: A Cross-Sectional Study

    Science.gov (United States)

    Xia, Yang; Meng, Ge; Zhang, Qing; Liu, Li; Wu, Hongmei; Shi, Hongbin; Bao, Xue; Su, Qian; Gu, Yeqing; Fang, Liyun; Yu, Fei; Yang, Huijun; Yu, Bin; Sun, Shaomei; Wang, Xing; Zhou, Ming; Jia, Qiyu; Zhao, Honglin; Song, Kun; Niu, Kaijun

    2016-01-01

    Previous studies indicated that food consumption was associated with Helicobacter pylori infection, but no study has yet investigated the association between Helicobacter pylori infection and dietary patterns. The aim of this study was to evaluate the associations between Helicobacter pylori infection and dietary patterns in Tianjin, China. The final cross-sectional study population comprised 10407 participants. Dietary consumption of participants was assessed via food frequency questionnaire. Factor analysis was used to identify dietary patterns, and Helicobacter pylori infection status was diagnosis by H. pylori urease Immunogold Testing kit. Participants in the highest quartile of the high-carbohydrate/sweet pattern showed a multivariable-adjusted OR (95% CI) of 1.65 (1.27–2.17) for the prevalence of H. pylori infection compared with those in the lowest quartile. The multiple adjusted OR for scores of the extreme quartile of high-protein/cholesterol pattern was 0.75 (95% CI, 0.57–0.98). This study demonstrated that a diet rich in carbohydrates and sweets was positively associated with the prevalence of H. pylori infection; interestingly, a diet characterized by high intake of animal offal, animal blood, fish, seafood, and poultry was associated with a reduction of prevalence of H. pylori infection. PMID:27573193

  14. 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.

  15. Dietary Patterns are Associated with Helicobacter Pylori Infection in Chinese Adults: A Cross-Sectional Study.

    Science.gov (United States)

    Xia, Yang; Meng, Ge; Zhang, Qing; Liu, Li; Wu, Hongmei; Shi, Hongbin; Bao, Xue; Su, Qian; Gu, Yeqing; Fang, Liyun; Yu, Fei; Yang, Huijun; Yu, Bin; Sun, Shaomei; Wang, Xing; Zhou, Ming; Jia, Qiyu; Zhao, Honglin; Song, Kun; Niu, Kaijun

    2016-01-01

    Previous studies indicated that food consumption was associated with Helicobacter pylori infection, but no study has yet investigated the association between Helicobacter pylori infection and dietary patterns. The aim of this study was to evaluate the associations between Helicobacter pylori infection and dietary patterns in Tianjin, China. The final cross-sectional study population comprised 10407 participants. Dietary consumption of participants was assessed via food frequency questionnaire. Factor analysis was used to identify dietary patterns, and Helicobacter pylori infection status was diagnosis by H. pylori urease Immunogold Testing kit. Participants in the highest quartile of the high-carbohydrate/sweet pattern showed a multivariable-adjusted OR (95% CI) of 1.65 (1.27-2.17) for the prevalence of H. pylori infection compared with those in the lowest quartile. The multiple adjusted OR for scores of the extreme quartile of high-protein/cholesterol pattern was 0.75 (95% CI, 0.57-0.98). This study demonstrated that a diet rich in carbohydrates and sweets was positively associated with the prevalence of H. pylori infection; interestingly, a diet characterized by high intake of animal offal, animal blood, fish, seafood, and poultry was associated with a reduction of prevalence of H. pylori infection. PMID:27573193

  16. 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

    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......-based cohort consisting of 20 249 individuals of European descent from Norfolk, UK. Logistic regression and generalized linear models were used to test the associations of the risk alleles with obesity and related quantitative traits, respectively. Neither of the SNPs was significantly associated with obesity...

  17. Association of eNOS Polymorphisms with Anterior Chamber Depth in Han Chinese: Jiangsu Eye Study

    Directory of Open Access Journals (Sweden)

    Haihong Shi

    2014-01-01

    Full Text Available Recently, a study reported that single nucleotide polymorphisms (SNP in endothelial nitric oxide synthase (eNOS were associated with primary angle closure glaucoma (PACG in Australian cohort. In this study, we aimed to investigate whether those eNOS SNPs are associated with primary angle closure (PAC or ocular biometric characteristics such as axial length (AL, anterior chamber depth (ACD, and diopter of spherical power (DS in Han Chinese. The samples consisted of 232 PAC subjects and 306 controls collected from a population-based prevalence survey conducted in Funing County of Jiangsu, China. The rs3793342 and rs11771443 in eNOS were genotyped by TaqMan-MGB probe using the RT-PCR system. Our data did not identify any association of the eNOS SNPs with PAC. However, the analysis on the quantitative traits of ocular biometrics showed that the ACD of rs11771443 AA and GA carriers is significantly deeper than that of rs11771443 GG carriers (P=0.0025, even though the AL and DS are not associated with rs11771443 genotypes. Rs3793342 was not associated with any biometric parameters including ACD, AL and DS. In summary, our data indicates that eNOS rs11771443 is associated with ACD and its role in the pathogenesis of PACG warranted further study.

  18. Developmental Associations Between Conduct Problems and Expressive Language in Early Childhood: A Population-Based Study.

    Science.gov (United States)

    Girard, Lisa-Christine; Pingault, Jean-Baptiste; Doyle, Orla; Falissard, Bruno; Tremblay, Richard E

    2016-08-01

    Conduct problems have been associated with poor language development, however the direction of this association in early childhood remains unclear. This study examined the longitudinal directional associations between conduct problems and expressive language ability. Children enrolled in the UK Millennium Cohort Study (N = 14, 004; 50.3 % boys) were assessed at 3 and 5 years of age. Parent reports of conduct problems and standardised assessments of expressive language were analyzed using cross-lagged modeling. Conduct problems at 3 years was associated with poorer expressive language at 5 years and poorer expressive language at 3 years was associated with increased conduct problems by 5 years. The results support reciprocal associations, rather than a specific unidirectional path, which is commonly found with samples of older children. The emergence of problems in either domain can thus negatively impact upon the other over time, albeit the effects were modest. Studies examining the effects of intervention targeting conduct problems and language acquisition prior to school entry may be warranted in testing the efficacy of prevention programmes related to conduct problems and poor language ability early in childhood. PMID:26496905

  19. Genetic association with overall survival of taxane-treated lung cancer patients - a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study

    International Nuclear Information System (INIS)

    Taxane is one of the first line treatments of lung cancer. In order to identify novel single nucleotide polymorphisms (SNPs) that might contribute to taxane response, we performed a genome-wide association study (GWAS) for two taxanes, paclitaxel and docetaxel, using 276 lymphoblastoid cell lines (LCLs), followed by genotyping of top candidate SNPs in 874 lung cancer patient samples treated with paclitaxel. GWAS was performed using 1.3 million SNPs and taxane cytotoxicity IC50 values for 276 LCLs. The association of selected SNPs with overall survival in 76 small or 798 non-small cell lung cancer (SCLC, NSCLC) patients were analyzed by Cox regression model, followed by integrated SNP-microRNA-expression association analysis in LCLs and siRNA screening of candidate genes in SCLC (H196) and NSCLC (A549) cell lines. 147 and 180 SNPs were associated with paclitaxel or docetaxel IC50s with p-values <10-4 in the LCLs, respectively. Genotyping of 153 candidate SNPs in 874 lung cancer patient samples identified 8 SNPs (p-value < 0.05) associated with either SCLC or NSCLC patient overall survival. Knockdown of PIP4K2A, CCT5, CMBL, EXO1, KMO and OPN3, genes within 200 kb up-/downstream of the 3 SNPs that were associated with SCLC overall survival (rs1778335, rs2662411 and rs7519667), significantly desensitized H196 to paclitaxel. SNPs rs2662411 and rs1778335 were associated with mRNA expression of CMBL or PIP4K2A through microRNA (miRNA) hsa-miR-584 or hsa-miR-1468. GWAS in an LCL model system, joined with clinical translational and functional studies, might help us identify genetic variations associated with overall survival of lung cancer patients treated paclitaxel

  20. Genome-wide Association Study of Biochemical Traits in Korčula Island, Croatia

    Science.gov (United States)

    Zemunik, Tatijana; Boban, Mladen; Lauc, Gordan; Janković, Stipan; Rotim, Krešimir; Vatavuk, Zoran; Benčić, Goran; Đogaš, Zoran; Boraska, Vesna; Torlak, Vesela; Sušac, Jelena; Zobić, Ivana; Rudan, Diana; Pulanić, Dražen; Modun, Darko; Mudnić, Ivana; Gunjača, Grgo; Budimir, Danijela; Hayward, Caroline; Vitart, Veronique; Wright, Alan F.; Campbell, Harry; Rudan, Igor

    2009-01-01

    Aim To identify genetic variants underlying biochemical traits – total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, uric acid, albumin, and fibrinogen, in a genome-wide association study in an isolated population where rare variants of larger effect may be more easily identified. Methods The study included 944 adult inhabitants of the island of Korčula, as a part of a larger DNA-based genetic epidemiological study in 2007. Biochemical measurements were performed in a single laboratory with stringent internal and external quality control procedures. Examinees were genotyped using Human Hap370CNV chip by Illumina, with a genome-wide scan containing 346 027 single nucleotide polymorphisms (SNP). Results A total of 31 SNPs were associated with 7 investigated traits at the level of P < 1.00 × 10−5. Nine of SNPs implicated the role of SLC2A9 in uric acid regulation (P = 4.10 × 10−6-2.58 × 10−12), as previously found in other populations. All 22 remaining associations fell into the P = 1.00 × 10−5-1.00 × 10−6 significance range. One of them replicated the association between cholesteryl ester transfer protein (CETP) and HDL, and 7 associations were more than 100 kilobases away from the closest known gene. Nearby SNPs, rs4767631 and rs10444502, in gene kinase suppressor of ras 2 (KSR2) on chromosome 12 were associated with LDL cholesterol levels, and rs10444502 in the same gene with total cholesterol levels. Similarly, rs2839619 in gene PBX/knotted 1 homeobox 1 (PKNOX1) on chromosome 21 was associated with total and LDL cholesterol levels. The remaining 9 findings implied possible associations between phosphatidylethanolamine N-methyltransferase (PEMT) gene and total cholesterol; USP46, RAP1GDS1, and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2 genes and albumin; and NR3C2, GRIK2, and PCSK2 genes and fibrinogen. Conclusion Although this study was

  1. Genome-wide association study of susceptibility loci for breast cancer in Sardinian population

    International Nuclear Information System (INIS)

    Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p < 10−6 level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10−5, we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16x10−5), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population. The online version of this article (doi:10.1186/s12885-015-1392-9) contains supplementary material, which is available to authorized users

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

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    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.

  3. Genome-wide association study of serum minerals levels in children of different ethnic background.

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    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.

  4. Association studies using random and "candidate" microsatellite loci in two infectious goat diseases

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    Obexer-Ruff Gabriela

    2003-06-01

    Full Text Available Abstract We established a set of 30 microsatellites of Bovidae origin for use in a biodiversity study in Swiss and Creole goats. Additional microsatellites located within or next to "candidate" genes of interest, such as cytokine genes (IL4, INF-gamma and MHC class II genes (DRB, DYA were tested in the caprine species in order to detect possible associations with two infectious caprine diseases. Microsatellite analysis was undertaken using automated sequencers (ABI373 & 3100. In the first study, a total of 82 unrelated Creole goats, 37 resistant and 45 susceptible to Heartwater disease (Cowdriosis were analysed. In this study, the two microsatellite loci DRBP1 (MHCII and BOBT24 (IL4 were positively associated with disease susceptibility, demonstrating a corrected P-value of 0.002 and 0.005, respectively. In a second investigation, we tested 36 goats, naturally infected with the nematode parasite Trichostrongylus colubriformis. These animals were divided into a "low" and "high" excreting group on the basis of two independently recorded fecal egg counts. For this nematode resistance study, we detected a significant association of one of the alleles of the microsatellite locus SPS113 with "low" excretion (resistance. The MHC class II locus DYA (P19, was weakly associated with susceptibility in both diseases (Pc = 0.05. In future experiments, we will extend the sample size in order to verify the described associations.

  5. 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.

  6. Ocular axial length and its associations in Chinese: the Beijing Eye Study.

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    Guo Yin

    Full Text Available PURPOSE: To investigate the normative data of ocular axial length and its associations in Chinese. METHOD: The population-based Beijing Eye Study 2011 is a cross-sectional study performed in Greater Beijing. The study included 3468 individuals (1963 (56.6% women with a mean age of 64.6±9.8 years (range: 50-93 years. A detailed ophthalmic and medical examination was performed. Axial length was measured by optical low-coherence reflectometry. RESULTS: Axial length measurements were available for 3159 (91.1% study participants. Mean axial length was 23.25±1.14 mm (range: 18.96-30.88 mm. In multivariate analysis, axial length was significantly associated with the systemic parameters of higher age (P<0.001, higher body height (P = 0.003, higher level of education (P<0.001 and urban region of habitation (P<0.001, and with the ocular parameters of thicker central cornea (P = 0.001, higher corneal curvature radius (P<0.001, deeper anterior chamber (P<0.001, thicker lens (P<0.001, more myopic refractive error (P<0.001, larger pupil diameter (P = 0.018, and higher best corrected visual acuity (P<0.001. It was additionally and negatively associated with the lens vault (P<0.001. In highly myopic eyes, axial length was significantly associated with lower level of education (P = 0.008, more myopic refractive error (P<0.001, and lower best corrected visual acuity (P = 0.034. CONCLUSIONS: Mean ocular axial length in the older adult population of Greater Beijing (23.25±1.14 mm was similar to the value measured in other urban populations and was higher than in a rural Central Indian population. The association between axial length and older age may potentially be associated with a survival artifact. The association between axial length and body height agrees with the general association between anthropomorphic measures and eye globe size. The association with the level of education and urban region of habitation confirms with previous

  7. 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

    2016-03-01

    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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. Visualization of species pairwise associations: a case study of surrogacy in bird assemblages.

    Science.gov (United States)

    Lane, Peter W; Lindenmayer, David B; Barton, Philip S; Blanchard, Wade; Westgate, Martin J

    2014-08-01

    Quantifying and visualizing species associations are important to many areas of ecology and conservation biology. Species networks are one way to analyze species associations, with a growing number of applications such as food webs, nesting webs, plant-animal mutualisms, and interlinked extinctions. We present a new method for assessing and visualizing patterns of co-occurrence of species. The method depicts interactions and associations in an analogous way with existing network diagrams for studying pollination and trophic interactions, but adds the assessment of sign, strength, and direction of the associations. This provides a distinct advantage over existing methods of quantifying and visualizing co-occurrence. We demonstrate the utility of our new approach by showing differences in associations among woodland bird species found in different habitats and by illustrating the way these can be interpreted in terms of underlying ecological mechanisms. Our new method is computationally feasible for large assemblages and provides readily interpretable effects with standard errors. It has wide applications for quantifying species associations within ecological communities, examining questions about particular species that occur with others, and how their associations can determine the structure and composition of communities. PMID:25473480

  13. Common genetic variants associated with sudden cardiac death: the FinSCDgen study.

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    Annukka M Lahtinen

    Full Text Available BACKGROUND: Sudden cardiac death (SCD accounts for up to half of cardiac mortality. The risk of SCD is heritable but the underlying genetic variants are largely unknown. We investigated whether common genetic variants predisposing to arrhythmia or related electrocardiographic phenotypes, including QT-interval prolongation, are associated with increased risk of SCD. METHODOLOGY/PRINCIPAL FINDINGS: We studied the association between 28 candidate SNPs and SCD in a meta-analysis of four population cohorts (FINRISK 1992, 1997, 2002 and Health 2000, n = 27,629 and two forensic autopsy series (The Helsinki Sudden Death Study and The Tampere Autopsy Study, n = 694. We also studied the association between established cardiovascular risk factors and SCD. Causes of death were reviewed using registry-based health and autopsy data. Cox regression and logistic regression models were adjusted for age, sex, and geographic region. The total number of SCDs was 716. Two novel SNPs were associated with SCD: SCN5A rs41312391 (relative risk [RR] 1.27 per minor T allele, 95% CI 1.11-1.45, P = 3.4×10(-4 and rs2200733 in 4q25 (RR 1.28 per minor T allele, 95% CI 1.11-1.48, P = 7.9×10(-4. We also replicated the associations for 9p21 (rs2383207, RR 1.13 per G allele, 95% CI 1.01-1.26, P = 0.036, as well as for male sex, systolic blood pressure, diabetes, cigarette smoking, low physical activity, coronary heart disease, and digoxin use (P<0.05. CONCLUSIONS/SIGNIFICANCE: Two novel genetic variants, one in the cardiac sodium channel gene SCN5A and another at 4q25 previously associated with atrial fibrillation, are associated with SCD.

  14. 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.

  15. Heart rate is associated with markers of fatty acid desaturation: the GOCADAN study

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    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.

  16. Association Between Geographic Elevation, Bone Status, and Exercise Habits: The Shimane CoHRE Study

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    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.

  17. Replication study of the vitamin D receptor (VDR) genotype association with skeletal muscle traits and sarcopenia.

    Science.gov (United States)

    Walsh, Sean; Ludlow, Andrew T; Metter, E Jeffrey; Ferrucci, Luigi; Roth, Stephen M

    2016-06-01

    Polymorphisms in the vitamin D receptor (VDR) gene are some of the most studied in relation to skeletal muscle traits and significant associations have been observed by multiple groups. One such paper by our group provided the first evidence of a genetic association with sarcopenia in men, but that finding has yet to be replicated in an independent cohort. In the present study, we examined multiple VDR polymorphisms in relation to skeletal muscle traits and sarcopenia in 864 men and women across the adult age span. In addition to VDR genotypes and haplotypes, measurements of skeletal muscle strength and fat-free mass (FFM) were determined in all subjects and a measure of sarcopenia was calculated. We observed significant associations between Fok1 and Bsm1 genotypes and skeletal muscle strength in men and women, though these associations were modest and no significant associations were observed for these polymorphisms and muscle mass traits nor for Bsm1-Taq1 haplotype with muscle strength. Fok1 FF genotype was associated with an increased the risk of sarcopenia in older women compared to f-allele carriers (1.3-fold higher risk). These results support previous findings that VDR genetic variation appears to impact skeletal muscle strength and risk for sarcopenia but the influence is modest. PMID:26415498

  18. Quantitative candidate gene association studies of metabolic traits in Han Chinese type 2 diabetes patients.

    Science.gov (United States)

    Wei, F J; Cai, C Y; Yu, P; Lv, J; Ling, C; Shi, W T; Jiao, H X; Chang, B C; Yang, F H; Tian, Y; Li, M S; Wang, Y H; Zou, L; Shi, J M; Chen, L M; Li, W D

    2015-01-01

    Recent genome-wide association studies have identified many loci associated with type 2 diabetes mellitus (T2DM), hyperuricemia, and obesity in various ethnic populations. However, quantitative traits have been less well investigated in Han Chinese T2DM populations. We investigated the association between candidate gene single nucleotide polymorphisms (SNPs) and metabolic syndrome-related quantitative traits in Han Chinese T2DM subjects. Unrelated Han Chinese T2DM patients (1975) were recruited. Eighty-six SNPs were genotyped and tested for association with quantitative traits including lipid profiles, blood pressure, body mass index (BMI), serum uric acid (SUA), glycated hemoglobin (HbA1c), plasma glucose [fasting plasma glucose (FPG)], plasma glucose 120 min post-OGTT (P2PG; OGTT = oral glucose tolerance test), and insulin resistance-related traits. We found that CAMTA1, ABI2, VHL, KAT2B, PKHD1, ESR1, TOX, SLC30A8, SFI1, and MYH9 polymorphisms were associated with HbA1c, FPG, and/or P2PG; GCK, HHEX, TCF7L2, KCNQ1, and TBX5 polymorphisms were associated with insulin resistance-related traits; ABCG2, SLC2A9, and PKHD1 polymorphisms were associated with SUA; CAMTA1, VHL, KAT2B, PON1, NUB1, SLITRK5, SMAD3, FTO, FANCA, and PCSK2 polymorphisms were associated with blood lipid traits; CAMTA1, SPAG16, TOX, KCNQ1, ACACB, and MYH9 polymorphisms were associated with blood pressure; and UBE2E3, SPAG16, SLC2A9, CDKAL1, CDKN2A/B, TCF7L2, SMAD3, and PNPLA3 polymorphisms were associated with BMI (all P values <0.05). Some of the candidate genes were associated with metabolic and anthropometric traits in T2DM in Han Chinese. Although none of these associations reached genome-wide significance (P < 5 x 10(-8)), genes and loci identified in this study are worthy of further replication and investigation. PMID:26634513

  19. INSIG2 SNPS ASSOCIATED WITH OBESITY & GLUCOSE HOMEOSTASIS TRAITS IN HISPANICS: THE IRAS FAMILY STUDY

    OpenAIRE

    Talbert, Matthew E.; Langefeld, Carl D.; Ziegler, Julie; Haffner, Steven M.; Norris, Jill M.; Donald W Bowden

    2009-01-01

    The genome-wide association study by Herbert and colleagues identified the INSIG2 single nucleotide polymorphism (SNP) rs7566605 as contributing to increased BMI in ethnically distinct cohorts. The present study sought to further clarify by testing whether SNPs of INSIG2 influenced quantitative adiposity or glucose homeostasis traits in Hispanics of the Insulin Resistance Atherosclerosis Family Study (IRASFS). Using a tagging SNP approach, rs7566605 and 31 additional SNPs were genotyped in 14...

  20. Population-based investigations to study the association of cardiovascular polymorphisms and adverse pregnancy outcome

    DEFF Research Database (Denmark)

    Lykke, Jacob Alexander; Langhoff-Roos, Jens; Young, Bradford;

    2007-01-01

    Adverse pregnancy outcome refers to placenta-mediated complications that may share a common etiopathogenesis in some cases. Unraveling associations between prothrombotic genetic predispositions and these pregnancy disorders, namely recurrent fetal loss, stillbirth, severe preeclampsia, intrauterine...... study focuses on pro-thrombotic and cardiovascular genetic polymorphisms in a nested-case control study comparing pregnancies with and without an adverse pregnancy outcome in the index pregnancy. This study will be adequately powered to determine the relationship between adverse pregnancy outcome and...

  1. Associations of Neighborhood Characteristics with Sleep Timing and Quality: The Multi-Ethnic Study of Atherosclerosis

    OpenAIRE

    De Santis, AS; Roux, AVD; Moore, K; Baron, KG; Mujahid, MS; Javier Nieto, F

    2013-01-01

    Study Objectives: To investigate the associations of specifc neighborhood features (disorder, safety, social cohesion, physical environment, and socioeconomic status) with sleep duration and quality. Design: Cross-sectional. One wave of a population-based study (Multi-Ethnic Study of Atherosclerosis). Setting: Community-dwelling participants in New York, NY and Los Angeles, CA. Participants: There were 1,406 participants (636 males, 770 females). Interventions: NA. Measurements and Results: S...

  2. Meta-analysis of genome-wide association studies of attention deficit/hyperactivity disorder

    OpenAIRE

    Neale, Benjamin M.; Medland, Sarah E.; Ripke, Stephan; Asherson, Philip; Franke, Barbara; Lesch, Klaus-Peter; Faraone, Stephen V.; Nguyen, Thuy Trang; Schaefer, Helmut; Holmans, Peter; Daly, Mark; STEINHAUSEN, HANS-CHRISTOPH; Freitag, Christine,; Reif, Andreas; Tobias J Renner

    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 existing studies to boost statistical power. Method: We used data from four projects: a) the Children's Hospital of Philadelphia (CHOP); b) phase I of ...

  3. Association of chronic periodontitis with metabolic syndrome: A cross-sectional study

    OpenAIRE

    Naresh Kumar; Ashu Bhardwaj; Prakash Chand Negi; Pravesh Kumar Jhingta; Deepak Sharma; Vinay Kumar Bhardwaj

    2016-01-01

    Background: Prevalence of metabolic syndrome (MeS) is high among Asians, including Indians and is rising, particularly with the adoption of modernized lifestyle. Various studies have reported a significant relationship between periodontal status and MeS. The objective of this study is to investigate the association between periodontitis and MeS. Materials and Methods: The study included 259 subjects (130 cases with chronic periodontitis, 129 controls without chronic periodontitis) who underwe...

  4. Association Between Epicardial Fat Thickness and Premature Coronary Artery Disease: A Case Control Study

    OpenAIRE

    Faghihi, Shadi; Vasheghani-Farahani, Ali; Parsaee, Mozhgan; Saedi, Sedigheh; Ghadrdoost, Behshid

    2015-01-01

    Background: The association between epicardial fat thickness (EFT) and premature coronary artery disease (CAD) has not been elaborately studied. Objectives: In the present study, we sought whether such a relationship between EFT and CAD exists. Patients and Methods: Sixty two consecutive subjects, under 50 years of age, who underwent coronary angiography (CAG) with the aspect of CAD, were included in this case control study. They were divided into two groups of 31 subjects, namely CAD (cases)...

  5. 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...

  6. The association between antenatal anxiety and fear of childbirth in nulliparous women: a prospective study

    OpenAIRE

    Alipour, Zahra; Lamyian, Minoor; Hajizadeh, Ebrahim; Vafaei, Maryam Agular

    2011-01-01

    BACKGROUND: This study aimed to examine the association of state and trait anxiety with fear of childbirth to explore whether there was any support for the hypothesis that state and trait anxiety are risk factors for the fear of childbirth or not. METHODS: In this prospective study, 156 pregnant women referred to the health centers of Qom. The study samples selected using simple random sampling method. Anxiety and fear of the childbirth in nulliparous women were measured using Spielberger's s...

  7. Vitamin D levels and associated factors: a population-based study in Switzerland

    OpenAIRE

    Guessous, I.; Dudler, V; Glatz, N; Theler, J M; Zoller, O; Paccaud, F.; Burnier, M.; M. Bochud

    2012-01-01

    QUESTIONS UNDER STUDY: To update the prevalence of vitamin D insufficiency and to identify factors associated with vitamin D status in the Swiss adult population. METHODS: Data from the 2010-2011 Swiss Study on Salt intake, a population-based study in the Swiss population, was used. Vitamin D concentration in serum was measured by liquid chromatography- tandem mass spectrometry. Major factors that influence vitamin D levels were taken into account. Survey statistical procedures were used t...

  8. An evaluation of different target enrichment methods in pooled sequencing designs for complex disease association studies.

    Directory of Open Access Journals (Sweden)

    Aaron G Day-Williams

    Full Text Available Pooled sequencing can be a cost-effective approach to disease variant discovery, but its applicability in association studies remains unclear. We compare sequence enrichment methods coupled to next-generation sequencing in non-indexed pools of 1, 2, 10, 20 and 50 individuals and assess their ability to discover variants and to estimate their allele frequencies. We find that pooled resequencing is most usefully applied as a variant discovery tool due to limitations in estimating allele frequency with high enough accuracy for association studies, and that in-solution hybrid-capture performs best among the enrichment methods examined regardless of pool size.

  9. 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

  10. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

    Directory of Open Access Journals (Sweden)

    Søren D Østergaard

    2015-06-01

    Full Text Available Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR.We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49, fasting glucose (NSNPs = 36, insulin resistance (NSNPs = 10, body mass index (BMI, NSNPs = 32, total cholesterol (NSNPs = 73, HDL-cholesterol (NSNPs = 71, LDL-cholesterol (NSNPs = 57, triglycerides (NSNPs = 39, systolic blood pressure (SBP, NSNPs = 24, smoking initiation (NSNPs = 1, smoking quantity (NSNPs = 3, university completion (NSNPs = 2, and years of education (NSNPs = 1. We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3. Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8. Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3, although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28. We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1. Potential limitations of this study

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Evaluation of the Association between Oral Lichen Planus and Hypothyroidism: a Retrospective Comparative Study

    Science.gov (United States)

    Lavaee, Fatemeh; Majd, Marjan

    2016-01-01

    Statement of the Problem Oral Lichen planus (OLP) is an autoimmune mucocutaneous disease. There are some reports of thyroid diseases, especially hypothyroidism, to have association with OLP in some studies. Purpose Based on the controversial results of former studies in other populations about the association of hypothyroidism and OLP, the current study aimed to evaluate this association in a sample of Iranian population. Materials and Method This retrospective comparative study evaluated 523 patients with OLP referring to the Oral and Maxillofacial Department of Shiraz Dental Faculty as the test group and 523 age- and sex-matched patients as the control group. Those participants with oral lichenoid reactions and other mucosal lesions were excluded. The odds ratio (OR) with 95% confidence intervals (CI) for the association of OLP and thyroid diseases were estimated by logistic regression adjusted for the matched age and sex. Results In the test group, 74% (n=387) and in the control group 73.8% of the patients were female (n=386). In the test group, 26% (n=136) and in the control group 26.2% of the samples were male (n=137). A total of 4% of the patients in the control group (n=21) and 6.7% in the case group (n=35) had a history of hypothyroidism. The reported OR for association of thyroid disease and OLP was 1.714 (CI=0.984-2.987). Conclusion The results of this study showed no significant association between hypothyroidism and OLP in comparison with the age- and sex-matched control group. PMID:26966707

  18. The association between gallstones and metabolic syndrome in urban Han Chinese: a longitudinal cohort study.

    Science.gov (United States)

    Zhu, Qian; Sun, Xiubin; Ji, Xiaokang; Zhu, Lin; Xu, Jing; Wang, Chunxia; Zhang, Chengqi; Xue, Fuzhong; Liu, Yanxun

    2016-01-01

    The precise association between metabolic syndrome (MetS) and gallstone disease remains unclear in China. This study aimed to clarify the relationship between MetS and gallstone and evaluate whether counts of metabolic abnormalities had influence on gallstone disease. We fitted gender-specific generalized estimating equation (GEE) regression models with data from a large-scale longitudinal study over 6-year follow-up to elucidate the real association. This study included 18291 participants with 3 times repeated measures at least who were free from a prior history of gallstone disease and cholecystectomy. A total of 873 cases of gallstones occurred during 6-year follow-up. The incidence density of gallstone in the group of subjects with MetS was higher than the group without MetS (10.27 vs 5.79). The GEE analyses confirmed and clarified the association between MetS and gallstone disease in males (RR = 1.33, P = 0.0020), while this association was not significant in females (RR = 1.15, P = 0.4962). With numbers of metabolic syndrome components increasing, the risk of gallstone disease showed corresponding increasing in males. In conclusion, the associations of MetS and gallstone are different in males and in females. And the risk of gallstone disease increases with the number of components of MetS for males but not for females.

  19. 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

    Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive...... ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary...... 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...

  20. 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

  1. An Observational Study of the Association between Adenovirus 36 Antibody Status and Weight Loss among Youth

    Directory of Open Access Journals (Sweden)

    Jillon S. Vander Wal

    2013-06-01

    Full Text Available Objective: Although the human adenovirus 36 (Ad-36 is associated with obesity and relative hypolipidemia, its role in pediatric weight loss treatment response is uncertain. Therefore, the primary study objective was to determine whether Ad-36 antibody (AB status was associated with response to a pediatric weight loss program. The secondary objective was to assess the association between Ad-36 AB status and baseline lipid values. Methods: Participants included 73 youth aged 10-17 years in a residential camp-based weight loss program. The study examined differences in baseline lipid values between Ad-36 AB+ and AB- youth as well as differences in response to treatment, including indices of body size and fitness. Results: At baseline, results showed that Ad-36 AB+ youth evidenced significantly lower levels of total cholesterol and triglycerides than Ad-36 AB- youth (all p Conclusion: Ad-36 AB status showed a weak association with treatment response, but was associated with a better lipid profile. Ad-36 AB status should be assessed in studies of pediatric obesity treatment and prevention.

  2. 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.

  3. Association between sleep duration and cancer risk: a meta-analysis of prospective cohort studies.

    Directory of Open Access Journals (Sweden)

    Yan Lu

    Full Text Available BACKGROUND: Sleep duration has been shown to play an important role in the development of cancer. However, the results have been inconsistent. A meta-analysis with prospective cohort studies was performed to clarify the association between short or long sleep duration and cancer risk. METHODS: PubMed and Embase databases were searched for eligible publications. Pooled relative risk (RR with 95% confidence interval (CI was calculated using random- or fixed- model. RESULTS: A total of 10 prospective studies (8392 incident cases and 555678 participants were included in the meta-analysis. Neither short nor long sleep duration was statistically associated with increased risk of cancer (short sleep duration: RR=1.05, 95%CI=0.90-1.24, p=0.523; long sleep duration: RR=0.92, 95%CI=0.76-1.12, p=0.415. In the subgroup by cancer type, long sleep duration was positively associated with colorectal cancer (RR=1.29, 95%CI=1.09-1.52, p=0.003. CONCLUSION: The present meta-analysis suggested that neither short nor long sleep duration was significantly associated with risk of cancer, although long sleep duration increased risk of with colorectal cancer. Large-scale well-design prospective studies are required to be conducted to further investigate the observed association.

  4. Impaired Fertility Associated with Subclinical Hypothyroidism and Thyroid Autoimmunity: The Danish General Suburban Population Study

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    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.

  5. Genome-wide association of lipid-lowering response to statins in combined study populations.

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    Mathew J Barber

    Full Text Available BACKGROUND: Statins effectively lower total and plasma LDL-cholesterol, but the magnitude of decrease varies among individuals. To identify single nucleotide polymorphisms (SNPs contributing to this variation, we performed a combined analysis of genome-wide association (GWA results from three trials of statin efficacy. METHODS AND PRINCIPAL FINDINGS: Bayesian and standard frequentist association analyses were performed on untreated and statin-mediated changes in LDL-cholesterol, total cholesterol, HDL-cholesterol, and triglyceride on a total of 3932 subjects using data from three studies: Cholesterol and Pharmacogenetics (40 mg/day simvastatin, 6 weeks, Pravastatin/Inflammation CRP Evaluation (40 mg/day pravastatin, 24 weeks, and Treating to New Targets (10 mg/day atorvastatin, 8 weeks. Genotype imputation was used to maximize genomic coverage and to combine information across studies. Phenotypes were normalized within each study to account for systematic differences among studies, and fixed-effects combined analysis of the combined sample were performed to detect consistent effects across studies. Two SNP associations were assessed as having posterior probability greater than 50%, indicating that they were more likely than not to be genuinely associated with statin-mediated lipid response. SNP rs8014194, located within the CLMN gene on chromosome 14, was strongly associated with statin-mediated change in total cholesterol with an 84% probability by Bayesian analysis, and a p-value exceeding conventional levels of genome-wide significance by frequentist analysis (P = 1.8 x 10(-8. This SNP was less significantly associated with change in LDL-cholesterol (posterior probability = 0.16, P = 4.0 x 10(-6. Bayesian analysis also assigned a 51% probability that rs4420638, located in APOC1 and near APOE, was associated with change in LDL-cholesterol. CONCLUSIONS AND SIGNIFICANCE: Using combined GWA analysis from three clinical trials involving nearly 4

  6. Epigenome-wide Association Studies and the Interpretation of Disease -Omics.

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    Ewan Birney

    2016-06-01

    Full Text Available Epigenome-wide association studies represent one means of applying genome-wide assays to identify molecular events that could be associated with human phenotypes. The epigenome is especially intriguing as a target for study, as epigenetic regulatory processes are, by definition, heritable from parent to daughter cells and are found to have transcriptional regulatory properties. As such, the epigenome is an attractive candidate for mediating long-term responses to cellular stimuli, such as environmental effects modifying disease risk. Such epigenomic studies represent a broader category of disease -omics, which suffer from multiple problems in design and execution that severely limit their interpretability. Here we define many of the problems with current epigenomic studies and propose solutions that can be applied to allow this and other disease -omics studies to achieve their potential for generating valuable insights.

  7. Epigenome-wide Association Studies and the Interpretation of Disease -Omics

    Science.gov (United States)

    Birney, Ewan; Smith, George Davey

    2016-01-01

    Epigenome-wide association studies represent one means of applying genome-wide assays to identify molecular events that could be associated with human phenotypes. The epigenome is especially intriguing as a target for study, as epigenetic regulatory processes are, by definition, heritable from parent to daughter cells and are found to have transcriptional regulatory properties. As such, the epigenome is an attractive candidate for mediating long-term responses to cellular stimuli, such as environmental effects modifying disease risk. Such epigenomic studies represent a broader category of disease -omics, which suffer from multiple problems in design and execution that severely limit their interpretability. Here we define many of the problems with current epigenomic studies and propose solutions that can be applied to allow this and other disease -omics studies to achieve their potential for generating valuable insights. PMID:27336614

  8. Association studies of dormancy and cooking quality traits in direct-seeded indica rice

    Indian Academy of Sciences (India)

    Sunayana Rathi; K. Pathak; R. N. S. Yadav; B. Kumar; R. N. Sarma

    2014-04-01

    Association analysis was applied to a panel of accessions of Assam rice (indica) using 98 SSR markers for dormancy-related traits and cooking quality. Analysis of population structure revealed 10 subgroups in the population. The mean $r^2$ and $D'$ value for all intrachromosomal loci pairs was 0.24 and 0.51, respectively. Linkage disequilibrium between linked markers decreased with distance. Marker-trait associations were investigated using the unified mixed-model approach, considering both population structure (Q) and kinship (K). Genome-wide scanning, detected a total of seven significant marker-trait associations $(P \\lt 0.01)$, with the $R^2$ values ranging from 12.0 to 18.0%. The significant marker associations were for grain dormancy (RM27 on chromosome 2), -amylase activity (RM27 and RM234 on chromosomes 2 and 7, respectively), germination (RM27 and RM106 on chromosome 2), amylose (RM282 on chromosome 3) and grain length elongation ratio (RM142 on chromosome 4). The present study revealed the association of marker RM27 with traits like dormancy, α-amylase activity and germination. Simple correlation analysis of these traits revealed that these traits were positively correlated with each other and this marker may be useful for simultaneous improvement of these traits. The study indicates the presence of novel QTLs for a few traits under consideration. The study reveals association of traits like dormancy, -amylase activity, germination, amylose content, grain length elongation ratio with SSR markers indicating the feasibility of undertaking association analysis in conjunction with germplasm characterization.

  9. Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

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    Rico Rueedi

    2014-02-01

    Full Text Available Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10(-8 and independent associations between single nucleotide polymorphisms (SNP and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44 and lysine (rs8101881, P = 1.2×10(-33, respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers.

  10. Use of Longitudinal Data in Genetic Studies in the Genome-wide Association Studies Era: Summary of Group 14

    OpenAIRE

    Kerner, Berit; North, Kari E; Fallin, M. Daniele

    2009-01-01

    Participants analyzed actual and simulated longitudinal data from the Framingham Heart Study for various metabolic and cardiovascular traits. The genetic information incorporated into these investigations ranged from selected single-nucleotide polymorphisms to genome-wide association arrays. Genotypes were incorporated using a broad range of methodological approaches including conditional logistic regression, linear mixed models, generalized estimating equations, linear growth curve estimatio...

  11. STrengthening the REporting of Genetic Association Studies (STREGA – An Extension of the STROBE Statement

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    Julian Little

    2009-09-01

    Full Text Available Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

  12. The application of the entropy-based statistic for genomic association study of QTL

    Institute of Scientific and Technical Information of China (English)

    Yang Xiang; Yumei Li; Zaiming Liu; Zhenqiu Sun

    2008-01-01

    An entropy-based statistic TPE has been proposed for genomic association study for disease-susceptibility locus.The statistic TPE may be directly adopted and/or extended to quantitative-trait locus (QTL)mapping for quantitative traits.In this article,the statistic TPE was extended and applied to quantitative trait for association analysis of QTL by means of selective genotyping.The statistical properties (the type I error rate and the power) were examined under a range of parameters and population-sampling strategies (e.g.,various genetic models,various heritabilities,and various sample-selection threshold values) by simulation studies.The results indicated that the statistic Tee is robust and powerful for genomic association study of QTL.A simulation study based on the haplotype frequencies of 10 single nucleotide polymorphisms (SNPs) of angiotensin-I converting enzyme genes was conducted to evaluate the performance of the statistic TPE for genetic association study.

  13. STrengthening the REporting of Genetic Association Studies (STREGA: an extension of the STROBE statement.

    Directory of Open Access Journals (Sweden)

    Julian Little

    2009-02-01

    Full Text Available Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

  14. Association Study between BDNF Gene Polymorphisms and Autism by Three-Dimensional Gel-Based Microarray

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    Zuhong Lu

    2009-06-01

    Full Text Available Single nucleotide polymorphisms (SNPs are important markers which can be used in association studies searching for susceptible genes of complex diseases. High-throughput methods are needed for SNP genotyping in a large number of samples. In this study, we applied polyacrylamide gel-based microarray combined with dual-color hybridization for association study of four BDNF polymorphisms with autism. All the SNPs in both patients and controls could be analyzed quickly and correctly. Among four SNPs, only C270T polymorphism showed significant differences in the frequency of the allele (χ2 = 7.809, p = 0.005 and genotype (χ2 = 7.800, p = 0.020. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (χ2 = 28.19,p = 3.44e-005. We suggest that BDNF has a possible role in the pathogenesis of autism. The study also show that the polyacrylamide gel-based microarray combined with dual-color hybridization is a rapid, simple and high-throughput method for SNPs genotyping, and can be used for association study of susceptible gene with disorders in large samples.

  15. Trick or treat: The effect of placebo on the power of pharmacogenetic association studies

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    Singer Clara

    2005-03-01

    Full Text Available Abstract The genetic mapping of drug-response traits is often characterised by a poor signal-to-noise ratio that is placebo related and which distinguishes pharmacogenetic association studies from classical case-control studies for disease susceptibility. The goal of this study was to evaluate the statistical power of candidate gene association studies under different pharmacogenetic scenarios, with special emphasis on the placebo effect. Genotype/phenotype data were simulated, mimicking samples from clinical trials, and response to the drug was modelled as a binary trait. Association was evaluated by a logistic regression model. Statistical power was estimated as a function of the number of single nucleotide polymorphisms (SNPs genotyped, the frequency of the placebo 'response', the genotype relative risk (GRR of the response polymorphism, the strategy for selecting SNPs for genotyping, the number of individuals in the trial and the ratio of placebo-treated to drugtreated patients. We show that: (i the placebo 'response' strongly affects the statistical power of association studies -- even a highly penetrant drug-response allele requires at least a 500-patient trial in order to reach 80 per cent power, several-fold more than the value estimated by standard tools that are not calibrated to pharmacogenetics; (ii the power of a pharmacogenetic association study depends primarily on the penetrance of the response genotype and, when this penetrance is fixed, power decreases for larger placebo effects; (iii power is dramatically increased when adding markers; (iv an optimal study design includes a similar number of placebo- and drugtreated patients; and (v in this setting, straightforward haplotype analysis does not seem to have an advantage over single marker analysis.

  16. Association of New Loci Identified in European Genome-Wide Association Studies with Susceptibility to Type 2 Diabetes in the Japanese

    OpenAIRE

    Toshihiko Ohshige; Minoru Iwata; Shintaro Omori; Yasushi Tanaka; Hiroshi Hirose; Kohei Kaku; Hiroshi Maegawa; Hirotaka Watada; Atsunori Kashiwagi; Ryuzo Kawamori; Kazuyuki Tobe; Takashi Kadowaki; Yusuke Nakamura; Shiro Maeda

    2011-01-01

    BACKGROUND: Several novel susceptibility loci for type 2 diabetes have been identified through genome-wide association studies (GWAS) for type 2 diabetes or quantitative traits related to glucose metabolism in European populations. To investigate the association of the 13 new European GWAS-derived susceptibility loci with type 2 diabetes in the Japanese population, we conducted a replication study using 3 independent Japanese case-control studies. METHODOLOGY/PRINCIPAL FINDINGS: We examined t...

  17. FGFR2 and other loci identified in genome-wide association studies are associated with breast cancer in African-American and younger women

    OpenAIRE

    Barnholtz-Sloan, Jill S; Shetty, Priya B; Guan, Xiaowei; Nyante, Sarah J; Luo, Jingchun; Brennan, Donal J.; Millikan, Robert C.

    2010-01-01

    Twenty-nine single-nucleotide polymorphisms (SNPs) from previously published genome-wide association studies (GWAS) and multiple ancestry informative markers were genotyped in the Carolina Breast Cancer Study (CBCS) (742 African-American (AA) cases, 1230 White cases; 658 AA controls, 1118 White controls). In the entire study population, 9/10 SNPs in fibroblast growth factor receptor 2 (FGFR2) were significantly associated with breast cancer after adjusting for age, race and European ancestry ...

  18. Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands

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    Schurink Anouk

    2012-10-01

    Full Text Available Abstract Background Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite hypersensitivity. Therefore, the aim of our study was to identify and quantify genomic associations with insect bite hypersensitivity in Shetland pony mares and Icelandic horses in the Netherlands. Methods Data on 200 Shetland pony mares and 146 Icelandic horses were collected according to a matched case–control design. Cases and controls were matched on various factors (e.g. region, sire to minimize effects of population stratification. Breed-specific genome-wide association studies were performed using 70 k single nucleotide polymorphisms genotypes. Bayesian variable selection method Bayes-C with a threshold model implemented in GenSel software was applied. A 1 Mb non-overlapping window approach that accumulated contributions of adjacent single nucleotide polymorphisms was used to identify associated genomic regions. Results The percentage of variance explained by all single nucleotide polymorphisms was 13% in Shetland pony mares and 28% in Icelandic horses. The 20 non-overlapping windows explaining the largest percentages of genetic variance were found on nine chromosomes in Shetland pony mares and on 14 chromosomes in Icelandic horses. Overlap in identified associated genomic regions between breeds would suggest interesting candidate regions to follow-up on. Such regions common to both breeds (within 15 Mb were found on chromosomes 3, 7, 11, 20 and 23. Positional candidate genes within 2 Mb from the associated windows were identified on chromosome 20 in both breeds. Candidate genes are within the equine lymphocyte antigen class II region, which evokes an immune response by recognizing many foreign molecules. Conclusions The genome-wide association

  19. Association Study between the FTCDNL1 (FONG and Susceptibility to Osteoporosis.

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    Hsing-Fang Lu

    Full Text Available Osteoporosis is a systemic skeletal disease characterized by a decreased bone mineral density that results in an increased risk of fragility fractures. Previous studies indicated that genetic factors are involved in the pathogenesis of osteoporosis. Polymorphisms of the FONG (FTCDNL1 gene (rs7605378 were reported to be associated with the risk of osteoporosis in a Japanese population. To assess whether polymorphisms of the FTCDNL1 gene contribute to the susceptibility and severity of osteoporosis in a Taiwanese population, 326 osteoporosis patients and 595 controls of a Taiwanese population were included in this study. Our results indicated that rs10203122 was significantly associated with osteoporosis susceptibility among female. Our findings provide evidence that rs10203122 in FTCDNL1 is associated with a susceptibility to osteoporosis.

  20. Association study between the Taq1A (rs1800497 polymorphism and schizophrenia in a Brazilian sample

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    Quirino Cordeiro

    2014-08-01

    Full Text Available Schizophrenia is a severe psychotic disorder with recurrent relapse and functional impairment. It results from a poorly understood gene-environment interaction. The Taq1A polymorphism (located in the gene cluster NTAD is a likely candidate for schizophrenia. Its rs1800497 polymorphism was shown to be associated with DRD2 gene expression. Therefore the present work aims to investigate a possible association between schizophrenia and such polymorphism. The compared distribution of the alleles and genotypes of the studied polymorphism was investigated in a Brazilian sample of 235 patients and 834 controls. Genotypic frequencies were in Hardy-Weinberg equilibrium. There was a trend of allelic association between the Taq1A polymorphism (rs1800497 with schizophrenia in the studied sample. However no statistically differences were found between cases and controls when analyzed by gender or schizophrenia subtypes.

  1. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

    DEFF Research Database (Denmark)

    Børglum, A D; Demontis, D; Grove, J;

    2014-01-01

    Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals...... and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144...... in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10...

  2. Genome-wide association study of periweaning failure-to-thrive syndrome (PFTS) in pigs.

    Science.gov (United States)

    Zanella, R; Morés, N; Morés, M A Z; Peixoto, J O; Zanella, E L; Ciacci-Zanella, J R; Ibelli, A M G; Gava, D; Cantão, M E; Ledur, M C

    2016-06-25

    Porcine periweaning-failure-to-thrive syndrome (PFTS) is a condition that affects newly weaned piglets. It is characterised by a progressive debilitation leading to death, in the absence of infectious, nutritional, management or environmental factors. In this study, we present the first report of PFTS in South America and the results of a genome-wide association study to identify the genetic markers associated with the appearance of this condition in a crossbred swine population. Four chromosomal regions were associated with PFTS predisposition, one located on SSCX, one on SSC8, and the two other regions on SSC14. Regions on SSC8 and SSC14 harbour important functional candidate genes involved in human depression and might have an important role in PFTS. Our findings contribute to the increasing knowledge about this syndrome, which has been investigated since 2007, and to the identification of the aetiology of this disease. PMID:27162284

  3. Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases

    Science.gov (United States)

    Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

    2016-01-01

    Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability

  4. A prospective study of maternal fatty acids, micronutrients and homocysteine and their association with birth outcome.

    Science.gov (United States)

    Wadhwani, Nisha S; Pisal, Hemlata R; Mehendale, Savita S; Joshi, Sadhana R

    2015-10-01

    Our earlier studies both in animals and in humans have indicated that micronutrients (folic acid, vitamin B12) and long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), are interlinked in the one-carbon cycle, which plays an important role in fetal 'programming' of adult diseases. The present study examines the levels of maternal and cord plasma fatty acids, maternal folate, vitamin B12 and homocysteine in healthy mothers at various time points during pregnancy and also examine an association between them. A longitudinal study of 106 normal pregnant women was carried out, and maternal blood was collected at three time points, viz., T1 = 16-20th week, T2 = 26-30th week and T3 = at delivery. Cord blood was collected at delivery. Fatty acids were estimated using a gas chromatograph. Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay (CMIA) technology. Maternal plasma folate (P < 0.05), vitamin B12 (P < 0.01) and DHA (P < 0.05) levels were lowest, while maternal homocysteine levels were highest (P < 0.01) at T3. There was a negative association between maternal DHA and homocysteine at T2 (P < 0.05) and T3 (P < 0.01). There was a positive association between plasma DHA in maternal blood at T3 and cord blood. Furthermore, there was a positive association between maternal folate and vitamin B12 at T3 and baby weight, whereas maternal homocysteine at T1 were inversely associated with baby weight at delivery. Our study provides evidence for the associations of folic acid, vitamin B12, homocysteine with DHA and baby weight, suggesting that a balanced dietary supplementation of folate-vitamin B12-DHA during pregnancy may be beneficial.

  5. Genome-wide association studies of the PR interval in African Americans.

    Directory of Open Access Journals (Sweden)

    J Gustav Smith

    Full Text Available The PR interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. The PR interval is heritable, provides important information about arrhythmia risk, and has been suggested to differ among human races. Genome-wide association (GWA studies have identified common genetic determinants of the PR interval in individuals of European and Asian ancestry, but there is a general paucity of GWA studies in individuals of African ancestry. We performed GWA studies in African American individuals from four cohorts (n = 6,247 to identify genetic variants associated with PR interval duration. Genotyping was performed using the Affymetrix 6.0 microarray. Imputation was performed for 2.8 million single nucleotide polymorphisms (SNPs using combined YRI and CEU HapMap phase II panels. We observed a strong signal (rs3922844 within the gene encoding the cardiac sodium channel (SCN5A with genome-wide significant association (p<2.5 x 10⁻⁸ in two of the four cohorts and in the meta-analysis. The signal explained 2% of PR interval variability in African Americans (beta  = 5.1 msec per minor allele, 95% CI  = 4.1-6.1, p = 3 x 10⁻²³. This SNP was also associated with PR interval (beta = 2.4 msec per minor allele, 95% CI = 1.8-3.0, p = 3 x 10⁻¹⁶ in individuals of European ancestry (n = 14,042, but with a smaller effect size (p for heterogeneity <0.001 and variability explained (0.5%. Further meta-analysis of the four cohorts identified genome-wide significant associations with SNPs in SCN10A (rs6798015, MEIS1 (rs10865355, and TBX5 (rs7312625 that were highly correlated with SNPs identified in European and Asian GWA studies. African ancestry was associated with increased PR duration (13.3 msec, p = 0.009 in one but not the other three cohorts. Our findings demonstrate the relevance of common variants to African Americans at four loci previously associated with PR interval in European and

  6. Association study between single nucleotide polymorphisms in leptin and growth traits in Cyprinus carpio var. Jian.

    Science.gov (United States)

    Tang, Y; Li, H; Li, J; Yu, F; Yu, J

    2016-01-01

    Leptin is a hormone that affects the regulation of body weight, energy expenditure, fat metabolism, food intake, and appetite. In this study, we cloned the jlLEP-A1 and jlLEP-A2 genes in Jian carp (Cyprinus carpio var. Jian) and performed an association analysis between identified polymorphisms and growth traits. Three polymorphisms in exons of jlLEP-A1 (A1-T113C) and jlLEP-A2 (A2-G415A and A2-G427A) were identified, and genotyped by the polymerase chain reaction - restriction fragment length polymorphism method in 263 female and 294 male Jian carp. All three SNPs were missense mutations. Association analysis revealed that the three SNPs were significantly associated with growth traits in male Jian carp. Only SNP A1-T113C was significantly associated with growth traits in female Jian carp. Analysis of diplotypes derived from jlLEP-A2 SNPs revealed an association with growth traits in male but not female Jian carp. These results demonstrate that polymorphisms in the leptin gene are associated with growth traits and may be used for marker-assisted selection programs in Jian carp breeding and production. PMID:27525905

  7. Association study of monoamine oxidase A/B genes and schizophrenia in Han Chinese

    Directory of Open Access Journals (Sweden)

    Li Sheng-Bin

    2011-10-01

    Full Text Available Abstract Background Monoamine oxidases (MAOs catalyze the metabolism of dopaminergic neurotransmitters. Polymorphisms of isoforms MAOA and MAOB have been implicated in the etiology of mental disorders such as schizophrenia. Association studies detected these polymorphisms in several populations, however the data have not been conclusive to date. Here, we investigated the association of MAOA and MAOB polymorphisms with schizophrenia in a Han Chinese population. Methods Two functional single nucleotide polymorphisms (SNPs, rs6323 of MAOA and rs1799836 of MAOB, were selected for association analysis in 537 unrelated schizophrenia patients and 536 healthy controls. Single-locus and Haplotype associations were calculated. Results No differences were found in the allelic distribution of rs6323. The G allele of rs1799836 was identified as a risk factor in the development of schizophrenia (P = 0.00001. The risk haplotype rs6323T-rs1799836G was associated with schizophrenia in female patients (P = 0.0002, but the frequency difference was not significant among male groups. Conclusions Our results suggest that MAOB is a susceptibility gene for schizophrenia. In contrast, no significant associations were observed for the MAOA functional polymorphism with schizophrenia in Han Chinese. These data support further investigation of the role of MAO genes in schizophrenia.

  8. Lithium chloride ionic association in dilute aqueous solution: a constrained molecular dynamics study

    Science.gov (United States)

    Zhang, Zhigang; Duan, Zhenhao

    2004-02-01

    Constrained molecular dynamics simulations were carried out to investigate the lithium chloride ionic associations in dilute aqueous solutions over a wide temperature range. Solvent mediated potentials of mean force have been carefully calculated at different thermodynamic conditions. Two intermediate states of ionic association can be well identified with an energy barrier from the oscillatory free energy profile. Clear pictures for the microscopic association structures are presented with a remarkable feature of strong hydration effect of lithium ion and the bridging role of its hydrating complex. Experimental association constants have been reasonably reproduced and a general trend of the increasing ionic association at high temperatures and low densities was observed. Additional simulations with different numbers of water molecules have been performed to check the possible artifacts introducing from periodic and finite size effects and confirm the reliability of our simulation results. Marginal differences of the simulated curves are believed to result from the significant compensation and canceling effect between the bare ionic forces and solvent induced mean force. Finally we confirmed the importance of accurate descriptions of dielectric properties of solvent in the ionic association study.

  9. Associations between Teacher Emotional Support and Depressive Symptoms in Australian Adolescents: A 5-Year Longitudinal Study

    Science.gov (United States)

    Pössel, Patrick; Rudasill, Kathleen Moritz; Sawyer, Michael G.; Spence, Susan H.; Bjerg, Annie C.

    2013-01-01

    Approximately 1/5 of adolescents develop depressive symptoms. Given that youths spend a good deal of their lives at school, it seems plausible that supportive relationships with teachers could benefit their emotional well-being. Thus, the purpose of this study is to examine the association between emotionally supportive teacher relationships and…

  10. Factors Associated with Recruitment and Screening in the Treatment for Adolescents with Depression Study (TADS)

    Science.gov (United States)

    May, Diane E.; Hallin, Mary J.; Kratochvil, Christopher J.; Puumala, Susan E.; Smith, Lynette S.; Reinecke, Mark A.; Silva, Susan G.; Weller, Elizabeth B.; Vitiello, Benedetto; Breland-Noble, Alfiee; March, John S.

    2007-01-01

    Objective: To examine factors associated with eligibility and randomization and consider the efficiency of recruitment methods. Method: Adolescents, ages 12 to 17 years, were telephone screened (N = 2,804) followed by in-person evaluation (N = 1,088) for the Treatment for Adolescents With Depression Study. Separate logistic regression models,…

  11. International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 Report

    NARCIS (Netherlands)

    Field, John K.; Smith, Robert A.; Aberle, Denise R.; Oudkerk, Matthijs; Baldwin, David R.; Yankelevitz, David; Pedersen, Jesper Holst; Swanson, Scott James; Travis, William D.; Wisbuba, Ignacio I.; Noguchi, Masayuki; Mulshine, Jim L.

    2012-01-01

    The International Association for the Study of Lung Cancer (IASLC) Board of Directors convened a computed tomography (CT) Screening Task Force to develop an IASLC position statement, after the National Cancer Institute press statement from the National Lung Screening Trial showed that lung cancer de

  12. Extrapyramidal syndromes associated with selective serotonin reuptake inhibitors : a case-control study using spontaneous reports

    NARCIS (Netherlands)

    Schillevoort, I; van Puijenbroek, E P; de Boer, A; Roos, R A C; Jansen, Paul A F; Leufkens, H G M

    2002-01-01

    The aim of this study was to assess whether use of selective serotonin reuptake inhibitors (SSRIs) is associated with extrapyramidal syndromes (EPS). We analysed the spontaneous reports of adverse drug reactions (ADRs) collected by The Netherlands Pharmacovigilance Foundation Lareb in the period 198

  13. Acute hospital, community, and indirect costs of stroke associated with atrial fibrillation: population-based study.

    LENUS (Irish Health Repository)

    Hannon, Niamh

    2014-10-30

    No economic data from population-based studies exist on acute or late hospital, community, and indirect costs of stroke associated with atrial fibrillation (AF-stroke). Such data are essential for policy development, service planning, and cost-effectiveness analysis of new therapeutic agents.

  14. A genome-wide association study of neuroticism in a population-based sample.

    Directory of Open Access Journals (Sweden)

    Federico C F Calboli

    Full Text Available 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 < 10(-6 and GPC6 showed suggestive evidence for interaction with age (p approximately = 10(-7. We found support for one previously-reported association (PDE4D, but failed to replicate other recent reports. These results suggest common SNP variation does not strongly influence 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.

  15. The Minnesota Center for Twin and Family Research Genome-Wide Association Study

    DEFF Research Database (Denmark)

    Miller, M. B.; Basu, S.; Cunningham, J.;

    2012-01-01

    As part of the Genes, Environment and Development Initiative, the Minnesota Center for Twin and Family Research (MCTFR) undertook a genome-wide association study, which we describe here. A total of 8,405 research participants, clustered in four-member families, have been successfully genotyped on...

  16. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci

    NARCIS (Netherlands)

    Stahl, Eli A.; Raychaudhuri, Soumya; Remmers, Elaine F.; Xie, Gang; Eyre, Stephen; Thomson, Brian P.; Li, Yonghong; Kurreeman, Fina A. S.; Zhernakova, Alexandra; Hinks, Anne; Guiducci, Candace; Chen, Robert; Alfredsson, Lars; Amos, Christopher I.; Ardlie, Kristin G.; Barton, Anne; Bowes, John; Brouwer, Elisabeth; Burtt, Noel P.; Catanese, Joseph J.; Coblyn, Jonathan; Coenen, Marieke J. H.; Costenbader, Karen H.; Criswell, Lindsey A.; Crusius, J. Bart A.; Cui, Jing; de Bakker, Paul I. W.; De Jager, Philip L.; Ding, Bo; Emery, Paul; Flynn, Edward; Harrison, Pille; Hocking, Lynne J.; Huizinga, Tom W. J.; Kastner, Daniel L.; Ke, Xiayi; Lee, Annette T.; Liu, Xiangdong; Martin, Paul; Morgan, Ann W.; Padyukov, Leonid; Posthumus, Marcel D.; Radstake, Timothy R. D. J.; Reid, David M.; Seielstad, Mark; Seldin, Michael F.; Shadick, Nancy A.; Steer, Sophia; Tak, Paul P.; Thomson, Wendy; van der Helm-van Mil, Annette H. M.; van der Horst-Bruinsma, Irene E.; van der Schoot, C. Ellen; van Riel, Piet L. C. M.; Weinblatt, Michael E.; Wilson, Anthony G.; Wolbink, Gert Jan; Wordsworth, B. Paul; Wijmenga, Cisca; Karlson, Elizabeth W.; Toes, Rene E. M.; de Vries, Niek; Begovich, Ann B.; Worthington, Jane; Siminovitch, Katherine A.; Gregersen, Peter K.; Klareskog, Lars; Plenge, Robert M.

    2010-01-01

    To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheum

  17. Directionality of the Associations of High School Expectancy-Value, Aspirations, and Attainment: A Longitudinal Study

    Science.gov (United States)

    Guo, Jiesi; Marsh, Herbert W.; Morin, Alexandre J. S.; Parker, Philip D.; Kaur, Gurvinder

    2015-01-01

    (This study examines the directionality of the associations among cognitive assets (IQ, academic achievement), motivational beliefs (academic self-concept, task values), and educational and occupational aspirations over time from late adolescence (Grade 10) into early adulthood (5 years post high school). Participants were from a nationally…

  18. Genome-wide association study of swine farrowing traits. Part II: Bayesian analysis of marker data

    Science.gov (United States)

    Reproductive efficiency has a great impact on the economic success of pork production. Number born alive (NBA) and average piglet birth weight (ABW) contribute greatly to reproductive efficiency. To better understand the underlying genetics of birth traits, a genome wide association study (GWAS) w...

  19. Institutional Change and Leadership Associated with Blended Learning Innovation: Two Case Studies

    Science.gov (United States)

    Garrison, D. Randy; Vaughan, Norman D.

    2013-01-01

    This article documents the institutional change and leadership associated with blended learning innovation in higher education. Two case studies are provided that demonstrate how transformational institutional change related to blended teaching and learning approaches is predicated upon committed collaborative leadership that engages all levels of…

  20. Objectively measured physical activity is negatively associated with academic achievement in adolescents: The GOALS Study

    NARCIS (Netherlands)

    Van Dijk, Martin; De Groot, Renate; Van Acker, Frederik; Savelberg, Hans; Kirschner, Paul A.

    2012-01-01

    Van Dijk, M. L., De Groot, R. H. M., Van Acker, F. H. M., Savelberg, H. C. M., & Kirschner, P. A. (2012, 7 November). Objectively measured physical activity is negatively associated with academic achievement in adolescents: The GOALS Study. Roundtable presentation at ICO Fall School 2012, Girona, Sp

  1. Objectively measured physical activity is negatively associated with academic achievement in adolescents: The GOALS Study

    OpenAIRE

    Van Dijk, Martin; De Groot, Renate; Van Acker, Frederik; Savelberg, Hans; Kirschner, Paul A.

    2012-01-01

    Van Dijk, M. L., De Groot, R. H. M., Van Acker, F. H. M., Savelberg, H. C. M., & Kirschner, P. A. (2012, 7 November). Objectively measured physical activity is negatively associated with academic achievement in adolescents: The GOALS Study. Roundtable presentation at ICO Fall School 2012, Girona, Spain.

  2. Associations between physical activity, cognitive performance, and academic achievement in Dutch adolescents: The GOALS Study

    NARCIS (Netherlands)

    Van Dijk, Martin; De Groot, Renate; Savelberg, Hans; Van Acker, Frederik; Kirschner, Paul A.

    2013-01-01

    Van Dijk, M. L., De Groot, R. H. M., Van Acker, F., Savelberg, H. C. M., & Kirschner, P. A. (2013, 12 November). Associations between physical activity, cognitive performance, and academic achievement in Dutch adolescents: The GOALS Study. Presentation at the Learning and Cognition plenary, Heerlen,

  3. Associations between physical activity, cognitive performance, and academic achievement in Dutch adolescents: The GOALS Study

    OpenAIRE

    Van Dijk, Martin; De Groot, Renate; Savelberg, Hans; Van Acker, Frederik; Kirschner, Paul A.

    2013-01-01

    Van Dijk, M. L., De Groot, R. H. M., Van Acker, F., Savelberg, H. C. M., & Kirschner, P. A. (2013, 12 November). Associations between physical activity, cognitive performance, and academic achievement in Dutch adolescents: The GOALS Study. Presentation at the Learning and Cognition plenary, Heerlen, The Netherlands.

  4. Leo named associate dean for research and graduate studies in College of Engineering

    OpenAIRE

    Virginia Tech News

    2007-01-01

    Don Leo, a program manager in the Defense Sciences Office of the Defense Advanced Research Projects Agency (DARPA) in Washington, D.C., has accepted the position of associate dean for research and graduate studies of the College of Engineering at Virginia Tech.

  5. Calcium intake is not associated with increased coronary artery calcification: The Framingham Study

    Science.gov (United States)

    Adequate calcium intake is known to protect the skeleton. However, studies that have reported adverse effects of calcium supplementation on vascular events have raised widespread concern. We assessed the association between calcium intake (from diet and supplements) and coronary artery calcification...

  6. Hypertension is independently associated with lumbar disc degeneration: a large-scale population-based study

    OpenAIRE

    Samartzis, D; Bow, HYC; Karppinen, JI; Luk, KDK; Cheung, BMY; Cheung, KMC

    2014-01-01

    INTRODUCTION: Hypertension, as elevated systolic blood pressure (SBP) and / or diastolic blood pressure (DBP), is a factor related to cardiovascular disease; however, its role in development of disc degeneration remains speculative. Hence, this large-scale population-based study addressed the association of blood pressure with lumbar disc ...

  7. Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Matheson, Melanie C; Pers, Tune Hannes;

    2013-01-01

    Allergen-specific immunoglobulin E (present in allergic sensitization) has a central role in the pathogenesis of allergic disease. We performed the first large-scale genome-wide association study (GWAS) of allergic sensitization in 5,789 affected individuals and 10,056 controls and followed up th...

  8. Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study

    Energy Technology Data Exchange (ETDEWEB)

    Le Jeune, Florence [Centre Eugene Marquis, Service de Medecine Nucleaire, Rennes (France); Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Centre Eugene Marquis, Service Medecine Nucleaire, Rennes (France); Peron, Julie [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Clinique Neurologique, Rennes (France); University of Geneva, Neuroscience of Emotion and Affective Dynamics, Department of Psychology and Swiss Center for Affective Sciences, Geneva (Switzerland); Grandjean, Didier [University of Geneva, Neuroscience of Emotion and Affective Dynamics, Department of Psychology and Swiss Center for Affective Sciences, Geneva (Switzerland); Drapier, Sophie; Verin, Marc [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Clinique Neurologique, Rennes (France); Haegelen, Claire [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Service de Neurochirurgie, Rennes (France); Garin, Etienne [Centre Eugene Marquis, Service de Medecine Nucleaire, Rennes (France); Millet, Bruno [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); S.H.U. Psychiatrie Adulte, CH Guillaume Regnier, Rennes (France)

    2010-08-15

    Although high-frequency deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in advanced Parkinson's disease (PD), clinical studies have reported cognitive, motivational and emotional changes. These results suggest that the STN forms part of a broadly distributed neural network encompassing the associative and limbic circuits. We sought to pinpoint the cortical and subcortical brain areas modulated by STN DBS, in order to assess the STN's functional role and explain neuropsychological modifications following STN DBS in PD. We studied resting state glucose metabolism in 20 PD patients before and after STN DBS and 13 age-matched healthy controls using {sup 18}F-FDG PET. We used statistical analysis (SPM2) first to compare pre-stimulation metabolism in PD patients with metabolism in healthy controls, then to study metabolic modifications in PD patients following STN DBS. The first analysis revealed no pre-stimulation metabolic abnormalities in associative or limbic circuitry. After STN DBS, metabolic modifications were found in several regions known for their involvement in the limbic and associative circuits. These metabolic results confirm the STN's central role in associative and limbic basal ganglia circuits. They will provide information for working hypotheses for future studies investigating neuropsychological changes and metabolic modifications related to STN DBS, with a view to improving our knowledge of this structure's functional role. (orig.)

  9. Genome-Wide Association Study for Response to Eimeria maxima Challenge in Broilers

    DEFF Research Database (Denmark)

    Hamzic, Edin; Bed'hom, Bertrand; Hérault, Frédéric;

    Use of genetic tools for improvement of host’s response is considered as a promising complementary approach for coccidiosis control. Therefore, we performed genome wide association study (GWAS) for response to Eimeria maxima challenge in broilers. The challenge was done on 2024 Cobb500 broilers. ...

  10. Genome-Wide Association Study of Retinopathy in Individuals without Diabetes

    NARCIS (Netherlands)

    R.A. Jensen (Richard); X. Sim (Xueling); X. Li (Xiaohui); M.F. Cotch (Mary Frances); M.K. Ikram (Kamran); E.G. Holliday (Elizabeth); G. Eiriksdottir (Gudny); T.B. Harris (Tamara); F. Jonasson (Fridbert); B.E.K. Klein (Barbara); L.J. Launer (Lenore); A.V. Smith (Albert Vernon); E. Boerwinkle (Eric); N. Cheung (Ning); A.W. Hewit (Alex); G. Liew (Gerald); P. Mitchell (Paul); J.J. Wang (Jie Jin); J. Attia (John); R.J. Scott (Rodney); N.L. Glazer (Nicole); T. Lumley (Thomas); B. McKnight (Barbara); B.M. Psaty (Bruce); K. Taylor (Kent); A. Hofman (Albert); P.T.V.M. de Jong (Paulus); F. Rivadeneira Ramirez (Fernando); A.G. Uitterlinden (André); W.-T. Tay (Wan-Ting); Y.Y. Teo (Yik Ying); M. Seielstad (Mark); J. Liu (Jianjun); C-Y. Cheng (Ching-Yu); S-M. Saw (Seang-Mei); T. Aung (Tin); S.K. Ganesh (Santhi); C.J. O'Donnell (Christopher); M.A. Nalls (Michael); K.L. Wiggins (Kerri); J.Z. Kuo (Jane); C.M. van Duijn (Cock); V. Gudnason (Vilmundur); R. Klein (Ronald); D.S. Siscovick (David); J.I. Rotter (Jerome); E.S. Tai (Shyong); J.R. Vingerling (Hans); T.Y. Wong (Tien)

    2013-01-01

    textabstractBackground: 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. Method

  11. SNPTrackTM : an integrated bioinformatics system for genetic association studies

    Directory of Open Access Journals (Sweden)

    Xu Joshua

    2012-07-01

    Full Text Available Abstract A genetic association study is a complicated process that involves collecting phenotypic data, generating genotypic data, analyzing associations between genotypic and phenotypic data, and interpreting genetic biomarkers identified. SNPTrack is an integrated bioinformatics system developed by the US Food and Drug Administration (FDA to support the review and analysis of pharmacogenetics data resulting from FDA research or submitted by sponsors. The system integrates data management, analysis, and interpretation in a single platform for genetic association studies. Specifically, it stores genotyping data and single-nucleotide polymorphism (SNP annotations along with study design data in an Oracle database. It also integrates popular genetic analysis tools, such as PLINK and Haploview. SNPTrack provides genetic analysis capabilities and captures analysis results in its database as SNP lists that can be cross-linked for biological interpretation to gene/protein annotations, Gene Ontology, and pathway analysis data. With SNPTrack, users can do the entire stream of bioinformatics jobs for genetic association studies. SNPTrack is freely available to the public at http://www.fda.gov/ScienceResearch/BioinformaticsTools/SNPTrack/default.htm.

  12. Acquired Affective Associations Induce Emotion Effects in Word Recognition: An ERP Study

    Science.gov (United States)

    Fritsch, Nathalie; Kuchinke, Lars

    2013-01-01

    The present study examined how contextual learning and in particular emotionality conditioning impacts the neural processing of words, as possible key factors for the acquisition of words' emotional connotation. 21 participants learned on five consecutive days associations between meaningless pseudowords and unpleasant or neutral pictures using an…

  13. Are rabbits a suitable model to study sheep-associated malignant catarrhal in susceptible hosts?

    Science.gov (United States)

    Sheep-associated malignant catarrhal fever (SA-MCF), caused by ovine herpesvirus 2 (OvHV-2), is often a fatal syndrome affecting mainly ruminants. SA-MCF pathogenesis and vaccine studies rely solely on live animals, since OvHV-2 has not been successfully propagated in vitro. Thus, the identification...

  14. Design of association studies with pooled or un-pooled next-generation sequencing data

    DEFF Research Database (Denmark)

    Kim, Su Yeon; Li, Yingrui; Guo, Yiran;

    2010-01-01

    Most common hereditary diseases in humans are complex and multifactorial. Large-scale genome-wide association studies based on SNP genotyping have only identified a small fraction of the heritable variation of these diseases. One explanation may be that many rare variants (a minor allele frequenc...

  15. Forensic Psychiatric Perspective on Criminality Associated with Intellectual Disability: A Nationwide Register-Based Study

    Science.gov (United States)

    Mannynsalo, L.; Putkonen, H.; Lindberg, N.; Kotilainen, I.

    2009-01-01

    Background: Contrasting views exist over the association of intellectual disability (ID) and criminal offending. This nationwide study attempts to shed further light to expand understanding to substantiate the relation between socio-demographic characteristics, psychiatric co-morbidity and criminal behaviour among the Finnish forensic population…

  16. A Population-Based Study of the Association between Pathological Gambling and Attempted Suicide.

    Science.gov (United States)

    Newman, Stephen C.; Thompson, Angus H.

    2003-01-01

    Examines the association between pathological gambling and attempted suicide using data from a prevalence study. The odds ratio for pathological gambling was statistically significant when major depression was the only comorbid mental disorder in the model. As terms for additional mental disorders were included, pathological gambling ceased to be…

  17. The association between maternal dietary micronutrient intake and neonatal anthropometry - secondary analysis from the ROLO study.

    LENUS (Irish Health Repository)

    Horan, Mary K

    2015-01-01

    Micronutrients are necessary for fetal growth. However increasingly pregnant women are nutritionally replete and little is known about the effect of maternal micronutrient intakes on fetal adiposity in mothers with increased BMI. The aim of this study was to examine the association of maternal dietary micronutrient intake with neonatal size and adiposity in a cohort at risk of macrosomia.

  18. Genome-wide association study for ovarian cancer susceptibility using pooled DNA

    DEFF Research Database (Denmark)

    Lu, Yi; Chen, Xiaoqing; Beesley, Jonathan;

    2012-01-01

    Recent Genome-Wide Association Studies (GWAS) have identified four low-penetrance ovarian cancer susceptibility loci. We hypothesized that further moderate- or low-penetrance variants exist among the subset of single-nucleotide polymorphisms (SNPs) not well tagged by the genotyping arrays used in...

  19. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

    NARCIS (Netherlands)

    Cerhan, James R.; Berndt, Sonja I.; Vijai, Joseph; Ghesquières, Hervé; McKay, James; Wang, Sophia S.; Wang, Zhaoming; Yeager, Meredith; Conde, Lucia; De Bakker, Paul I W; Nieters, Alexandra; Cox, David; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R.; De Roos, Anneclaire J.; Brooks-Wilson, Angela R.; Lan, Qing; Severi, Gianluca; Melbye, Mads; Gu, Jian; Jackson, Rebecca D.; Kane, Eleanor; Teras, Lauren R.; Purdue, Mark P.; Vajdic, Claire M.; Spinelli, John J.; Giles, Graham G.; Albanes, Demetrius; Kelly, Rachel S.; Zucca, Mariagrazia; Bertrand, Kimberly A.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M.; Link, Brian K.; Novak, Anne J.; Dogan, Ahmet; Asmann, Yan W.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.; Weiner, George J.; Veron, Amelie S.; Zelenika, Diana; Tilly, Hervé; Haioun, Corinne; Molina, Thierry Jo; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans Olov; Bracci, Paige M.; Riby, Jacques; Smith, Martyn T.; Holly, Elizabeth A.; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Tinker, Lesley F.; North, Kari E.; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W. Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.; Villano, Danylo J.; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Kricker, Anne; Turner, Jenny; Southey, Melissa C.; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Trichopoulos, Dimitrios; Vermeulen, Roel C H; Boeing, Heiner; Tjonneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; Birmann, Brenda M.; Laden, Francine; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Sampson, Joshua; Liang, Liming; Park, Ju Hyun; Chung, Charles C.; Weisenburger, Dennis D.; Chatterjee, Nilanjan; Fraumeni, Joseph F.; Slager, Susan L.; Wu, Xifeng; De Sanjose, Silvia; Smedby, Karin E.; Salles, Gilles; Skibola, Christine F.; Rothman, Nathaniel; Chanock, Stephen J.

    2014-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of Euro

  20. Nonallergic rhinitis and its association with smoking and lower airway disease: A general population study

    DEFF Research Database (Denmark)

    Håkansson, Kåre; von Buchwald, Christian; Thomsen, Simon F;

    2011-01-01

    The cause of nonallergic rhinitis (NAR) and its relation to lower airway disease remains unclear. The purpose of this study was to perform a descriptive analysis of the occurrence of rhinitis in a Danish general population with focus on NAR and its association with smoking and lower airway disease....