WorldWideScience

Sample records for underlying genetic risk

  1. Preimplantation genetic diagnosis and rational choice under risk or uncertainty.

    Science.gov (United States)

    Zuradzki, Tomasz

    2014-11-01

    In this paper I present an argument in favour of a parental duty to use preimplantation genetic diagnosis (PGD). I argue that if embryos created in vitro were able to decide for themselves in a rational manner, they would sometimes choose PGD as a method of selection. Couples, therefore, should respect their hypothetical choices on a principle similar to that of patient autonomy. My thesis shows that no matter which moral doctrine couples subscribe to, they ought to conduct the PGD procedure in the situations when it is impossible to implant all of the created embryos and if there is a significant risk for giving birth to a child with a serious condition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Genetic risk

    OpenAIRE

    ten Kate, Leo P.

    2012-01-01

    In this paper I will review different aspects of genetic risk in the context of preconception care. I restrict myself to the knowledge of risk which is relevant for care and/or enables reproductive choice. The paper deals with chromosomes, genes and the genetic classification of diseases, and it explains why Mendelian disorders frequently do not show the expected pattern of occurrence in families. Factors that amplify genetic risk are also discussed. Of the two methods of genetic risk assessm...

  3. Genetic risk

    NARCIS (Netherlands)

    ten Kate, L.P.

    2012-01-01

    In this paper I will review different aspects of genetic risk in the context of preconception care. I restrict myself to the knowledge of risk which is relevant for care and/or enables reproductive choice. The paper deals with chromosomes, genes and the genetic classification of diseases, and it

  4. Genetic dyslexia risk variant is related to neural connectivity patterns underlying phonological awareness in children.

    Science.gov (United States)

    Skeide, Michael A; Kirsten, Holger; Kraft, Indra; Schaadt, Gesa; Müller, Bent; Neef, Nicole; Brauer, Jens; Wilcke, Arndt; Emmrich, Frank; Boltze, Johannes; Friederici, Angela D

    2015-09-01

    Phonological awareness is the best-validated predictor of reading and spelling skill and therefore highly relevant for developmental dyslexia. Prior imaging genetics studies link several dyslexia risk genes to either brain-functional or brain-structural factors of phonological deficits. However, coherent evidence for genetic associations with both functional and structural neural phenotypes underlying variation in phonological awareness has not yet been provided. Here we demonstrate that rs11100040, a reported modifier of SLC2A3, is related to the functional connectivity of left fronto-temporal phonological processing areas at resting state in a sample of 9- to 12-year-old children. Furthermore, we provide evidence that rs11100040 is related to the fractional anisotropy of the arcuate fasciculus, which forms the structural connection between these areas. This structural connectivity phenotype is associated with phonological awareness, which is in turn associated with the individual retrospective risk scores in an early dyslexia screening as well as to spelling. These results suggest a link between a dyslexia risk genotype and a functional as well as a structural neural phenotype, which is associated with a phonological awareness phenotype. The present study goes beyond previous work by integrating genetic, brain-functional and brain-structural aspects of phonological awareness within a single approach. These combined findings might be another step towards a multimodal biomarker for developmental dyslexia. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Genetic Factors Underlying the Risk of Thalidomide-Related Neuropathy in Patients With Multiple Myeloma

    NARCIS (Netherlands)

    Johnson, David C.; Corthals, Sophie L.; Walker, Brian A.; Ross, Fiona M.; Gregory, Walter M.; Dickens, Nicholas J.; Lokhorst, Henk M.; Goldschmidt, Hartmut; Davies, Faith E.; Durie, Brian G. M.; Van Ness, Brian; Child, J. Anthony; Sonneveld, Pieter; Morgan, Gareth J.

    2011-01-01

    Purpose To indentify genetic variation that can modulate and predict the risk of developing thalidomide-related peripheral neuropathy (TrPN). Patients and Methods We analyzed DNA from 1,495 patients with multiple myeloma. Using a custom-built single nucleotide polymorphism (SNP) array, we tested the

  6. Finding Risk Groups by Optimizing Artificial Neural Networks on the Area under the Survival Curve Using Genetic Algorithms.

    Directory of Open Access Journals (Sweden)

    Jonas Kalderstam

    Full Text Available We investigate a new method to place patients into risk groups in censored survival data. Properties such as median survival time, and end survival rate, are implicitly improved by optimizing the area under the survival curve. Artificial neural networks (ANN are trained to either maximize or minimize this area using a genetic algorithm, and combined into an ensemble to predict one of low, intermediate, or high risk groups. Estimated patient risk can influence treatment choices, and is important for study stratification. A common approach is to sort the patients according to a prognostic index and then group them along the quartile limits. The Cox proportional hazards model (Cox is one example of this approach. Another method of doing risk grouping is recursive partitioning (Rpart, which constructs a decision tree where each branch point maximizes the statistical separation between the groups. ANN, Cox, and Rpart are compared on five publicly available data sets with varying properties. Cross-validation, as well as separate test sets, are used to validate the models. Results on the test sets show comparable performance, except for the smallest data set where Rpart's predicted risk groups turn out to be inverted, an example of crossing survival curves. Cross-validation shows that all three models exhibit crossing of some survival curves on this small data set but that the ANN model manages the best separation of groups in terms of median survival time before such crossings. The conclusion is that optimizing the area under the survival curve is a viable approach to identify risk groups. Training ANNs to optimize this area combines two key strengths from both prognostic indices and Rpart. First, a desired minimum group size can be specified, as for a prognostic index. Second, the ability to utilize non-linear effects among the covariates, which Rpart is also able to do.

  7. Genetic risks from radiation

    International Nuclear Information System (INIS)

    Selby, P.B.

    Two widely-recognized committees, UNSCEAR and BEIR, have reevaluated their estimates of genetic risks from radiation. Their estimates for gene mutations are based on two different approaches, one being the doubling-dose approach and the other being a new direct approach based on an empirical determination of the amount of dominant induced damage in the skeletons of mice in the first generation following irradiation. The estimates made by these committees are in reasonably good agreement and suggest that the genetic risks from present exposures resultng from nuclear power production are small. There is room for much improvement in the reliability of the risk estimates. The relatively new approach of measuring the amount of induced damage to the mouse skeleton shows great promise of improving knowledge about how changes in the mutation frequency affect the incidence of genetic disorders. Such findings may have considerable influence on genetic risk estimates for radiation and on the development of risk estimates for other less-well-understood environmental mutagens. (author)

  8. Genetic risks of ionizing radiation

    International Nuclear Information System (INIS)

    Sankaranarayanan, K.

    1990-01-01

    Quantitative genetic risk estimation is made using two methods: the direct method, and the doubling dose (DD) method. The doubling dose currently used is 1 Gy for low LET, low dose, low dose rate irradiation, and is based on mouse data. Tables present the 1988 UNSCEAR estimates of genetic risk using both methods. (L.L.) (Tab.)

  9. Ionizing radiation and genetic risks

    International Nuclear Information System (INIS)

    Sankaranarayanan, K.; Wassom, J.S.

    2005-01-01

    in certain regions of the genome is related to the presence of large segments of repetitive DNA called segmental duplications (also called duplicons or low copy repeats, LCRs) in such regions. The mechanism that is envisaged for the origin of deletions and other rearrangements involves misalignment of region-specific LCRs of homologous chromosomes in meiosis followed by unequal crossing-over (i.e., non-allelic homologous recombination, NAHR). We hypothesize that: (a) in spermatogonial stem cells, NHEJ is probably the principal mechanism underlying the origin of radiation-induced deletions, although SSA and NAHR may also be involved to some extent, especially at low doses; and (b) in irradiated oocytes, NAHR is likely to be the main mechanism for generating deletions. We suggest future research possibilities, including the development of models for identifying regions of the genome that are susceptible to radiation-induced deletions. Such efforts may have particular significance in the context of the estimation of genetic risks of radiation exposure of human females, a problem that is still with us

  10. Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia.

    Science.gov (United States)

    Smith, Caitlin J; Saftlas, Audrey F; Spracklen, Cassandra N; Triche, Elizabeth W; Bjonnes, Andrew; Keating, Brendan; Saxena, Richa; Breheny, Patrick J; Dewan, Andrew T; Robinson, Jennifer G; Hoh, Josephine; Ryckman, Kelli K

    2016-01-01

    Preeclampsia is a hypertensive complication of pregnancy characterized by novel onset of hypertension after 20 weeks gestation, accompanied by proteinuria. Epidemiological evidence suggests that genetic susceptibility exists for preeclampsia; however, whether preeclampsia is the result of underlying genetic risk for essential hypertension has yet to be investigated. Based on the hypertensive state that is characteristic of preeclampsia, we aimed to determine if established genetic risk scores (GRSs) for hypertension and blood pressure are associated with preeclampsia. Subjects consisted of 162 preeclamptic cases and 108 normotensive pregnant controls, all of Iowa residence. Subjects' DNA was extracted from buccal swab samples and genotyped on the Affymetrix Genome-wide Human SNP Array 6.0 (Affymetrix, Santa Clara, CA). Missing genotypes were imputed using MaCH and Minimac software. GRSs were calculated for hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) using established genetic risk loci for each outcome. Regression analyses were performed to determine the association between GRS and risk of preeclampsia. These analyses were replicated in an independent US population of 516 cases and 1,097 controls of European ancestry. GRSs for hypertension, SBP, DBP, and MAP were not significantly associated with risk for preeclampsia (P > 0.189). The results of the replication analysis also yielded nonsignificant associations. GRSs for hypertension and blood pressure are not associated with preeclampsia, suggesting that an underlying predisposition to essential hypertension is not on the causal pathway of preeclampsia. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Genetic cancer risk assessment in practice

    International Nuclear Information System (INIS)

    Gruber, S.

    2004-01-01

    The advent of genetic testing has made a dramatic impact on the management of individuals with inherited susceptibility to cancer and their relatives. Genetic counsel ing, with or without testing, is warranted when clues to familial cancer are recognized. Today, genetic testing for classic cancer genetic syndromes is now the standard of care, and has been complemented by genetic testing for other situations commonly encountered in clinical practice. Genetic testing for colorectal cancer, breast cancer, kidney cancer, thyroid cancer, melanoma, and pancreatic cancer raise important issues about the parameters for testing. Genetic cancer risk assessment can lead to measurable reductions in morbidity and mortality through strategies that rely on surveillance, chemo prevention, and risk-reducing surgery

  12. Integrating Genetics and Social Science: Genetic Risk Scores

    Science.gov (United States)

    Belsky, Daniel W.; Israel, Salomon

    2014-01-01

    The sequencing of the human genome and the advent of low-cost genome-wide assays that generate millions of observations of individual genomes in a matter of hours constitute a disruptive innovation for social science. Many public-use social science datasets have or will soon add genome-wide genetic data. With these new data come technical challenges, but also new possibilities. Among these, the lowest hanging fruit and the most potentially disruptive to existing research programs is the ability to measure previously invisible contours of health and disease risk within populations. In this article, we outline why now is the time for social scientists to bring genetics into their research programs. We discuss how to select genetic variants to study. We explain how the polygenic architecture of complex traits and the low penetrance of individual genetic loci pose challenges to research integrating genetics and social science. We introduce genetic risk scores as a method of addressing these challenges and provide guidance on how genetic risk scores can be constructed. We conclude by outlining research questions that are ripe for social science inquiry. PMID:25343363

  13. Genetic variants and multiple myeloma risk

    DEFF Research Database (Denmark)

    Martino, Alessandro; Campa, Daniele; Jurczyszyn, Artur

    2014-01-01

    BACKGROUND: Genetic background plays a role in multiple myeloma susceptibility. Several single-nucleotide polymorphisms (SNP) associated with genetic susceptibility to multiple myeloma were identified in the last years, but only a few of them were validated in independent studies. METHODS...... with multiple myeloma risk (P value range, 0.055-0.981), possibly with the exception of the SNP rs2227667 (SERPINE1) in women. CONCLUSIONS: We can exclude that the selected polymorphisms are major multiple myeloma risk factors. IMPACT: Independent validation studies are crucial to identify true genetic risk...

  14. Stroke Risk Factors, Genetics, and Prevention.

    Science.gov (United States)

    Boehme, Amelia K; Esenwa, Charles; Elkind, Mitchell S V

    2017-02-03

    Stroke is a heterogeneous syndrome, and determining risk factors and treatment depends on the specific pathogenesis of stroke. Risk factors for stroke can be categorized as modifiable and nonmodifiable. Age, sex, and race/ethnicity are nonmodifiable risk factors for both ischemic and hemorrhagic stroke, while hypertension, smoking, diet, and physical inactivity are among some of the more commonly reported modifiable risk factors. More recently described risk factors and triggers of stroke include inflammatory disorders, infection, pollution, and cardiac atrial disorders independent of atrial fibrillation. Single-gene disorders may cause rare, hereditary disorders for which stroke is a primary manifestation. Recent research also suggests that common and rare genetic polymorphisms can influence risk of more common causes of stroke, due to both other risk factors and specific stroke mechanisms, such as atrial fibrillation. Genetic factors, particularly those with environmental interactions, may be more modifiable than previously recognized. Stroke prevention has generally focused on modifiable risk factors. Lifestyle and behavioral modification, such as dietary changes or smoking cessation, not only reduces stroke risk, but also reduces the risk of other cardiovascular diseases. Other prevention strategies include identifying and treating medical conditions, such as hypertension and diabetes, that increase stroke risk. Recent research into risk factors and genetics of stroke has not only identified those at risk for stroke but also identified ways to target at-risk populations for stroke prevention. © 2017 American Heart Association, Inc.

  15. Identifying the genetic components underlying the pathophysiology of movement disorders

    Directory of Open Access Journals (Sweden)

    Ezquerra M

    2011-06-01

    Full Text Available Mario Ezquerra, Yaroslau Compta, Maria J MartiParkinson’s Disease and Movement Disorders Unit, Service of Neurology, Institute of Clinical Neurosciences, Hospital Clinic of Barcelona, IDIBAPS, CIBERNED, SpainAbstract: Movement disorders are a heterogeneous group of neurological conditions, few of which have been classically described as bona fide hereditary illnesses (Huntington’s chorea, for instance. Most are considered to be either sporadic or to feature varying degrees of familial aggregation (parkinsonism and dystonia. In the late twentieth century, Mendelian monogenic mutations were found for movement disorders with a clear and consistent family history. Although important, these findings apply only to very rare forms of movement disorders. Already in the twenty-first century, and taking advantage of the modern developments in genetics and molecular biology, growing attention is being paid to the complex genetics of movement disorders. The search for risk genetic variants (polymorphisms in large cohorts and the identification of different risk variants across different populations and ethnic groups are under way, with the most relevant findings to date corresponding to recent genome wide association studies in Parkinson’s disease. These new approaches focusing on risk variants may enable the design of screening tests for early or even preclinical disease, and the identification of likely therapeutic targets.Keywords: genetics, movement disorders, Parkinson’s disease, parkinsonism, dystonia

  16. Quantifying introgression risk with realistic population genetics.

    Science.gov (United States)

    Ghosh, Atiyo; Meirmans, Patrick G; Haccou, Patsy

    2012-12-07

    Introgression is the permanent incorporation of genes from the genome of one population into another. This can have severe consequences, such as extinction of endemic species, or the spread of transgenes. Quantification of the risk of introgression is an important component of genetically modified crop regulation. Most theoretical introgression studies aimed at such quantification disregard one or more of the most important factors concerning introgression: realistic genetical mechanisms, repeated invasions and stochasticity. In addition, the use of linkage as a risk mitigation strategy has not been studied properly yet with genetic introgression models. Current genetic introgression studies fail to take repeated invasions and demographic stochasticity into account properly, and use incorrect measures of introgression risk that can be manipulated by arbitrary choices. In this study, we present proper methods for risk quantification that overcome these difficulties. We generalize a probabilistic risk measure, the so-called hazard rate of introgression, for application to introgression models with complex genetics and small natural population sizes. We illustrate the method by studying the effects of linkage and recombination on transgene introgression risk at different population sizes.

  17. The Genetic and Environmental Factors Underlying Hypospadias

    Science.gov (United States)

    Pask, Andrew; Heloury, Yves; Sinclair, Andrew H.

    2016-01-01

    Hypospadias results from a failure of urethral closure in the male phallus and affects 1 in 200–300 boys. It is thought to be due to a combination of genetic and environmental factors. The development of the penis progresses in 2 stages: an initial hormone-independent phase and a secondary hormone-dependent phase. Here, we review the molecular pathways that contribute to each of these stages, drawing on studies from both human and mouse models. Hypospadias can occur when normal development of the phallus is disrupted, and we provide evidence that mutations in genes underlying this developmental process are causative. Finally, we discuss the environmental factors that may contribute to hypospadias and their potential immediate and transgen erational epigenetic impacts. PMID:26613581

  18. Methods to estimate the genetic risk

    International Nuclear Information System (INIS)

    Ehling, U.H.

    1989-01-01

    The estimation of the radiation-induced genetic risk to human populations is based on the extrapolation of results from animal experiments. Radiation-induced mutations are stochastic events. The probability of the event depends on the dose; the degree of the damage dose not. There are two main approaches in making genetic risk estimates. One of these, termed the direct method, expresses risk in terms of expected frequencies of genetic changes induced per unit dose. The other, referred to as the doubling dose method or the indirect method, expresses risk in relation to the observed incidence of genetic disorders now present in man. The advantage of the indirect method is that not only can Mendelian mutations be quantified, but also other types of genetic disorders. The disadvantages of the method are the uncertainties in determining the current incidence of genetic disorders in human and, in addition, the estimasion of the genetic component of congenital anomalies, anomalies expressed later and constitutional and degenerative diseases. Using the direct method we estimated that 20-50 dominant radiation-induced mutations would be expected in 19 000 offspring born to parents exposed in Hiroshima and Nagasaki, but only a small proportion of these mutants would have been detected with the techniques used for the population study. These methods were used to predict the genetic damage from the fallout of the reactor accident at Chernobyl in the vicinity of Southern Germany. The lack of knowledge for the interaction of chemicals with ionizing radiation and the discrepancy between the high safety standards for radiation protection and the low level of knowledge for the toxicological evaluation of chemical mutagens will be emphasized. (author)

  19. Risk Assessment of Genetically Modified Microorganisms

    DEFF Research Database (Denmark)

    Jacobsen, B. L.; Wilcks, Andrea

    2001-01-01

    the industry, national administration and research institutions were gathered to discuss which elements should be considered in a risk assessment of genetically modified microorganisms used as food or food ingredients. The existing EU and national regulations were presented, together with the experiences...

  20. Quantifying introgression risk with realistic population genetics

    NARCIS (Netherlands)

    Ghosh, A.; Meirmans, P.G.; Haccou, P.

    2012-01-01

    Introgression is the permanent incorporation of genes from the genome of one population into another. This can have severe consequences, such as extinction of endemic species, or the spread of transgenes. Quantification of the risk of introgression is an important component of genetically modified

  1. Channelopathies, genetic testing and risk stratification.

    Science.gov (United States)

    Wilde, Arthur A M; Amin, Ahmad

    2017-06-15

    The cardiac channelopathies are a group of diseases with (disease-) specific electrocardiographic (ECG) characteristics and a disease-specific risk of sudden cardiac death (SCD). This group includes the Long QT Syndromes (LQTS), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), Brugada Syndrome (BrS), Short QT Syndromes (SQTS), and Early Repolarization Syndrome (ERS). In the past 2 decades the genetic basis for these disease entities has largely been unraveled and that, together with the identification of the genetic basis of the cardiomyopathies, has paved the way for the complete new field of Cardiogenetics. By virtue of the identification of the genetic underpinning of a given disease, presymptomatic carriers of the genetic aberrancy can be identified and timely treatment can be installed. In addition, it has become clear that the pathophysiological substrate of some diseases previously considered to be one disease is not identical, and this has led to gene-specific treatment in some and complete new treatment, based on the newly developed insight, in others. Finally, the genetic information proved to be important in the prediction of risk on lethal ventricular arrhythmias of affected individuals and that is the topic of this brief review. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Risk allocation under liquidity constraints

    NARCIS (Netherlands)

    Csóka, P.; Herings, P.J.J.

    2013-01-01

    Risk allocation games are cooperative games that are used to attribute the risk of a financial entity to its divisions. In this paper, we extend the literature on risk allocation games by incorporating liquidity considerations. A liquidity policy specifies state-dependent liquidity requirements that

  3. Inflammatory Genetic Markers of Prostate Cancer Risk

    Energy Technology Data Exchange (ETDEWEB)

    Tindall, Elizabeth A.; Hayes, Vanessa M. [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia); University of New South Wales, Kensington Campus, Sydney, NSW 2052 (Australia); Petersen, Desiree C., E-mail: dpetersen@ccia.unsw.edu.au [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia)

    2010-06-08

    Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk.

  4. Inflammatory Genetic Markers of Prostate Cancer Risk

    International Nuclear Information System (INIS)

    Tindall, Elizabeth A.; Hayes, Vanessa M.; Petersen, Desiree C.

    2010-01-01

    Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk

  5. Risk preferences under acute stress

    Czech Academy of Sciences Publication Activity Database

    Cahlíková, Jana; Cingl, L.

    2017-01-01

    Roč. 20, č. 1 (2017), s. 209-236 ISSN 1386-4157 Institutional support: RVO:67985998 Keywords : risk preferences * risk aversion * stress Subject RIV: AH - Economics OBOR OECD: Applied Economics, Econometrics Impact factor: 2.391, year: 2016

  6. Risk preferences under acute stress

    Czech Academy of Sciences Publication Activity Database

    Cahlíková, Jana; Cingl, L.

    2017-01-01

    Roč. 20, č. 1 (2017), s. 209-236 ISSN 1386-4157 R&D Projects: GA MŠk(CZ) SVV 265801/2012 Institutional support: Progres-Q24 Keywords : risk preferences * risk aversion * stress Subject RIV: AH - Economics OBOR OECD: Applied Economics, Econometrics Impact factor: 2.391, year: 2016

  7. Genetic and epigenetic risks of assisted reproduction.

    Science.gov (United States)

    Jiang, Ziru; Wang, Yinyu; Lin, Jing; Xu, Jingjing; Ding, Guolian; Huang, Hefeng

    2017-10-01

    Assisted reproductive technology (ART) is used primarily for infertility treatments to achieve pregnancy and involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and cryopreservation. Moreover, preimplantation genetic diagnosis (PGD) of ART is used in couples for genetic reasons. In ART treatments, gametes and zygotes are exposed to a series of non-physiological processes and culture media. Although the majority of children born with this treatment are healthy, some concerns remain regarding the safety of this technology. Animal studies and follow-up studies of ART-borne children suggested that ART was associated with an increased incidence of genetic, physical, or developmental abnormalities, although there are also observations that contradict these findings. As IVF, ICSI, frozen-thawed embryo transfer, and PGD manipulate gametes and embryo at a time that is important for reprogramming, they may affect epigenetic stability, leading to gamete/embryo origins of adult diseases. In fact, ART offspring have been reported to have an increased risk of gamete/embryo origins of adult diseases, such as early-onset diabetes, cardiovascular disease, and so on. In this review, we will discuss evidence related to genetic, especially epigenetic, risks of assisted reproduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Genetic risk from diagnostic X-ray procedures

    International Nuclear Information System (INIS)

    Stephan, G.

    1980-01-01

    This essay introduces epidemiologic studies concerned with the question whether diagnostic X-ray procedures might be the cause of an increased genetic risk. All studies have selected Down's syndrome (mongolism) as genetic indicator. They indiscriminately present the opinion of the respective author. Approximately one half of the studies conclude that radiation exposure will not influence the spontaneous incidence of Down's syndrome in diagnostics, the other half finds a positive relationship between frequent radiation exposure and the incidence of the syndrome. For various reasons, explained in detail, the results of the studies under discussion are suitable for forming hypotheses, but should not be viewed as providing evidence. (orig.) [de

  9. Medical radiation exposure and genetic risks

    International Nuclear Information System (INIS)

    Baker, D.G.

    1980-01-01

    Everyone is exposed to background radiation throughout life (100 mrem/year to the gonads or 4 to 5 rem during the reproductive years). A lumbosacral series might deliver 2500 mrem to the male or 400 mrem to the female gonads. A radiologic procedure is a cost/benefit decision, and genetic risk is a part of the cost. Although cost is usually very low compared to benefit, if the procedure is unnecessary then the cost may be unacceptable. On the basis of current estimates, the doubling dose is assumed to be 40 rem (range 20 to 200) for an acute dose, and 100 rem for protracted exposure. Although there is no satisfactory way to predict the size of the risk for an individual exposed, any risk should be incentive to avoid unnecessary radiation to the gonads. Conception should be delayed for at least ten months for women and three or four months for men after irradiation of the gonads. The current incidence of genetically related diseases in the United States population is 60,000 per million live births. Based on the most conservative set of assumptions, an average gonadal dose of 1000 mrem to the whole population would increase the incidence of genetically related diseases by 0.2%

  10. Generator scheduling under competitive environment using genetic ...

    African Journals Online (AJOL)

    In this paper, genetic algorithm (GA) is used to solve the GENCOs profit based unit commitment problem (PBUCP) in a dayahead competitive electricity markets considering power and reserve generations simultaneously, whereas enhanced lambda iteration (ELI) method is used to solve the economic dispatch (ED) ...

  11. Intraspecific Genetic dynamics under Climate Change

    DEFF Research Database (Denmark)

    Florez Rodriguez, Alexander

    Climate change has a deep influence on the maintenance and generation of global biodiversity. Past contractions, expansions and shifts in species’ ranges drove to changes in species genetic diversity. Noteworthy, the interaction among: climate change, range, population size and extinction is ofte...

  12. Body Mass Index Genetic Risk Score and Endometrial Cancer Risk.

    Directory of Open Access Journals (Sweden)

    Jennifer Prescott

    Full Text Available Genome-wide association studies (GWAS have identified common variants that predispose individuals to a higher body mass index (BMI, an independent risk factor for endometrial cancer. Composite genotype risk scores (GRS based on the joint effect of published BMI risk loci were used to explore whether endometrial cancer shares a genetic background with obesity. Genotype and risk factor data were available on 3,376 endometrial cancer case and 3,867 control participants of European ancestry from the Epidemiology of Endometrial Cancer Consortium GWAS. A BMI GRS was calculated by summing the number of BMI risk alleles at 97 independent loci. For exploratory analyses, additional GRSs were based on subsets of risk loci within putative etiologic BMI pathways. The BMI GRS was statistically significantly associated with endometrial cancer risk (P = 0.002. For every 10 BMI risk alleles a woman had a 13% increased endometrial cancer risk (95% CI: 4%, 22%. However, after adjusting for BMI, the BMI GRS was no longer associated with risk (per 10 BMI risk alleles OR = 0.99, 95% CI: 0.91, 1.07; P = 0.78. Heterogeneity by BMI did not reach statistical significance (P = 0.06, and no effect modification was noted by age, GWAS Stage, study design or between studies (P≥0.58. In exploratory analyses, the GRS defined by variants at loci containing monogenic obesity syndrome genes was associated with reduced endometrial cancer risk independent of BMI (per BMI risk allele OR = 0.92, 95% CI: 0.88, 0.96; P = 2.1 x 10-5. Possessing a large number of BMI risk alleles does not increase endometrial cancer risk above that conferred by excess body weight among women of European descent. Thus, the GRS based on all current established BMI loci does not provide added value independent of BMI. Future studies are required to validate the unexpected observed relation between monogenic obesity syndrome genetic variants and endometrial cancer risk.

  13. Genetic risk variants for social anxiety.

    Science.gov (United States)

    Stein, Murray B; Chen, Chia-Yen; Jain, Sonia; Jensen, Kevin P; He, Feng; Heeringa, Steven G; Kessler, Ronald C; Maihofer, Adam; Nock, Matthew K; Ripke, Stephan; Sun, Xiaoying; Thomas, Michael L; Ursano, Robert J; Smoller, Jordan W; Gelernter, Joel

    2017-03-01

    Social anxiety is a neurobehavioral trait characterized by fear and reticence in social situations. Twin studies have shown that social anxiety has a heritable basis, shared with neuroticism and extraversion, but genetic studies have yet to demonstrate robust risk variants. We conducted genomewide association analysis (GWAS) of subjects within the Army Study To Assess Risk and Resilience in Servicemembers (Army STARRS) to (i) determine SNP-based heritability of social anxiety; (ii) discern genetic risk loci for social anxiety; and (iii) determine shared genetic risk with neuroticism and extraversion. GWAS were conducted within ancestral groups (EUR, AFR, LAT) using linear regression models for each of the three component studies in Army STARRS, and then meta-analyzed across studies. SNP-based heritability for social anxiety was significant (h 2 g  = 0.12, P = 2.17 × 10 -4 in EUR). One meta-analytically genomewide significant locus was seen in each of EUR (rs708012, Chr 6: BP 36965970, P = 1.55 × 10 -8 ; beta = 0.073) and AFR (rs78924501, Chr 1: BP 88406905, P = 3.58 × 10 -8 ; beta = 0.265) samples. Social anxiety in Army STARRS was significantly genetically correlated (negatively) with extraversion (r g  = -0.52, se = 0.22, P = 0.02) but not with neuroticism (r g  = 0.05, se = 0.22, P = 0.81) or with an anxiety disorder factor score (r g  = 0.02, se = 0.32, P = 0.94) from external GWAS meta-analyses. This first GWAS of social anxiety confirms a genetic basis for social anxiety, shared with extraversion but possibly less so with neuroticism. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Project cost analysis under risk

    Directory of Open Access Journals (Sweden)

    Florica LUBAN

    2010-12-01

    Full Text Available In this paper, an integrated approach based on Monte Carlo simulation and Six Sigma methodology is used to analyze the risk associated with a project's total cost. Monte Carlo simulation is applied to understand the variability in total cost caused by the probabilistic cost items. By Six Sigma methodology the range of variation of the project cost can be reduced by operating on the input factors with the greatest impact on total cost to cover the variation of 6 between the limits that were established in the design phase of Six Sigma.

  15. Guidance on the environmental risk assessment of genetically modified plants

    DEFF Research Database (Denmark)

    Bartsch, Detlef; Chueca, Cristina; De-Schrijver, Adinda

    relatives, including plant-to-plant gene transfer ; (2) plant-to-micro-organism gene transfer; (3) interaction of the GM plant with target organisms and (4) interaction of the GM plant with non-target organisms, including criteria for selection of appropriate species and relevant functional groups for risk......This document provides guidance for the environmental risk assessment (ERA) of genetically modified (GM) plants submitted within the framework of Regulation (EC) No. 1829/2003 on GM food and feed or under Directive 2001/18/EC on the deliberate release into the environment of genetically modified...... organisms (GMOs). This document provides guidance for assessing potential effects of GM plants on the environment and the rationales for the data requirements for a comprehensive ERA of GM plants. The ERA should be carried out on a case-by-case basis, following a step-by-step assessment approach...

  16. Adaptive genetic potential of coniferous forest tree species under climate change: implications for sustainable forest management

    Science.gov (United States)

    Mihai, Georgeta; Birsan, Marius-Victor; Teodosiu, Maria; Dumitrescu, Alexandru; Daia, Mihai; Mirancea, Ionel; Ivanov, Paula; Alin, Alexandru

    2017-04-01

    Mountain ecosystems are extremely vulnerable to climate change. The real potential for adaptation depends upon the existence of a wide genetic diversity in trees populations, upon the adaptive genetic variation, respectively. Genetic diversity offers the guarantee that forest species can survive, adapt and evolve under the influence of changing environmental conditions. The aim of this study is to evaluate the genetic diversity and adaptive genetic potential of two local species - Norway spruce and European silver fir - in the context of regional climate change. Based on data from a long-term provenance experiments network and climate variables spanning over more than 50 years, we have investigated the impact of climatic factors on growth performance and adaptation of tree species. Our results indicate that climatic and geographic factors significantly affect forest site productivity. Mean annual temperature and annual precipitation amount were found to be statistically significant explanatory variables. Combining the additive genetic model with the analysis of nuclear markers we obtained different images of the genetic structure of tree populations. As genetic indicators we used: gene frequencies, genetic diversity, genetic differentiation, genetic variance, plasticity. Spatial genetic analyses have allowed identifying the genetic centers holding high genetic diversity which will be valuable sources of gene able to buffer the negative effects of future climate change. Correlations between the marginal populations and in the optimal vegetation, between the level of genetic diversity and ecosystem stability, will allow the assessment of future risks arising from current genetic structure. Therefore, the strategies for sustainable forest management have to rely on the adaptive genetic variation and local adaptation of the valuable genetic resources. This work was realized within the framework of the project GENCLIM (Evaluating the adaptive potential of the main

  17. Genetic risk factors in colorectal cancer.

    Science.gov (United States)

    Bonaïti-Pellié, C

    1999-12-01

    Familial risk factors are known to play an important role in colorectal cancer (CRC) risk, particularly when the relatives are affected by early-onset cancer. Part of this familial aggregation can be accounted for by inherited forms of colorectal cancer, i.e. familial adenomatous polyposis (less than 1% of all CRC) and hereditary nonpolyposis colorectal cancer (about 3%). Other genetic factors may be involved in the development of adenoma or in the transformation of adenoma into carcinoma. That the existence of polymorphisms of the adenomatous polyposis coli gene increase susceptibility to both adenomas and cancer favours this hypothesis. Interactions between environmental factors, and most of all dietary factors, and polymorphisms of carcinogen-metabolizing enzymes may also be involved. Better knowledge of these mechanisms will substantially widen the scope of colorectal cancer prevention.

  18. The evolving genetic risk for sporadic ALS.

    Science.gov (United States)

    Gibson, Summer B; Downie, Jonathan M; Tsetsou, Spyridoula; Feusier, Julie E; Figueroa, Karla P; Bromberg, Mark B; Jorde, Lynn B; Pulst, Stefan M

    2017-07-18

    To estimate the genetic risk conferred by known amyotrophic lateral sclerosis (ALS)-associated genes to the pathogenesis of sporadic ALS (SALS) using variant allele frequencies combined with predicted variant pathogenicity. Whole exome sequencing and repeat expansion PCR of C9orf72 and ATXN2 were performed on 87 patients of European ancestry with SALS seen at the University of Utah. DNA variants that change the protein coding sequence of 31 ALS-associated genes were annotated to determine which were rare and deleterious as predicted by MetaSVM. The percentage of patients with SALS with a rare and deleterious variant or repeat expansion in an ALS-associated gene was calculated. An odds ratio analysis was performed comparing the burden of ALS-associated genes in patients with SALS vs 324 normal controls. Nineteen rare nonsynonymous variants in an ALS-associated gene, 2 of which were found in 2 different individuals, were identified in 21 patients with SALS. Further, 5 deleterious C9orf72 and 2 ATXN2 repeat expansions were identified. A total of 17.2% of patients with SALS had a rare and deleterious variant or repeat expansion in an ALS-associated gene. The genetic burden of ALS-associated genes in patients with SALS as predicted by MetaSVM was significantly higher than in normal controls. Previous analyses have identified SALS-predisposing variants only in terms of their rarity in normal control populations. By incorporating variant pathogenicity as well as variant frequency, we demonstrated that the genetic risk contributed by these genes for SALS is substantially lower than previous estimates. © 2017 American Academy of Neurology.

  19. Modelling the genetic risk in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

    Full Text Available Late-stage age-related macular degeneration (AMD is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05 than patients aged 75 and above (1.45, 95% CI: 1.36-1.54. Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96 for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population. The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.

  20. Assessing reservoir operations risk under climate change

    Science.gov (United States)

    Brekke, Levi D.; Maurer, Edwin P.; Anderson, Jamie D.; Dettinger, Michael D.; Townsley, Edwin S.; Harrison, Alan; Pruitt, Tom

    2009-04-01

    Risk-based planning offers a robust way to identify strategies that permit adaptive water resources management under climate change. This paper presents a flexible methodology for conducting climate change risk assessments involving reservoir operations. Decision makers can apply this methodology to their systems by selecting future periods and risk metrics relevant to their planning questions and by collectively evaluating system impacts relative to an ensemble of climate projection scenarios (weighted or not). This paper shows multiple applications of this methodology in a case study involving California's Central Valley Project and State Water Project systems. Multiple applications were conducted to show how choices made in conducting the risk assessment, choices known as analytical design decisions, can affect assessed risk. Specifically, risk was reanalyzed for every choice combination of two design decisions: (1) whether to assume climate change will influence flood-control constraints on water supply operations (and how), and (2) whether to weight climate change scenarios (and how). Results show that assessed risk would motivate different planning pathways depending on decision-maker attitudes toward risk (e.g., risk neutral versus risk averse). Results also show that assessed risk at a given risk attitude is sensitive to the analytical design choices listed above, with the choice of whether to adjust flood-control rules under climate change having considerably more influence than the choice on whether to weight climate scenarios.

  1. Assessing reservoir operations risk under climate change

    Science.gov (United States)

    Brekke, L.D.; Maurer, E.P.; Anderson, J.D.; Dettinger, M.D.; Townsley, E.S.; Harrison, A.; Pruitt, T.

    2009-01-01

    Risk-based planning offers a robust way to identify strategies that permit adaptive water resources management under climate change. This paper presents a flexible methodology for conducting climate change risk assessments involving reservoir operations. Decision makers can apply this methodology to their systems by selecting future periods and risk metrics relevant to their planning questions and by collectively evaluating system impacts relative to an ensemble of climate projection scenarios (weighted or not). This paper shows multiple applications of this methodology in a case study involving California's Central Valley Project and State Water Project systems. Multiple applications were conducted to show how choices made in conducting the risk assessment, choices known as analytical design decisions, can affect assessed risk. Specifically, risk was reanalyzed for every choice combination of two design decisions: (1) whether to assume climate change will influence flood-control constraints on water supply operations (and how), and (2) whether to weight climate change scenarios (and how). Results show that assessed risk would motivate different planning pathways depending on decision-maker attitudes toward risk (e.g., risk neutral versus risk averse). Results also show that assessed risk at a given risk attitude is sensitive to the analytical design choices listed above, with the choice of whether to adjust flood-control rules under climate change having considerably more influence than the choice on whether to weight climate scenarios. Copyright 2009 by the American Geophysical Union.

  2. Experiments in Decision-Making under Risk

    NARCIS (Netherlands)

    Krawczyk, M.W.

    2009-01-01

    This thesis presents experimental research on deviations from the standard theory of decision-making under risk. It focuses on two types of situations in which they are likely to occur. In the first part, the case of individual decision making with delayed resolution of risk is considered. It is

  3. Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women

    Science.gov (United States)

    Understanding Task Force Recommendations Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-related Cancer in Women The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation ...

  4. Assessing the impact of a combined analysis of four common low-risk genetic variants on autism risk

    Directory of Open Access Journals (Sweden)

    Carayol Jerome

    2010-02-01

    Full Text Available Abstract Background Autism is a complex disorder characterized by deficits involving communication, social interaction, and repetitive and restrictive patterns of behavior. Twin studies have shown that autism is strongly heritable, suggesting a strong genetic component. In other disease states with a complex etiology, such as type 2 diabetes, cancer and cardiovascular disease, combined analysis of multiple genetic variants in a genetic score has helped to identify individuals at high risk of disease. Genetic scores are designed to test for association of genetic markers with disease. Method The accumulation of multiple risk alleles markedly increases the risk of being affected, and compared with studying polymorphisms individually, it improves the identification of subgroups of individuals at greater risk. In the present study, we show that this approach can be applied to autism by specifically looking at a high-risk population of children who have siblings with autism. A two-sample study design and the generation of a genetic score using multiple independent genes were used to assess the risk of autism in a high-risk population. Results In both samples, odds ratios (ORs increased significantly as a function of the number of risk alleles, with a genetic score of 8 being associated with an OR of 5.54 (95% confidence interval [CI] 2.45 to 12.49. The sensitivities and specificities for each genetic score were similar in both analyses, and the resultant area under the receiver operating characteristic curves were identical (0.59. Conclusions These results suggest that the accumulation of multiple risk alleles in a genetic score is a useful strategy for assessing the risk of autism in siblings of affected individuals, and may be better than studying single polymorphisms for identifying subgroups of individuals with significantly greater risk.

  5. Genetic risk factors and Mendelian randomization in cardiovascular disease.

    Science.gov (United States)

    Swerdlow, Daniel I; Hingorani, Aroon D; Humphries, Steve E

    2015-05-01

    Cardiovascular disease encompasses several diverse pathological states that place a heavy burden on individual and population health. The aetiological basis of many cardiovascular disorders is not fully understood. Growing knowledge of the genetic architecture underlying coronary heart disease, stroke, cardiac arrhythmias and peripheral vascular disease has confirmed some suspected causal pathways in these conditions but also uncovered many previously unknown mechanisms. Here, we consider the contribution of genetics to the understanding of cardiovascular disease risk. We evaluate the utility and relevance of findings from genome-wide association studies and explore the role that Mendelian randomisation has to play in exploiting these. Mendelian randomisation permits robust causal inference in an area of research where this has been hampered by bias and confounding in observational studies. In doing so, it provides evidence for causal processes in cardiovascular disease that could represent novel targets for much-needed new drugs for disease prevention and treatment.

  6. Genetic Variants Influencing Circulating Lipid Levels and Risk of Coronary Artery Disease

    NARCIS (Netherlands)

    Waterworth, Dawn M.; Ricketts, Sally L.; Song, Kijoung; Chen, Li; Zhao, Jing Hua; Ripatti, Samuli; Aulchenko, Yurii S.; Zhang, Weihua; Yuan, Xin; Lim, Noha; Luan, Jian'an; Ashford, Sofie; Wheeler, Eleanor; Young, Elizabeth H.; Hadley, David; Thompson, John R.; Braund, Peter S.; Johnson, Toby; Struchalin, Maksim; Surakka, Ida; Luben, Robert; Khaw, Kay-Tee; Rodwell, Sheila A.; Loos, Ruth J. F.; Boekholdt, S. Matthijs; Inouye, Michael; Deloukas, Panagiotis; Elliott, Paul; Schlessinger, David; Sanna, Serena; Scuteri, Angelo; Jackson, Anne; Mohlke, Karen L.; Tuomilehto, Jaako; Roberts, Robert; Stewart, Alexandre; Kesäniemi, Y. Antero; Mahley, Robert W.; Grundy, Scott M.; McArdle, Wendy; Cardon, Lon; Waeber, Gérard; Vollenweider, Peter; Chambers, John C.; Boehnke, Michael; Abecasis, Gonçalo R.; Salomaa, Veikko; Järvelin, Marjo-Riitta; Ruokonen, Aimo; Barroso, Inês; Epstein, Stephen E.; Hakonarson, Hakon H.; Rader, Daniel J.; Reilly, Muredach P.; Witteman, Jacqueline C. M.; Hall, Alistair S.; Samani, Nilesh J.; Strachan, David P.; Barter, Philip; van Duijn, Cornelia M.; Kooner, Jaspal S.; Peltonen, Leena; Wareham, Nicholas J.; McPherson, Ruth; Mooser, Vincent; Sandhu, Manjinder S.

    2010-01-01

    Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol

  7. A common genetic factor underlies hypertension and other cardiovascular disorders

    Directory of Open Access Journals (Sweden)

    Spector Tim D

    2004-11-01

    Full Text Available Abstract Background Certain conditions characterised by blood vessel occlusion or vascular spasm have been found to cluster together in epidemiological studies. However the biological causes for these associations remain controversial. This study used a classical twin design to examine whether these conditions are linked through shared environmental exposures or by a common underlying genetic propensity to vasospasm. Methods We investigated the association between hypertension, migraine, Raynaud's phenomenon and coronary artery disease in twins from a national register. Phenotype status was determined using a questionnaire and the genetic and environmental association between phenotypes was estimated through variance components analysis. Results Responses were obtained from 2,204 individuals comprising 525 monozygotic and 577 dizygotic pairs. There was a significant genetic contribution to all four traits with heritabilities ranging from 0.34 to 0.64. Multivariate model-fitting demonstrated that a single common genetic factor underlies the four conditions. Conclusions We have confirmed an association between hypertension, migraine, Raynaud's phenomenon and coronary artery disease, and shown that a single genetic factor underlies them. The demonstration of a shared genetic factor explains the association between them and adds weight to the theory of an inherited predisposition to vasospasm.

  8. Common Gene Variants Account for Most Genetic Risk for Autism

    Science.gov (United States)

    ... gene variants account for most genetic risk for autism Roles of heritability, mutations, environment estimated – NIH-funded study. The bulk of risk, or liability, for autism spectrum disorders (ASD) was traced to inherited variations ...

  9. Comparative analyses of genetic risk prediction methods reveal ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 94; Issue 1. Comparative analyses of genetic risk prediction methods reveal extreme diversity of genetic predisposition to nonalcoholic fatty liver disease (NAFLD) among ethnic populations of India. Ankita Chatterjee Analabha Basu Abhijit Chowdhury Kausik Das Neeta ...

  10. Cognitive mechanisms underlying disorganization of thought in a genetic syndrome (47,XXY)

    NARCIS (Netherlands)

    Van Rijn, Sophie; Aleman, Andre; De Sonneville, Leo; Swaab, Hanna

    Because of the risk for development of psychopathology such as psychotic symptoms, it has been suggested that studying men with the XXY karyotype may help in the search for underlying cognitive, neural and genetic mechanisms. The aim of this study was to identify cognitive mechanisms that may

  11. Genetic variation underlying psychosis-inducing effects of cannabis: critical review and future directions.

    Science.gov (United States)

    Decoster, Jeroen; van Os, Jim; Myin-Germeys, Inez; De Hert, Marc; van Winkel, Ruud

    2012-01-01

    Cannabis use is associated with an increased risk for psychotic disorder, yet most cannabis users do not develop psychosis, suggesting that other factors are also involved. This paper reviews the available evidence suggesting that differential sensitivity to the psychosis-inducing effects of cannabis may be related to underlying genetic liability. There is robust evidence that persons at psychometric risk for psychosis are most vulnerable to display psychotic symptoms subsequent to the use of cannabis. Multiple studies have also found that persons at familial risk for psychosis have an increased sensitivity to the effects of cannabis. Together, these findings support the concept of a biological interaction between cannabis use and one's underlying genetic vulnerability. At the molecular-genetic level, however, few (if any) interactions have been consistently replicated, although a reported interaction with variation in AKT1 is promising and deserves further follow-up. The apparent lack of consistent replication can be ascribed to problems of initial gene selection, statistical power, a bias towards positive results and insufficient attempts at true replication, leading to the conclusion that increased sample sizes, greater density of genetic markers and a stronger focus on true replication are necessary. The major challenge for molecular-genetic gene-environment interaction research will be to combine the agnostic detection of disorder-associated genetic variants from genome-wide studies with the hypothesis-based approach from epidemiological and neurobiological studies. Possible strategies for future cannabis interaction studies are discussed.

  12. Genetic Ancestry and Risk of Breast Cancer among US Latinas

    OpenAIRE

    Fejerman, Laura; John, Esther M.; Huntsman, Scott; Beckman, Kenny; Choudhry, Shweta; Perez-Stable, Eliseo; Burchard, Esteban González; Ziv, Elad

    2008-01-01

    US Latinas have a lower incidence of breast cancer compared to non-Latina White women. This difference is partially explained by differences in the prevalence of known risk factors. Genetic factors may also contribute to this difference in incidence. Latinas are an admixed population with most of their genetic ancestry from Europeans and Indigenous Americans. We used genetic markers to estimate the ancestry of Latina breast cancer cases and controls and assessed the association with genetic a...

  13. Optimal annuity portfolio under inflation risk

    DEFF Research Database (Denmark)

    Konicz, Agnieszka Karolina; Pisinger, David; Weissensteiner, Alex

    2015-01-01

    The paper investigates the importance of in ation-linked annuities to individuals facing in ation risk. Given the investment opportunities in nominal, real, and variable annuities, as well as cash and stocks, we investigate the consumption and investment decisions under two different objective fu...

  14. Risk Management and Insurance Decisions under Ambiguity

    DEFF Research Database (Denmark)

    Martínez-Correa, Jimmy

    portfolio theory that assumes Subjective Expected Utility theory; however, it provides hints to a possible solution of the under-diversification puzzle of households. I also identify conditions under which more risk or ambiguity aversion decreases the demand for coinsurance. Additionally, I show......I study the impact of ambiguity on insurance decisions and the optimality of insurance contracts. My tractable approach allows me to study the interaction between risk and ambiguity attitudes. When insurance decisions are made independently of other assets, for a given increase in wealth, both risk...... and ambiguity attitudes interact in nontrivial ways to determine the change of coinsurance demand. I derive sufficient conditions to guarantee that the optimal coinsurance demand is decreasing in wealth. When a non-traded asset is introduced, my model predicts behavior that is inconsistent with the classical...

  15. Revisiting the relationship between baseline risk and risk under treatment

    Directory of Open Access Journals (Sweden)

    Nony Patrice

    2009-02-01

    Full Text Available Abstract Background In medical practice, it is generally accepted that the 'effect model' describing the relationship between baseline risk and risk under treatment is linear, i.e. 'relative risk' is constant. Absolute benefit is then proportional to a patient's baseline risk and the treatment is most effective among high-risk patients. Alternatively, the 'effect model' becomes curvilinear when 'odds ratio' is considered to be constant. However these two models are based on purely empirical considerations, and there is still no theoretical approach to support either the linear or the non-linear relation. Presentation of the hypothesis From logistic and sigmoidal Emax (Hill models, we derived a phenomenological model which includes the possibility of integrating both beneficial and harmful effects. Instead of a linear relation, our model suggests that the relationship is curvilinear i.e. the moderate-risk patients gain most from the treatment in opposition to those with low or high risk. Testing the hypothesis Two approaches can be proposed to investigate in practice such a model. The retrospective one is to perform a meta-analysis of clinical trials with subgroups of patients including a great range of baseline risks. The prospective one is to perform a large clinical trial in which patients are recruited according to several prestratified diverse and high risk groups. Implications of the hypothesis For the quantification of the treatment effect and considering such a model, the discrepancy between odds ratio and relative risk may be related not only to the level of risk under control conditions, but also to the characteristics of the dose-effect relation and the amount of dose administered. In the proposed approach, OR may be considered as constant in the whole range of Rc, and depending only on the intrinsic characteristics of the treatment. Therefore, OR should be preferred rather than RR to summarize information on treatment efficacy.

  16. A genetic risk score combining ten psoriasis risk loci improves disease prediction.

    Directory of Open Access Journals (Sweden)

    Haoyan Chen

    2011-04-01

    Full Text Available Psoriasis is a chronic, immune-mediated skin disease affecting 2-3% of Caucasians. Recent genetic association studies have identified multiple psoriasis risk loci; however, most of these loci contribute only modestly to disease risk. In this study, we investigated whether a genetic risk score (GRS combining multiple loci could improve psoriasis prediction. Two approaches were used: a simple risk alleles count (cGRS and a weighted (wGRS approach. Ten psoriasis risk SNPs were genotyped in 2815 case-control samples and 858 family samples. We found that the total number of risk alleles in the cases was significantly higher than in controls, mean 13.16 (SD 1.7 versus 12.09 (SD 1.8, p = 4.577×10(-40. The wGRS captured considerably more risk than any SNP considered alone, with a psoriasis OR for high-low wGRS quartiles of 10.55 (95% CI 7.63-14.57, p = 2.010×10(-65. To compare the discriminatory ability of the GRS models, receiver operating characteristic curves were used to calculate the area under the curve (AUC. The AUC for wGRS was significantly greater than for cGRS (72.0% versus 66.5%, p = 2.13×10(-8. Additionally, the AUC for HLA-C alone (rs10484554 was equivalent to the AUC for all nine other risk loci combined (66.2% versus 63.8%, p = 0.18, highlighting the dominance of HLA-C as a risk locus. Logistic regression revealed that the wGRS was significantly associated with two subphenotypes of psoriasis, age of onset (p = 4.91×10(-6 and family history (p = 0.020. Using a liability threshold model, we estimated that the 10 risk loci account for only 11.6% of the genetic variance in psoriasis. In summary, we found that a GRS combining 10 psoriasis risk loci captured significantly more risk than any individual SNP and was associated with early onset of disease and a positive family history. Notably, only a small fraction of psoriasis heritability is captured by the common risk variants identified to date.

  17. Risk assessment: the importance of genetic polymorphisms in man

    DEFF Research Database (Denmark)

    E. Knudsen, Lisbeth; Loft, Steffen; Autrup, Herman

    2001-01-01

    Many genetic polymorphisms in metabolism enzymes are important for the risk of cancer as shown in a large number of case-control studies. The relative risk estimates have shown large variations between such population studies. However, in most studies the relative risk estimates are in the range...... the application in insurance situations is criticised....

  18. Genetic and physiological controls of growth under water deficit.

    Science.gov (United States)

    Tardieu, François; Parent, Boris; Caldeira, Cecilio F; Welcker, Claude

    2014-04-01

    The sensitivity of expansive growth to water deficit has a large genetic variability, which is higher than that of photosynthesis. It is observed in several species, with some genotypes stopping growth in a relatively wet soil, whereas others continue growing until the lower limit of soil-available water. The responses of growth to soil water deficit and evaporative demand share an appreciable part of their genetic control through the colocation of quantitative trait loci as do the responses of the growth of different organs to water deficit. This result may be caused by common mechanisms of action discussed in this paper (particularly, plant hydraulic properties). We propose that expansive growth, putatively linked to hydraulic processes, determines the sink strength under water deficit, whereas photosynthesis determines source strength. These findings have large consequences for plant modeling under water deficit and for the design of breeding programs.

  19. Search for Genetic Variants Underlying Musical Aptitude and Related Traits

    OpenAIRE

    Ukkola-Vuoti, Liisa

    2013-01-01

    Music perception and practice represents complex cognitive functions of the brain. There is an abundance of data about the neurophysiological effects of music on the human brain, but heritability and especially molecular studies have been lacking. The development of genome technologies and bioinformatics has enabled the identification of genetic variants underlying complex human traits. These methods can be applied to normal human traits like music perception and performance. Prior to th...

  20. Genetically Predicted Body Mass Index and Breast Cancer Risk

    DEFF Research Database (Denmark)

    Guo, Yan; Warren Andersen, Shaneda; Shu, Xiao-Ou

    2016-01-01

    BACKGROUND: Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or enviro...... for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer....

  1. Genetic toxicology and cancer risk assessment

    National Research Council Canada - National Science Library

    Choy, Wai Nang

    2001-01-01

    ... their risks to humans are obvious goals for the protection of public health. When exposure is unavoidable, an accurate estimation of human risk as a result of exposure is essential for making regulatory decisions. Quantitative cancer risk assessment is an intricate process that utilizes knowledge from many different scien...

  2. Investment risks under uncertain climate change policy

    International Nuclear Information System (INIS)

    Blyth, William; Bradley, Richard; Yang, Ming; Bunn, Derek; Clarke, Charlie; Wilson, Tom

    2007-01-01

    This paper describes results from a model of decision-making under uncertainty using a real options methodology, developed by the International Energy Agency (IEA). The model represents investment decisions in power generation from the perspective of a private company. The investments are subject to uncertain future climate policy, which is treated as an external risk factor over which the company has no control. The aims of this paper are to (i) quantify these regulatory risks in order to improve understanding of how policy uncertainty may affect investment behaviour by private companies and (ii) illustrate the effectiveness of the real options approach as a policy analysis tool. The study analysed firms' investment options of coal- and gas-fired power plants and carbon capture and storage (CCS) technologies. Policy uncertainty is represented as an exogenous event that creates uncertainty in the carbon price. Our findings indicate that climate policy uncertainty creates a risk premium for power generation investments. In the case of gas- and coal-fired power generation, the risk premium would lead to an increase in electricity prices of 5-10% in order to stimulate investment. In the case of CCS, the risk premium would increase the carbon price required to stimulate investment by 16-37% compared to a situation of perfect certainty. The option to retrofit CCS acts as a hedge against high future carbon prices, and could accelerate investment in coal plant. This paper concludes that to minimise investment risks in low carbon technologies, policy-makers should aim to provide some long-term regulatory certainty. (author)

  3. Computerised Genetic Risk Assessment and Decision Support in Primary Care

    Directory of Open Access Journals (Sweden)

    Andrew Coulson

    2000-09-01

    To address these issues, a new computer application called RAGs (Risk Assessment in Genetics has been designed. The system allows a doctor to create family trees and assess genetic risk of breast cancer. RAGs possesses two features that distinguish it from similar software: (a a user-centred design, which takes into account the requirements of the doctor-patient encounter; (b risk reporting using qualitative evidence for or against an increased risk, which the authors believe to be more useful and accessible than numerical probabilities are. In that the system allows for any genetic risk guideline to be implemented, it can be used with all diseases for which evaluation guidelines exist. The software may be easily modified to cater for the amount of detail required by different specialists.

  4. Referral for genetic counselling during pregnancy: limited alertness and awareness about genetic risk factors among GPs

    NARCIS (Netherlands)

    Aalfs, Cora M.; Smets, Ellen M. A.; de Haes, Hanneke C. J. M.; Leschot, Nico J.

    2003-01-01

    Background. In many countries, GPs play a key role in the referral to other medical specialists. Referral for reproductive genetic counselling during a pregnancy of women with a genetic risk factor already present before pregnancy has many disadvantages. Nevertheless, some 10-20% of the counsellees

  5. Common Genetic Risk for Melanoma Encourages Preventive Behavior Change

    Directory of Open Access Journals (Sweden)

    Lori Diseati

    2015-02-01

    Full Text Available There is currently great interest in using genetic risk estimates for common disease in personalized healthcare. Here we assess melanoma risk-related preventive behavioral change in the context of the Coriell Personalized Medicine Collaborative (CPMC. As part of on-going reporting activities within the project, participants received a personalized risk assessment including information related to their own self-reported family history of melanoma and a genetic risk variant showing a moderate effect size (1.7, 3.0 respectively for heterozygous and homozygous individuals. Participants who opted to view their report were sent an optional outcome survey assessing risk perception and behavioral change in the months that followed. Participants that report family history risk, genetic risk, or both risk factors for melanoma were significantly more likely to increase skin cancer preventive behaviors when compared to participants with neither risk factor (ORs = 2.04, 2.79, 4.06 and p-values = 0.02, 2.86 × 10−5, 4.67 × 10−5, respectively, and we found the relationship between risk information and behavior to be partially mediated by anxiety. Genomic risk assessments appear to encourage positive behavioral change in a manner that is complementary to family history risk information and therefore may represent a useful addition to standard of care for melanoma prevention.

  6. Genetic variation associated with cardiovascular risk in autoimmune diseases.

    Science.gov (United States)

    Perrotti, Pedro P; Aterido, Adrià; Fernández-Nebro, Antonio; Cañete, Juan D; Ferrándiz, Carlos; Tornero, Jesús; Gisbert, Javier P; Domènech, Eugeni; Fernández-Gutiérrez, Benjamín; Gomollón, Fernando; García-Planella, Esther; Fernández, Emilia; Sanmartí, Raimon; Gratacós, Jordi; Martínez-Taboada, Víctor Manuel; Rodríguez-Rodríguez, Luís; Palau, Núria; Tortosa, Raül; Corbeto, Mireia L; Lasanta, María L; Marsal, Sara; Julià, Antonio

    2017-01-01

    Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity.

  7. Genetic variation associated with cardiovascular risk in autoimmune diseases.

    Directory of Open Access Journals (Sweden)

    Pedro P Perrotti

    Full Text Available Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways. The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity.

  8. Risk assessment: the importance of genetic polymorphisms in man

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Loft, S H; Autrup, H

    2001-01-01

    Many genetic polymorphisms in metabolism enzymes are important for the risk of cancer as shown in a large number of case-control studies. The relative risk estimates have shown large variations between such population studies. However, in most studies the relative risk estimates are in the range...... and increased cancer risk, such results indicate effect modification regarding cancer risk. In risk assessment the safety 'factor' of 10 is generally accepted to allow for variation in individual susceptibility. Reviewing the literature justifies the factor of 10 when considering single polymorphisms. However...... in an individual with several susceptible metabolism genotypes as well as other determinants of susceptibility, e.g. defective DNA repair, poor-nutritional state, etc. the risk may increase far above a safety of 10.Historically, genetic polymorphisms have been taken into consideration in employment and currently...

  9. Genetic risk factors of venous thrombosis

    NARCIS (Netherlands)

    Franco, R. F.; Reitsma, P. H.

    2001-01-01

    Venous thrombosis, whose main clinical presentations include deep vein thrombosis and pulmonary embolism, represents a major health problem worldwide. Numerous conditions are known to predispose to venous thrombosis and these conditions are commonly referred to as risk indicators or risk factors.

  10. Genetic Predisposition to Ischemic Stroke: A Polygenic Risk Score.

    Science.gov (United States)

    Hachiya, Tsuyoshi; Kamatani, Yoichiro; Takahashi, Atsushi; Hata, Jun; Furukawa, Ryohei; Shiwa, Yuh; Yamaji, Taiki; Hara, Megumi; Tanno, Kozo; Ohmomo, Hideki; Ono, Kanako; Takashima, Naoyuki; Matsuda, Koichi; Wakai, Kenji; Sawada, Norie; Iwasaki, Motoki; Yamagishi, Kazumasa; Ago, Tetsuro; Ninomiya, Toshiharu; Fukushima, Akimune; Hozawa, Atsushi; Minegishi, Naoko; Satoh, Mamoru; Endo, Ryujin; Sasaki, Makoto; Sakata, Kiyomi; Kobayashi, Seiichiro; Ogasawara, Kuniaki; Nakamura, Motoyuki; Hitomi, Jiro; Kita, Yoshikuni; Tanaka, Keitaro; Iso, Hiroyasu; Kitazono, Takanari; Kubo, Michiaki; Tanaka, Hideo; Tsugane, Shoichiro; Kiyohara, Yutaka; Yamamoto, Masayuki; Sobue, Kenji; Shimizu, Atsushi

    2017-02-01

    The prediction of genetic predispositions to ischemic stroke (IS) may allow the identification of individuals at elevated risk and thereby prevent IS in clinical practice. Previously developed weighted multilocus genetic risk scores showed limited predictive ability for IS. Here, we investigated the predictive ability of a newer method, polygenic risk score (polyGRS), based on the idea that a few strong signals, as well as several weaker signals, can be collectively informative to determine IS risk. We genotyped 13 214 Japanese individuals with IS and 26 470 controls (derivation samples) and generated both multilocus genetic risk scores and polyGRS, using the same derivation data set. The predictive abilities of each scoring system were then assessed using 2 independent sets of Japanese samples (KyushuU and JPJM data sets). In both validation data sets, polyGRS was shown to be significantly associated with IS, but weighted multilocus genetic risk scores was not. Comparing the highest with the lowest polyGRS quintile, the odds ratios for IS were 1.75 (95% confidence interval, 1.33-2.31) and 1.99 (95% confidence interval, 1.19-3.33) in the KyushuU and JPJM samples, respectively. Using the KyushuU samples, the addition of polyGRS to a nongenetic risk model resulted in a significant improvement of the predictive ability (net reclassification improvement=0.151; P<0.001). The polyGRS was shown to be superior to weighted multilocus genetic risk scores as an IS prediction model. Thus, together with the nongenetic risk factors, polyGRS will provide valuable information for individual risk assessment and management of modifiable risk factors. © 2016 The Authors.

  11. Class II HLA interactions modulate genetic risk for multiple sclerosis

    DEFF Research Database (Denmark)

    Moutsianas, Loukas; Jostins, Luke; Beecham, Ashley H

    2015-01-01

    ,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles...

  12. Atrial Fibrillation Genetic Risk and Ischemic Stroke Mechanisms.

    Science.gov (United States)

    Lubitz, Steven A; Parsons, Owen E; Anderson, Christopher D; Benjamin, Emelia J; Malik, Rainer; Weng, Lu-Chen; Dichgans, Martin; Sudlow, Cathie L; Rothwell, Peter M; Rosand, Jonathan; Ellinor, Patrick T; Markus, Hugh S; Traylor, Matthew

    2017-06-01

    Atrial fibrillation (AF) is a leading cause of cardioembolic stroke, but the relationship between AF and noncardioembolic stroke subtypes are unclear. Because AF may be unrecognized, and because AF has a substantial genetic basis, we assessed for predisposition to AF across ischemic stroke subtypes. We examined associations between AF genetic risk and Trial of Org 10172 in Acute Stroke Treatment stroke subtypes in 2374 ambulatory individuals with ischemic stroke and 5175 without from the Wellcome Trust Case-Control Consortium 2 using logistic regression. We calculated AF genetic risk scores using single-nucleotide polymorphisms associated with AF in a previous independent analysis across a range of preselected significance thresholds. There were 460 (19.4%) individuals with cardioembolic stroke, 498 (21.0%) with large vessel, 474 (20.0%) with small vessel, and 814 (32.3%) individuals with strokes of undetermined cause. Most AF genetic risk scores were associated with stroke, with the strongest association ( P =6×10 - 4 ) attributed to scores of 944 single-nucleotide polymorphisms (each associated with AF at P risk and stroke were enriched in the cardioembolic stroke subset (strongest P =1.2×10 - 9 , 944 single-nucleotide polymorphism score). In contrast, AF genetic risk was not significantly associated with noncardioembolic stroke subtypes. Comprehensive AF genetic risk scores were specific for cardioembolic stroke. Incomplete workups and subtype misclassification may have limited the power to detect associations with strokes of undetermined pathogenesis. Future studies are warranted to determine whether AF genetic risk is a useful biomarker to enhance clinical discrimination of stroke pathogeneses. © 2017 American Heart Association, Inc.

  13. Genetic Cancer Risk Assessment for Breast Cancer in Latin America

    Science.gov (United States)

    Chavarri-Guerra, Yanin; Blazer, Kathleen Reilly; Weitzel, Jeffrey Nelson

    2017-01-01

    In Latin America, breast cancer is the most common malignancy in women, and limited available data suggest that up to 15% of all breast cancer cases in the region are hereditary. Genetic cancer risk assessment and counseling is a critical component of the appropriate clinical care of patients with hereditary breast cancer and their families. Unfortunately, genetic services are underdeveloped across Latin America, and access to genetic testing and counseling is very scarce in the region. Barriers contributing to the access to genetic care are high cost and lack of insurance coverage for genetic tests, insufficient oncogenetics training or expertise, nonexistence of genetic counseling as a clinical discipline and lack of supportive healthcare policies. In this review, we highlight relevant initiatives undertaken in several Latin American countries aimed at creating genetic cancer risk assessment programs. Additionally, we present a review of the scientific literature on the current status of breast cancer genomics in Latin America, with specific emphasis on demographic indicators, access to cancer genetic care, training and strategies to improve outcomes and international collaborations. PMID:28453507

  14. Biology, Genetics, and Environment: Underlying Factors Influencing Alcohol Metabolism.

    Science.gov (United States)

    Wall, Tamara L; Luczak, Susan E; Hiller-Sturmhöfel, Susanne

    2016-01-01

    Gene variants encoding several of the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), are among the largest genetic associations with risk for alcohol dependence. Certain genetic variants (i.e., alleles)--particularly the ADH1B*2, ADH1B*3, ADH1C*1, and ALDH2*2 alleles--have been associated with lower rates of alcohol dependence. These alleles may lead to an accumulation of acetaldehyde during alcohol metabolism, which can result in heightened subjective and objective effects. The prevalence of these alleles differs among ethnic groups; ADH1B*2 is found frequently in northeast Asians and occasionally Caucasians, ADH1B*3 is found predominantly in people of African ancestry, ADH1C*1 varies substantially across populations, and ALDH2*2 is found almost exclusively in northeast Asians. Differences in the prevalence of these alleles may account at least in part for ethnic differences in alcohol consumption and alcohol use disorder (AUD). However, these alleles do not act in isolation to influence the risk of AUD. For example, the gene effects of ALDH2*2 and ADH1B*2 seem to interact. Moreover, other factors have been found to influence the extent to which these alleles affect a person's alcohol involvement, including developmental stage, individual characteristics (e.g., ethnicity, antisocial behavior, and behavioral undercontrol), and environmental factors (e.g., culture, religion, family environment, and childhood adversity).

  15. Channelopathies, genetic testing and risk stratification

    NARCIS (Netherlands)

    Wilde, Arthur A. M.; Amin, Ahmad

    2017-01-01

    The cardiac channelopathies are a group of diseases with (disease-) specific electrocardiographic (ECG) characteristics and a disease-specific risk of sudden cardiac death (SCD). This group includes the Long QT Syndromes (LQTS), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), Brugada

  16. Cytoplasmic FMR1-Interacting Protein 2 Is a Major Genetic Factor Underlying Binge Eating.

    Science.gov (United States)

    Kirkpatrick, Stacey L; Goldberg, Lisa R; Yazdani, Neema; Babbs, R Keith; Wu, Jiayi; Reed, Eric R; Jenkins, David F; Bolgioni, Amanda F; Landaverde, Kelsey I; Luttik, Kimberly P; Mitchell, Karen S; Kumar, Vivek; Johnson, W Evan; Mulligan, Megan K; Cottone, Pietro; Bryant, Camron D

    2017-05-01

    Eating disorders are lethal and heritable; however, the underlying genetic factors are unknown. Binge eating is a highly heritable trait associated with eating disorders that is comorbid with mood and substance use disorders. Therefore, understanding its genetic basis will inform therapeutic development that could improve several comorbid neuropsychiatric conditions. We assessed binge eating in closely related C57BL/6 mouse substrains and in an F 2 cross to identify quantitative trait loci associated with binge eating. We used gene targeting to validate candidate genetic factors. Finally, we used transcriptome analysis of the striatum via messenger RNA sequencing to identify the premorbid transcriptome and the binge-induced transcriptome to inform molecular mechanisms mediating binge eating susceptibility and establishment. C57BL/6NJ but not C57BL/6J mice showed rapid and robust escalation in palatable food consumption. We mapped a single genome-wide significant quantitative trait locus on chromosome 11 (logarithm of the odds = 7.4) to a missense mutation in cytoplasmic FMR1-interacting protein 2 (Cyfip2). We validated Cyfip2 as a major genetic factor underlying binge eating in heterozygous knockout mice on a C57BL/6N background that showed reduced binge eating toward a wild-type C57BL/6J-like level. Transcriptome analysis of premorbid genetic risk identified the enrichment terms morphine addiction and retrograde endocannabinoid signaling, whereas binge eating resulted in the downregulation of a gene set enriched for decreased myelination, oligodendrocyte differentiation, and expression. We identified Cyfip2 as a major significant genetic factor underlying binge eating and provide a behavioral paradigm for future genome-wide association studies in populations with increased genetic complexity. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  17. Risk-based in situ bioremediation design using a noisy genetic algorithm

    Science.gov (United States)

    Smalley, J. Bryan; Minsker, Barbara S.; Goldberg, David E.

    2000-10-01

    Risk-based corrective action (RBCA) is rapidly becoming the method of choice for remediating contaminated groundwater. In this paper, a management model is presented that simultaneously predicts risk and proposes cost-effective options for reducing risk to acceptable levels under conditions of uncertainty. The model combines a noisy genetic algorithm with a numerical fate and transport model and an exposure and risk assessment model. The noisy genetic algorithm uses sampling from parameter distributions to assess the performance of candidate designs. Results from an application to a site from the literature show that the noisy genetic algorithm is capable of identifying highly reliable designs from a small number of samples, a significant advantage for computationally intensive groundwater management models. For the site considered, time-dependent costs associated with monitoring and the remedial system were significant, illustrating the potential importance of allowing variable cleanup lengths and a realistic cost function.

  18. Quantification of the genetic risk of environmental mutagens

    International Nuclear Information System (INIS)

    Ehling, U.H.

    1988-01-01

    Screening methods are used for hazard identification. Assays for heritable mutations in mammals are used for the confirmation of short-term test results and for the quantification of the genetic risk. There are two main approaches in making genetic risk estimates. One of these, termed the direct method, expresses risk in terms of the expected frequency of genetic changes induced per unit. The other, referred to as the doubling dose method or the indirect method, expresses risk in relation to the observed incidence of genetic disorders now present in man. The indirect method uses experimental data only for the calculation of the doubling dose. The quality of the risk estimation depends on the assumption of persistence of the induced mutations and the ability to determine the current incidence of genetic diseases. The difficulties of improving the estimates of current incidences of genetic diseases or the persistence of the genes in the population led them to the development of an alternative method, the direct estimation of the genetic risk. The direct estimation uses experimental data for the induced frequency for dominant mutations in mice. For the verification of these quantifications one can use the data of Hiroshima and Nagasaki. According to the estimation with the direct method, one would expect less than 1 radiation-induced dominant cataract in 19,000 children with one or both parents exposed. The expected overall frequency of dominant mutations in the first generation would be 20-25, based on radiation-induced dominant cataract mutations. It is estimated that 10 times more recessive than dominant mutations are induced. The same approaches can be used to determine the impact of chemical mutagens

  19. Novel genetic markers improve measures of atrial fibrillation risk prediction

    Science.gov (United States)

    Everett, Brendan M.; Cook, Nancy R.; Conen, David; Chasman, Daniel I.; Ridker, Paul M; Albert, Christine M.

    2013-01-01

    Aims Atrial fibrillation (AF) is associated with adverse outcome. Whether recently discovered genetic risk markers improve AF risk prediction is unknown. Methods and results We derived and validated a novel AF risk prediction model from 32 possible predictors in the Women's Health Study (WHS), a cohort of 20 822 women without cardiovascular disease (CVD) at baseline followed prospectively for incident AF (median: 14.5 years). We then created a genetic risk score (GRS) comprised of 12 risk alleles in nine loci and assessed model performance in the validation cohort with and without the GRS. The newly derived WHS AF risk algorithm included terms for age, weight, height, systolic blood pressure, alcohol use, and smoking (current and past). In the validation cohort, this model was well calibrated with good discrimination [C-index (95% CI) = 0.718 (0.684–0.753)] and improved all reclassification indices when compared with age alone. The addition of the genetic score to the WHS AF risk algorithm model improved the C-index [0.741 (0.709–0.774); P = 0.001], the category-less net reclassification [0.490 (0.301–0.670); P < 0.0001], and the integrated discrimination improvement [0.00526 (0.0033–0.0076); P < 0.0001]. However, there was no improvement in net reclassification into 10-year risk categories of <1, 1–5, and 5+% [0.041 (−0.044–0.12); P = 0.33]. Conclusion Among women without CVD, a simple risk prediction model utilizing readily available risk markers identified women at higher risk for AF. The addition of genetic information resulted in modest improvements in predictive accuracy that did not translate into improved reclassification into discrete AF risk categories. PMID:23444395

  20. Disclosing genetic risk for coronary heart disease: effects on perceived personal control and genetic counseling satisfaction.

    Science.gov (United States)

    Robinson, C L; Jouni, H; Kruisselbrink, T M; Austin, E E; Christensen, K D; Green, R C; Kullo, I J

    2016-02-01

    We investigated whether disclosure of coronary heart disease (CHD) genetic risk influences perceived personal control (PPC) and genetic counseling satisfaction (GCS). Participants (n = 207, age: 45-65 years) were randomized to receive estimated 10-year risk of CHD based on a conventional risk score (CRS) with or without a genetic risk score (GRS). Risk estimates were disclosed by a genetic counselor who also reviewed how GRS altered risk in those randomized to CRS+GRS. Each participant subsequently met with a physician and then completed surveys to assess PPC and GCS. Participants who received CRS+GRS had higher PPC than those who received CRS alone although the absolute difference was small (25.2 ± 2.7 vs 24.1 ± 3.8, p = 0.04). A greater proportion of CRS+GRS participants had higher GCS scores (17.3 ± 5.3 vs 15.9 ± 6.3, p = 0.06). In the CRS+GRS group, PPC and GCS scores were not correlated with GRS. Within both groups, PPC and GCS scores were similar in patients with or without family history (p = NS). In conclusion, patients who received their genetic risk of CHD had higher PPC and tended to have higher GCS. Our findings suggest that disclosure of genetic risk of CHD together with conventional risk estimates is appreciated by patients. Whether this results in improved outcomes needs additional investigation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Designing cellular manufacturing system under risk conditions ...

    African Journals Online (AJOL)

    Thus we propose a mixed integer programming approach to decision making and incorporate subcontracting risk . To control the risk of sub-contracting (cost) , the two popular percentile measures of risk are applied: value-at-risk and conditional value-at-risk. This model is capable of optimizing production cost of parts and ...

  2. Illusions of controlling the future: Risk and genetic inheritance.

    Science.gov (United States)

    Finkler, Kaja

    2003-01-01

    The aim of this paper is to analyse the implications of current beliefs that human beings can control the risk of inheriting a genetic disease and influence their present and future health. To accomplish this goal, materials will be drawn from disparate literatures bearing on concepts of probability, risk and genetic inheritance, and on empirical data gathered on cancer survivors and healthy persons with a family history of cancer. The concept of risk has been theorised on a grand scale but, as Lupton (1999, Introduction, Risk and Sociological Theory , Cambridge University Press) correctly observes, there has been very little empirical work done on how people experience risk as part of their lived world. In this paper, notions of probabilities and risk will be examined as applied to beliefs in genetic inheritance that are shaped by historical and cultural forces and in turn how they shape people's lives. It will be proposed that the belief that knowledge of one's genetic inheritance can control one's future health and disease is an illusion, and also replicates in part a religious notion of predestination.

  3. Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era

    Directory of Open Access Journals (Sweden)

    Costain G

    2012-02-01

    Full Text Available Gregory Costain1,2, Anne S Bassett1–41Clinical Genetics Research Program, Centre for Addiction and Mental Health, 2Institute of Medical Science, University of Toronto, 3Division of Cardiology, Department of Medicine and Department of Psychiatry, University Health Network, 4Department of Psychiatry, University of Toronto, Toronto, Ontario, CanadaAbstract: Schizophrenia is a complex neuropsychiatric disease with documented clinical and genetic heterogeneity, and evidence for neurodevelopmental origins. Driven by new genetic technologies and advances in molecular medicine, there has recently been concrete progress in understanding some of the specific genetic causes of this serious psychiatric illness. In particular, several large rare structural variants have been convincingly associated with schizophrenia, in targeted studies over two decades with respect to 22q11.2 microdeletions, and more recently in large-scale, genome-wide case-control studies. These advances promise to help many families afflicted with this disease. In this review, we critically appraise recent developments in the field of schizophrenia genetics through the lens of immediate clinical applicability. Much work remains in translating the recent surge of genetic research discoveries into the clinic. The epidemiology and basic genetic parameters (such as penetrance and expression of most genomic disorders associated with schizophrenia are not yet well characterized. To date, 22q11.2 deletion syndrome is the only established genetic subtype of schizophrenia of proven clinical relevance. We use this well-established association as a model to chart the pathway for translating emerging genetic discoveries into clinical practice. We also propose new directions for research involving general genetic risk prediction and counseling in schizophrenia.Keywords: schizophrenia, genetics, 22q11 deletion syndrome, copy number variation, genetic counseling, genetic predisposition to disease

  4. Genetic risk profiles for a childhood with severe overweight.

    Science.gov (United States)

    González, J R; Estévez, M N; Giralt, P S; Cáceres, A; Pérez, L M L; González-Carpio, M; Ballester, F; Sunyer, J; Rodríguez-López, R

    2014-08-01

    The objective of this study was the description of a valid genetic risk score (GRS) to predict individuals with high susceptibility to childhood overweight by their genetic profiles. Case-control study including a group of children with high-risk familial predisposition to morbid obesity. Birth cohort from general population constituted the validation sample. For the discovery sample, 218 children with non-syndromic obesity and 190 control individuals were included. The validation sample was 653 children from two birth cohorts belonging to the INMA (Infancia y Medio Ambiente [Environment and Childhood] )project. 109 SNPs located in the genes FTO, SEC16B, BDNF, ETV5, SH2B1, GNPDA2, LYPLAL1, MSRA, TFAP2, KCTD15, MTCH2 and NEGR1, previously reported in association to body mass index (BMI) were analysed. For the validation sample, association between genome-wide data and BMI measurements between 3.5 and 5 years of age, were evaluated. The GRS includes six SNPs in the genes FTO, TFAP2B, SEC16B, ETV5 and SH2B1. The score distribution differs among cases and controls (P = 9.2 × 10(-14) ) showing a significant linear association with obesity (odds ratio [OR] per allele = 1.69; confidence interval [CI] 95% = 1.46-1.97; P = 4.3 × 10(-1) and area under the receiver operating characteristic curve [AUC] = 0.727; CI 95% = 0.676-0.778). The results were validated by the INMA cohort (OR per allele = 1.23 CI 95% = 1.03-1.48 and AUC = 0.601 CI 95% = 0.522-0.680). The use of our proposed genetic score provides useful information to determine those children who are susceptible to obesity. To improve the efficiency of clinical prevention and treatment of obesity, it is essential to design individualized based protocols in advance knowledge of the molecular basis of inherited susceptibility. © 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.

  5. Imaging-Genetics in Dyslexia: Connecting risk genetic variants to brain neuroimaging and ultimately to reading impairments

    Science.gov (United States)

    Eicher, John D.; Gruen, Jeffrey R.

    2013-01-01

    Dyslexia is a common pediatric disorder that affects 5-17% of schoolchildren in the United States. It is marked by unexpected difficulties in fluent reading despite adequate intelligence, opportunity, and instruction. Classically, neuropsychologists have studied dyslexia using a variety of neurocognitive batteries to gain insight into the specific deficits and impairments in affected children. Since dyslexia is a complex genetic trait with high heritability, analyses conditioned on performance on these neurocognitive batteries have been used to try to identify associated genes. This has led to some successes in identifying contributing genes, although much of the heritability remains unexplained. Additionally, the lack of relevant human brain tissue for analysis and the challenges of modeling a uniquely human trait in animals are barriers to advancing our knowledge of the underlying pathophysiology. In vivo imaging technologies, however, present new opportunities to examine dyslexia and reading skills in a clearly relevant context in human subjects. Recent investigations have started to integrate these imaging data with genetic data in attempts to gain a more complete and complex understanding of reading processes. In addition to bridging the gap from genetic risk variant to a discernible neuroimaging phenotype and ultimately to the clinical impairments in reading performance, the use of neuroimaging phenotypes will reveal novel risk genes and variants. In this article, we briefly discuss the genetic and imaging investigations and take an in-depth look at the recent imaging-genetics investigations of dyslexia. PMID:23916419

  6. Applying personal genetic data to injury risk assessment in athletes.

    Directory of Open Access Journals (Sweden)

    Gabrielle T Goodlin

    Full Text Available Recent studies have identified genetic markers associated with risk for certain sports-related injuries and performance-related conditions, with the hope that these markers could be used by individual athletes to personalize their training and diet regimens. We found that we could greatly expand the knowledge base of sports genetic information by using published data originally found in health and disease studies. For example, the results from large genome-wide association studies for low bone mineral density in elderly women can be re-purposed for low bone mineral density in young endurance athletes. In total, we found 124 single-nucleotide polymorphisms associated with: anterior cruciate ligament tear, Achilles tendon injury, low bone mineral density and stress fracture, osteoarthritis, vitamin/mineral deficiencies, and sickle cell trait. Of these single nucleotide polymorphisms, 91% have not previously been used in sports genetics. We conducted a pilot program on fourteen triathletes using this expanded knowledge base of genetic variants associated with sports injury. These athletes were genotyped and educated about how their individual genetic make-up affected their personal risk profile during an hour-long personal consultation. Overall, participants were favorable of the program, found it informative, and most acted upon their genetic results. This pilot program shows that recent genetic research provides valuable information to help reduce sports injuries and to optimize nutrition. There are many genetic studies for health and disease that can be mined to provide useful information to athletes about their individual risk for relevant injuries.

  7. Insurance loss coverage under restricted risk classification

    OpenAIRE

    Hao, Mingjie; Radfall Charitable Trust

    2017-01-01

    Insurers hope to make profit through pooling policies from a large number of individuals. Unless the risk in question is similar for all potential customers, an insurer is exposed to the possibility of adverse selection by attracting only high-risk individuals. To counter this, insurers have traditionally employed underwriting principles, identifying suitable risk factors to subdivide their potential customers into homogeneous risk groups, based on which risk-related premiums can be charged. ...

  8. THERAPEUTIC IMPLICATIONS OF GENETIC RISK VARIANTS FOR CORONARY ARTERY DISEASE

    Directory of Open Access Journals (Sweden)

    Rajiv Kumar Srivastava

    2017-02-01

    Full Text Available BACKGROUND This review covers therapeutic implication of genetic risk variant responsible for coronary artery disease by utilising the highdensity single-nucleotide microarrays to screen the entire human genome. The sequence of the human genome provides the blueprint for life. Approximately, 99.5% of the human genome Deoxyribonucleic Acid (DNA sequence is identical among humans with 0.5% of the genome sequence (15 million bps accounting for all individual differences. MATERIALS AND METHODS The new technology of the computerised chip array of millions of Single-Nucleotide Polymorphisms (SNPs as Deoxyribonucleic Acid (DNA markers makes it possible to study and detect genetic predisposition to common polygenic disorders such as Coronary Artery Disease (CAD. The sample sizes required for these studies are massive and large; worldwide consortiums such as Coronary Artery Disease Genome-wide Replication and Meta-Analysis (CARDIoGRAM study have been formed to accommodate this requirement. After the identification of 9p21 progress to detect genetic predisposition has been remarkable. RESULTS There are currently a total of 50 genetic risk variants predisposing to CAD of genome-wide significance with confirmation in independent populations. Rare variants (Minor Allele Frequency, MAF <5% will require direct sequencing to detect genetic predisposition. CONCLUSION We can develop new biomarkers for detecting early CAD as well as unique targets for novel therapy. The challenge for the future will be to identify the molecular mechanisms mediating the risk of those genetic risk variants that act through nonconventional risk factors. The ultimate objective for the future is the sequencing and functional analysis of the causative polymorphisms for its therapeutic implications.

  9. Risks from mammography - Physical and genetics aspects

    International Nuclear Information System (INIS)

    Frankenberg, D.; Kuehn, H.; Frankenberg-Schwager, M.

    1996-01-01

    Prevention and early diagnosis are the most intelligent and powerful methods in the battle against cancer. Breast cancer is one of the most frequent cancers of women. Therefore, methods for early diagnosis were developed among which mammography using soft X-rays is most frequently applied. Experimental data about chromosomal aberrations and neoplastic cell transformation induced by soft and ultrasoft X-rays show that the quality factor Q of one currently used for soft X-rays of mammography is by far too low. About 5% of all women with breast cancer carry a familial predisposition (heterozygocity of the gene BRCA1 or BRCA2). In Germany about 2000-2500 women per year develop breast cancer because of this heterozygocity. Therfore, an urgent need exists to determine for these women the elevated radiation risk by mammography using soft X-rays. Based on the mutation frequency of the HPRT-gene by ionizing radiation the probability of homozygocity by knocking out the other allel of the BRCA1- or BRCA2-gene in one of the target cells of the breast was calculated. This probability is elevated by a factor of 10 7 compared with women carrying both allels of the BRCA1- and BRCA2-gene which have to be knocked out both to become homozygous. A similar elevated radiation risk of breast cancer for women heterozygous in the BRCA1- or BRCA2-gene was calculated by Chakraborty and Sankaranarayanan [11]. (orig.) [de

  10. Genetically Modified Crops: Risks and Promise

    Directory of Open Access Journals (Sweden)

    Gordon Conway

    2000-07-01

    Full Text Available GM foods have the potential to provide significant benefits for developing countries. Over 800 million people are chronically undernourished, and 180 million children are severely underweight for their age. By 2020, there will be an extra two billion mouths to feed. Ecological approaches that underpin sustainable agriculture (e.g., integrated pest management and participatory approaches that strengthen farmers' own experimentation and decision making are key. Biotechnology will be an essential partner, if yield ceilings are to be raised, if crops are to be grown without excessive reliance on pesticides, and if farmers on less favored lands are to be provided with crops that are resistant to drought and salinity, and that can use nitrogen and other nutrients more efficiently. Over the past 10 years, in addition supporting ecological approaches, the Rockefeller Foundation has funded the training of some 400 developing-country scientists in the techniques of biotechnology. Most of the new crop varieties are the result of tissue culture and marker-aided selection. The Foundation also supports the production of genetically engineered rices, including a new rice engineered for beta carotene (the precursor of Vitamin A in the grain. Some specific steps can be taken by Monsanto that would improve acceptance of plant biotechnology in both the developing and the industrialized worlds: label; disavow gene protection (terminator systems; phase out the use of antibiotic resistance markers; agree (with big seed companies to use the plant variety protection system, rather than patents, in developing countries; establish an independently administered fellowship program to train developing-country scientists in crop biotechnology, biosafety, and intellectual property; donate useful technologies to developing countries; agree to share financial rewards from intellectual property rights on varieties such as basmati or jasmine rice with the countries of origin; and

  11. Prediction of Adulthood Obesity Using Genetic and Childhood Clinical Risk Factors in the Cardiovascular Risk in Young Finns Study.

    Science.gov (United States)

    Seyednasrollah, Fatemeh; Mäkelä, Johanna; Pitkänen, Niina; Juonala, Markus; Hutri-Kähönen, Nina; Lehtimäki, Terho; Viikari, Jorma; Kelly, Tanika; Li, Changwei; Bazzano, Lydia; Elo, Laura L; Raitakari, Olli T

    2017-06-01

    Obesity is a known risk factor for cardiovascular disease. Early prediction of obesity is essential for prevention. The aim of this study is to assess the use of childhood clinical factors and the genetic risk factors in predicting adulthood obesity using machine learning methods. A total of 2262 participants from the Cardiovascular Risk in YFS (Young Finns Study) were followed up from childhood (age 3-18 years) to adulthood for 31 years. The data were divided into training (n=1625) and validation (n=637) set. The effect of known genetic risk factors (97 single-nucleotide polymorphisms) was investigated as a weighted genetic risk score of all 97 single-nucleotide polymorphisms (WGRS97) or a subset of 19 most significant single-nucleotide polymorphisms (WGRS19) using boosting machine learning technique. WGRS97 and WGRS19 were validated using external data (n=369) from BHS (Bogalusa Heart Study). WGRS19 improved the accuracy of predicting adulthood obesity in training (area under the curve [AUC=0.787 versus AUC=0.744, P obesity. Predictive accuracy is highest among young children (3-6 years), whereas among older children (9-18 years) the risk can be identified using childhood clinical factors. The model is helpful in screening children with high risk of developing obesity. © 2017 American Heart Association, Inc.

  12. Genetic risk factors for type 1 diabetes

    DEFF Research Database (Denmark)

    Pociot, Flemming; Lernmark, Åke

    2016-01-01

    Type 1 diabetes is diagnosed at the end of a prodrome of β-cell autoimmunity. The disease is most likely triggered at an early age by autoantibodies primarily directed against insulin or glutamic acid decarboxylase, or both, but rarely against islet antigen-2. After the initial appearance of one...... of the three stages can differ. Type 1 diabetes could serve as a disease model for organ-specific autoimmune disorders such as coeliac disease, thyroiditis, and Addison's disease, which show similar early markers of a prolonged disease process before clinical diagnosis....... of these autoantibody biomarkers, a second, third, or fourth autoantibody against either islet antigen-2 or the ZnT8 transporter might also appear. The larger the number of β-cell autoantibody types, the greater the risk of rapid progression to clinical onset of diabetes. This association does not necessarily mean...

  13. Retinal vein occlusion: genetic predisposition and systemic risk factors.

    Science.gov (United States)

    Giannaki, Kassiani; Politou, Marianna; Rouvas, Alexandros; Merkouri, Efrossyni; Travlou, Anthi; Theodosiadis, Panayiotis; Gialeraki, Argyri

    2013-04-01

    The role of systemic risk factors (age, smoking, diabetes, arterial hypertension) in the development of retinal vein occlusion (RVO) is well established. However, the association of RVO with genetic predisposition to thrombosis remains poorly understood. The aim of the study was to assess any possible additional effect of genetic predisposition to the already well known 'classical' risk factors of RVO in a cohort of elderly Greek patients. Fifty-one elderly patients with RVO and 51 healthy individuals matched for age and sex were evaluated for systemic risk factors (smoking, diabetes, dyslipidemia, arterial hypertension) and coagulation defects (lupus anticoagulant, natural inhibitors of coagulation). Additionally, genotyping was performed for mutations/polymorphisms involved in haemostasis such as: FV G1691A, FV G4070A, FIIG 20210A, MTHFR C677T and A1298C, PAI-1-675 4G/5G, F XIII exon 2G/T, EPCR A4600G and G4678C. We identified systemic risk factors in the majority of the patients Hypertension (P=0.001), dyslipidemia (P=0.029) and diabetes (P=0.01) are associated with RVO in the majority of the patients. The prevalence of prothrombotic risk factors was not significantly different in the patients with RVO compared to controls. Apart from systemic risk factors, genetic predisposition to thrombosis does not seem to have an important association with RVO in this group of elderly patients.

  14. Genetic, Maternal, and Environmental Risk Factors for Cryptorchidism

    DEFF Research Database (Denmark)

    Barthold, Julia Spencer; Reinhardt, Susanne; Thorup, Jorgen

    2016-01-01

    Unilateral or bilateral cryptorchidism is an isolated anomaly in the majority of cases, with evidence to date suggesting that it is a complex disorder resulting from interactions between genetic and environmental factors. Population, family, and limited genome-wide association data suggest moderate...... or gubernacular response to hormonal stimulation. However, we have yet to determine the degree to which EDCs contribute to cryptorchidism risk in humans, in part due to the varying methodology used in epidemiological and exposure studies. Large populations will be required to define the gene......-environment interactions that predispose to cryptorchidism, in view of multiple small effect genetic susceptibility loci, ubiquitous exposure to mixtures of EDCs, and possible epigenetic effects. The present review provides an update of potential genetic and environmental risk factors for cryptorchidism, and future work...

  15. Shared genetic risk factors of intracranial, abdominal, and thoracic aneurysms

    NARCIS (Netherlands)

    van 't Hof, Femke N G; Ruigrok, Ynte M; Lee, Cue Hyunkyu; Ripke, Stephan; Anderson, Graig; de Andrade, Mariza; Baas, Annette F; Blankensteijn, Jan D; Böttinger, Erwin P; Bown, Matthew J; Broderick, Joseph; Bijlenga, Philippe; Carrell, David S; Crawford, Dana C; Crosslin, David R; Ebeling, Christian; Eriksson, Johan G; Fornage, Myriam; Foroud, Tatiana; von Und Zu Fraunberg, Mikael; Friedrich, Christoph M; Gaál, Emília I; Gottesman, Omri; Guo, Dong-Chuan; Harrison, Seamus C; Hernesniemi, Juha; Hofman, Albert; Inoue, Ituro; Jääskeläinen, Juha E; Jones, Gregory T; Kiemeney, Lambertus A L M; Kivisaari, Riku; Ko, Nerissa; Koskinen, Seppo; Kubo, Michiaki; Kullo, Iftikhar J; Kuivaniemi, Helena; Kurki, Mitja I; Laakso, Aki; Lai, Dongbing; Leal, Suzanne M; Lehto, Hanna; LeMaire, Scott A; Low, Siew-Kee; Malinowski, Jennifer; McCarty, Catherine A; Milewicz, Dianna M; Mosley, Thomas H; Nakamura, Yusuke; Nakaoka, Hirofumi; Niemelä, Mika; Pacheco, Jennifer; Peissig, Peggy L; Pera, Joanna; Rasmussen-Torvik, Laura; Ritchie, Marylyn D; Rivadeneira, Fernando; van Rij, Andre M; Santos-Cortez, Regie Lyn P; Saratzis, Athanasios; Slowik, Agnieszka; Takahashi, Atsushi; Tromp, Gerard; Uitterlinden, André G; Verma, Shefali S; Vermeulen, Sita H; Wang, Gao T; Han, Buhm; Rinkel, Gabriël J E; de Bakker, Paul I W

    2016-01-01

    Background--Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and

  16. Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

    NARCIS (Netherlands)

    van 't Hof, Femke N G; Ruigrok, Ynte M; Lee, Cue Hyunkyu; Ripke, Stephan; Anderson, Graig; de Andrade, Mariza; Baas, Annette F; Blankensteijn, Jan D; Böttinger, Erwin P; Bown, Matthew J; Broderick, Joseph; Bijlenga, Philippe; Carrell, David S; Crawford, Dana C; Crosslin, David R; Ebeling, Christian; Eriksson, Johan G; Fornage, Myriam; Foroud, Tatiana; von Und Zu Fraunberg, Mikael; Friedrich, Christoph M; Gaál, Emília I; Gottesman, Omri; Guo, Dong-Chuan; Harrison, Seamus C; Hernesniemi, Juha; Hofman, Albert; Inoue, Ituro; Jääskeläinen, Juha E; Jones, Gregory T; Kiemeney, Lambertus A L M; Kivisaari, Riku; Ko, Nerissa; Koskinen, Seppo; Kubo, Michiaki; Kullo, Iftikhar J; Kuivaniemi, Helena; Kurki, Mitja I; Laakso, Aki; Lai, Dongbing; Leal, Suzanne M; Lehto, Hanna; LeMaire, Scott A; Low, Siew-Kee; Malinowski, Jennifer; McCarty, Catherine A; Milewicz, Dianna M; Mosley, Thomas H; Nakamura, Yusuke; Nakaoka, Hirofumi; Niemelä, Mika; Pacheco, Jennifer; Peissig, Peggy L; Pera, Joanna; Rasmussen-Torvik, Laura; Ritchie, Marylyn D; Rivadeneira, Fernando; van Rij, Andre M; Santos-Cortez, Regie Lyn P; Saratzis, Athanasios; Slowik, Agnieszka; Takahashi, Atsushi; Tromp, Gerard; Uitterlinden, André G; Verma, Shefali S; Vermeulen, Sita H; Wang, Gao T; Han, Buhm; Rinkel, Gabriël J E; de Bakker, Paul I W

    2016-01-01

    BACKGROUND: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. METHODS AND

  17. Associations between genetic risk, functional brain network organization and neuroticism

    NARCIS (Netherlands)

    Servaas, Michelle N.; Geerligs, Linda; Bastiaansen, Jojanneke A.; Renken, Remco J.; Marsman, Jan-Bernard C.; Nolte, Ilja M.; Ormel, Johan; Aleman, Andre; Riese, Harriette

    2017-01-01

    Neuroticism and genetic variation in the serotonin-transporter (SLC6A4) and catechol-O-methyltransferase (COMT) gene are risk factors for psychopathology. Alterations in the functional integration and segregation of neural circuits have recently been found in individuals scoring higher on

  18. Chronic disease risk management: Combining genetic testing with ...

    African Journals Online (AJOL)

    Nutrigenetics has been used for decades to prevent rare monogenic disorders such as phenylketonuria. Gene-diet interaction can now also be targeted to prevent or reduce the risk of many chronic conditions long before clinical manifestation. This multidisciplinary approach unites conventional medicine with genetics and ...

  19. Genetically Manipulated Foods: Is the Human Health Risk, Real or

    African Journals Online (AJOL)

    Genetically Manipulated Foods: Is the Human Health Risk, Real or. Imaginary? Wilfred MBACHAM, ScD ... From when Thomas Malthus 'vropounded his theory of world population growth outpacing food production, rich and poor world populations have .... are rarely broken down fast, there is the possibil- ity that antibiotic ...

  20. Risk assessment of genetically modified organisms (GMOs) | Amin ...

    African Journals Online (AJOL)

    Risk assessment is a procedure normally carried out prior to decision-making on the release of genetically modified organisms (GMOs) into the environment. ... biosafety laws of more developed countries and to ensure adequate level of protection for the Malaysian people against any adverse effects of GMOs and products.

  1. Genetic Variants Influencing Lipid Levels and Risk of Dyslipidemia ...

    Indian Academy of Sciences (India)

    Navya

    2017-03-24

    Mar 24, 2017 ... Provincial People's Hospital,32 The First Ring Road West ,Chengdu, Sichuan. 610072,china;;Email:liny042000@aliyun.com. All other author' contacted ..... identified loci that influence lipid concentrations and risk of coronary artery disease. Nat. Genet. 40,161-169. Yan T. T., Yin R. X., Li Q., Huang P., Zeng ...

  2. Prediction of Adult Dyslipidemia Using Genetic and Childhood Clinical Risk Factors: The Cardiovascular Risk in Young Finns Study.

    Science.gov (United States)

    Nuotio, Joel; Pitkänen, Niina; Magnussen, Costan G; Buscot, Marie-Jeanne; Venäläinen, Mikko S; Elo, Laura L; Jokinen, Eero; Laitinen, Tomi; Taittonen, Leena; Hutri-Kähönen, Nina; Lyytikäinen, Leo-Pekka; Lehtimäki, Terho; Viikari, Jorma S; Juonala, Markus; Raitakari, Olli T

    2017-06-01

    Dyslipidemia is a major modifiable risk factor for cardiovascular disease. We examined whether the addition of novel single-nucleotide polymorphisms for blood lipid levels enhances the prediction of adult dyslipidemia in comparison to childhood lipid measures. Two thousand four hundred and twenty-two participants of the Cardiovascular Risk in Young Finns Study who had participated in 2 surveys held during childhood (in 1980 when aged 3-18 years and in 1986) and at least once in a follow-up study in adulthood (2001, 2007, and 2011) were included. We examined whether inclusion of a lipid-specific weighted genetic risk score based on 58 single-nucleotide polymorphisms for low-density lipoprotein cholesterol, 71 single-nucleotide polymorphisms for high-density lipoprotein cholesterol, and 40 single-nucleotide polymorphisms for triglycerides improved the prediction of adult dyslipidemia compared with clinical childhood risk factors. Adjusting for age, sex, body mass index, physical activity, and smoking in childhood, childhood lipid levels, and weighted genetic risk scores were associated with an increased risk of adult dyslipidemia for all lipids. Risk assessment based on 2 childhood lipid measures and the lipid-specific weighted genetic risk scores improved the accuracy of predicting adult dyslipidemia compared with the approach using only childhood lipid measures for low-density lipoprotein cholesterol (area under the receiver-operating characteristic curve 0.806 versus 0.811; P =0.01) and triglycerides (area under the receiver-operating characteristic curve 0.740 versus area under the receiver-operating characteristic curve 0.758; P dyslipidemia in adulthood. © 2017 American Heart Association, Inc.

  3. An animal model of differential genetic risk for methamphetamine intake

    Directory of Open Access Journals (Sweden)

    Tamara ePhillips

    2015-09-01

    Full Text Available The question of whether genetic factors contribute to risk for methamphetamine (MA use and dependence has not been intensively investigated. Compared to human populations, genetic animal models offer the advantages of control over genetic family history and drug exposure. Using selective breeding, we created lines of mice that differ in genetic risk for voluntary MA intake and identified the chromosomal addresses of contributory genes. A quantitative trait locus was identified on chromosome 10 that accounts for more than 50% of the genetic variance in MA intake in the selected mouse lines. In addition, behavioral and physiological screening identified differences corresponding with risk for MA intake that have generated hypotheses that are testable in humans. Heightened sensitivity to aversive and certain physiological effects of MA, such as MA-induced reduction in body temperature, are hallmarks of mice bred for low MA intake. Furthermore, unlike MA-avoiding mice, MA-preferring mice are sensitive to rewarding and reinforcing MA effects, and to MA-induced increases in brain extracellular dopamine levels. Gene expression analyses implicate the importance of a network enriched in transcription factor genes, some of which regulate the mu opioid receptor gene, Oprm1, in risk for MA use. Neuroimmune factors appear to play a role in differential response to MA between the mice bred for high and low intake. In addition, chromosome 10 candidate gene studies provide strong support for a trace amine associated receptor 1 gene, Taar1, polymorphism in risk for MA intake. MA is a trace amine-associated receptor 1 (TAAR1 agonist, and a non-functional Taar1 allele segregates with high MA consumption. Thus, reduced TAAR1 function has the potential to increase risk for MA use. Overall, existing findings support the MA drinking lines as a powerful model for identifying genetic factors involved in determining risk for harmful MA use. Future directions include the

  4. [Chronic lymphocytic leukemia. Treatment and genetic risk profile].

    Science.gov (United States)

    Stilgenbauer, S; Hallek, M

    2013-02-01

    Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. Among the biological features underlying this heterogeneity, genetic lesions and the mutational status of the immunoglobulin heavy chain variable genes (IGHV) are of importance. Therapeutic options in CLL have been considerably expanded during recent years. The combination of fludarabine, cyclophosphamide and rituximab (FCR) has become gold standard in the first-line treatment of physically fit patients. Bendamustine plus rituximab (BR) is currently being compared to FCR in studies and chlorambucil is still of relevance for elderly patients with comorbidities. Alemtuzumab is an alternative for high-risk patients (refractory CLL, 17p deletion, TP53 mutation). Allogeneic stem cell transplantation (allo-SCT) offers the only chance of cure but not without substantial mortality. Innovative approaches focus on individualized, targeted therapies. A number of novel agents are in clinical trials and show marked efficacy combined with good tolerability. This review provides an overview of the current therapeutic options and of promising novel approaches.

  5. Occupational and genetic risk factors associated with intervertebral disc disease.

    Science.gov (United States)

    Virtanen, Iita M; Karppinen, Jaro; Taimela, Simo; Ott, Jürg; Barral, Sandra; Kaikkonen, Kaisu; Heikkilä, Olli; Mutanen, Pertti; Noponen, Noora; Männikkö, Minna; Tervonen, Osmo; Natri, Antero; Ala-Kokko, Leena

    2007-05-01

    Cross-sectional epidemiologic study. To evaluate the interaction between known genetic risk factors and whole-body vibration for symptomatic intervertebral disc disease (IDD) in an occupational sample. Risk factors of IDD include, among others, whole-body vibration and heredity. In this study, the importance of a set of known genetic risk factors and whole-body vibration was evaluated in an occupational sample of train engineers and sedentary controls. Eleven variations in 8 genes (COL9A2, COL9A3, COL11A2, IL1A, IL1B, IL6, MMP-3, and VDR) were genotyped in 150 male train engineers with an average of 21-year exposure to whole-body vibration and 61 male paper mill workers with no exposure to vibration. Subjects were classified into IDD-phenotype and asymptomatic groups, based on the latent class analysis. The number of individuals belonging to the IDD-phenotype was significantly higher among train engineers (42% of train engineers vs. 17.5% of sedentary workers; P = 0.005). IL1A -889T allele represented a significant risk factor for the IDD-phenotype both in the single marker allelic association test (P = 0.043) and in the logistic regression analysis (P = 0.01). None of the other allele markers was significantly associated with symptoms when analyzed independently. However, for all the SNP markers considered, whole-body vibration represents a nominally significant risk factor. The results suggest that whole-body vibration is a risk factor for symptomatic IDD. Moreover, whole-body vibration had an additive effect with genetic risk factors increasing the likelihood of belonging to the IDD-phenotype group. Of the independent genetic markers, IL1A -889T allele had strongest association with IDD-phenotype.

  6. Genetic Predisposition to Dyslipidemia and Risk of Preeclampsia.

    Science.gov (United States)

    Spracklen, Cassandra N; Saftlas, Audrey F; Triche, Elizabeth W; Bjonnes, Andrew; Keating, Brendan; Saxena, Richa; Breheny, Patrick J; Dewan, Andrew T; Robinson, Jennifer G; Hoh, Josephine; Ryckman, Kelli K

    2015-07-01

    Large epidemiologic studies support the role of dyslipidemia in preeclampsia; however, the etiology of preeclampsia or whether dyslipidemia plays a causal role remains unclear. We examined the association between the genetic predisposition to dyslipidemia and risk of preeclampsia using validated genetic markers of dyslipidemia. Preeclampsia cases (n = 164) and normotensive controls (n = 110) were selected from live birth certificates to nulliparous Iowa women during the period August 2002 to May 2005. Disease status was verified by medical chart review. Genetic predisposition to dyslipidemia was estimated by 4 genetic risk scores (GRS) (total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides) on the basis of established loci for blood lipids. Logistic regression analyses were used to evaluate the relationships between each of the 4 genotype scores and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry. The GRS related to higher levels of TC, LDL-C, and triglycerides demonstrated no association with the risk of preeclampsia in either the Iowa or replication population. The GRS related to lower HDL-C was marginally associated with an increased risk for preeclampsia (odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.99-1.07; P = 0.10). In the independent replication population, the association with the HDL-C GRS was also marginally significant (OR = 1.03, 95% CI: 1.00-1.06; P = 0.04). Our data suggest a potential effect between the genetic predisposition to dyslipidemic levels of HDL-C and an increased risk of preeclampsia, and, as such, suggest that dyslipidemia may be a component along the causal pathway to preeclampsia. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Multiple sclerosis in families: risk factors beyond known genetic polymorphisms.

    Science.gov (United States)

    Akkad, Denis A; Lee, De-Hyung; Bruch, Kathrin; Haghikia, Aiden; Epplen, Jörg T; Hoffjan, Sabine; Linker, Ralf A

    2016-04-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that predominantly affects young adults. The genetic contributions to this multifactorial disease were underscored by genome wide association studies and independent replication studies. A weighted genetic risk score (wGRS) was recently established using the identified MS risk loci in order to predict MS outcome including clinical and paraclinical features. Here, we present the results on a family with several affected siblings including a monozygotic triplet. The individuals were genotyped for 57 non-MHC risk loci as well as the HLA DRB1*1501 tagging SNP rs3135388 with subsequent calculation of the wGRS. Additionally, SNP array based analyses for aberrant chromosomal regions were performed for all individuals.

  8. A genome-wide association study demonstrates significant genetic variation for fracture risk in Thoroughbred racehorses

    Science.gov (United States)

    2014-01-01

    Background Thoroughbred racehorses are subject to non-traumatic distal limb bone fractures that occur during racing and exercise. Susceptibility to fracture may be due to underlying disturbances in bone metabolism which have a genetic cause. Fracture risk has been shown to be heritable in several species but this study is the first genetic analysis of fracture risk in the horse. Results Fracture cases (n = 269) were horses that sustained catastrophic distal limb fractures while racing on UK racecourses, necessitating euthanasia. Control horses (n = 253) were over 4 years of age, were racing during the same time period as the cases, and had no history of fracture at the time the study was carried out. The horses sampled were bred for both flat and National Hunt (NH) jump racing. 43,417 SNPs were employed to perform a genome-wide association analysis and to estimate the proportion of genetic variance attributable to the SNPs on each chromosome using restricted maximum likelihood (REML). Significant genetic variation associated with fracture risk was found on chromosomes 9, 18, 22 and 31. Three SNPs on chromosome 18 (62.05 Mb – 62.15 Mb) and one SNP on chromosome 1 (14.17 Mb) reached genome-wide significance (p fracture than cases, p = 1 × 10-4), while a second haplotype increases fracture risk (cases at 3.39 times higher risk of fracture than controls, p = 0.042). Conclusions Fracture risk in the Thoroughbred horse is a complex condition with an underlying genetic basis. Multiple genomic regions contribute to susceptibility to fracture risk. This suggests there is the potential to develop SNP-based estimators for genetic risk of fracture in the Thoroughbred racehorse, using methods pioneered in livestock genetics such as genomic selection. This information would be useful to racehorse breeders and owners, enabling them to reduce the risk of injury in their horses. PMID:24559379

  9. Accuracy of predicting the genetic risk of disease using a genome-wide approach.

    Directory of Open Access Journals (Sweden)

    Hans D Daetwyler

    Full Text Available The prediction of the genetic disease risk of an individual is a powerful public health tool. While predicting risk has been successful in diseases which follow simple Mendelian inheritance, it has proven challenging in complex diseases for which a large number of loci contribute to the genetic variance. The large numbers of single nucleotide polymorphisms now available provide new opportunities for predicting genetic risk of complex diseases with high accuracy.We have derived simple deterministic formulae to predict the accuracy of predicted genetic risk from population or case control studies using a genome-wide approach and assuming a dichotomous disease phenotype with an underlying continuous liability. We show that the prediction equations are special cases of the more general problem of predicting the accuracy of estimates of genetic values of a continuous phenotype. Our predictive equations are responsive to all parameters that affect accuracy and they are independent of allele frequency and effect distributions. Deterministic prediction errors when tested by simulation were generally small. The common link among the expressions for accuracy is that they are best summarized as the product of the ratio of number of phenotypic records per number of risk loci and the observed heritability.This study advances the understanding of the relative power of case control and population studies of disease. The predictions represent an upper bound of accuracy which may be achievable with improved effect estimation methods. The formulae derived will help researchers determine an appropriate sample size to attain a certain accuracy when predicting genetic risk.

  10. Population-based, risk-stratified genetic testing for ovarian cancer risk: a focus group study.

    Science.gov (United States)

    Meisel, S F; Side, L; Fraser, L; Gessler, S; Wardle, J; Lanceley, A

    2013-01-01

    A population-based risk stratification programme for ovarian cancer (OC) may improve OC survival by identifying women at increased risk and implementing an appropriate risk management strategy. The present study explored attitudes towards an OC risk stratification programme incorporating predictive genetic testing and risk-stratified screening as part of a larger study investigating OC screening. Focus groups consisting of 56 members of the general public (mean age 45 years; 34% non-white) were conducted using a hypothetical scenario. The group sessions were recorded, transcribed verbatim and analysed using Framework Analysis. There was strong support for the proposed programme. Genetic testing and risk-stratified screening was thought to raise awareness, offer reassurance and offer opportunities for early intervention. Anxiety was only mentioned in relation to receiving a diagnosis of OC and not with screening per se. Perhaps because lay models of cancer already embrace both environmental and genetic factors, a low-risk result was not anticipated to result in a false sense of immunity. Unexpectedly, participants also wanted to receive cancer prevention advice in conjunction with genetic testing; screening alone was not regarded as sufficient. The encouraging results from this small study warrant further large-scale research into risk-stratified OC screening. Copyright © 2013 S. Karger AG, Basel.

  11. Genetic Predisposition, Nongenetic Risk Factors, and Coronary Infarct

    Science.gov (United States)

    Trichopoulou, Antonia; Yiannakouris, Nikos; Bamia, Christina; Benetou, Vassiliki; Trichopoulos, Dimitrios; Ordovas, Jose M.

    2015-01-01

    Background Using a genetic predisposition score (GPS), additively integrating the associations of 11 polymorphisms with coronary heart disease (CHD), we examined the consequences of the joint presence of a high GPS and nongenetic CHD risk factors. Methods Within the European Prospective Investigation Into Cancer and Nutrition, 202 case patients with medically confirmed incident coronary infarct and 197 control subjects were identified in Greece. Each polymorphism contributed 1 unit (high-risk homozygous), one-half unit (heterozygous), or no units (low-risk homozygous) to the GPS. Odds ratios of coronary infarction for those at high risk because of genetic predisposition and simultaneous presence of an established CHD risk factor were estimated, compared with subjects at low risk, for both GPS and each CHD risk factor. Results The joint presence of a high GPS (≥3.5) and each studied CHD risk factor was in all instances associated with a significantly increased risk of coronary infarction. The odds ratio (95% confidence interval) was 2.62 (1.14–6.02) for ever smoking, 2.88 (1.33–6.24) for hypertension, 3.50 (1.67–7.33) for low high-density lipoprotein (HDL) level, 3.05 (1.53–6.08) for high non-HDL level, and 3.66 (1.75–7.65) for poor adherence to the Mediterranean diet. The odds ratios were always lower and nonsignificant when the GPS was low. There was suggestive evidence for interaction of a high GPS with hypertension (P =.05) and non-HDL cholesterol level (P =.13). Conclusions Genetic predisposition may interact with hypertension and, perhaps, also with the level of non-HDL cholesterol, in the causation of CHD. Genetic predisposition and the other studied exposures seem to have converging effects. Thus, the GPS may identify individuals who could realize disproportional benefits by controlling their hypertension and, possibly, their non-HDL cholesterol level. PMID:18443266

  12. Exchange rate policy under sovereign default risk

    OpenAIRE

    Schabert, Andreas

    2011-01-01

    We examine monetary policy options for a small open economy where sovereign default might occur due to intertemporal insolvency. Under interest rate policy and floating exchange rates the equilibrium is indetermined. Under a fixed exchange rate the equilibrium is uniquely determined and independent of sovereign default.

  13. An overall genetic risk assessment for radiological protection purposes

    International Nuclear Information System (INIS)

    Oftedal, P.; Searle, A.G.

    1980-01-01

    Risks of serious hereditary damage in the first and second generations after low level radiation exposure and at equilibrium were calculated by using a doubling dose of 100 rem (based on experimental work with the mouse) and by considering separately the various categories of genic and chromosomal defect. Prenatal lethality was not included. It is estimated that after the exposure of a population of future parents to a collective dose of 1 million man-rem, about 125 extra cases of serious genetic ill health would appear in children and grandchildren. In all future generations, a total of about 320 cases is expected, provided the population remains of constant size. It is emphasised however, that a number of major assumptions have to be made in order to arrive at any overall genetic risk estimate, so that the confidence limits of these figures are bound to be wide. (author)

  14. PCSK9 genetic variants and risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Schmidt, Amand F; Swerdlow, Daniel I; Holmes, Michael V

    2017-01-01

    diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. METHODS: In this mendelian randomisation study, we...... used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using...... a standardised analysis plan, meta-analyses, and weighted gene-centric scores. FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL...

  15. Population-standardized genetic risk score: the SNP-based method of choice for inherited risk assessment of prostate cancer

    Directory of Open Access Journals (Sweden)

    Carly A Conran

    2016-01-01

    Full Text Available Several different approaches are available to clinicians for determining prostate cancer (PCa risk. The clinical validity of various PCa risk assessment methods utilizing single nucleotide polymorphisms (SNPs has been established; however, these SNP-based methods have not been compared. The objective of this study was to compare the three most commonly used SNP-based methods for PCa risk assessment. Participants were men (n = 1654 enrolled in a prospective study of PCa development. Genotypes of 59 PCa risk-associated SNPs were available in this cohort. Three methods of calculating SNP-based genetic risk scores (GRSs were used for the evaluation of individual disease risk such as risk allele count (GRS-RAC, weighted risk allele count (GRS-wRAC, and population-standardized genetic risk score (GRS-PS. Mean GRSs were calculated, and performances were compared using area under the receiver operating characteristic curve (AUC and positive predictive value (PPV. All SNP-based methods were found to be independently associated with PCa (all P 0.05 for comparisons between the three methods, and all three SNP-based methods had a significantly higher AUC than family history (all P < 0.05. Results from this study suggest that while the three most commonly used SNP-based methods performed similarly in discriminating PCa from non-PCa at the population level, GRS-PS is the method of choice for risk assessment at the individual level because its value (where 1.0 represents average population risk can be easily interpreted regardless of the number of risk-associated SNPs used in the calculation.

  16. Skin barrier and contact allergy: Genetic risk factor analyses

    DEFF Research Database (Denmark)

    Ross-Hansen, Katrine

    2013-01-01

    Background Contact allergy is frequent in the general population and arises from prolonged or repeated skin contact with chemical substances. The environmental risk factor is obvious, yet some studies report on associations between genetic variance and an increased risk of developing contact...... by extracting epidermal proteins from human surgical waste samples and stratum corneum scrapings followed by binding studies using immobilized metal affinity chromatography. Results As suggested by Kaplan-Meier event history analyses, FLG null mutations lowered the age of onset of nickel dermatitis, when ear...

  17. Summary of the BEIR V committee's estimates of genetic risks

    International Nuclear Information System (INIS)

    Grahn, D.

    1990-01-01

    The Committee on the Biological Effects of Ionizing Radiations (BEIR V) was constituted in late 1986 to conduct a comprehensive review of the biological effects of ionizing radiations focusing on information reported since the conclusion of the 1980 BEIR study, and to provide new estimates of the risks of genetic and somatic effects in humans due to low-level exposures of ionizing radiation. The Committee preferred the doubling-dose method of genetic risk estimation over the direct method. Data from animal (mouse) studies provide a median value of 100 to 114 cGy for long-term low dose rate exposure doubling doses. These values are lower than the median from human studies. The BEIR Committee believed that a doubling dose of 100 cGy would be a prudent value leading to conservative estimates. The estimated risks themselves are not much different from those generated by previous BEIR committees, UNSCEAR, and other published estimates. The Committee estimates that between 100 and 200 added cases per million live births will be observed at genetic equilibrium if the population is exposed each generation to a dose of 0.01 Sv (1 rem). Nearly half ware attributed to clinically mild dominant defects, and the balance to congenital abnormalities. (L.L.) (2 tabs.)

  18. A Realistic Model Under Which the Genetic Code is Optimal

    NARCIS (Netherlands)

    Buhrman, Harry; van der Gulik, Peter T. S.; Klau, Gunnar W.; Schaffner, Christian; Speijer, Dave; Stougie, Leen

    2013-01-01

    The genetic code has a high level of error robustness. Using values of hydrophobicity scales as a proxy for amino acid character, and the mean square measure as a function quantifying error robustness, a value can be obtained for a genetic code which reflects the error robustness of that code. By

  19. Coeliac disease : investigation of the genetic factors underlying coeliac disease

    NARCIS (Netherlands)

    Belzen, M.J. (Martine Juliana) van

    2003-01-01

    Coeliac disease is a common food intolerance with a complex genetic aetiology. It is caused by ingestion of gluten peptides from wheat and related proteins from barley and rye in genetically susceptible individuals. The disease affects the small intestine and leads to abnormalities ranging from the

  20. Genetic Circuit Performance under Conditions Relevant for Industrial Bioreactors

    NARCIS (Netherlands)

    Moser, Felix; Broers, Nicolette J.; Hartmans, Sybe; Tamsir, Alvin; Kerkman, Richard; Roubos, Johannes A.; Bovenberg, Roel; Voigt, Christopher A.

    2012-01-01

    Synthetic genetic programs promise to enable novel applications in industrial processes. For such applications, the genetic circuits that compose programs will require fidelity in varying and complex environments. In this work, we report the performance of two synthetic circuits in Escherichia coli

  1. Worms under stress: unravelling genetic complex traits through perturbation

    NARCIS (Netherlands)

    Rodriguez Sanchez, M.

    2014-01-01

    The genetic architecture of an organism could be considered ‘the most amazing piece of engineering’ existing in nature. Looking from a certain distance, the genetic complexity of an organism could be described as an immense jigsaw puzzle. As in a real jigsaw, the connection between two pieces

  2. A Realistic Model under which the Genetic Code is Optimal

    NARCIS (Netherlands)

    Buhrman, H.; van der Gulik, P.T.S.; Klau, G.W.; Schaffner, C.; Speijer, D.; Stougie, L.

    2013-01-01

    The genetic code has a high level of error robustness. Using values of hydrophobicity scales as a proxy for amino acid character, and the mean square measure as a function quantifying error robustness, a value can be obtained for a genetic code which reflects the error robustness of that code. By

  3. Urban flood risk warning under rapid urbanization.

    Science.gov (United States)

    Chen, Yangbo; Zhou, Haolan; Zhang, Hui; Du, Guoming; Zhou, Jinhui

    2015-05-01

    In the past decades, China has observed rapid urbanization, the nation's urban population reached 50% in 2000, and is still in steady increase. Rapid urbanization in China has an adverse impact on urban hydrological processes, particularly in increasing the urban flood risks and causing serious urban flooding losses. Urban flooding also increases health risks such as causing epidemic disease break out, polluting drinking water and damaging the living environment. In the highly urbanized area, non-engineering measurement is the main way for managing urban flood risk, such as flood risk warning. There is no mature method and pilot study for urban flood risk warning, the purpose of this study is to propose the urban flood risk warning method for the rapidly urbanized Chinese cities. This paper first presented an urban flood forecasting model, which produces urban flood inundation index for urban flood risk warning. The model has 5 modules. The drainage system and grid dividing module divides the whole city terrain into drainage systems according to its first-order river system, and delineates the drainage system into grids based on the spatial structure with irregular gridding technique; the precipitation assimilation module assimilates precipitation for every grids which is used as the model input, which could either be the radar based precipitation estimation or interpolated one from rain gauges; runoff production module classifies the surface into pervious and impervious surface, and employs different methods to calculate the runoff respectively; surface runoff routing module routes the surface runoff and determines the inundation index. The routing on surface grid is calculated according to the two dimensional shallow water unsteady flow algorithm, the routing on land channel and special channel is calculated according to the one dimensional unsteady flow algorithm. This paper then proposed the urban flood risk warning method that is called DPSIR model based

  4. Optimal dividends and ALM under unhedgeable risk

    NARCIS (Netherlands)

    Pelsser, A.A.J.; Laeven, R.J.A.

    2013-01-01

    In this paper we develop a framework for optimal investment decisions for insurance companies in the presence of (partially) unhedgeable risk. The perspective that we choose is from an insurance company that maximises the stream of dividends paid to its shareholders. The policy instruments that the

  5. Genetic Predisposition, Clinical Risk Factor Burden, and Lifetime Risk of Atrial Fibrillation.

    Science.gov (United States)

    Weng, Lu-Chen; Preis, Sarah R; Hulme, Olivia L; Larson, Martin G; Choi, Seung Hoan; Wang, Biqi; Trinquart, Ludovic; McManus, David D; Staerk, Laila; Lin, Honghuang; Lunetta, Kathryn L; Ellinor, Patrick T; Benjamin, Emelia J; Lubitz, Steven A

    2018-03-06

    The long-term probability of developing atrial fibrillation (AF) considering genetic predisposition and clinical risk factor burden is unknown. We estimated the lifetime risk of AF in individuals from the community-based Framingham Heart Study. Polygenic risk for AF was derived using a score of ≈1000 AF-associated single-nucleotide polymorphisms. Clinical risk factor burden was calculated for each individual using a validated risk score for incident AF comprised of height, weight, systolic and diastolic blood pressure, current smoking status, antihypertensive medication use, diabetes mellitus, history of myocardial infarction, and history of heart failure. We estimated the lifetime risk of AF within tertiles of polygenic and clinical risk. Among 4606 participants without AF at 55 years of age, 580 developed incident AF (median follow-up, 9.4 years; 25th-75th percentile, 4.4-14.3 years). The lifetime risk of AF >55 years of age was 37.1% and was substantially influenced by both polygenic and clinical risk factor burden. Among individuals free of AF at 55 years of age, those in low-polygenic and clinical risk tertiles had a lifetime risk of AF of 22.3% (95% confidence interval, 15.4-9.1), whereas those in high-risk tertiles had a risk of 48.2% (95% confidence interval, 41.3-55.1). A lower clinical risk factor burden was associated with later AF onset after adjusting for genetic predisposition ( P <0.001). In our community-based cohort, the lifetime risk of AF was 37%. Estimation of polygenic AF risk is feasible and together with clinical risk factor burden explains a substantial gradient in long-term AF risk. © 2018 American Heart Association, Inc.

  6. Essential elements of genetic cancer risk assessment, counseling, and testing: updated recommendations of the National Society of Genetic Counselors.

    Science.gov (United States)

    Riley, Bronson D; Culver, Julie O; Skrzynia, Cécile; Senter, Leigha A; Peters, June A; Costalas, Josephine W; Callif-Daley, Faith; Grumet, Sherry C; Hunt, Katherine S; Nagy, Rebecca S; McKinnon, Wendy C; Petrucelli, Nancie M; Bennett, Robin L; Trepanier, Angela M

    2012-04-01

    Updated from their original publication in 2004, these cancer genetic counseling recommendations describe the medical, psychosocial, and ethical ramifications of counseling at-risk individuals through genetic cancer risk assessment with or without genetic testing. They were developed by members of the Practice Issues Subcommittee of the National Society of Genetic Counselors Familial Cancer Risk Counseling Special Interest Group. The information contained in this document is derived from extensive review of the current literature on cancer genetic risk assessment and counseling as well as the personal expertise of genetic counselors specializing in cancer genetics. The recommendations are intended to provide information about the process of genetic counseling and risk assessment for hereditary cancer disorders rather than specific information about individual syndromes. Essential components include the intake, cancer risk assessment, genetic testing for an inherited cancer syndrome, informed consent, disclosure of genetic test results, and psychosocial assessment. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. These recommendations do not displace a health care provider's professional judgment based on the clinical circumstances of a client.

  7. Currency Risk Management under Floating Rates

    Directory of Open Access Journals (Sweden)

    Nicu Duret

    2016-09-01

    Full Text Available As for the research into this subject, we find, therefore, that one of the most important indicators that quantify the international competitiveness is the exchange rate, together with other fundamental macroeconomic variables such as the size of the potential GDP, the equilibrium real exchange rate, gives a certain insight into the functioning of the fundamental macroeconomic mechanisms and their regulation. Commercial and financial operations imply relationships between partners from different currency countries or areas that involve conversion operations, of replacement of a currency to another. Exchange rate fluctuations of one currency create currency risk, to the extent that it is used to carry out international transactions. These operations are subjected to currency risk as exchange rates change frequently from one period to another and, on the other hand, speculations in the forex market influence the exchange rate by the interventions of those who perform them.

  8. Cerivastatin, Genetic Variants, and the Risk of Rhabdomyolysis

    Science.gov (United States)

    Marciante, Kristin D.; Durda, Jon P.; Heckbert, Susan R.; Lumley, Thomas; Rice, Ken; McKnight, Barbara; Totah, Rheem A.; Tamraz, Bani; Kroetz, Deanna L.; Fukushima, Hisayo; Kaspera, Rüdiger; Bis, Joshua C.; Glazer, Nicole L.; Li, Guo; Austin, Thomas R.; Taylor, Kent D.; Rotter, Jerome I.; Jaquish, Cashell E.; Kwok, Pui-Yan; Tracy, Russell P.; Psaty, Bruce M.

    2011-01-01

    Objective The withdrawal of cerivastatin involved an uncommon but serious adverse reaction, rhabdomyolysis. The bimodal response--rhabdomyolysis in a small proportion of users-- points to genetic factors as a potential cause. We conducted a case-control study to evaluate genetic markers for cerivastatin-associated rhabdomyolysis. Methods The study had two components: a candidate gene study to evaluate variants in CYP2C8, UGT1A1, UGT1A3, and SLCO1B1; and a genome-wide association (GWA) study to identify risk factors in other regions of the genome. 185 rhabdomyolysis cases were frequency matched to statin-using controls from the Cardiovascular Health Study (n=374) and the Heart and Vascular Health Study (n=358). Validation relied on functional studies. Results Permutation test results suggested an association between cerivastatin-associated rhabdomyolysis and variants in SLCO1B1 (p = 0.002), but not variants in CYP2C8 (p = 0.073) or the UGTs (p = 0.523). An additional copy of the minor allele of SLCO1B1 rs4149056 (p.Val174Ala) was associated with the risk of rhabdomyolysis (OR: 1.89, 95% CI: 1.40 to 2.56). In transfected cells, this variant reduced cerivastatin transport by 40% compared with the reference transporter (p rhabdomyolysis (OR: 0.48; 95% CI: 0.36 to 0.63). Conclusion We identified modest genetic risk factors for an extreme response to cerivastatin. Disabling genetic variants in the candidate genes were not responsible for the bimodal response to cerivastatin. PMID:21386754

  9. Stochastic optimization under risk constraint and utility functions

    International Nuclear Information System (INIS)

    Seck, B.

    2008-09-01

    In a context of concurrence and emergence of energy markets, the production of electricity is affected by the new sources of risks which are the price variations on the energy markets. These new sources of risks generate a new risk: the market risk. In this research, the author explores the possibility of introducing constraints, expressed by measurements of risk, into the process of optimization of electricity production when financial contracts are signed on the energy market. The author makes the distinction between the engineering approach (taking the risk into account by risk measurements) and the economist approach (taking the risk into account by utility functions). After an overview of these both approaches in a static framework, he gives an economical formulation (a Maccheroni type one) for a static optimization problem under a risk constraint when the risk measurement is written under the form of an expected infimum like the variance, the 'conditional value at risk', and so on. The obtained results are then extended to a dynamic optimization framework under risk constraints. A numerical application of this approach is presented to solve a problem of electricity production management under a constraint of 'conditional value at risk' on a middle term

  10. Genetic determinants of telomere length and risk of common cancers: a Mendelian randomization study.

    Science.gov (United States)

    Zhang, Chenan; Doherty, Jennifer A; Burgess, Stephen; Hung, Rayjean J; Lindström, Sara; Kraft, Peter; Gong, Jian; Amos, Christopher I; Sellers, Thomas A; Monteiro, Alvaro N A; Chenevix-Trench, Georgia; Bickeböller, Heike; Risch, Angela; Brennan, Paul; Mckay, James D; Houlston, Richard S; Landi, Maria Teresa; Timofeeva, Maria N; Wang, Yufei; Heinrich, Joachim; Kote-Jarai, Zsofia; Eeles, Rosalind A; Muir, Ken; Wiklund, Fredrik; Grönberg, Henrik; Berndt, Sonja I; Chanock, Stephen J; Schumacher, Fredrick; Haiman, Christopher A; Henderson, Brian E; Amin Al Olama, Ali; Andrulis, Irene L; Hopper, John L; Chang-Claude, Jenny; John, Esther M; Malone, Kathleen E; Gammon, Marilie D; Ursin, Giske; Whittemore, Alice S; Hunter, David J; Gruber, Stephen B; Knight, Julia A; Hou, Lifang; Le Marchand, Loic; Newcomb, Polly A; Hudson, Thomas J; Chan, Andrew T; Li, Li; Woods, Michael O; Ahsan, Habibul; Pierce, Brandon L

    2015-09-15

    Epidemiological studies have reported inconsistent associations between telomere length (TL) and risk for various cancers. These inconsistencies are likely attributable, in part, to biases that arise due to post-diagnostic and post-treatment TL measurement. To avoid such biases, we used a Mendelian randomization approach and estimated associations between nine TL-associated SNPs and risk for five common cancer types (breast, lung, colorectal, ovarian and prostate cancer, including subtypes) using data on 51 725 cases and 62 035 controls. We then used an inverse-variance weighted average of the SNP-specific associations to estimate the association between a genetic score representing long TL and cancer risk. The long TL genetic score was significantly associated with increased risk of lung adenocarcinoma (P = 6.3 × 10(-15)), even after exclusion of a SNP residing in a known lung cancer susceptibility region (TERT-CLPTM1L) P = 6.6 × 10(-6)). Under Mendelian randomization assumptions, the association estimate [odds ratio (OR) = 2.78] is interpreted as the OR for lung adenocarcinoma corresponding to a 1000 bp increase in TL. The weighted TL SNP score was not associated with other cancer types or subtypes. Our finding that genetic determinants of long TL increase lung adenocarcinoma risk avoids issues with reverse causality and residual confounding that arise in observational studies of TL and disease risk. Under Mendelian randomization assumptions, our finding suggests that longer TL increases lung adenocarcinoma risk. However, caution regarding this causal interpretation is warranted in light of the potential issue of pleiotropy, and a more general interpretation is that SNPs influencing telomere biology are also implicated in lung adenocarcinoma risk. © The Author 2015. Published by Oxford University Press.

  11. Genetic susceptibility loci, pesticide exposure and prostate cancer risk.

    Directory of Open Access Journals (Sweden)

    Stella Koutros

    Full Text Available Uncovering SNP (single nucleotide polymorphisms-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs and 95% confidence intervals (CIs. Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1 SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44-8.15 (P-interaction= 0.003. Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41 (P-interaction= 0.006. In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.

  12. Decision-making under risk and uncertainty

    International Nuclear Information System (INIS)

    Gatev, G.I.

    2006-01-01

    Fuzzy sets and interval analysis tools to make computations and solve optimisation problems are presented. Fuzzy and interval extensions of Decision Theory criteria for decision-making under parametric uncertainty of prior information (probabilities, payoffs) are developed. An interval probability approach to the mean-value criterion is proposed. (author)

  13. Benefits and risks associated with genetically modified food products

    Directory of Open Access Journals (Sweden)

    Marta Kramkowska

    2013-09-01

    Full Text Available Scientists employing methods of genetic engineering have developed a new group of living organisms, termed ‘modified organisms’, which found application in, among others, medicine, the pharmaceutical industry and food distribution. The introduction of transgenic products to the food market resulted in them becoming a controversial topic, with their proponents and contestants. The presented study aims to systematize objective data on the potential benefits and risks resulting from the consumption of transgenic food. Genetic modifications of plants and animals are justified by the potential for improvement of the food situation worldwide, an increase in yield crops, an increase in the nutritional value of food, and the development of pharmaceutical preparations of proven clinical significance. In the opinions of critics, however, transgenic food may unfavourably affect the health of consumers. Therefore, particular attention was devoted to the short- and long-lasting undesirable effects, such as alimentary allergies, synthesis of toxic agents or resistance to antibiotics. Examples arguing for the justified character of genetic modifications and cases proving that their use can be dangerous are innumerable. In view of the presented facts, however, complex studies are indispensable which, in a reliable way, evaluate effects linked to the consumption of food produced with the application of genetic engineering techniques. Whether one backs up or negates transgenic products, the choice between traditional and non-conventional food remains to be decided exclusively by the consumers.

  14. Benefits and risks associated with genetically modified food products.

    Science.gov (United States)

    Kramkowska, Marta; Grzelak, Teresa; Czyżewska, Krystyna

    2013-01-01

    Scientists employing methods of genetic engineering have developed a new group of living organisms, termed 'modified organisms', which found application in, among others, medicine, the pharmaceutical industry and food distribution. The introduction of transgenic products to the food market resulted in them becoming a controversial topic, with their proponents and contestants. The presented study aims to systematize objective data on the potential benefits and risks resulting from the consumption of transgenic food. Genetic modifications of plants and animals are justified by the potential for improvement of the food situation worldwide, an increase in yield crops, an increase in the nutritional value of food, and the development of pharmaceutical preparations of proven clinical significance. In the opinions of critics, however, transgenic food may unfavourably affect the health of consumers. Therefore, particular attention was devoted to the short- and long-lasting undesirable effects, such as alimentary allergies, synthesis of toxic agents or resistance to antibiotics. Examples arguing for the justified character of genetic modifications and cases proving that their use can be dangerous are innumerable. In view of the presented facts, however, complex studies are indispensable which, in a reliable way, evaluate effects linked to the consumption of food produced with the application of genetic engineering techniques. Whether one backs up or negates transgenic products, the choice between traditional and non-conventional food remains to be decided exclusively by the consumers.

  15. Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry.

    Science.gov (United States)

    Wen, Wanqing; Shu, Xiao-Ou; Guo, Xingyi; Cai, Qiuyin; Long, Jirong; Bolla, Manjeet K; Michailidou, Kyriaki; Dennis, Joe; Wang, Qin; Gao, Yu-Tang; Zheng, Ying; Dunning, Alison M; García-Closas, Montserrat; Brennan, Paul; Chen, Shou-Tung; Choi, Ji-Yeob; Hartman, Mikael; Ito, Hidemi; Lophatananon, Artitaya; Matsuo, Keitaro; Miao, Hui; Muir, Kenneth; Sangrajrang, Suleeporn; Shen, Chen-Yang; Teo, Soo H; Tseng, Chiu-Chen; Wu, Anna H; Yip, Cheng Har; Simard, Jacques; Pharoah, Paul D P; Hall, Per; Kang, Daehee; Xiang, Yongbing; Easton, Douglas F; Zheng, Wei

    2016-12-08

    Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry. We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk. We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P women in the middle quintile of the PRS, women in the top 1% group had a 2.70-fold elevated risk of breast cancer (95% CI: 2.15-3.40). The risk prediction model with the PRS had an area under the receiver operating characteristic curve of 0.606. The lifetime risk of breast cancer for Shanghai Chinese women in the lowest and highest 1% of the PRS was 1.35% and 10.06%, respectively. Approximately one-half of GWAS-identified breast cancer risk variants can be directly replicated in East Asian women. Collectively, common genetic variants are important predictors for breast cancer risk. Using common genetic variants for breast cancer could help identify women at high risk of breast cancer.

  16. Risk Management and Insurance Decisions under Ambiguity

    DEFF Research Database (Denmark)

    Martínez-Correa, Jimmy

    a counterexample to a classical result in insurance economics where an insurance contract with straight deductible is dominated by a coinsurance contract. Finally, I find that a modified Borch rule characterizes the optimal insurance contract with bilateral risk and ambiguity attitudes and heterogeneity in beliefs....... and ambiguity attitudes interact in nontrivial ways to determine the change of coinsurance demand. I derive sufficient conditions to guarantee that the optimal coinsurance demand is decreasing in wealth. When a non-traded asset is introduced, my model predicts behavior that is inconsistent with the classical...

  17. Characterizing genetic syndromes involved in cancer and radiogenic cancer risk

    International Nuclear Information System (INIS)

    Unrau, P.; Doerffer, K.

    1998-01-01

    The COG project 2806A (1995), reviewed the On-line Mendelian Inheritance in Man (OMIM) database of genetic syndromes to identify those syndromes, genes, and DNA sequences implicated in some way in the cancer process, and especially in radiogenic cancer risk. The current report describes a recent update of the survey in light of two years of further progress in the Human Genome project, and is intended to supply a comprehensive list of those genetic syndromes, genes, DNA sequences and map locations that define genes likely to be involved in cancer risk. Of the 8203 syndromes in OMIM in 1997 June, 814 are associated, even if marginally, with cancer. Of the 814 syndromes so linked, 672 have been mapped to a chromosome, and 476 have been mapped to a chromosome and had a DNA sequence associated with their messenger RNA (or cDNA) sequences. In addition, 35 syndromes have sequences not associated with map locations, and the remaining 107 have neither been mapped nor sequenced. We supply the list of the various genetic syndromes sorted by chromosome location and by OMIM descriptor, together with all the associated but unmapped and unsequenced syndromes. (author)

  18. Birth Characteristics and Childhood Leukemia Risk: Correlations With Genetic Markers.

    Science.gov (United States)

    Kennedy, Amy E; Kamdar, Kala Y; Lupo, Philip J; Okcu, Mehmet F; Scheurer, Michael E; Dorak, Mehmet T

    2015-07-01

    Birth characteristics such as birth order, birth weight, birth defects, and Down syndrome showed some of the first risk associations with childhood leukemia. Examinations of correlations between birth characteristics and leukemia risk markers have been limited to birth weight-related genetic polymorphisms. We integrated information on nongenetic and genetic markers by evaluating the relationship of birth characteristics, genetic markers for childhood acute lymphoblastic leukemia (ALL) susceptibility, and ALL risk together. The multiethnic study consisted of cases with childhood ALL (n=161) and healthy controls (n=261). Birth characteristic data were collected through questionnaires, and genotyping was achieved by TaqMan SNP Genotyping Assays. We observed risk associations for birth weight over 4000 g (odds ratios [OR]=1.93; 95% confidence interval [CI], 1.16-3.19), birth length (OR=1.18 per inch; 95% CI, 1.01-1.38), and with gestational age (OR=1.10 per week; 95% CI, 1.00-1.21). Only the HFE tag single-nucleotide polymorphism (SNP) rs9366637 showed an inverse correlation with a birth characteristic, gestational age, with a gene-dosage effect (P=0.005), and in interaction with a transferrin receptor rs3817672 genotype (Pinteraction=0.05). This correlation translated into a strong association for rs9366637 with preterm birth (OR=5.0; 95% CI, 1.19-20.9). Our study provides evidence for the involvement of prenatal events in the development of childhood ALL. The inverse correlation of rs9366637 with gestational age has implications on the design of HFE association studies in birth weight and childhood conditions using full-term newborns as controls.

  19. Skin barrier and contact allergy: Genetic risk factor analyses

    DEFF Research Database (Denmark)

    Ross-Hansen, Katrine

    2013-01-01

    piercing status was regarded. Nickel patch test readings indicated that proportionally more mutation carriers than wild types had stronger reactions. Epidermally derived filaggrin binds nickel. The GST gene polymorphisms did not associate with contact allergy among adult Danes. The CLDN1 polymorphisms rs......Background Contact allergy is frequent in the general population and arises from prolonged or repeated skin contact with chemical substances. The environmental risk factor is obvious, yet some studies report on associations between genetic variance and an increased risk of developing contact...... allergy. Objectives To evaluate the effect of specific gene polymorphisms on the risk of developing contact allergy by a candidate gene approach. These included polymorphisms in the glutathione S-transferase genes (GSTM1, -T1 and -P1 variants), the claudin-1 gene (CLDN1), and the filaggrin gene (FLG...

  20. Lead, genetic susceptibility, and risk of adult brain tumors.

    Science.gov (United States)

    Rajaraman, Preetha; Stewart, Patricia A; Samet, Jonathan M; Schwartz, Brian S; Linet, Martha S; Zahm, Shelia Hoar; Rothman, Nathaniel; Yeager, Meredith; Fine, Howard A; Black, Peter M; Loeffler, Jay; Shapiro, William R; Selker, Robert G; Inskip, Peter D

    2006-12-01

    Although few etiologic factors for brain tumors have been identified, limited data suggest that lead may increase the risk of brain tumors, particularly meningioma. The ALAD G177C polymorphism affects the toxicokinetics of lead and may confer genetic susceptibility to adverse effects of lead exposure. We examined occupational exposure to lead and risk of brain tumors in a multisite, hospital-based, case-control study of 489 patients with glioma, 197 with meningioma, and 799 non-cancer controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to hospital. ALAD genotype was assessed by a Taqman assay for 355 glioma patients, 151 meningioma patients, and 505 controls. Exposure to lead was estimated using a rigorous questionnaire-based exposure assessment strategy incorporating lead measurement and other occupational data abstracted from published articles and reports. Increased risk of meningioma with occupational lead exposure (estimated by odds ratios and 95% confidence intervals) was most apparent in individuals with the ALAD2 variant allele, for whom risk increased from 1.1 (0.3-4.5) to 5.6 (0.7-45.5) and 12.8 (1.4-120.8) for estimated cumulative lead exposures of 1 to 49 microg/m3-y, 50 to 99 microg/m3-y, and >or=100 microg/m3-y, respectively, compared with unexposed individuals (two-sided P trend = 0.06). This relationship became stronger after excluding occupational lead exposures characterized by a low confidence level or occurring in the 10 years before meningioma diagnosis. Occupational lead exposure was not associated with glioma risk. Although our results indicate that lead may be implicated in meningioma risk in genetically susceptible individuals, these results need to be interpreted with caution given the small numbers of exposed cases with a variant genotype.

  1. Uptake of Predictive Genetic Testing and Cardiac Evaluation for Children at Risk for an Inherited Arrhythmia or Cardiomyopathy.

    Science.gov (United States)

    Christian, Susan; Atallah, Joseph; Clegg, Robin; Giuffre, Michael; Huculak, Cathleen; Dzwiniel, Tara; Parboosingh, Jillian; Taylor, Sherryl; Somerville, Martin

    2018-02-01

    Predictive genetic testing in minors should be considered when clinical intervention is available. Children who carry a pathogenic variant for an inherited arrhythmia or cardiomyopathy require regular cardiac screening and may be prescribed medication and/or be told to modify their physical activity. Medical genetics and pediatric cardiology charts were reviewed to identify factors associated with uptake of genetic testing and cardiac evaluation for children at risk for long QT syndrome, hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. The data collected included genetic diagnosis, clinical symptoms in the carrier parent, number of children under 18 years of age, age of children, family history of sudden cardiac arrest/death, uptake of cardiac evaluation and if evaluated, phenotype for each child. We identified 97 at risk children from 58 families found to carry a pathogenic variant for one of these conditions. Sixty six percent of the families pursued genetic testing and 73% underwent cardiac screening when it was recommended. Declining predictive genetic testing was significantly associated with genetic specialist recommendation (p testing (p = 0.007). This study provides a greater understanding of factors associated with uptake of genetic testing and cardiac evaluation in children at risk of an inherited arrhythmia or cardiomyopathy. It also identifies a need to educate families about the importance of cardiac evaluation even in the absence of genetic testing.

  2. Genetic studies on leaf rolling and some root traits under drought ...

    African Journals Online (AJOL)

    Genetic studies on leaf rolling and some root traits under drought conditions in rice (Oryza sativa L.) AA Allah. Abstract. Crossing was made between three resistant and two susceptible parents to determine the genetic characteristics under drought conditions during 2002 and 2003 rice growing seasons. The resistant ...

  3. A developmental behavior-genetic perspective on alcoholism risk.

    Science.gov (United States)

    Rose, R J

    1998-01-01

    Although behavioral problems associated with abuse of alcohol emerge during late adolescence and adulthood, some behavioral characteristics indicative of an increased risk of alcoholism may already be obvious during early childhood. Studies in several countries have demonstrated that children with high levels of novelty-seeking behavior and low levels of harm-avoidance behavior are more likely to develop alcohol-related problems during adolescence. Moreover, as early as age 3, children at high risk of future alcoholism because of a family history are more active, more impatient, and more aggressive than matched controls of low-risk children. Causal influences on the initiation of drinking must be distinguished from those that affect patterns of consumption once drinking is initiated. Studies of adolescent twins have demonstrated that initiation of drinking is primarily influenced by the drinking status of parents, siblings, and friends and by socioregional differences in the environments within which adolescent twins reside. The influence of genetic factors is negligible. Conversely, once initiated, differences in frequency and quantity of drinking are strongly influenced by genetic factors. However, these influences, too, are modulated by sibling and peer effects and by regional environmental variation.

  4. Molecular genetics and livestock selection. Approaches, opportunities and risks

    International Nuclear Information System (INIS)

    Williams, J.L.

    2005-01-01

    Following domestication, livestock were selected both naturally through adaptation to their environments and by man so that they would fulfil a particular use. As selection methods have become more sophisticated, rapid progress has been made in improving those traits that are easily measured. However, selection has also resulted in decreased diversity. In some cases, improved breeds have replaced local breeds, risking the loss of important survival traits. The advent of molecular genetics provides the opportunity to identify the genes that control particular traits by a gene mapping approach. However, as with selection, the early mapping studies focused on traits that are easy to measure. Where molecular genetics can play a valuable role in livestock production is by providing the means to select effectively for traits that are difficult to measure. Identifying the genes underpinning particular traits requires a population in which these traits are segregating. Fortunately, several experimental populations have been created that have allowed a wide range of traits to be studied. Gene mapping work in these populations has shown that the role of particular genes in controlling variation in a given trait can depend on the genetic background. A second finding is that the most favourable alleles for a trait may in fact. be present in animals that perform poorly for the trait. In the long term, knowledge of -the genes controlling particular traits, and the way they interact with the genetic background, will allow introgression between breeds and the assembly of genotypes that are best suited to particular environments, producing animals with the desired characteristics. If used wisely, this approach will maintain genetic diversity while improving performance over a wide range of desired traits. (author)

  5. Dietary Magnesium and Genetic Interactions in Diabetes and Related Risk Factors: A Brief Overview of Current Knowledge

    Science.gov (United States)

    Hruby, Adela; McKeown, Nicola M.; Song, Yiqing; Djoussé, Luc

    2013-01-01

    Nutritional genomics has exploded in the last decade, yielding insights—both nutrigenomic and nutrigenetic—into the physiology of dietary interactions and our genes. Among these are insights into the regulation of magnesium transport and homeostasis and mechanisms underlying magnesium’s role in insulin and glucose handling. Recent observational evidence has attempted to examine some promising research avenues on interaction between genetics and dietary magnesium in relation to diabetes and diabetes risk factors. This brief review summarizes the recent evidence on dietary magnesium’s role in diabetes and related traits in the presence of underlying genetic risk, and discusses future potential research directions. PMID:24322525

  6. A genetic-algorithm-aided stochastic optimization model for regional air quality management under uncertainty.

    Science.gov (United States)

    Qin, Xiaosheng; Huang, Guohe; Liu, Lei

    2010-01-01

    A genetic-algorithm-aided stochastic optimization (GASO) model was developed in this study for supporting regional air quality management under uncertainty. The model incorporated genetic algorithm (GA) and Monte Carlo simulation techniques into a general stochastic chance-constrained programming (CCP) framework and allowed uncertainties in simulation and optimization model parameters to be considered explicitly in the design of least-cost strategies. GA was used to seek the optimal solution of the management model by progressively evaluating the performances of individual solutions. Monte Carlo simulation was used to check the feasibility of each solution. A management problem in terms of regional air pollution control was studied to demonstrate the applicability of the proposed method. Results of the case study indicated the proposed model could effectively communicate uncertainties into the optimization process and generate solutions that contained a spectrum of potential air pollutant treatment options with risk and cost information. Decision alternatives could be obtained by analyzing tradeoffs between the overall pollutant treatment cost and the system-failure risk due to inherent uncertainties.

  7. Evidence for shared genetic risk between ADHD symptoms and reduced mathematics ability: a twin study.

    Science.gov (United States)

    Greven, Corina U; Kovas, Yulia; Willcutt, Erik G; Petrill, Stephen A; Plomin, Robert

    2014-01-01

    Attention-deficit/hyperactivity disorder (ADHD) symptoms and mathematics ability are associated, but little is known about the genetic and environmental influences underlying this association. Data came from more than 6,000 twelve-year-old twin pairs from the UK population-representative Twins Early Development Study. Parents rated each twin's behaviour using a DSM-IV-based 18-item questionnaire of inattentive and hyperactive-impulsive ADHD symptoms. Mathematics tests based on the UK National Curriculum were completed by each twin. The twins also completed standardised tests of reading and general cognitive ability. Multivariate twin model fitting was applied. Inattentive and hyperactive-impulsive ADHD symptoms were highly heritable (67% and 73% respectively). Mathematics ability was moderately heritable (46%). Mathematics ability and inattentiveness showed a significantly greater phenotypic correlation (r(p) = -.26) and genetic correlation (r(A) = -.41) than mathematics ability and hyperactivity-impulsivity (r(p) = -.18; r(A) = -.22). The genetic correlation between inattentiveness and mathematics ability was largely independent from hyperactivity-impulsivity, and was only partially accounted for by genetic influences related to reading and general cognitive ability. Results revealed the novel finding that mathematics ability shows significantly stronger phenotypic and genetic associations with inattentiveness than with hyperactivity-impulsivity. Genetic associations between inattentiveness and mathematics ability could only partially be accounted for by hyperactivity-impulsivity, reading and general cognitive ability. Results suggest that mathematics ability is associated with ADHD symptoms largely because it shares genetic risk factors with inattentiveness, and provide further evidence for considering inattentiveness and hyperactivity-impulsivity separately. DNA markers for ADHD symptoms (especially inattentiveness) may also be candidate risk factors for

  8. Evidence for shared genetic risk between ADHD symptoms and reduced mathematics ability: a twin study

    Science.gov (United States)

    Greven, Corina U.; Kovas, Yulia; Willcutt, Erik G.; Petrill, Stephen A.; Plomin, Robert

    2013-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD) symptoms and mathematics ability are associated, but little is known about the genetic and environmental influences underlying this association. Methods Data came from more than 6,000 12-year-old twin pairs from the U.K. population-representative Twins Early Development Study. Parents rated each twin’s behaviour using a DSM-IV-based 18-item questionnaire of inattentive and hyperactive-impulsive ADHD symptoms. Mathematics tests based on the U.K. National Curriculum were completed by each twin. The twins also completed standardised tests of reading and general cognitive ability. Multivariate twin model fitting was applied. Results Inattentive and hyperactive-impulsive ADHD symptoms were highly heritable (67% and 73%, respectively). Mathematics ability was moderately heritable (46%). Mathematics ability and inattentiveness showed a significantly greater phenotypic correlation (rp=−0.26) and genetic correlation (rA=−0.41) than mathematics ability and hyperactivity-impulsivity (rp=−0.18; rA=−0.22). The genetic correlation between inattentiveness and mathematics ability was largely independent from hyperactivity-impulsivity, and was only partially accounted for by genetic influences related to reading and general cognitive ability. Conclusions Results revealed the novel finding that mathematics ability shows significantly stronger phenotypic and genetic associations with inattentiveness than with hyperactivity-impulsivity. Genetic associations between inattentiveness and mathematics ability could only partially be accounted for by hyperactivity-impulsivity, reading and general cognitive ability. Results suggest that mathematics ability is associated with ADHD symptoms largely because it shares genetic risk factors with inattentiveness, and provide further evidence for considering inattentiveness and hyperactivity-impulsivity separately. DNA markers for ADHD symptoms (especially inattentiveness) may also

  9. Class II HLA interactions modulate genetic risk for multiple sclerosis

    Science.gov (United States)

    Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil

    2016-01-01

    Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388

  10. Genetic analysis of fertility restoration under CGMS system in rice ...

    Indian Academy of Sciences (India)

    Cytoplasmic genetic male sterility (CGMS) resulting from nuclear-cytoplasmic interaction has been commercially exploited for the production of F1 hybrid seed in rice. The. CGMS system involves three lines, namely a cytoplasmic male sterile (CMS) line, a maintainer line and a restorer line where restorer line (R line) ...

  11. Genetic analysis of fertility restoration under CGMS system in rice ...

    Indian Academy of Sciences (India)

    Abstract. We studied the genetics of fertility restoration by producing three-way test cross (TWTC) hybrids involved different combi- nations of restorers, maintainers and partial restorers of rice. Pollen and spikelet fertility of 16 TWTC hybrids were studied. Six TWTC involving restorer/restorer combinations as male parents ...

  12. Epidemiological, neurobiological, and genetic clues to the mechanisms linking cannabis use to risk for nonaffective psychosis.

    Science.gov (United States)

    van Winkel, Ruud; Kuepper, Rebecca

    2014-01-01

    Epidemiological studies have shown that the association between cannabis and psychosis is robust and consistent across different samples, with compelling evidence for a dose-response relationship. Because longitudinal work indicates that cannabis use precedes psychotic symptoms, it seems reasonable to assume a causal relationship. However, more work is needed to address the possibility of gene-environment correlation (for example, genetic risk for psychosis causing onset of cannabis use). Moreover, knowledge about underlying biological mechanisms linking cannabis use and psychosis is still relatively limited. In order to understand how cannabis use may lead to an increased risk for psychosis, in the present article we (a) review the epidemiological, neurobiological, and genetic evidence linking cannabinoids and psychosis, (b) assess the quality of the evidence, and finally (c) try to integrate the most robust findings into a neurodevelopmental model of cannabis-induced psychosis and identify the gaps in knowledge that are in need of further investigation.

  13. Women-specific risk factors for heart failure: A genetic approach.

    Science.gov (United States)

    van der Kemp, Jet; van der Schouw, Yvonne T; Asselbergs, Folkert W; Onland-Moret, N Charlotte

    2018-03-01

    Heart failure is a complex disease, which is presented differently by men and women. Several studies have shown that reproductive factors, such as age at natural menopause, parity and polycystic ovarian syndrome (PCOS), may play a role in the development of heart failure. Shared genetics may provide clues to underlying mechanisms; however, this has never been examined. Therefore, the aim of the current study was to explore whether any reproductive factor is potentially related to heart failure in women, based on genetic similarities. Conducting a systematic literature review, single nucleotide polymorphisms (SNPs) associated with reproductive factors, heart failure and its risk factors were extracted from recent genome-wide association studies. We tested whether there was any overlap between the SNPs and their proxies of reproductive risk factors with those known for heart failure or its risk factors. In total, 520 genetic variants were found that are associated with reproductive factors, namely age at menarche, age at natural menopause, menstrual cycle length, PCOS, preeclampsia, preterm delivery and spontaneous dizygotic twinning. For heart failure and associated phenotypes, 25 variants were found. Genetic variants for reproductive factors did not overlap with those for heart failure. However, age at menarche, gestational diabetes and PCOS were found to be genetically linked to risk factors for heart failure, such as atrial fibrillation, diabetes and smoking. Corresponding implicated genes, such as TNNI3K, ErbB3, MKL2, MTNR1B and PRKD1, may explain the associations between reproductive factors and heart failure. Exact effector mechanisms of these genes remain to be investigated further. Copyright © 2017. Published by Elsevier B.V.

  14. Environmental Risk Assessment of Genetically Modified Organisms (GMOs)

    DEFF Research Database (Denmark)

    Strandberg, B.; Kjær, C.; Hindar, K.

    of genetically modified plants. This chapter describes both the legislation within the EU and the state of the technology (existing and coming cases). Furthermore, a presentation of the ecological concerns discussed in the report, i.e. invasion, introgression and adverse effects on non-target organisms...... for annual plants, trees and fish, respectively, and suggests a structural/hierarchical decision system for information requirements. The latter should aid to eliminate the 'high-risk' products at an early stage and to improve the design of tests at higher tiers. The second section works with specific...... requirements for the ecological risk assessment of long-lived species like tree species and fish. The third and last section characterises the specific conditions and requirements prevailing in the Nordic region. It is recommended that new field releases and applications for marketing are accompanied...

  15. Cancer Genetics Risk Assessment and Counseling (PDQ®)—Health Professional Version

    Science.gov (United States)

    Expert-reviewed information summary in which cancer risk perception, risk communication, and risk counseling are discussed. The summary also contains information about recording and analyzing a family history of cancer and factors to consider when offering genetic testing.

  16. Predicting the risk of rheumatoid arthritis and its age of onset through modelling genetic risk variants with smoking.

    Directory of Open Access Journals (Sweden)

    Ian C Scott

    Full Text Available The improved characterisation of risk factors for rheumatoid arthritis (RA suggests they could be combined to identify individuals at increased disease risks in whom preventive strategies may be evaluated. We aimed to develop an RA prediction model capable of generating clinically relevant predictive data and to determine if it better predicted younger onset RA (YORA. Our novel modelling approach combined odds ratios for 15 four-digit/10 two-digit HLA-DRB1 alleles, 31 single nucleotide polymorphisms (SNPs and ever-smoking status in males to determine risk using computer simulation and confidence interval based risk categorisation. Only males were evaluated in our models incorporating smoking as ever-smoking is a significant risk factor for RA in men but not women. We developed multiple models to evaluate each risk factor's impact on prediction. Each model's ability to discriminate anti-citrullinated protein antibody (ACPA-positive RA from controls was evaluated in two cohorts: Wellcome Trust Case Control Consortium (WTCCC: 1,516 cases; 1,647 controls; UK RA Genetics Group Consortium (UKRAGG: 2,623 cases; 1,500 controls. HLA and smoking provided strongest prediction with good discrimination evidenced by an HLA-smoking model area under the curve (AUC value of 0.813 in both WTCCC and UKRAGG. SNPs provided minimal prediction (AUC 0.660 WTCCC/0.617 UKRAGG. Whilst high individual risks were identified, with some cases having estimated lifetime risks of 86%, only a minority overall had substantially increased odds for RA. High risks from the HLA model were associated with YORA (P<0.0001; ever-smoking associated with older onset disease. This latter finding suggests smoking's impact on RA risk manifests later in life. Our modelling demonstrates that combining risk factors provides clinically informative RA prediction; additionally HLA and smoking status can be used to predict the risk of younger and older onset RA, respectively.

  17. Identification of novel genetic risk loci in Maltese dogs with necrotizing meningoencephalitis and evidence of a shared genetic risk across toy dog breeds.

    Science.gov (United States)

    Schrauwen, Isabelle; Barber, Renee M; Schatzberg, Scott J; Siniard, Ashley L; Corneveaux, Jason J; Porter, Brian F; Vernau, Karen M; Keesler, Rebekah I; Matiasek, Kaspar; Flegel, Thomas; Miller, Andrew D; Southard, Teresa; Mariani, Christopher L; Johnson, Gayle C; Huentelman, Matthew J

    2014-01-01

    Necrotizing meningoencephalitis (NME) affects toy and small breed dogs causing progressive, often fatal, inflammation and necrosis in the brain. Genetic risk loci for NME previously were identified in pug dogs, particularly associated with the dog leukocyte antigen (DLA) class II complex on chromosome 12, but have not been investigated in other susceptible breeds. We sought to evaluate Maltese and Chihuahua dogs, in addition to pug dogs, to identify novel or shared genetic risk factors for NME development. Genome-wide association testing of single nucleotide polymorphisms (SNPs) in Maltese dogs with NME identified 2 regions of genome-wide significance on chromosomes 4 (chr4:74522353T>A, p = 8.1×10-7) and 15 (chr15:53338796A>G, p = 1.5×10-7). Haplotype analysis and fine-mapping suggests that ILR7 and FBXW7, respectively, both important for regulation of immune system function, could be the underlying associated genes. Further evaluation of these regions and the previously identified DLA II locus across all three breeds, revealed an enrichment of nominal significant SNPs associated with chromosome 15 in pug dogs and DLA II in Maltese and Chihuahua dogs. Meta-analysis confirmed effect sizes the same direction in all three breeds for both the chromosome 15 and DLA II loci (p = 8.6×10-11 and p = 2.5×10-7, respectively). This suggests a shared genetic background exists between all breeds and confers susceptibility to NME, but effect sizes might be different among breeds. In conclusion, we identified the first genetic risk factors for NME development in the Maltese, chromosome 4 and chromosome 15, and provide evidence for a shared genetic risk between breeds associated with chromosome 15 and DLA II. Last, DLA II and IL7R both have been implicated in human inflammatory diseases of the central nervous system such as multiple sclerosis, suggesting that similar pharmacotherapeutic targets across species should be investigated.

  18. Risk, Robustness and Water Resources Planning Under Uncertainty

    Science.gov (United States)

    Borgomeo, Edoardo; Mortazavi-Naeini, Mohammad; Hall, Jim W.; Guillod, Benoit P.

    2018-03-01

    Risk-based water resources planning is based on the premise that water managers should invest up to the point where the marginal benefit of risk reduction equals the marginal cost of achieving that benefit. However, this cost-benefit approach may not guarantee robustness under uncertain future conditions, for instance under climatic changes. In this paper, we expand risk-based decision analysis to explore possible ways of enhancing robustness in engineered water resources systems under different risk attitudes. Risk is measured as the expected annual cost of water use restrictions, while robustness is interpreted in the decision-theoretic sense as the ability of a water resource system to maintain performance—expressed as a tolerable risk of water use restrictions—under a wide range of possible future conditions. Linking risk attitudes with robustness allows stakeholders to explicitly trade-off incremental increases in robustness with investment costs for a given level of risk. We illustrate the framework through a case study of London's water supply system using state-of-the -art regional climate simulations to inform the estimation of risk and robustness.

  19. Strongly enhanced colorectal cancer risk stratification by combining family history and genetic risk score

    Directory of Open Access Journals (Sweden)

    Weigl K

    2018-01-01

    Full Text Available Korbinian Weigl,1,2 Jenny Chang-Claude,3,4 Phillip Knebel,5 Li Hsu,6 Michael Hoffmeister,1 Hermann Brenner1,2,7 1Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ, Heidelberg, 2German Cancer Consortium (DKTK, German Cancer Research Center (DKFZ, Heidelberg, 3Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ, Heidelberg, 4University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, 5Department for General, Visceral and Transplantation Surgery, University Heidelberg, Heidelberg, Germany; 6Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 7Division of Preventive Oncology, German Cancer Research Center (DKFZ and National Center for Tumor Diseases (NCT, Heidelberg, Germany Background and aim: Family history (FH and genetic risk scores (GRSs are increasingly used for risk stratification for colorectal cancer (CRC screening. However, they were mostly considered alternatively rather than jointly. The aim of this study was to assess the potential of individual and joint risk stratification for CRC by FH and GRS.Patients and methods: A GRS was built based on the number of risk alleles in 53 previously identified single-nucleotide polymorphisms among 2,363 patients with a first diagnosis of CRC and 2,198 controls in DACHS [colorectal cancer: chances for prevention through screening], a population-based case-control study in Germany. Associations between GRS and FH with CRC risk were quantified by multiple logistic regression.Results: A total of 316 cases (13.4% and 214 controls (9.7% had a first-degree relative (FDR with CRC (adjusted odds ratio [aOR] 1.86, 95% CI 1.52–2.29. A GRS in the highest decile was associated with a 3.0-fold increased risk of CRC (aOR 3.00, 95% CI 2.24–4.02 compared with the lowest decile. This association was tentatively more pronounced in older age groups. FH and GRS were essentially unrelated, and their

  20. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

    DEFF Research Database (Denmark)

    Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N

    2015-01-01

    Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address...... this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested...... that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We...

  1. Barriers and Facilitators for Utilization of Genetic Counseling and Risk Assessment Services in Young Female Breast Cancer Survivors

    Directory of Open Access Journals (Sweden)

    Beth Anderson

    2012-01-01

    Full Text Available Introduction. Women diagnosed with breast cancer at a young age are more likely to carry a cancer predisposing genetic mutation. Per the current NCCN recommendations, women diagnosed under age 50 should be referred to cancer genetic counseling for further risk evaluation. This study seeks to assess patient-reported barriers and facilitators to receiving genetic counseling and risk assessment among a community-based population of young breast cancer survivors (YBCS. Methods. Through the Michigan Cancer Surveillance Program, a state-based cancer registry, 488 women diagnosed with breast cancer before age 50 in 2006-2007 were identified. They received a mail survey regarding family history and facilitators and barriers to receiving genetic counseling and risk assessment. Results. Responses were received from 289 women (59.2%. One hundred twenty-two (42.2% reported having received cancer genetic counseling. The most frequent reason identified for receiving services was to benefit their family's future. The top reasons for not attending were “no one recommended it” and “medical insurance coverage issues.” Discussion. This study is the first published report using a state cancer registry to determine facilitators and barriers to receiving genetic counseling and risk assessment among YBCS. These findings demonstrate the need for additional awareness and education about appropriate indications for genetic services.

  2. Barriers and Facilitators for Utilization of Genetic Counseling and Risk Assessment Services in Young Female Breast Cancer Survivors

    International Nuclear Information System (INIS)

    Anderson, B.; McLosky, J.; Wasilevich, E.; Callo, S. L.; Duquette, D.; Copeland, G.

    2012-01-01

    Introduction. Women diagnosed with breast cancer at a young age are more likely to carry a cancer predisposing genetic mutation. Per the current NCCN recommendations, women diagnosed under age 50 should be referred to cancer genetic counseling for further risk evaluation. This study seeks to assess patient-reported barriers and facilitators to receiving genetic counseling and risk assessment among a community-based population of young breast cancer survivors (YBCS). Methods. Through the Michigan Cancer Surveillance Program, a state-based cancer registry, 488 women diagnosed with breast cancer before age 50 in 2006-2007 were identified. They received a mail survey regarding family history and facilitators and barriers to receiving genetic counseling and risk assessment. Results. Responses were received from 289 women (59.2%). One hundred twenty-two (42.2%) reported having received cancer genetic counseling. The most frequent reason identified for receiving services was to benefit their family's future. The top reasons for not attending were “no one recommended it” and “medical insurance coverage issues.” Discussion. This study is the first published report using a state cancer registry to determine facilitators and barriers to receiving genetic counseling and risk assessment among YBCS. These findings demonstrate the need for additional awareness and education about appropriate indications for genetic services.

  3. Improvement of operational risk measurement under the Solvency II framework

    Directory of Open Access Journals (Sweden)

    Darja Stepchenko

    2015-06-01

    Full Text Available Operational risk is one of the core risks of every insurance company in accordance to the solvency capital requirement under the Solvency II regime. The target of the research is to investigate the improvement possibilities of the operational risk measurement under Solvency II regime. The authors have prepared the algorithm of the operational risk measurement under Solvency II framework that helps improve the understanding of the operational risk capital requirements. Moreover, the authors have prepared the case study about a practical usage of the suggested algorithm through the example of one non-life insurance company. The authors use, in order to perform the research, such corresponding methods as theoretical and methodological analysis of scientific literature, analytical, statistical and mathematical methods.

  4. Gastrointestinal stromal tumors, somatic mutations and candidate genetic risk variants.

    Directory of Open Access Journals (Sweden)

    Katie M O'Brien

    Full Text Available Gastrointestinal stromal tumors (GISTs are rare but treatable soft tissue sarcomas. Nearly all GISTs have somatic mutations in either the KIT or PDGFRA gene, but there are no known inherited genetic risk factors. We assessed the relationship between KIT/PDGFRA mutations and select deletions or single nucleotide polymorphisms (SNPs in 279 participants from a clinical trial of adjuvant imatinib mesylate. Given previous evidence that certain susceptibility loci and carcinogens are associated with characteristic mutations, or "signatures" in other cancers, we hypothesized that the characteristic somatic mutations in the KIT and PDGFRA genes in GIST tumors may similarly be mutational signatures that are causally linked to specific mutagens or susceptibility loci. As previous epidemiologic studies suggest environmental risk factors such as dioxin and radiation exposure may be linked to sarcomas, we chose 208 variants in 39 candidate genes related to DNA repair and dioxin metabolism or response. We calculated adjusted odds ratios (ORs and 95% confidence intervals (CIs for the association between each variant and 7 categories of tumor mutation using logistic regression. We also evaluated gene-level effects using the sequence kernel association test (SKAT. Although none of the association p-values were statistically significant after adjustment for multiple comparisons, SNPs in CYP1B1 were strongly associated with KIT exon 11 codon 557-8 deletions (OR = 1.9, 95% CI: 1.3-2.9 for rs2855658 and OR = 1.8, 95% CI: 1.2-2.7 for rs1056836 and wild type GISTs (OR = 2.7, 95% CI: 1.5-4.8 for rs1800440 and OR = 0.5, 95% CI: 0.3-0.9 for rs1056836. CYP1B1 was also associated with these mutations categories in the SKAT analysis (p = 0.002 and p = 0.003, respectively. Other potential risk variants included GSTM1, RAD23B and ERCC2. This preliminary analysis of inherited genetic risk factors for GIST offers some clues about the disease's genetic

  5. Parent of origin, mosaicism, and recurrence risk: probabilistic modeling explains the broken symmetry of transmission genetics.

    Science.gov (United States)

    Campbell, Ian M; Stewart, Jonathan R; James, Regis A; Lupski, James R; Stankiewicz, Paweł; Olofsson, Peter; Shaw, Chad A

    2014-10-02

    Most new mutations are observed to arise in fathers, and increasing paternal age positively correlates with the risk of new variants. Interestingly, new mutations in X-linked recessive disease show elevated familial recurrence rates. In male offspring, these mutations must be inherited from mothers. We previously developed a simulation model to consider parental mosaicism as a source of transmitted mutations. In this paper, we extend and formalize the model to provide analytical results and flexible formulas. The results implicate parent of origin and parental mosaicism as central variables in recurrence risk. Consistent with empirical data, our model predicts that more transmitted mutations arise in fathers and that this tendency increases as fathers age. Notably, the lack of expansion later in the male germline determines relatively lower variance in the proportion of mutants, which decreases with paternal age. Subsequently, observation of a transmitted mutation has less impact on the expected risk for future offspring. Conversely, for the female germline, which arrests after clonal expansion in early development, variance in the mutant proportion is higher, and observation of a transmitted mutation dramatically increases the expected risk of recurrence in another pregnancy. Parental somatic mosaicism considerably elevates risk for both parents. These findings have important implications for genetic counseling and for understanding patterns of recurrence in transmission genetics. We provide a convenient online tool and source code implementing our analytical results. These tools permit varying the underlying parameters that influence recurrence risk and could be useful for analyzing risk in diverse family structures. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  6. Polygenic Risk for Depression Increases Risk of Ischemic Stroke: From the Stroke Genetics Network Study.

    Science.gov (United States)

    Wassertheil-Smoller, Sylvia; Qi, Qibin; Dave, Tushar; Mitchell, Braxton D; Jackson, Rebecca D; Liu, Simin; Park, Ki; Salinas, Joel; Dunn, Erin C; Leira, Enrique C; Xu, Huichun; Ryan, Kathleen; Smoller, Jordan W

    2018-03-01

    Although depression is a risk factor for stroke in large prospective studies, it is unknown whether these conditions have a shared genetic basis. We applied a polygenic risk score (PRS) for major depressive disorder derived from European ancestry analyses by the Psychiatric Genomics Consortium to a genome-wide association study of ischemic stroke in the Stroke Genetics Network of National Institute of Neurological Disorders and Stroke. Included in separate analyses were 12 577 stroke cases and 25 643 controls of European ancestry and 1353 cases and 2383 controls of African ancestry. We examined the association between depression PRS and ischemic stroke overall and with pathogenic subtypes using logistic regression analyses. The depression PRS was associated with higher risk of ischemic stroke overall in both European ( P =0.025) and African ancestry ( P =0.011) samples from the Stroke Genetics Network. Ischemic stroke risk increased by 3.0% (odds ratio, 1.03; 95% confidence interval, 1.00-1.05) for every 1 SD increase in PRS for those of European ancestry and by 8% (odds ratio, 1.08; 95% confidence interval, 1.04-1.13) for those of African ancestry. Among stroke subtypes, elevated risk of small artery occlusion was observed in both European and African ancestry samples. Depression PRS was also associated with higher risk of cardioembolic stroke in European ancestry and large artery atherosclerosis in African ancestry persons. Higher polygenic risk for major depressive disorder is associated with increased risk of ischemic stroke overall and with small artery occlusion. Additional associations with ischemic stroke subtypes differed by ancestry. © 2018 American Heart Association, Inc.

  7. A flexible model for actuarial risks under dependence

    NARCIS (Netherlands)

    Albers, Willem/Wim; Kallenberg, W.C.M.; Lukocius, V.

    Methods for computing risk measures, such as stop-loss premiums, tacitly assume independence of the underlying individual risks. This can lead to huge errors even when only small dependencies occur. In the present paper, a general model is developed which covers what happens in practice in a

  8. Personalized medicine: Genetic risk prediction of drug response.

    Science.gov (United States)

    Zhang, Ge; Nebert, Daniel W

    2017-07-01

    Pharmacogenomics (PGx), a substantial component of "personalized medicine", seeks to understand each individual's genetic composition to optimize drug therapy -- maximizing beneficial drug response, while minimizing adverse drug reactions (ADRs). Drug responses are highly variable because innumerable factors contribute to ultimate phenotypic outcomes. Recent genome-wide PGx studies have provided some insight into genetic basis of variability in drug response. These can be grouped into three categories. [a] Monogenic (Mendelian) traits include early examples mostly of inherited disorders, and some severe (idiosyncratic) ADRs typically influenced by single rare coding variants. [b] Predominantly oligogenic traits represent variation largely influenced by a small number of major pharmacokinetic or pharmacodynamic genes. [c] Complex PGx traits resemble most multifactorial quantitative traits -- influenced by numerous small-effect variants, together with epigenetic effects and environmental factors. Prediction of monogenic drug responses is relatively simple, involving detection of underlying mutations; due to rarity of these events and incomplete penetrance, however, prospective tests based on genotype will have high false-positive rates, plus pharmacoeconomics will require justification. Prediction of predominantly oligogenic traits is slowly improving. Although a substantial fraction of variation can be explained by limited numbers of large-effect genetic variants, uncertainty in successful predictions and overall cost-benefit ratios will make such tests elusive for everyday clinical use. Prediction of complex PGx traits is almost impossible in the foreseeable future. Genome-wide association studies of large cohorts will continue to discover relevant genetic variants; however, these small-effect variants, combined, explain only a small fraction of phenotypic variance -- thus having limited predictive power and clinical utility. Copyright © 2017 Elsevier Inc. All

  9. Motivational state and reward content determine choice behavior under risk in mice.

    Directory of Open Access Journals (Sweden)

    Mona Leblond

    Full Text Available Risk is a ubiquitous feature of the environment for most organisms, who must often choose between a small and certain reward and a larger but less certain reward. To study choice behavior under risk in a genetically well characterized species, we trained mice (C57BL/6 on a discrete trial, concurrent-choice task in which they must choose between two levers. Pressing one lever (safe choice is always followed by a small reward. Pressing the other lever (risky choice is followed by a larger reward, but only on some of the trials. The overall payoff is the same on both levers. When mice were not food deprived, they were indifferent to risk, choosing both levers with equal probability regardless of the level of risk. In contrast, following food or water deprivation, mice earning 10% sucrose solution were risk-averse, though the addition of alcohol to the sucrose solution dose-dependently reduced risk aversion, even before the mice became intoxicated. Our results falsify the budget rule in optimal foraging theory often used to explain behavior under risk. Instead, they suggest that the overall demand or desired amount for a particular reward determines risk preference. Changes in motivational state or reward identity affect risk preference by changing demand. Any manipulation that increases the demand for a reward also increases risk aversion, by selectively increasing the frequency of safe choices without affecting frequency of risky choices.

  10. Risk related behaviour under different ambient scent conditions

    Directory of Open Access Journals (Sweden)

    Alina Gagarina

    2016-09-01

    Full Text Available The article analyses the effect of two ambient scents (peppermint and vanilla and their intensiveness on risk related behaviour that is expressed through selected decision making heuristics. Purpose of the article: The purpose of this article is to identify the relationship of ambient scent type and intensiveness with risk related behaviour that is expressed through selected decision making heuristics. Methodology/methods: 2×2 factorial experiment with control group was run. Ambient scent type (vanilla vs. peppermint and intensiveness (8 (1mg vs. 16 sprays (2mg of scent concentrate in the same room were manipulated as between subject variables. Risk aversion, effect of anchoring heuristic on bidding, and affect (risk and benefit heuristics were tracked as dependent variables. Scientific aim: To identify whether ambient scent type and intensiveness have effect on risk related behaviour. Findings: Evidence suggests that there are effects of ambient scent on risk related behaviour, thus fulfilling the missing gap to relate ambient environment to decision making heuristics when risks are involved. However, not all heuristics were affected by experimental conditions. Subjects were bidding significantly higher amounts under low anchor conditions, when peppermint scent was around (if compared to vanilla group. Affect risk was perceived as lower in peppermint ambient scent conditions, if compared to the control group. Intensity of ambient scent also had influence on affect risk: subjects perceived less risk under high scent intensity conditions. Conclusions: By manipulating ambient scent, marketers may reduce or increase consumers risk perception and behaviour and as a consequence influence their purchase decisions. Marketers could use peppermint scent in high intensiveness in the situations where they want consumers to undertake higher risks (expensive purchases, gambling, insurance, since stakes were higher under peppermint ambient scent condition

  11. Genetic risk factors for ovarian cancer and their role for endometriosis risk.

    Science.gov (United States)

    Burghaus, Stefanie; Fasching, Peter A; Häberle, Lothar; Rübner, Matthias; Büchner, Kathrin; Blum, Simon; Engel, Anne; Ekici, Arif B; Hartmann, Arndt; Hein, Alexander; Beckmann, Matthias W; Renner, Stefan P

    2017-04-01

    Several genetic variants have been validated as risk factors for ovarian cancer. Endometriosis has also been described as a risk factor for ovarian cancer. Identifying genetic risk factors that are common to the two diseases might help improve our understanding of the molecular pathogenesis potentially linking the two conditions. In a hospital-based case-control analysis, 12 single nucleotide polymorphisms (SNPs), validated by the Ovarian Cancer Association Consortium (OCAC) and the Collaborative Oncological Gene-environment Study (COGS) project, were genotyped using TaqMan® OpenArray™ analysis. The cases consisted of patients with endometriosis, and the controls were healthy individuals without endometriosis. A total of 385 cases and 484 controls were analyzed. Odds ratios and P values were obtained using simple logistic regression models, as well as from multiple logistic regression models with adjustment for clinical predictors. rs11651755 in HNF1B was found to be associated with endometriosis in this case-control study. The OR was 0.66 (95% CI, 0.51 to 0.84) and the P value after correction for multiple testing was 0.01. None of the other genotypes was associated with a risk for endometriosis. As rs11651755 in HNF1B modified both the ovarian cancer risk and also the risk for endometriosis, HNF1B may be causally involved in the pathogenetic pathway leading from endometriosis to ovarian cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. What risk assessments of genetically modified organisms can learn from institutional analyses of public health risks.

    Science.gov (United States)

    Rajan, S Ravi; Letourneau, Deborah K

    2012-01-01

    The risks of genetically modified organisms (GMOs) are evaluated traditionally by combining hazard identification and exposure estimates to provide decision support for regulatory agencies. We question the utility of the classical risk paradigm and discuss its evolution in GMO risk assessment. First, we consider the problem of uncertainty, by comparing risk assessment for environmental toxins in the public health domain with genetically modified organisms in the environment; we use the specific comparison of an insecticide to a transgenic, insecticidal food crop. Next, we examine normal accident theory (NAT) as a heuristic to consider runaway effects of GMOs, such as negative community level consequences of gene flow from transgenic, insecticidal crops. These examples illustrate how risk assessments are made more complex and contentious by both their inherent uncertainty and the inevitability of failure beyond expectation in complex systems. We emphasize the value of conducting decision-support research, embracing uncertainty, increasing transparency, and building interdisciplinary institutions that can address the complex interactions between ecosystems and society. In particular, we argue against black boxing risk analysis, and for a program to educate policy makers about uncertainty and complexity, so that eventually, decision making is not the burden that falls upon scientists but is assumed by the public at large.

  13. What Risk Assessments of Genetically Modified Organisms Can Learn from Institutional Analyses of Public Health Risks

    Directory of Open Access Journals (Sweden)

    S. Ravi Rajan

    2012-01-01

    Full Text Available The risks of genetically modified organisms (GMOs are evaluated traditionally by combining hazard identification and exposure estimates to provide decision support for regulatory agencies. We question the utility of the classical risk paradigm and discuss its evolution in GMO risk assessment. First, we consider the problem of uncertainty, by comparing risk assessment for environmental toxins in the public health domain with genetically modified organisms in the environment; we use the specific comparison of an insecticide to a transgenic, insecticidal food crop. Next, we examine normal accident theory (NAT as a heuristic to consider runaway effects of GMOs, such as negative community level consequences of gene flow from transgenic, insecticidal crops. These examples illustrate how risk assessments are made more complex and contentious by both their inherent uncertainty and the inevitability of failure beyond expectation in complex systems. We emphasize the value of conducting decision-support research, embracing uncertainty, increasing transparency, and building interdisciplinary institutions that can address the complex interactions between ecosystems and society. In particular, we argue against black boxing risk analysis, and for a program to educate policy makers about uncertainty and complexity, so that eventually, decision making is not the burden that falls upon scientists but is assumed by the public at large.

  14. DYNAMIC HYBRIDS UNDER SOLVENCY II: RISK ANALYSIS AND MODIFICATION POSSIBILITIES

    Directory of Open Access Journals (Sweden)

    Christian Maier

    2017-06-01

    Full Text Available In this study, we investigate the new and standardized European system of supervisory called Solvency II. In essence, asymmetric distribution of information between policyholder and insurer triggered this new regulation which aims at better protecting policyholders. Its three-pillar model is about to challenge both, insurers as well as policyholders. The first pillar includes quantitative aspects, the second pillar contains qualitative aspects and the third pillar comprises market transparency and reporting obligations. Underwriting risks, the default risk of a bank and market risks can be identified for the dynamic hybrid. Solvency II covers all these risks in the first pillar and insurers shall deposit sufficient risk-bearing capital. In our analysis, we first identify the dynamic hybrid specific risks under the Solvency II regime und then develop product modifications to reduce this risk.

  15. Can genetic pleiotropy replicate common clinical constellations of cardiovascular disease and risk?

    Science.gov (United States)

    Gottesman, Omri; Drill, Esther; Lotay, Vaneet; Bottinger, Erwin; Peter, Inga

    2012-01-01

    The relationship between obesity, diabetes, hyperlipidemia, hypertension, kidney disease and cardiovascular disease (CVD) is established when looked at from a clinical, epidemiological or pathophysiological perspective. Yet, when viewed from a genetic perspective, there is comparatively little data synthesis that these conditions have an underlying relationship. We sought to investigate the overlap of genetic variants independently associated with each of these commonly co-existing conditions from the NHGRI genome-wide association study (GWAS) catalog, in an attempt to replicate the established notion of shared pathophysiology and risk. We used pathway-based analyses to detect subsets of pleiotropic genes involved in similar biological processes. We identified 107 eligible GWAS studies related to CVD and its established comorbidities and risk factors and assigned genes that correspond to the associated signals based on their position. We found 44 positional genes shared across at least two CVD-related phenotypes that independently recreated the established relationship between the six phenotypes, but only if studies representing non-European populations were included. Seven genes revealed pleiotropy across three or more phenotypes, mostly related to lipid transport and metabolism. Yet, many genes had no relationship to each other or to genes with established functional connection. Whilst we successfully reproduced established relationships between CVD risk factors using GWAS findings, interpretation of biological pathways involved in the observed pleiotropy was limited. Further studies linking genetic variation to gene expression, as well as describing novel biological pathways will be needed to take full advantage of GWAS results.

  16. Can genetic pleiotropy replicate common clinical constellations of cardiovascular disease and risk?

    Directory of Open Access Journals (Sweden)

    Omri Gottesman

    Full Text Available The relationship between obesity, diabetes, hyperlipidemia, hypertension, kidney disease and cardiovascular disease (CVD is established when looked at from a clinical, epidemiological or pathophysiological perspective. Yet, when viewed from a genetic perspective, there is comparatively little data synthesis that these conditions have an underlying relationship. We sought to investigate the overlap of genetic variants independently associated with each of these commonly co-existing conditions from the NHGRI genome-wide association study (GWAS catalog, in an attempt to replicate the established notion of shared pathophysiology and risk. We used pathway-based analyses to detect subsets of pleiotropic genes involved in similar biological processes. We identified 107 eligible GWAS studies related to CVD and its established comorbidities and risk factors and assigned genes that correspond to the associated signals based on their position. We found 44 positional genes shared across at least two CVD-related phenotypes that independently recreated the established relationship between the six phenotypes, but only if studies representing non-European populations were included. Seven genes revealed pleiotropy across three or more phenotypes, mostly related to lipid transport and metabolism. Yet, many genes had no relationship to each other or to genes with established functional connection. Whilst we successfully reproduced established relationships between CVD risk factors using GWAS findings, interpretation of biological pathways involved in the observed pleiotropy was limited. Further studies linking genetic variation to gene expression, as well as describing novel biological pathways will be needed to take full advantage of GWAS results.

  17. Legume genetic resources and transcriptome dynamics under abiotic stress conditions.

    Science.gov (United States)

    Abdelrahman, Mostafa; Jogaiah, Sudisha; Burritt, David J; Tran, Lam-Son Phan

    2018-01-04

    Grain legumes are an important source of nutrition and income for billions of consumers and farmers around the world. However, the low productivity of new legume varieties, due to the limited genetic diversity available for legume breeding programmes and poor policymaker support, combined with an increasingly unpredictable global climate is resulting in a large gap between current yields and the increasing demand for legumes as food. Hence, there is a need for novel approaches to develop new high-yielding legume cultivars that are able to cope with a range of environmental stressors. Next-generation technologies are providing the tools that could enable the more rapid and cost-effective genomic and transcriptomic studies for most major crops, allowing the identification of key functional and regulatory genes involved in abiotic stress resistance. In this review, we provide an overview of the recent achievements regarding abiotic stress resistance in a wide range of legume crops and highlight the transcriptomic and miRNA approaches that have been used. In addition, we critically evaluate the availability and importance of legume genetic resources with desirable abiotic stress resistance traits. © 2018 John Wiley & Sons Ltd.

  18. A simple genetic architecture underlies morphological variation in dogs.

    Directory of Open Access Journals (Sweden)

    Adam R Boyko

    2010-08-01

    Full Text Available Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms (SNPs. Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (< or = 3 explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness. Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species.

  19. Risk Perception and Psychological Distress in Genetic Counselling for Hereditary Breast and/or Ovarian Cancer.

    Science.gov (United States)

    Cicero, G; De Luca, R; Dorangricchia, P; Lo Coco, G; Guarnaccia, C; Fanale, D; Calò, V; Russo, A

    2017-10-01

    Oncological Genetic Counselling (CGO) allows the identification of a genetic component that increases the risk of developing a cancer. Individuals' psychological reactions are influenced by both the content of the received information and the subjective perception of their own risk of becoming ill or being a carrier of a genetic mutation. This study included 120 participants who underwent genetic counselling for breast and/or ovarian cancer. The aim of the study was to examine the relation between their cancer risk perception and the genetic risk during CGO before receiving genetic test results, considering the influence of some psychological variables, in particular distress, anxiety and depression. Participants completed the following tools during a psychological interview: a socio-demographic form, Cancer Risk Perception (CRP) and Genetic Risk Perception (GRP), Hospital Anxiety and Depression Scale (HADS) and Distress Thermometer (DT). The data seem to confirm our hypothesis. Positive and significant correlations were found between the observed variables. Moreover, genetic risk perception determined an increase in depressive symptomatology and cancer risk perception led to an increase in anxious symptomatology, specifically in participants during cancer treatment. The present results suggest the importance of assessing genetic and cancer risk perception in individuals who undergo CGO, to identify those who are at risk of a decrease in psychological well-being and of developing greater psychological distress.

  20. Making sense of risk diagnosis in case of prenatal and reproductive genetic counselling for neuromuscular diseases.

    Science.gov (United States)

    Zaccaro, Antonella; Freda, Maria Francesca

    2014-03-01

    This study explored the processes of significance about the risk communication in prenatal/preconception setting within 1 month to the end of genetic counselling intervention. Participants were all attending a programme of Cardiomyology and Medical Genetics in Naples, Italy, for the first time. Transcripts of 18 semi-structured interviews were analysed using interpretative phenomenological analysis. Themes arising included the following: the familiar outcomes of genetic counselling, the risk representation and the impacts on decision-making. The findings suggest the significance of the experience of genetic risk and the implications for the support of individuals and their family after the conclusion of the genetic counselling intervention.

  1. Genetic dissection of seed vigour traits in maize (Zea mays L.) under ...

    Indian Academy of Sciences (India)

    [Shi Y., Li G., Tian Z., Wang Z., Wang X., Zhu Y., Chen Y., Guo S., Qi J., Zhang X. and Ku L. 2016 Genetic dissection of seed vigour traits in maize (Zea mays L.) under low-temperature conditions. J. Genet. 95, 1017–1022]. Introduction. Seed vigour, an important factor governing the seed qual- ity, reflects potential seed ...

  2. Genetic risk prediction and neurobiological understanding of alcoholism.

    Science.gov (United States)

    Levey, D F; Le-Niculescu, H; Frank, J; Ayalew, M; Jain, N; Kirlin, B; Learman, R; Winiger, E; Rodd, Z; Shekhar, A; Schork, N; Kiefer, F; Kiefe, F; Wodarz, N; Müller-Myhsok, B; Dahmen, N; Nöthen, M; Sherva, R; Farrer, L; Smith, A H; Kranzler, H R; Rietschel, M; Gelernter, J; Niculescu, A B

    2014-05-20

    We have used a translational Convergent Functional Genomics (CFG) approach to discover genes involved in alcoholism, by gene-level integration of genome-wide association study (GWAS) data from a German alcohol dependence cohort with other genetic and gene expression data, from human and animal model studies, similar to our previous work in bipolar disorder and schizophrenia. A panel of all the nominally significant P-value SNPs in the top candidate genes discovered by CFG  (n=135 genes, 713 SNPs) was used to generate a genetic  risk prediction score (GRPS), which showed a trend towards significance (P=0.053) in separating  alcohol dependent individuals from controls in an independent German test cohort. We then validated and prioritized our top findings from this discovery work, and subsequently tested them in three independent cohorts, from two continents. A panel of all the nominally significant P-value single-nucleotide length polymorphisms (SNPs) in the top candidate genes discovered by CFG (n=135 genes, 713 SNPs) were used to generate a Genetic Risk Prediction Score (GRPS), which showed a trend towards significance (P=0.053) in separating alcohol-dependent individuals from controls in an independent German test cohort. In order to validate and prioritize the key genes that drive behavior without some of the pleiotropic environmental confounds present in humans, we used a stress-reactive animal model of alcoholism developed by our group, the D-box binding protein (DBP) knockout mouse, consistent with the surfeit of stress theory of addiction proposed by Koob and colleagues. A much smaller panel (n=11 genes, 66 SNPs) of the top CFG-discovered genes for alcoholism, cross-validated and prioritized by this stress-reactive animal model showed better predictive ability in the independent German test cohort (P=0.041). The top CFG scoring gene for alcoholism from the initial discovery step, synuclein alpha (SNCA) remained the top gene after the stress

  3. Lobular breast cancer: incidence and genetic and non-genetic risk factors.

    Science.gov (United States)

    Dossus, Laure; Benusiglio, Patrick R

    2015-03-13

    While most invasive breast cancers consist of carcinomas of the ductal type, about 10% are invasive lobular carcinomas. Invasive lobular and ductal carcinomas differ with respect to risk factors. Invasive lobular carcinoma is more strongly associated with exposure to female hormones, and therefore its incidence is more subject to variation. This is illustrated by US figures during the 1987 to 2004 period: after 12 years of increases, breast cancer incidence declined steadily from 1999 to 2004, reflecting among other causes the decreasing use of menopausal hormone therapy, and these variations were stronger for invasive lobular than for invasive ductal carcinoma. Similarly, invasive lobular carcinoma is more strongly associated with early menarche, late menopause and late age at first birth. As for genetic risk factors, four high-penetrance genes are tested in clinical practice when genetic susceptibility to breast cancer is suspected, BRCA1, BRCA2, TP53 and CDH1. Germline mutations in BRCA1 and TP53 are predominantly associated with invasive ductal carcinoma, while BRCA2 mutations are associated with both ductal and lobular cancers. CDH1, the gene coding for the E-cadherin adhesion protein, is of special interest as mutations are associated with invasive lobular carcinoma, but never with ductal carcinoma. It was initially known as the main susceptibility gene for gastric cancer of the diffuse type, but the excess of breast cancers of the lobular type in CDH1 families led researchers to identify it also as a susceptibility gene for invasive lobular carcinoma. The risk of invasive lobular carcinoma is high in female mutation carriers, as about 50% are expected to develop the disease. Carriers must therefore undergo intensive breast cancer screening, with, for example, yearly magnetic resonance imaging and mammogram starting at age 30 years.

  4. BRCA Genetic Counseling Among At-Risk Latinas in New York City: New Beliefs Shape New Generation

    Science.gov (United States)

    Edwards, Tiffany; Villagra, Cristina; Rodriguez, M. Carina; Thompson, Hayley S.; Jandorf, Lina; Valdimarsdottir, Heiddis B.

    2015-01-01

    Despite the life-saving information that genetic counseling can provide for women at hereditary breast and/or ovarian cancer (HBOC) risk, Latinas disproportionately underuse such services. Understanding Latinas’ beliefs and attitudes about BRCA genetic counseling may be the key to better health promotion within this underserved, at-risk group. We conducted 12 focus groups (N=54) with at-risk Latina women in New York City, followed by 30 in-depth interviews among a subset of the focus group women. Both were professionally transcribed, translated where applicable and data analysis was completed by two coders trained in qualitative methods. Results revealed personal and community knowledge about BRCA genetic counseling was relatively low, although women felt largely positive about counseling. The main motivator to undergo genetic counseling was concerns about learning family members’ cancer status, while the main barrier was competing demands. Generational differences were apparent, with younger women (approximately machismo, fatalismo, destino) to undergoing genetic counseling. Participants were largely enthusiastic about educational efforts to increase awareness of genetic counseling among Latinos. Revealing the beliefs and attitudes of underserved Latinas may help shape culturally appropriate educational materials and promotion programs to increase BRCA genetic counseling uptake within this under-represented community. PMID:25120034

  5. Blood lipid genetic scores, the HMGCR gene and cancer risk: a Mendelian randomization study.

    Science.gov (United States)

    Orho-Melander, Marju; Hindy, George; Borgquist, Signe; Schulz, Christina-Alexandra; Manjer, Jonas; Melander, Olle; Stocks, Tanja

    2017-11-20

    It is unclear whether there are causal associations between blood lipids, statin use and cancer risks. Under certain assumptions, Mendelian randomization analysis of a genetic marker for an exposure eliminates reverse causation and confounding. We applied Mendelian randomization analysis to genetic scores, comprising 26-41 single-nucleotide polymorphisms (SNPs), as instrumental variables (IVs) for triglycerides and low- and high-density lipoprotein cholesterol (LDLC, HDLC), using a prospective cohort of 26 904 individuals in which there were 6607 incident cancers. We also investigated cancer risk for a SNP (rs12916) in the gene encoding hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the targeted enzyme in statin treatment. We used logistic regression and SNP pleiotropy-adjusted analyses to estimate the odds ratio per standard deviation (OR). The OR for the triglyceride IV as a predictor of any cancer was 0.91 [95% confidence interval (CI): 0.80-1.03] unadjusted, and 0.87 (95% CI: 0.78-0.95) from the pleiotropy-adjusted analysis. For the HMGCR rs12916 per LDLC-lowering T-allele, the OR was 1.09 (95% CI: 1.01-1.18) for prostate cancer and 0.89 (95% CI: 0.82-0.96) for breast cancer. The LDLC IV was not associated with prostate cancer or breast cancer. There were no associations between IVs and cancers of the lung, colon or bladder. Under the assumptions of Mendelian randomization, there is a causal and negative association between serum triglycerides and risk of any cancer. Further, the HMGCR genetic variant might be associated with risks of prostate and breast cancers but the biological mechanisms behind these findings are unclear, as the LDLC IV was not associated with these cancers. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

  6. Performance of diverse wheat genetic stocks under moisture stress condition

    International Nuclear Information System (INIS)

    Seher, M.; Shabbir, G.; Rasheed, A.

    2015-01-01

    This study was conducted to evaluate divergent wheat germplasm for their performance under drought and control conditions. The germplasm consists of wheat land races of Pakistan, advanced D-genome synthetic derivatives and high yielding varieties of Pakistan. This wide array of germplasm was selected to identify sources, which can be opted later by the wheat breeders while breeding for drought tolerance. The evaluation parameters involved some important physiochemical testing and morphological characteristics in the field under drought and control conditions. Based on these parameters, 13 wheat genotypes were selected on the basis of their best performance regarding morphological and physiological parameters. These genotypes exhibited higher yield under drought stress conditions and increased percentage of proline, sugar, SOD and protein content under laboratory conditions as compared to the susceptible genotypes. Correlation studies revealed that grains per spike (GPS) and thousand grain weight (TGW) had direct relationship with spike length (SL), proline and sugar content under both control and drought conditions. Thus, these parameters can be used as selection criteria for the identification of tolerant genotypes. (author)

  7. Genetic variation of loci potentially under selection confounds species-genetic diversity correlations in a fragmented habitat.

    Science.gov (United States)

    Bertin, Angeline; Gouin, Nicolas; Baumel, Alex; Gianoli, Ernesto; Serratosa, Juan; Osorio, Rodomiro; Manel, Stephanie

    2017-01-01

    Positive species-genetic diversity correlations (SGDCs) are often thought to result from the parallel influence of neutral processes on genetic and species diversity. Yet, confounding effects of non-neutral mechanisms have not been explored. Here, we investigate the impact of non-neutral genetic diversity on SGDCs in high Andean wetlands. We compare correlations between plant species diversity and genetic diversity (GD) calculated with and without loci potentially under selection (outlier loci). The study system includes 2188 specimens from five species (three common aquatic macroinvertebrate and two dominant plant species) that were genotyped for 396 amplified fragment length polymorphism loci. We also appraise the importance of neutral processes on SGDCs by investigating the influence of habitat fragmentation features. Significant positive SGDCs were detected for all five species (mean SGDC = 0.52 ± 0.05). While only a few outlier loci were detected in each species, they resulted in significant decreases in GD and in SGDCs. This supports the hypothesis that neutral processes drive species-genetic diversity relationships in high Andean wetlands. Unexpectedly, the effects on genetic diversity GD of the habitat fragmentation characteristics in this study increased with the presence of outlier loci in two species. Overall, our results reveal pitfalls in using habitat features to infer processes driving SGDCs and show that a few loci potentially under selection are enough to cause a significant downward bias in SGDC. Investigating confounding effects of outlier loci thus represents a useful approach to evidence the contribution of neutral processes on species-genetic diversity relationships. © 2016 John Wiley & Sons Ltd.

  8. Investigating Gender Differences under Time Pressure in Financial Risk Taking.

    Science.gov (United States)

    Xie, Zhixin; Page, Lionel; Hardy, Ben

    2017-01-01

    There is a significant gender imbalance on financial trading floors. This motivated us to investigate gender differences in financial risk taking under pressure. We used a well-established approach from behavior economics to analyze a series of risky monetary choices by male and female participants with and without time pressure. We also used second to fourth digit ratio (2D:4D) and face width-to-height ratio (fWHR) as correlates of pre-natal exposure to testosterone. We constructed a structural model and estimated the participants' risk attitudes and probability perceptions via maximum likelihood estimation under both expected utility (EU) and rank-dependent utility (RDU) models. In line with existing research, we found that male participants are less risk averse and that the gender gap in risk attitudes increases under moderate time pressure. We found that female participants with lower 2D:4D ratios and higher fWHR are less risk averse in RDU estimates. Males with lower 2D:4D ratios were less risk averse in EU estimations, but more risk averse using RDU estimates. We also observe that men whose ratios indicate a greater prenatal exposure to testosterone exhibit a greater optimism and overestimation of small probabilities of success.

  9. Investigating Gender Differences under Time Pressure in Financial Risk Taking

    Directory of Open Access Journals (Sweden)

    Zhixin Xie

    2017-12-01

    Full Text Available There is a significant gender imbalance on financial trading floors. This motivated us to investigate gender differences in financial risk taking under pressure. We used a well-established approach from behavior economics to analyze a series of risky monetary choices by male and female participants with and without time pressure. We also used second to fourth digit ratio (2D:4D and face width-to-height ratio (fWHR as correlates of pre-natal exposure to testosterone. We constructed a structural model and estimated the participants' risk attitudes and probability perceptions via maximum likelihood estimation under both expected utility (EU and rank-dependent utility (RDU models. In line with existing research, we found that male participants are less risk averse and that the gender gap in risk attitudes increases under moderate time pressure. We found that female participants with lower 2D:4D ratios and higher fWHR are less risk averse in RDU estimates. Males with lower 2D:4D ratios were less risk averse in EU estimations, but more risk averse using RDU estimates. We also observe that men whose ratios indicate a greater prenatal exposure to testosterone exhibit a greater optimism and overestimation of small probabilities of success.

  10. Genome-wide Association Study of Cannabis Dependence Severity, Novel Risk Variants, and Shared Genetic Risks.

    Science.gov (United States)

    Sherva, Richard; Wang, Qian; Kranzler, Henry; Zhao, Hongyu; Koesterer, Ryan; Herman, Aryeh; Farrer, Lindsay A; Gelernter, Joel

    2016-05-01

    Cannabis dependence (CAD) is a serious problem worldwide and is of growing importance in the United States because cannabis is increasingly available legally. Although genetic factors contribute substantially to CAD risk, at present no well-established specific genetic risk factors for CAD have been elucidated. To report findings for DSM-IV CAD criteria from association analyses performed in large cohorts of African American and European American participants from 3 studies of substance use disorder genetics. This genome-wide association study for DSM-IV CAD criterion count was performed in 3 independent substance dependence cohorts (the Yale-Penn Study, Study of Addiction: Genetics and Environment [SAGE], and International Consortium on the Genetics of Heroin Dependence [ICGHD]). A referral sample and volunteers recruited in the community and from substance abuse treatment centers included 6000 African American and 8754 European American participants, including some from small families. Participants from the Yale-Penn Study were recruited from 2000 to 2013. Data were collected for the SAGE trial from 1990 to 2007 and for the ICGHD from 2004 to 2009. Data were analyzed from January 2, 2013, to November 9, 2015. Criterion count for DSM-IV CAD. Among the 14 754 participants, 7879 were male, 6875 were female, and the mean (SD) age was 39.2 (10.2) years. Three independent regions with genome-wide significant single-nucleotide polymorphism associations were identified, considering the largest possible sample. These included rs143244591 (β = 0.54, P = 4.32 × 10-10 for the meta-analysis) in novel antisense transcript RP11-206M11.7;rs146091982 (β = 0.54, P = 1.33 × 10-9 for the meta-analysis) in the solute carrier family 35 member G1 gene (SLC35G1); and rs77378271 (β = 0.29, P = 2.13 × 10-8 for the meta-analysis) in the CUB and Sushi multiple domains 1 gene (CSMD1). Also noted was evidence of genome-level pleiotropy between CAD and

  11. Genetic risk profiles for cancer susceptibility and therapy response.

    Science.gov (United States)

    Bartsch, Helmut; Dally, Heike; Popanda, Odilia; Risch, Angela; Schmezer, Peter

    2007-01-01

    Cells in the body are permanently attacked by DNA-reactive species, both from intracellular and environmental sources. Inherited and acquired deficiencies in host defense mechanisms against DNA damage (metabolic and DNA repair enzymes) can modify cancer susceptibility as well as therapy response. Genetic profiles should help to identify high-risk individuals who subsequently can be enrolled in preventive measures or treated by tailored therapy regimens. Some of our attempts to define such risk profiles are presented. Cancer susceptibility: Single nucleotide polymorphisms (SNPs) in metabolic and repair genes were investigated in a hospital-based lung cancer case-control study. When evaluating the risk associated with different genotypes for N-acetyltransferases (Wikman et al. 2001) and glutathione-S-transferases (Risch et al. 2001), it is mandatory to distinguish between the three major histological subtypes of lung tumors. A promoter polymorphism of the myeloperoxidase gene MPO was shown to decrease lung cancer susceptibility mainly in small cell lung cancer (SCLC) (Dally et al. 2002). The CYP3A4*1B allele was also linked to an increased SCLC risk and in smoking women increased the risk of lung cancer eightfold (Dally et al. 2003b). Polymorphisms in DNA repair genes were shown to modulate lung cancer risk in smokers, and reduced DNA repair capacity elevated the disease risk (Rajaee-Behbahani et al. 2001). Investigations of several DNA repair gene variants revealed that lung cancer risk was only moderately affected by a single variant but was enhanced up to approximately threefold by specific risk allele combinations (Popanda et al. 2004). Therapy response: Inter-individual differences in therapy response are consistently observed with cancer chemotherapeutic agents. Initial results from ongoing studies showed that certain polymorphisms in drug transporter genes (ABCB1) differentially affect response outcome in histological subgroups of lung cancer. Stronger

  12. Genetics of Triglycerides and the Risk of Atherosclerosis.

    Science.gov (United States)

    Dron, Jacqueline S; Hegele, Robert A

    2017-07-01

    Plasma triglycerides are routinely measured with a lipid profile, and elevated plasma triglycerides are commonly encountered in the clinic. The confounded nature of this trait, which is correlated with numerous other metabolic perturbations, including depressed high-density lipoprotein cholesterol (HDL-C), has thwarted efforts to directly implicate triglycerides as causal in atherogenesis. Human genetic approaches involving large-scale populations and high-throughput genomic assessment under a Mendelian randomization framework have undertaken to sort out questions of causality. We review recent large-scale meta-analyses of cohorts and population-based sequencing studies designed to address whether common and rare variants in genes whose products are determinants of plasma triglycerides are also associated with clinical cardiovascular endpoints. The studied loci include genes encoding lipoprotein lipase and proteins that interact with it, such as apolipoprotein (apo) A-V, apo C-III and angiopoietin-like proteins 3 and 4, and common polymorphisms identified in genome-wide association studies. Triglyceride-raising variant alleles of these genes showed generally strong associations with clinical cardiovascular endpoints. However, in most cases, a second lipid disturbance-usually depressed HDL-C-was concurrently associated. While the findings collectively shift our understanding towards a potential causal role for triglycerides, we still cannot rule out the possibilities that triglycerides are a component of a joint phenotype with low HDL-C or that they are but markers of deeper causal metabolic disturbances that are not routinely measured in epidemiological-scale genetic studies.

  13. Problems and solutions in the estimation of genetic risks from radiation and chemicals

    International Nuclear Information System (INIS)

    Russell, W.L.

    1980-01-01

    Extensive investigations with mice on the effects of various physical and biological factors, such as dose rate, sex and cell stage, on radiation-induced mutation have provided an evaluation of the genetics hazards of radiation in man. The mutational results obtained in both sexes with progressive lowering of the radiation dose rate have permitted estimation of the mutation frequency expected under the low-level radiation conditions of most human exposure. Supplementing the studies on mutation frequency are investigations on the phenotypic effects of mutations in mice, particularly anatomical disorders of the skeleton, which allow an estimation of the degree of human handicap associated with the occurrence of parallel defects in man. Estimation of the genetic risk from chemical mutagens is much more difficult, and the research is much less advanced. Results on transmitted mutations in mice indicate a poor correlation with mutation induction in non-mammalian organisms

  14. Problems and solutions in the estimation of genetic risks from radiation and chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Russell, W. L.

    1980-01-01

    Extensive investigations with mice on the effects of various physical and biological factors, such as dose rate, sex and cell stage, on radiation-induced mutation have provided an evaluation of the genetics hazards of radiation in man. The mutational results obtained in both sexes with progressive lowering of the radiation dose rate have permitted estimation of the mutation frequency expected under the low-level radiation conditions of most human exposure. Supplementing the studies on mutation frequency are investigations on the phenotypic effects of mutations in mice, particularly anatomical disorders of the skeleton, which allow an estimation of the degree of human handicap associated with the occurrence of parallel defects in man. Estimation of the genetic risk from chemical mutagens is much more difficult, and the research is much less advanced. Results on transmitted mutations in mice indicate a poor correlation with mutation induction in non-mammalian organisms.

  15. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease.

    Science.gov (United States)

    Imhann, Floris; Vich Vila, Arnau; Bonder, Marc Jan; Fu, Jingyuan; Gevers, Dirk; Visschedijk, Marijn C; Spekhorst, Lieke M; Alberts, Rudi; Franke, Lude; van Dullemen, Hendrik M; Ter Steege, Rinze W F; Huttenhower, Curtis; Dijkstra, Gerard; Xavier, Ramnik J; Festen, Eleonora A M; Wijmenga, Cisca; Zhernakova, Alexandra; Weersma, Rinse K

    2018-01-01

    Patients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case-control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD. Stool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2 , CARD9 , ATG16L1 , IRGM and FUT2 . Strikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10 -13 ). We show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. Decision making under ambiguity but not under risk is related to problem gambling severity

    NARCIS (Netherlands)

    Brevers, Damien; Cleeremans, Axel; Goudriaan, Anna E.; Bechara, Antoine; Kornreich, Charles; Verbanck, Paul; Noël, Xavier

    2012-01-01

    The aim of the present study was to examine the relationship between problem gambling severity and decision-making situations that vary in two degrees of uncertainty (probability of outcome is known: decision-making under risk; probability of outcome is unknown: decision-making under ambiguity). For

  17. Continuous Time Portfolio Selection under Conditional Capital at Risk

    Directory of Open Access Journals (Sweden)

    Gordana Dmitrasinovic-Vidovic

    2010-01-01

    Full Text Available Portfolio optimization with respect to different risk measures is of interest to both practitioners and academics. For there to be a well-defined optimal portfolio, it is important that the risk measure be coherent and quasiconvex with respect to the proportion invested in risky assets. In this paper we investigate one such measure—conditional capital at risk—and find the optimal strategies under this measure, in the Black-Scholes continuous time setting, with time dependent coefficients.

  18. A method for minimum risk portfolio optimization under hybrid uncertainty

    Science.gov (United States)

    Egorova, Yu E.; Yazenin, A. V.

    2018-03-01

    In this paper, we investigate a minimum risk portfolio model under hybrid uncertainty when the profitability of financial assets is described by fuzzy random variables. According to Feng, the variance of a portfolio is defined as a crisp value. To aggregate fuzzy information the weakest (drastic) t-norm is used. We construct an equivalent stochastic problem of the minimum risk portfolio model and specify the stochastic penalty method for solving it.

  19. Climate change policy in a growing economy under catastrophic risks

    OpenAIRE

    Tsur, Yacov; Zemel, Amos

    2007-01-01

    Under risk of catastrophic climate change, the occurrence hazard is added to the social discount rate. As a result, the social discount rate (i) increases and (ii) turns endogenous to the global warming policy. The second effect bears profound policy implications that are magnifed by economic growth. In particular, it implies that green- house gases (GHG) emission should gradually be brought to a halt. Due to the public bad nature of the catastrophic risk, the second effect is ignored in a co...

  20. Kalirin: a novel genetic risk factor for ischemic stroke.

    Science.gov (United States)

    Krug, Tiago; Manso, Helena; Gouveia, Liliana; Sobral, João; Xavier, Joana M; Albergaria, Isabel; Gaspar, Gisela; Correia, Manuel; Viana-Baptista, Miguel; Simões, Rita Moiron; Pinto, Amélia Nogueira; Taipa, Ricardo; Ferreira, Carla; Fontes, João Ramalho; Silva, Mário Rui; Gabriel, João Paulo; Matos, Ilda; Lopes, Gabriela; Ferro, José M; Vicente, Astrid M; Oliveira, Sofia A

    2010-03-01

    Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene with susceptibility to cardiovascular and metabolic phenotypes, but no studies have yet been performed in stroke patients. KALRN is involved, among others, in the inhibition of inducible nitric oxide synthase, in the regulation of ischemic signal transduction, and in neuronal morphogenesis, plasticity, and stability. The goal of the present study was to determine whether SNPs in the KALRN region on 3q13, which includes the Ropporin gene (ROPN1), predispose to ischemic stroke (IS) in a cohort of Portuguese patients and controls. We genotyped 34 tagging SNPs in the KALRN and ROPN1 chromosomal region on 565 IS patients and 517 unrelated controls, and performed genotype imputation for 405 markers on chromosome 3. We tested the single-marker association of these SNPs with IS. One SNP (rs4499545) in the ROPN1-KALRN intergenic region and two SNPs in KALRN (rs17286604 and rs11712619) showed significant (P < 0.05) allelic and genotypic (unadjusted and adjusted for hypertension, diabetes, and ever smoking) association with IS risk. Thirty-two imputed SNPs also showed an association at P < 0.05, and actual genotyping of three of these polymorphisms (rs7620580, rs6438833, and rs11712039) validated their association. Furthermore, rs11712039 was associated with IS (0.001 < P < 0.01) in a recent well-powered genomewide association study (Ikram et al. 2009). These studies suggest that variants in the KALRN gene region constitute risk factors for stroke and that KALRN may represent a common risk factor for vascular diseases.

  1. A genetic risk score predicts cardiovascular events in patients with stable coronary artery disease

    DEFF Research Database (Denmark)

    Christiansen, Morten Krogh; Nyegaard, Mette; Larsen, Sanne Bøjet

    2017-01-01

    BACKGROUND: Genetic risk scores (GRSs) may predict cardiovascular risk in community-based populations. However, studies investigating the association with recurrent cardiovascular events in patients with established coronary artery disease (CAD) are conflicting. METHODS: We genotyped 879 patients...

  2. Identification of Hotspots of Genetic Risk for Type 2 Diabetes Using GIS Methods

    Science.gov (United States)

    BACKGROUND: Having the ability to scan the entire country for potential "hotspots" with increased risk of developing chronic diseases due to various environmental, demographic, and genetic susceptibility factors may inform risk management decisions and enable better env...

  3. Pediatric Predispositional Genetic Risk Communication: Potential Utility for Prevention and Control of Melanoma Risk as an Exemplar.

    Science.gov (United States)

    Wu, Yelena P; Mays, Darren; Kohlmann, Wendy; Tercyak, Kenneth P

    2017-10-01

    Predispositional genetic testing among minor children is intensely debated due to the potential benefits and harms of providing this type of genetic information to children and their families. Existing guidelines on pediatric genetic testing state that predispositional testing could be appropriate for minors if preventive services exist that mitigate children's risk for or severity of the health condition in question. We use the example of hereditary melanoma to illustrate the rationale for and potential application of genetic risk communication for an adult-onset cancer to a pediatric population where childhood behaviors may reduce risk of disease later in life. We draw from the adult melanoma genetic risk communication and pediatric health behavior change literatures to suggest ways in which genetic test reporting and complementary education could be delivered to children who carry a hereditary risk for melanoma and their families in order to foster children's engagement in melanoma preventive behaviors. Genetic discoveries will continue to yield new opportunities to provide predispositional genetic risk information to unaffected individuals, including children, and could be delivered within programs that provide personalized and translational approaches to cancer prevention.

  4. Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD.

    Science.gov (United States)

    Guo, W; Samuels, J F; Wang, Y; Cao, H; Ritter, M; Nestadt, P S; Krasnow, J; 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; Cullen, B A; Piacentini, J; Pauls, D L; Bienvenu, O J; Stewart, S E; Goes, F S; Maher, B; Pulver, A E; Valle, D; Mattheisen, M; Qian, J; Nestadt, G; Shugart, Y Y

    2017-07-01

    Obsessive-compulsive disorder (OCD) and Autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders that conceivably share genetic risk factors. However, the underlying genetic determinants remain largely unknown. In this work, the authors describe a combined genome-wide association study (GWAS) of ASD and OCD. The OCD dataset includes 2998 individuals in nuclear families. The ASD dataset includes 6898 individuals in case-parents trios. GWAS summary statistics were examined for potential enrichment of functional variants associated with gene expression levels in brain regions. The top ranked SNP is rs4785741 (chromosome 16) with P value=6.9×10 -7 in our re-analysis. Polygenic risk score analyses were conducted to investigate the genetic relationship within and across the two disorders. These analyses identified a significant polygenic component of ASD, predicting 0.11% of the phenotypic variance in an independent OCD data set. In addition, we examined the genomic architecture of ASD and OCD by estimating heritability on different chromosomes and different allele frequencies, analyzing genome-wide common variant data by using the Genome-wide Complex Trait Analysis (GCTA) program. The estimated global heritability of OCD is 0.427 (se=0.093) and 0.174 (se=0.053) for ASD in these imputed data. Published by Elsevier B.V.

  5. Environmental and genetic risk factors for eating disorders: what the clinician needs to know.

    Science.gov (United States)

    Mazzeo, Suzanne E; Bulik, Cynthia M

    2009-01-01

    Patients and families often are aware of research on genetic factors influencing eating disorders. Accurate interpretations of research on environmental and genetic risk factors can be empowering to patients and families; however, misinterpretations could prove detrimental. Clinicians who are not versed in genetic research may believe they are ill prepared to discuss the nuances of genetic research with patients and families. In this article the authors discuss what is known about genetic and environmental risk factors with an emphasis on gene-environment interplay to improve clinicians' comfort level in discussing these complex issues with their patients.

  6. Subjective versus objective risk in genetic counseling for hereditary breast and/or ovarian cancers

    Directory of Open Access Journals (Sweden)

    Sperduti Isabella

    2009-12-01

    Full Text Available Abstract Background Despite the fact that genetic counseling in oncology provides information regarding objective risks, it can be found a contrast between the subjective and objective risk. The aims of this study were to evaluate the accuracy of the perceived risk compared to the objective risk estimated by the BRCApro computer model and to evaluate any associations between medical, demographic and psychological variables and the accuracy of risk perception. Methods 130 subjects were given medical-demographic file, Cancer and Genetic Risk Perception, Hospital Anxiety-Depression Scale. It was also computed an objective evaluation of the risk by the BRCApro model. Results The subjective risk was significantly higher than objective risk. The risk of tumour was overestimated by 56%, and the genetic risk by 67%. The subjects with less cancer affected relatives significantly overestimated their risk of being mutation carriers and made a more innacurate estimation than high risk subjects. Conclusion The description of this sample shows: general overestimation of the risk, inaccurate perception compared to BRCApro calculation and a more accurate estimation in those subjects with more cancer affected relatives (high risk subjects. No correlation was found between the levels of perception of risk and anxiety and depression. Based on our findings, it is worth pursuing improved communication strategies about the actual cancer and genetic risk, especially for subjects at "intermediate and slightly increased risk" of developing an hereditary breast and/or ovarian cancer or of being mutation carrier.

  7. Impact of a Genetic Risk Score on Myocardial Infarction Risk Across Different Ethnic Populations.

    Science.gov (United States)

    Joseph, Philip G; Pare, Guillaume; Asma, Senay; Engert, James C; Yusuf, Salim; Anand, Sonia S

    2016-12-01

    Myocardial infarction (MI) risk varies by ethnicity, although the influence of genetic factors remains unclear. Using a genetic risk score (GRS), we examined the association between 25 coronary artery disease (CAD)-related single nucleotide polymorphisms and MI across 6 ethnic groups. We studied 8556 participants in the INTERHEART case-control study from 6 ethnic groups: Europeans, South Asians, Southeast Asians, Arabs, Latin Americans, and Africans. Associations between the GRS and MI were tested in each group by logistic regression and overall by meta-analysis. Overall, the GRS increased the odds of MI by 1.07 (95% confidence interval [CI], 1.04-1.09) per risk allele in the unadjusted model, with little change (odds ratio, 1.06; 95% CI, 1.04-1.09) after adjusting for demographic and modifiable factors. In Europeans, South Asians, Southeast Asians, and Arabs, the GRS was significantly associated with MI, with minimal heterogeneity observed. In these groups, a score > 23 risk alleles (highest 4 quintiles) was associated with only a 5% difference in population attributable risk (PAR) (36% to 41%) for MI. The GRS was not significant in Latin Americans or Africans. In the overall cohort, modest changes, beyond clinical factors, in PAR (88% to 91%), concordance statistic (0.73 to 0.74), and continuous net reclassification improvement (12%) were observed with the GRS. A CAD GRS is associated with MI across a multiethnic cohort, with significant and consistent effects across 4 distinct ethnicities. However, it only modestly improves MI risk prediction beyond clinical factors. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  8. Genetic variants influencing lipid levels and risk of dyslipidemia in ...

    Indian Academy of Sciences (India)

    Keywords. dyslipidemia; lipid levels; single-nucleotide polymorphisms; cardiovascular disease; genetics. Abstract. Recently, several human genetic and genomewide association studies (GWAS) have discovered many genetic loci that are associated with the concentration of the blood lipids. To confirm the reported loci in ...

  9. Interaction between common breast cancer susceptibility variants, genetic ancestry, and non-genetic risk factors in Hispanic women

    Science.gov (United States)

    Fejerman, Laura; Stern, Mariana C.; John, Esther M.; Torres-Mejía, Gabriela; Hines, Lisa M.; Wolff, Roger K.; Baumgartner, Kathy B.; Giuliano, Anna R.; Ziv, Elad; Pérez-Stable, Eliseo J.; Slattery, Martha L.

    2015-01-01

    Background Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified single nucleotide polymorphisms (SNPs) among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population. Methods We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions. Results We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele odds ratio (OR): 0.94 (95% confidence interval 0.74–1.20), 1.20 (0.94–1.53) and 1.49 (1.28–1.75) for current, former and never hormone therapy users, respectively, P-interaction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72–1.42), 1.19 (0.98–1.45) and 1.69 (1.26–2.26) for never, 12 months breastfeeding, respectively, P-interaction 0.014]. Conclusions The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women. Impact These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and non-genetic risk factors and their contribution to breast cancer risk. PMID:26364163

  10. Epileptic Encephalopathy in Childhood: A Stepwise Approach for Identification of Underlying Genetic Causes.

    Science.gov (United States)

    Patel, Jaina; Mercimek-Mahmutoglu, Saadet

    2016-10-01

    Epilepsy is one of the most common neurological disorders in childhood. Epilepsy associated with global developmental delay and cognitive dysfunction is defined as epileptic encephalopathy. Certain inherited metabolic disorders presenting with epileptic encephalopathy can be treated with disease specific diet, vitamin, amino acid or cofactor supplementations. In those disorders, disease specific therapy is successful to achieve good seizure control and improve long-term neurodevelopmental outcome. For this reason, intractable epilepsy with global developmental delay or history of developmental regression warrants detailed metabolic investigations for the possibility of an underlying treatable inherited metabolic disorder, which should be undertaken as first line investigations. An underlying genetic etiology in epileptic encephalopathy has been supported by recent studies such as array comparative genomic hybridization, targeted next generation sequencing panels, whole exome and whole genome sequencing. These studies report a diagnostic yield up to 70%, depending on the applied genetic testing as well as number of patients enrolled. In patients with epileptic encephalopathy, a stepwise approach for diagnostic work-up will help to diagnose treatable inherited metabolic disorders quickly. Application of detailed genetic investigations such as targeted next generation sequencing as second line and whole exome sequencing as third line testing will diagnose underlying genetic disease which will help for genetic counseling as well as guide for prenatal diagnosis. Knowledge of underlying genetic cause will provide novel insights into the pathogenesis of epileptic encephalopathy and pave the ground towards the development of targeted neuroprotective treatment strategies to improve the health outcome of children with epileptic encephalopathy.

  11. A Shared Genetic Propensity Underlies Experiences of Bullying Victimization in Late Childhood and Self-Rated Paranoid Thinking in Adolescence

    Science.gov (United States)

    Shakoor, Sania; McGuire, Phillip; Cardno, Alastair G.; Freeman, Daniel; Plomin, Robert; Ronald, Angelica

    2015-01-01

    Background: Bullying is a risk factor for developing psychotic experiences (PEs). Whether bullying is associated with particular PEs, and the extent to which genes and environments influence the association, are unknown. This study investigated which specific PEs in adolescence are associated with earlier bullying victimization and the genetic and environmental contributions underlying their association. Method: Participants were 4826 twin pairs from a longitudinal community-based twin study in England and Wales who reported on their bullying victimization at the age of 12 years. Measures of specific PEs (self-rated Paranoia, Hallucinations, Cognitive disorganization, Grandiosity, Anhedonia, and parent-rated Negative Symptoms) were recorded at age of 16 years. Results: Childhood bullying victimization was most strongly associated with Paranoia in adolescence (r = .26; P bullying victimization and Paranoia were both heritable (35% and 52%, respectively) with unique environmental influences (39% and 48%, respectively), and bullying victimization showed common environmental influences (26%). The association between bullying victimization and Paranoia operated almost entirely via genetic influences (bivariate heritability = 93%), with considerable genetic overlap (genetic correlation = .55). Conclusion: In contrast to the assumed role of bullying victimization as an environmental trigger, these data suggest that bullying victimization in late childhood is particularly linked to self-rated Paranoia in adolescence via a shared genetic propensity. Clinically, individuals with a history of bullying victimization are predicted to be particularly susceptible to paranoid symptoms. PMID:25323579

  12. A shared genetic propensity underlies experiences of bullying victimization in late childhood and self-rated paranoid thinking in adolescence.

    Science.gov (United States)

    Shakoor, Sania; McGuire, Phillip; Cardno, Alastair G; Freeman, Daniel; Plomin, Robert; Ronald, Angelica

    2015-05-01

    Bullying is a risk factor for developing psychotic experiences (PEs). Whether bullying is associated with particular PEs, and the extent to which genes and environments influence the association, are unknown. This study investigated which specific PEs in adolescence are associated with earlier bullying victimization and the genetic and environmental contributions underlying their association. Participants were 4826 twin pairs from a longitudinal community-based twin study in England and Wales who reported on their bullying victimization at the age of 12 years. Measures of specific PEs (self-rated Paranoia, Hallucinations, Cognitive disorganization, Grandiosity, Anhedonia, and parent-rated Negative Symptoms) were recorded at age of 16 years. Childhood bullying victimization was most strongly associated with Paranoia in adolescence (r = .26; P bullying victimization and Paranoia were both heritable (35% and 52%, respectively) with unique environmental influences (39% and 48%, respectively), and bullying victimization showed common environmental influences (26%). The association between bullying victimization and Paranoia operated almost entirely via genetic influences (bivariate heritability = 93%), with considerable genetic overlap (genetic correlation = .55). In contrast to the assumed role of bullying victimization as an environmental trigger, these data suggest that bullying victimization in late childhood is particularly linked to self-rated Paranoia in adolescence via a shared genetic propensity. Clinically, individuals with a history of bullying victimization are predicted to be particularly susceptible to paranoid symptoms. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  13. Risk management of exposure to chemicals under operational conditions

    NARCIS (Netherlands)

    Langenberg, J.P.

    2007-01-01

    The HFM panel has decided to install an Exploratory Team, ET-078, which should advise whether or not a Technical Group (TG) should be established on the subject of risk management of exposure to chemicals under operational conditions. This paper described the context and approach of ET-078.

  14. Altered Decision-Making under Risk in Obesity.

    Directory of Open Access Journals (Sweden)

    Juan F Navas

    Full Text Available The negative consequences of energy dense foods are well known, yet people increasingly make unhealthy food choices leading to obesity (i.e., risky decisions. The aims of this study were: [1] to compare performance in decision-making tasks under risk and under ambiguity between individuals with obesity, overweight and normal weight; [2] to examine the associations between body mass index (BMI and decision-making, and the degree to which these associations are modulated by reward sensitivity.Seventy-nine adults were recruited and classified in three groups according to their BMI: obesity, overweight and normal-weight. Groups were similar in terms of age, education and socio-economic status, and were screened for comorbid medical and mental health conditions. Decision-making under risk was measured via the Wheel of Fortune Task (WoFT and decision-making under ambiguity via the Iowa Gambling Task (IGT. Reward sensitivity was indicated by the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ.Individuals with obesity made riskier choices in the WoFT, specifically in choices with an expected value close to zero and in the propensity to risk index. No differences were found in IGT performance or SPSRQ scores. BMI was associated with risk-taking (WoFT performance, independently of reward sensitivity.Obesity is linked to a propensity to make risky decisions in experimental conditions analogous to everyday food choices.

  15. Neural mechanisms underlying context-dependent shifts in risk preferences

    NARCIS (Netherlands)

    Losecaat Vermeer, A.B.; Boksem, M.A.S.; Sanfey, A.G.

    2014-01-01

    Studies of risky decision-making have demonstrated that humans typically prefer risky options after incurring a financial loss, while generally preferring safer options after a monetary gain. Here, we examined the neural processes underlying these inconsistent risk preferences by investigating the

  16. Empirical Analysis of Farm Credit Risk under the Structure Model

    Science.gov (United States)

    Yan, Yan

    2009-01-01

    The study measures farm credit risk by using farm records collected by Farm Business Farm Management (FBFM) during the period 1995-2004. The study addresses the following questions: (1) whether farm's financial position is fully described by the structure model, (2) what are the determinants of farm capital structure under the structure model, (3)…

  17. Evaluation of forest management systems under risk of wildfire

    Science.gov (United States)

    Kari Hyytiainen; Robert G. Haight

    2010-01-01

    We evaluate the economic efficiency of even- and uneven-aged management systems under risk of wildfire. The management problems are formulated for a mixed-conifer stand and approximations of the optimal solutions are obtained using simulation optimization. The Northern Idaho variant of the Forest Vegetation Simulator and its Fire and Fuels Extension is used to predict...

  18. Genetically modified organisms: do the benefits outweigh the risks?

    Science.gov (United States)

    Hug, Kristina

    2008-01-01

    The objective of this literature review is to analyze the implications of using genetically modified organisms (GMOs) as well as international and European position regarding such organisms. Review of international and European legal requirements and ethical guidelines and relevant publications, found and accessed with the help of PubMed and Lund University Library databases. The article discusses the main application areas of GMOs, the expansion of using GMOs in the world as well as the advantages and disadvantages of the implications of their usage. It further provides an overview of the suggested ways to tackle or avoid the GMO-related risks. The international and European positions regarding the application of GMOs are discussed and European Directives, Regulations, and ethical guidelines are overviewed. The article further presents the public attitudes towards GMOs in Europe as well as overviews surveys conducted at the national level. Suggested steps to tackle the challenge of developing and managing biotechnology for the benefit of public health and the environment are presented.

  19. KCNJ11: Genetic Polymorphisms and Risk of Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Polin Haghvirdizadeh

    2015-01-01

    Full Text Available Diabetes mellitus (DM is a major worldwide health problem and its prevalence has been rapidly increasing in the last century. It is caused by defects in insulin secretion or insulin action or both, leading to hyperglycemia. Of the various types of DM, type 2 occurs most frequently. Multiple genes and their interactions are involved in the insulin secretion pathway. Insulin secretion is mediated through the ATP-sensitive potassium (KATP channel in pancreatic beta cells. This channel is a heteromeric protein, composed of four inward-rectifier potassium ion channel (Kir6.2 tetramers, which form the pore of the KATP channel, as well as sulfonylurea receptor 1 subunits surrounding the pore. Kir6.2 is encoded by the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11 gene, a member of the potassium channel genes. Numerous studies have reported the involvement of single nucleotide polymorphisms of the KCNJ11 gene and their interactions in the susceptibility to DM. This review discusses the current evidence for the contribution of common KCNJ11 genetic variants to the development of DM. Future studies should concentrate on understanding the exact role played by these risk variants in the development of DM.

  20. Applying Evolutionary Genetics to Developmental Toxicology and Risk Assessment

    Science.gov (United States)

    Leung, Maxwell C. K.; Procter, Andrew C.; Goldstone, Jared V.; Foox, Jonathan; DeSalle, Robert; Mattingly, Carolyn J.; Siddall, Mark E.; Timme-Laragy, Alicia R.

    2018-01-01

    Evolutionary thinking continues to challenge our views on health and disease. Yet, there is a communication gap between evolutionary biologists and toxicologists in recognizing the connections among developmental pathways, high-throughput screening, and birth defects in humans. To increase our capability in identifying potential developmental toxicants in humans, we propose to apply evolutionary genetics to improve the experimental design and data interpretation with various in vitro and whole-organism models. We review five molecular systems of stress response and update 18 consensual cell-cell signaling pathways that are the hallmark for early development, organogenesis, and differentiation; and revisit the principles of teratology in light of recent advances in high-throughput screening, big data techniques, and systems toxicology. Multiscale systems modeling plays an integral role in the evolutionary approach to cross-species extrapolation. Phylogenetic analysis and comparative bioinformatics are both valuable tools in identifying and validating the molecular initiating events that account for adverse developmental outcomes in humans. The discordance of susceptibility between test species and humans (ontogeny) reflects their differences in evolutionary history (phylogeny). This synthesis not only can lead to novel applications in developmental toxicity and risk assessment, but also can pave the way for applying an evo-devo perspective to the study of developmental origins of health and disease. PMID:28267574

  1. Fatalistic responses to different types of genetic risk information: exploring the role of self-malleability

    NARCIS (Netherlands)

    Claassen, E.A.M.; Henneman, L.; de Vet, H.C.W.; Knol, D.L.; Marteau, T.; Timmermans, D.R.M.

    2010-01-01

    Providing people with genetic risk information may induce a sense of fatalism, the belief that little can be done to reduce the risk. We postulated that fatalism is a function of health risk information and individual differences in self-perception. DNA-based risk information was hypothesised to

  2. Pathways and barriers to genetic testing and screening: Molecular genetics meets the high-risk family. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Duster, T.

    1998-11-01

    The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of these diseases is found primarily in a different ethnic/racial group (CF in Americans of North European descent and SC in Americans of West African descent). This has permitted them to have a certain additional lens on the role of culture in integrating genetic testing into family life and reproductive planning. A third type of genetic disorder, the thalassemias was added to the sample in order to extent the comparative frame and to include other ethnic and racial groups.

  3. Incorporating Known Genetic Variants Does Not Improve the Accuracy of PSA Testing to Identify High Risk Prostate Cancer on Biopsy.

    Directory of Open Access Journals (Sweden)

    Rebecca Gilbert

    Full Text Available Prostate-specific antigen (PSA testing is a widely accepted screening method for prostate cancer, but with low specificity at thresholds giving good sensitivity. Previous research identified four single nucleotide polymorphisms (SNPs principally associated with circulating PSA levels rather than with prostate cancer risk (TERT rs2736098, FGFR2 rs10788160, TBX3 rs11067228, KLK3 rs17632542. Removing the genetic contribution to PSA levels may improve the ability of the remaining biologically-determined variation in PSA to discriminate between high and low risk of progression within men with identified prostate cancer. We investigate whether incorporating information on the PSA-SNPs improves the discrimination achieved by a single PSA threshold in men with raised PSA levels.Men with PSA between 3-10 ng/mL and histologically-confirmed prostate cancer were categorised as high or low risk of progression (Low risk: Gleason score≤6 and stage T1-T2a; High risk: Gleason score 7-10 or stage T2C. We used the combined genetic effect of the four PSA-SNPs to calculate a genetically corrected PSA risk score. We calculated the Area under the Curve (AUC to determine how well genetically corrected PSA risk scores distinguished men at high risk of progression from low risk men.The analysis includes 868 men with prostate cancer (Low risk: 684 (78.8%; High risk: 184 (21.2%. Receiver operating characteristic (ROC curves indicate that including the 4 PSA-SNPs does not improve the performance of measured PSA as a screening tool for high/low risk prostate cancer (measured PSA level AUC = 59.5% (95% CI: 54.7,64.2 vs additionally including information from the 4 PSA-SNPs AUC = 59.8% (95% CI: 55.2,64.5 (p-value = 0.40.We demonstrate that genetically correcting PSA for the combined genetic effect of four PSA-SNPs, did not improve discrimination between high and low risk prostate cancer in men with raised PSA levels (3-10 ng/mL. Replication and gaining more accurate

  4. Incorporating Known Genetic Variants Does Not Improve the Accuracy of PSA Testing to Identify High Risk Prostate Cancer on Biopsy

    Science.gov (United States)

    Gilbert, Rebecca; Martin, Richard M.; Evans, David M.; Tilling, Kate; Davey Smith, George; Kemp, John P.; Lane, J. Athene; Hamdy, Freddie C.; Neal, David E.; Donovan, Jenny L.; Metcalfe, Chris

    2015-01-01

    Introduction Prostate-specific antigen (PSA) testing is a widely accepted screening method for prostate cancer, but with low specificity at thresholds giving good sensitivity. Previous research identified four single nucleotide polymorphisms (SNPs) principally associated with circulating PSA levels rather than with prostate cancer risk (TERT rs2736098, FGFR2 rs10788160, TBX3 rs11067228, KLK3 rs17632542). Removing the genetic contribution to PSA levels may improve the ability of the remaining biologically-determined variation in PSA to discriminate between high and low risk of progression within men with identified prostate cancer. We investigate whether incorporating information on the PSA-SNPs improves the discrimination achieved by a single PSA threshold in men with raised PSA levels. Materials and Methods Men with PSA between 3-10ng/mL and histologically-confirmed prostate cancer were categorised as high or low risk of progression (Low risk: Gleason score≤6 and stage T1-T2a; High risk: Gleason score 7–10 or stage T2C). We used the combined genetic effect of the four PSA-SNPs to calculate a genetically corrected PSA risk score. We calculated the Area under the Curve (AUC) to determine how well genetically corrected PSA risk scores distinguished men at high risk of progression from low risk men. Results The analysis includes 868 men with prostate cancer (Low risk: 684 (78.8%); High risk: 184 (21.2%)). Receiver operating characteristic (ROC) curves indicate that including the 4 PSA-SNPs does not improve the performance of measured PSA as a screening tool for high/low risk prostate cancer (measured PSA level AU C = 59.5% (95% CI: 54.7,64.2) vs additionally including information from the 4 PSA-SNPs AUC = 59.8% (95% CI: 55.2,64.5) (p-value = 0.40)). Conclusion We demonstrate that genetically correcting PSA for the combined genetic effect of four PSA-SNPs, did not improve discrimination between high and low risk prostate cancer in men with raised PSA levels (3-10ng

  5. Facial emotion perception differs in young persons at genetic and clinical high-risk for psychosis.

    Science.gov (United States)

    Kohler, Christian G; Richard, Jan A; Brensinger, Colleen M; Borgmann-Winter, Karin E; Conroy, Catherine G; Moberg, Paul J; Gur, Ruben C; Gur, Raquel E; Calkins, Monica E

    2014-05-15

    A large body of literature has documented facial emotion perception impairments in schizophrenia. More recently, emotion perception has been investigated in persons at genetic and clinical high-risk for psychosis. This study compared emotion perception abilities in groups of young persons with schizophrenia, clinical high-risk, genetic risk and healthy controls. Groups, ages 13-25, included 24 persons at clinical high-risk, 52 first-degree relatives at genetic risk, 91 persons with schizophrenia and 90 low risk persons who completed computerized testing of emotion recognition and differentiation. Groups differed by overall emotion recognition abilities and recognition of happy, sad, anger and fear expressions. Pairwise comparisons revealed comparable impairments in recognition of happy, angry, and fearful expressions for persons at clinical high-risk and schizophrenia, while genetic risk participants were less impaired, showing reduced recognition of fearful expressions. Groups also differed for differentiation of happy and sad expressions, but differences were mainly between schizophrenia and control groups. Emotion perception impairments are observable in young persons at-risk for psychosis. Preliminary results with clinical high-risk participants, when considered along findings in genetic risk relatives, suggest social cognition abilities to reflect pathophysiological processes involved in risk of schizophrenia. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Genetic variants associated with breast size also influence breast cancer risk

    Directory of Open Access Journals (Sweden)

    Eriksson Nicholas

    2012-06-01

    Full Text Available Abstract Background While some factors of breast morphology, such as density, are directly implicated in breast cancer, the relationship between breast size and cancer is less clear. Breast size is moderately heritable, yet the genetic variants leading to differences in breast size have not been identified. Methods To investigate the genetic factors underlying breast size, we conducted a genome-wide association study (GWAS of self-reported bra cup size, controlling for age, genetic ancestry, breast surgeries, pregnancy history and bra band size, in a cohort of 16,175 women of European ancestry. Results We identified seven single-nucleotide polymorphisms (SNPs significantly associated with breast size (p−8: rs7816345 near ZNF703, rs4849887 and (independently rs17625845 flanking INHBB, rs12173570 near ESR1, rs7089814 in ZNF365, rs12371778 near PTHLH, and rs62314947 near AREG. Two of these seven SNPs are in linkage disequilibrium (LD with SNPs associated with breast cancer (those near ESR1 and PTHLH, and a third (ZNF365 is near, but not in LD with, a breast cancer SNP. The other three loci (ZNF703, INHBB, and AREG have strong links to breast cancer, estrogen regulation, and breast development. Conclusions These results provide insight into the genetic factors underlying normal breast development and show that some of these factors are shared with breast cancer. While these results do not directly support any possible epidemiological relationships between breast size and cancer, this study may contribute to a better understanding of the subtle interactions between breast morphology and breast cancer risk.

  7. Genetic risk by experience interaction for childhood internalizing problems: converging evidence across multiple methods.

    Science.gov (United States)

    Vendlinski, Matthew K; Lemery-Chalfant, Kathryn; Essex, Marilyn J; Goldsmith, H Hill

    2011-05-01

    Identifying how genetic risk interacts with experience to predict psychopathology is an important step toward understanding the etiology of mental health problems. Few studies have examined genetic risk by experience interaction (G×E) in the development of childhood psychopathology. We used both co-twin and parent mental health as markers of genetic risk to test whether G×E predicted internalizing problems in a sample of 8-year-old twins. Multi-instrument composites were used to characterize both parent and child psychopathology, and five experiential risk factors (socioeconomic status, single parent upbringing, negative parent-child interactions, number of negative life events, negative impact of negative life events) composed a cumulative risk index. We found consistent evidence for G×E for child internalizing problems, with significant interaction effects emerging both when genetic risk was indexed by co-twin mental health and when it was based on parent mental health. When co-twin mental health was used to estimate genetic risk, child internalizing problems were more heritable for children at low rather than high experiential risk. When parent mental health was used to estimate genetic risk, the association between genetic risk and internalizing problems was stronger for children at elevated experiential risk. Consideration of the interaction effect sizes helps to reconcile these findings. Our results suggest that the processes involved in both diathesis-stress and bioecological models of development may operate for child internalizing problems. Effect sizes indicated that the main effects of genetic and experiential risk were much better predictors of child internalizing problems than was their interaction. © 2010 The Authors. Journal of Child Psychology and Psychiatry © 2010 Association for Child and Adolescent Mental Health.

  8. The impact of advances in human molecular biology on radiation genetic risk estimation in man

    International Nuclear Information System (INIS)

    Sankaranarayanan, K.

    1996-01-01

    This paper provides an overview of the conceptual framework, the data base, methods and assumptions used thus far to assess the genetic risks of exposure of human populations to ionising radiation. These are then re-examined in the contemporary context of the rapidly expanding knowledge of the molecular biology of human mendelian diseases. This re-examination reveals that (i) many of the assumptions used thus far in radiation genetic risk estimation may not be fully valid and (ii) the current genetic risk estimates are probably conservative, but provide an adequate margin of safety for radiological protection. The view is expressed that further advances in the field of genetic risk estimation will be largely driven by advances in the molecular biology of human genetic diseases. (author). 37 refs., 5 tabs

  9. Risk management for sulfur dioxide abatement under multiple uncertainties

    Science.gov (United States)

    Dai, C.; Sun, W.; Tan, Q.; Liu, Y.; Lu, W. T.; Guo, H. C.

    2016-03-01

    In this study, interval-parameter programming, two-stage stochastic programming (TSP), and conditional value-at-risk (CVaR) were incorporated into a general optimization framework, leading to an interval-parameter CVaR-based two-stage programming (ICTP) method. The ICTP method had several advantages: (i) its objective function simultaneously took expected cost and risk cost into consideration, and also used discrete random variables and discrete intervals to reflect uncertain properties; (ii) it quantitatively evaluated the right tail of distributions of random variables which could better calculate the risk of violated environmental standards; (iii) it was useful for helping decision makers to analyze the trade-offs between cost and risk; and (iv) it was effective to penalize the second-stage costs, as well as to capture the notion of risk in stochastic programming. The developed model was applied to sulfur dioxide abatement in an air quality management system. The results indicated that the ICTP method could be used for generating a series of air quality management schemes under different risk-aversion levels, for identifying desired air quality management strategies for decision makers, and for considering a proper balance between system economy and environmental quality.

  10. Cognitive Processes in Decisions Under Risk Are Not the Same As in Decisions Under Uncertainty

    Directory of Open Access Journals (Sweden)

    Kirsten G Volz

    2012-07-01

    Full Text Available We deal with risk versus uncertainty, a distinction that is of fundamental importance for cognitive neuroscience yet largely neglected. In a world of risk (small world, all alternatives, consequences, and probabilities are known. In uncertain (large worlds, some of this information is unknown or unknowable. Most of cognitive neuroscience studies exclusively study the neural correlates for decisions under risk (e.g., lotteries, with the tacit implication that understanding these would lead to an understanding of decision making in general. First, we show that normative strategies for decisions under risk do not generalize to uncertain worlds, where simple heuristics are often the more accurate strategies. Second, we argue that the cognitive processes for making decisions in a world of risk are not the same as those for dealing with uncertainty. Because situations with known risks are the exception rather than the rule in human evolution, it is unlikely that our brains are adapted to them. We therefore suggest a paradigm shift towards studying decision processes in uncertain worlds and provide first examples.

  11. Designing a Supply Chain Network under the Risk of Disruptions

    Directory of Open Access Journals (Sweden)

    Armin Jabbarzadeh

    2012-01-01

    Full Text Available This paper studies a supply chain design problem with the risk of disruptions at facilities. At any point of time, the facilities are subject to various types of disruptions caused by natural disasters, man-made defections, and equipment breakdowns. We formulate the problem as a mixed-integer nonlinear program which maximizes the total profit for the whole system. The model simultaneously determines the number and location of facilities, the subset of customers to serve, the assignment of customers to facilities, and the cycle-order quantities at facilities. In order to obtain near-optimal solutions with reasonable computational requirements for large problem instances, two solution methods based on Lagrangian relaxation and genetic algorithm are developed. The effectiveness of the proposed solution approaches is shown using numerical experiments. The computational results, in addition, demonstrate that the benefits of considering disruptions in the supply chain design model can be significant.

  12. BRCA1 and BRCA2: Cancer Risk and Genetic Testing

    Science.gov (United States)

    ... MR imaging in women with a familial or genetic predisposition. Breast Cancer Research and Treatment 2010; 119(2):399–407. [PubMed Abstract] Evans DG, Gaarenstroom KN, Stirling D, et al. Screening for familial ovarian cancer: Poor ... Genetics 2009; 46(9):593–597. [PubMed Abstract] Domchek ...

  13. Perspectives of couples with high risk of transmitting genetic disorders.

    NARCIS (Netherlands)

    Musters, A.M.; Twisk, M.; Leschot, N.J.; Oosterwijk, C.; Korevaar, J.C.; Repping, S.; Veen, F. van der; Goddijn, M.

    2010-01-01

    Objective: To investigate the preference for preimplantation genetic diagnosis (PGD) as an alternative to prenatal diagnosis (PND) in a large group of couples representing a wide array of genetic disorders. We also investigated the couple's familiarity with PGD and presented time trade-off scenarios

  14. Revealing the underlying drivers of disaster risk: a global analysis

    Science.gov (United States)

    Peduzzi, Pascal

    2017-04-01

    Disasters events are perfect examples of compound events. Disaster risk lies at the intersection of several independent components such as hazard, exposure and vulnerability. Understanding the weight of each component requires extensive standardisation. Here, I show how footprints of past disastrous events were generated using GIS modelling techniques and used for extracting population and economic exposures based on distribution models. Using past event losses, it was possible to identify and quantify a wide range of socio-politico-economic drivers associated with human vulnerability. The analysis was applied to about nine thousand individual past disastrous events covering earthquakes, floods and tropical cyclones. Using a multiple regression analysis on these individual events it was possible to quantify each risk component and assess how vulnerability is influenced by various hazard intensities. The results show that hazard intensity, exposure, poverty, governance as well as other underlying factors (e.g. remoteness) can explain the magnitude of past disasters. Analysis was also performed to highlight the role of future trends in population and climate change and how this may impacts exposure to tropical cyclones in the future. GIS models combined with statistical multiple regression analysis provided a powerful methodology to identify, quantify and model disaster risk taking into account its various components. The same methodology can be applied to various types of risk at local to global scale. This method was applied and developed for the Global Risk Analysis of the Global Assessment Report on Disaster Risk Reduction (GAR). It was first applied on mortality risk in GAR 2009 and GAR 2011. New models ranging from global assets exposure and global flood hazard models were also recently developed to improve the resolution of the risk analysis and applied through CAPRA software to provide probabilistic economic risk assessments such as Average Annual Losses (AAL

  15. Analysis of coastal protection under rising flood risk

    Directory of Open Access Journals (Sweden)

    Megan J. Lickley

    2014-01-01

    Full Text Available Infrastructure located along the U.S. Atlantic and Gulf coasts is exposed to rising risk of flooding from sea level rise, increasing storm surge, and subsidence. In these circumstances coastal management commonly based on 100-year flood maps assuming current climatology is no longer adequate. A dynamic programming cost–benefit analysis is applied to the adaptation decision, illustrated by application to an energy facility in Galveston Bay. Projections of several global climate models provide inputs to estimates of the change in hurricane and storm surge activity as well as the increase in sea level. The projected rise in physical flood risk is combined with estimates of flood damage and protection costs in an analysis of the multi-period nature of adaptation choice. The result is a planning method, using dynamic programming, which is appropriate for investment and abandonment decisions under rising coastal risk.

  16. Genetic Analysis of Elevated Mastitis Risk Based on Mastitis Indicator Data

    DEFF Research Database (Denmark)

    Sørensen, Lars Peter; Løvendahl, Peter

    . These modeling approaches have proven to be highly useful to determine population genetic parameters as well as prediction of genetic risk or value. We present statistical modelling approaches that use prior biological information for evaluating the collective action of sets of genetic variants. We have applied......Whole-genome sequences and multiple trait phenotypes from large numbers of individuals will soon be available. Well established statistical modeling approaches enable the genetic analyses of complex trait phenotypes while accounting for a variety of additive and non-additive genetic mechanisms...

  17. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

    Science.gov (United States)

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C.A.; Patsopoulos, Nikolaos A.; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E.; Edkins, Sarah; Gray, Emma; Booth, David R.; Potter, Simon C.; Goris, An; Band, Gavin; Oturai, Annette Bang; Strange, Amy; Saarela, Janna; Bellenguez, Céline; Fontaine, Bertrand; Gillman, Matthew; Hemmer, Bernhard; Gwilliam, Rhian; Zipp, Frauke; Jayakumar, Alagurevathi; Martin, Roland; Leslie, Stephen; Hawkins, Stanley; Giannoulatou, Eleni; D’alfonso, Sandra; Blackburn, Hannah; Boneschi, Filippo Martinelli; Liddle, Jennifer; Harbo, Hanne F.; Perez, Marc L.; Spurkland, Anne; Waller, Matthew J; Mycko, Marcin P.; Ricketts, Michelle; Comabella, Manuel; Hammond, Naomi; Kockum, Ingrid; McCann, Owen T.; Ban, Maria; Whittaker, Pamela; Kemppinen, Anu; Weston, Paul; Hawkins, Clive; Widaa, Sara; Zajicek, John; Dronov, Serge; Robertson, Neil; Bumpstead, Suzannah J.; Barcellos, Lisa F.; Ravindrarajah, Rathi; Abraham, Roby; Alfredsson, Lars; Ardlie, Kristin; Aubin, Cristin; Baker, Amie; Baker, Katharine; Baranzini, Sergio E.; Bergamaschi, Laura; Bergamaschi, Roberto; Bernstein, Allan; Berthele, Achim; Boggild, Mike; Bradfield, Jonathan P.; Brassat, David; Broadley, Simon A.; Buck, Dorothea; Butzkueven, Helmut; Capra, Ruggero; Carroll, William M.; Cavalla, Paola; Celius, Elisabeth G.; Cepok, Sabine; Chiavacci, Rosetta; Clerget-Darpoux, Françoise; Clysters, Katleen; Comi, Giancarlo; Cossburn, Mark; Cournu-Rebeix, Isabelle; Cox, Mathew B.; Cozen, Wendy; Cree, Bruce A.C.; Cross, Anne H.; Cusi, Daniele; Daly, Mark J.; Davis, Emma; de Bakker, Paul I.W.; Debouverie, Marc; D’hooghe, Marie Beatrice; Dixon, Katherine; Dobosi, Rita; Dubois, Bénédicte; Ellinghaus, David; Elovaara, Irina; Esposito, Federica; Fontenille, Claire; Foote, Simon; Franke, Andre; Galimberti, Daniela; Ghezzi, Angelo; Glessner, Joseph; Gomez, Refujia; Gout, Olivier; Graham, Colin; Grant, Struan F.A.; Guerini, Franca Rosa; Hakonarson, Hakon; Hall, Per; Hamsten, Anders; Hartung, Hans-Peter; Heard, Rob N.; Heath, Simon; Hobart, Jeremy; Hoshi, Muna; Infante-Duarte, Carmen; Ingram, Gillian; Ingram, Wendy; Islam, Talat; Jagodic, Maja; Kabesch, Michael; Kermode, Allan G.; Kilpatrick, Trevor J.; Kim, Cecilia; Klopp, Norman; Koivisto, Keijo; Larsson, Malin; Lathrop, Mark; Lechner-Scott, Jeannette S.; Leone, Maurizio A.; Leppä, Virpi; Liljedahl, Ulrika; Bomfim, Izaura Lima; Lincoln, Robin R.; Link, Jenny; Liu, Jianjun; Lorentzen, Åslaug R.; Lupoli, Sara; Macciardi, Fabio; Mack, Thomas; Marriott, Mark; Martinelli, Vittorio; Mason, Deborah; McCauley, Jacob L.; Mentch, Frank; Mero, Inger-Lise; Mihalova, Tania; Montalban, Xavier; Mottershead, John; Myhr, Kjell-Morten; Naldi, Paola; Ollier, William; Page, Alison; Palotie, Aarno; Pelletier, Jean; Piccio, Laura; Pickersgill, Trevor; Piehl, Fredrik; Pobywajlo, Susan; Quach, Hong L.; Ramsay, Patricia P.; Reunanen, Mauri; Reynolds, Richard; Rioux, John D.; Rodegher, Mariaemma; Roesner, Sabine; Rubio, Justin P.; Rückert, Ina-Maria; Salvetti, Marco; Salvi, Erika; Santaniello, Adam; Schaefer, Catherine A.; Schreiber, Stefan; Schulze, Christian; Scott, Rodney J.; Sellebjerg, Finn; Selmaj, Krzysztof W.; Sexton, David; Shen, Ling; Simms-Acuna, Brigid; Skidmore, Sheila; Sleiman, Patrick M.A.; Smestad, Cathrine; Sørensen, Per Soelberg; Søndergaard, Helle Bach; Stankovich, Jim; Strange, Richard C.; Sulonen, Anna-Maija; Sundqvist, Emilie; Syvänen, Ann-Christine; Taddeo, Francesca; Taylor, Bruce; Blackwell, Jenefer M.; Tienari, Pentti; Bramon, Elvira; Tourbah, Ayman; Brown, Matthew A.; Tronczynska, Ewa; Casas, Juan P.; Tubridy, Niall; Corvin, Aiden; Vickery, Jane; Jankowski, Janusz; Villoslada, Pablo; Markus, Hugh S.; Wang, Kai; Mathew, Christopher G.; Wason, James; Palmer, Colin N.A.; Wichmann, H-Erich; Plomin, Robert; Willoughby, Ernest; Rautanen, Anna; Winkelmann, Juliane; Wittig, Michael; Trembath, Richard C.; Yaouanq, Jacqueline; Viswanathan, Ananth C.; Zhang, Haitao; Wood, Nicholas W.; Zuvich, Rebecca; Deloukas, Panos; Langford, Cordelia; Duncanson, Audrey; Oksenberg, Jorge R.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Olsson, Tomas; Hillert, Jan; Ivinson, Adrian J.; De Jager, Philip L.; Peltonen, Leena; Stewart, Graeme J.; Hafler, David A.; Hauser, Stephen L.; McVean, Gil; Donnelly, Peter; Compston, Alastair

    2011-01-01

    Multiple sclerosis (OMIM 126200) is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability.1 Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals;2,3 and systematic attempts to identify linkage in multiplex families have confirmed that variation within the Major Histocompatibility Complex (MHC) exerts the greatest individual effect on risk.4 Modestly powered Genome-Wide Association Studies (GWAS)5-10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects play a key role in disease susceptibility.11 Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the Class I region. Immunologically relevant genes are significantly over-represented amongst those mapping close to the identified loci and particularly implicate T helper cell differentiation in the pathogenesis of multiple sclerosis. PMID:21833088

  18. Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease.

    Science.gov (United States)

    Gutierrez-Achury, Javier; Zhernakova, Alexandra; Pulit, Sara L; Trynka, Gosia; Hunt, Karen A; Romanos, Jihane; Raychaudhuri, Soumya; van Heel, David A; Wijmenga, Cisca; de Bakker, Paul I W

    2015-06-01

    Although dietary gluten is the trigger for celiac disease, risk is strongly influenced by genetic variation in the major histocompatibility complex (MHC) region. We fine mapped the MHC association signal to identify additional risk factors independent of the HLA-DQA1 and HLA-DQB1 alleles and observed five new associations that account for 18% of the genetic risk. Taking these new loci together with the 57 known non-MHC loci, genetic variation can now explain up to 48% of celiac disease heritability.

  19. Genetic predisposition to higher blood pressure increases risk of incident hypertension and cardiovascular diseases in Chinese.

    Science.gov (United States)

    Lu, Xiangfeng; Huang, Jianfeng; Wang, Laiyuan; Chen, Shufeng; Yang, Xueli; Li, Jianxin; Cao, Jie; Chen, Jichun; Li, Ying; Zhao, Liancheng; Li, Hongfan; Liu, Fangcao; Huang, Chen; Shen, Chong; Shen, Jinjin; Yu, Ling; Xu, Lihua; Mu, Jianjun; Wu, Xianping; Ji, Xu; Guo, Dongshuang; Zhou, Zhengyuan; Yang, Zili; Wang, Renping; Yang, Jun; Yan, Weili; Gu, Dongfeng

    2015-10-01

    Although multiple genetic markers associated with blood pressure have been identified by genome-wide association studies, their aggregate effect on risk of incident hypertension and cardiovascular disease is uncertain, particularly among East Asian who may have different genetic and environmental exposures from Europeans. We aimed to examine the association between genetic predisposition to higher blood pressure and risk of incident hypertension and cardiovascular disease in 26 262 individuals in 2 Chinese population-based prospective cohorts. A genetic risk score was calculated based on 22 established variants for blood pressure in East Asian. We found the genetic risk score was significantly and independently associated with linear increases in blood pressure and risk of incident hypertension and cardiovascular disease (P range from 4.57×10(-3) to 3.10×10(-6)). In analyses adjusted for traditional risk factors including blood pressure, individuals carrying most blood pressure-related risk alleles (top quintile of genetic score distribution) had 40% (95% confidence interval, 18-66) and 26% (6-45) increased risk for incident hypertension and cardiovascular disease, respectively, when compared with individuals in the bottom quintile. The genetic risk score also significantly improved discrimination for incident hypertension and cardiovascular disease and led to modest improvements in risk reclassification for cardiovascular disease (all the Pgenetic predisposition to higher blood pressure is an independent risk factor for blood pressure increase and incident hypertension and cardiovascular disease and provides modest incremental information to cardiovascular disease risk prediction. The potential clinical use of this panel of blood pressure-associated polymorphisms remains to be determined. © 2015 American Heart Association, Inc.

  20. [Current problems of estimation of genetic risk of human exposure to radiation].

    Science.gov (United States)

    Shevchenko, V A

    2000-01-01

    The methodology of assessing the genetic risk of radiation exposure is based on the concept of "hitting the target" in development of which N.V. Timofeeff-Ressovsky has played and important role. To predict genetic risk posed by irradiation, the UN Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) has worked out direct and indirect methods of assessment, extrapolational, integral and populational criteria of risk analysis that together permit calculating the risk from human exposure on the basis of data obtained for mice. Laboratory mice are the main objects in studying radiation mutagenesis due to the fact that the data on the frequency of radiation-induced human mutations are rather scarce. The method of doubling dose based on the determination of a dose doubling the level of natural mutational process in humans is the main one used to predict the genetic risk. The evolution of views about the genetics risk of human exposure to radiation for last 40 years is considered. Till 1972 the main model for assessing the genetic risk was the "human/mouse" model (the use of data on the spontaneous human variability and data on the frequency of induced mutations in mice). In the period form 1972 till 1994 the "mouse/mouse" model was intensively elaborated in many laboratories. This model was also used in this period by UNSCEAR experts to analyze the genetic risk from human irradiation. Recent achievements associated with the study of the molecular nature of many hereditary human diseases as well as the criticism of number fundamental principles of the "mouse/mouse" model for estimating the genetic risk on a new basis. The estimates of risk for the different classes of genetic diseases have been obtained using the doubling-dose method. The estimate of doubling dose used in the calculations is 1 Gy for low dose/chronic low-LET radiation conditions.

  1. Portfolio balancing and risk adjusted values under constrained budget conditions

    International Nuclear Information System (INIS)

    MacKay, J.A.; Lerche, I.

    1996-01-01

    For a given hydrocarbon exploration opportunity, the influences of value, cost, success probability and corporate risk tolerance provide an optimal working interest that should be taken in the opportunity in order to maximize the risk adjusted value. When several opportunities are available, but when the total budget is insufficient to take optimal working interest in each, an analytic procedure is given for optimizing the risk adjusted value of the total portfolio; the relevant working interests are also derived based on a cost exposure constraint. Several numerical illustrations are provided to exhibit the use of the method under different budget conditions, and with different numbers of available opportunities. When value, cost, success probability, and risk tolerance are uncertain for each and every opportunity, the procedure is generalized to allow determination of probable optimal risk adjusted value for the total portfolio and, at the same time, the range of probable working interest that should be taken in each opportunity is also provided. The result is that the computations of portfolio balancing can be done quickly in either deterministic or probabilistic manners on a small calculator, thereby providing rapid assessments of opportunities and their worth to a corporation. (Author)

  2. GENETIC VARIABILITY OF CULTURED PLANT TISSUES UNDER NORMAL CONDITIONS AND UNDER STRESS

    Directory of Open Access Journals (Sweden)

    Dolgikh Yu.I.

    2012-08-01

    Full Text Available The genetic variability induced by in vitro conditions known as somaclonal variation is of practical interest due to its potential uses in plant breeding but, on the other hand, if clonal propagation or transformation is main goal, it becomes an unwelcome phenomenon. Thus, it is important to know frequency, the genomic distribution, the mechanisms and factors influencing somaclonal variation. We studied variability of PCR-based DNA markers of cultured tissues and regenerated plants of maize and bread wheat. The original A188 line of maize and the somaclones obtained were tested using 38 RAPD and 10 ISSR primers. None of the A188 plants showed variation in the RAPD and ISSR spectra for any of the primers used. However, the PCR spectra obtained from the somaclones demonstrated some variations, i.e., 22 RAPD primers and 6 ISSR primers differentiated at least one somaclonal variant from the progenitor line. Six SCAR markers were developed based on several RAPD and ISSR fragments. The inheritance of these SCAR markers was verified in the selfing progeny of each somaclone in the R1–R4 generations and in the hybrids, with A188 as the parental line in the F1 and F2 generations. These markers were sequenced and bioinformatic searches were performed to understand the molecular events that may underlie the variability observed in the somaclones. All changes were found in noncoding sequences and were induced by different molecular events, such as the insertion of long terminal repeat transposon, precise miniature inverted repeat transposable element (MITE excision, microdeletion, recombination, and a change in the pool of mitochondrial DNA. In two groups of independently produced somaclones, the same features (morphological, molecular were variable, which confirms the theory of ‘hot spots’ occurring in the genome. The presence of the same molecular markers in the somaclones and in different non-somaclonal maize variants suggests that in some cases

  3. Germline genetic variants in the Wnt/beta-catenin pathway as predictors of colorectal cancer risk

    Science.gov (United States)

    Hildebrandt, Michelle A.T.; Reyes, Monica E.; Lin, Moubin; He, Yonggang; Nguyen, Son V.; Hawk, Ernest T.; Wu, Xifeng

    2016-01-01

    Background The Wnt/beta-catenin signaling pathway plays a key role in stem cell maintenance in the colorectum. Rare high penetrance genetic mutations in components of this pathway result in familial colorectal cancer, yet the impact of common, germline variants remains unknown. Methods We assessed 172 variants in 26 genes from the Wnt/beta-catenin pathway in 809 CRC cases and 814 healthy controls, followed by replication of the top findings in another 691 cases and 775 controls. In silico informatic tools were used to predict functional effects of variants. Results Eighteen SNPs in the pathway were significantly associated with CRC risk (P <0.05) in the discovery phase. We observed a significant dose-response increase in CRC risk by number of risk genotypes carried (P = 4.19 × 10−8). Gene-based analysis implicated CSNK1D (P = 0.014), FZD3 (P = 0.023), and APC (P = 0.027) as significant for CRC risk. In the replication phase, FZD3:rs11775139 remained significantly associated with reduced risk with a pooled OR of 0.85 (95% CI: 0.76–0.94, P = 0.001). Although borderline significant in the replication population, APC:rs2545162 was highly significant in the pooled analysis - OR: 1.42, 95% CI: 1.16–1.74, P =0.00085. Functional assessment identified several potential biological mechanisms underlying these associations. Conclusions Our findings suggest that common germline variants in the Wnt/beta-catenin pathway maybe involved in CRC development. Impact These variants may be informative in CRC risk assessment to identify individuals at increased risk who would be candidates for screening. PMID:26809274

  4. Joint modeling of genetically correlated diseases and functional annotations increases accuracy of polygenic risk prediction.

    Directory of Open Access Journals (Sweden)

    Yiming Hu

    2017-06-01

    Full Text Available Accurate prediction of disease risk based on genetic factors is an important goal in human genetics research and precision medicine. Advanced prediction models will lead to more effective disease prevention and treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome-wide association studies (GWAS in the past decade, accuracy of genetic risk prediction remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes. In this work, we introduce PleioPred, a principled framework that leverages pleiotropy and functional annotations in genetic risk prediction for complex diseases. PleioPred uses GWAS summary statistics as its input, and jointly models multiple genetically correlated diseases and a variety of external information including linkage disequilibrium and diverse functional annotations to increase the accuracy of risk prediction. Through comprehensive simulations and real data analyses on Crohn's disease, celiac disease and type-II diabetes, we demonstrate that our approach can substantially increase the accuracy of polygenic risk prediction and risk population stratification, i.e. PleioPred can significantly better separate type-II diabetes patients with early and late onset ages, illustrating its potential clinical application. Furthermore, we show that the increment in prediction accuracy is significantly correlated with the genetic correlation between the predicted and jointly modeled diseases.

  5. [The forecast of illicit drug use in adolescents with addictive behavior: personality traits and the level of genetic risk of substance dependence.

    Science.gov (United States)

    Yakovlev, A N; Brodyansky, V M; Schurina, A V; Romashkin, R A; Kibitov, A O

    2016-01-01

    To clarify the psychological mechanism underlying the genetic risk of substance addiction at the first stage of drug use by adolescents. Genetic risk was evaluated by genotyping of 5 polymorphisms of the dopaminergic system genes (dopamine receptor D2 and D4 genes and tyrosine hydroxylase gene). Psychological testing was performed using the Russian version of Temperament and Character Inventory (TCI-125). Seventy-five adolescents, aged 14-17 years, (girls 32%), who misused alcohol, including 22 adolescents using drugs, were examined. The level of genetic risk was directly correlated with the probability of drug use by boys, for girls the correlation was not confirmed. The increase of the level of genetic risk for boys was correlated with the increase on the scale «Self-directedness» of TCI-125 that may reflect a probable tendency to replacement of negative information, feeling of illusory wellbeing. The findings clarify the direction of measures for the prevention of drug use.

  6. Genetic influence on blood pressure measured in the office, under laboratory stress and during real life

    NARCIS (Netherlands)

    Wang, Xiaoling; Ding, Xiuhua; Su, Shaoyong; Harshfield, Gregory; Treiber, Frank; Snieder, Harold

    To determine to what extent the genetic influences on blood pressure (BP) measured in the office, under psychologically stressful conditions in the laboratory and during real life are different from each other. Office BP, BP during a video game challenge and a social stressor interview, and 24-h

  7. A genetic analysis of relative growth rate and underlying components in Hordeum spontaneum

    NARCIS (Netherlands)

    Poorter, H.; Van Rijn, C.P.E.; Vanhala, T.K.; Verhoeven, K.J.F.; de Jong, Y.E.M.; Stams, A.J.M.; Lambers, H.

    2005-01-01

    Species from productive and unproductive habitats differ inherently in their relative growth rate (RGR) and a wide range of correlated quantitative traits. We investigated the genetic basis of this trait complex, and specifically assessed whether it is under the control of just one or a few genes

  8. The Structure of Genetic and Environmental Risk Factors for DSM-IV Personality Disorders

    Science.gov (United States)

    Kendler, Kenneth S.; Aggen, Steven H.; Czajkowski, Nikolai; Røysamb, Espen; Tambs, Kristian; Torgersen, Svenn; Neale, Michael C.; Reichborn-Kjennerud, Ted

    2009-01-01

    Context Although both genetic and environmental factors affect risk of individual personality disorders (PDs), we know little of how they contribute to the pattern of comorbidity between the PDs in the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV). Objective To clarify the structure of the genetic and environmental risk factors for the 10 DSM-IV PDs. Design Assessment of PDs at personal interview and multivariate twin modeling with the Mx program. Setting General community. Participants A total of 2794 young adult members of the Norwegian Institute of Public Health Twin Panel. Main Outcome Measure Number of endorsed criteria for the 10 DSM-IV PDs. Results The best-fit multivariate twin model required 3 genetic and 3 individual-specific environmental factors and genetic and individual-specific factors unique to each PD. The first genetic factor had high loadings on PDs from all 3 clusters including paranoid, histrionic, borderline, narcissistic, dependent, and obsessive-compulsive. The second genetic factor had substantial loadings only on borderline and antisocial PD. The third genetic factor had high loadings only on schizoid and avoidant PD. Several PDs had substantial disorder-specific genetic risk factors. The first, second, and third individual-specific environmental factors had high loadings on the cluster B, A, and C PDs, respectively, with 1 exception: obsessive-compulsive PD loaded with cluster B and not cluster C PDs. Conclusions Genetic risk factors for DSM-IV PDs do not reflect the cluster A, B, and C typology. Rather, 1 genetic factor reflects a broad vulnerability to PD pathology and/or negative emotionality. The 2 other genetic factors are more specific and reflect high impulsivity/low agreeableness and introversion. Unexpectedly, the cluster A, B, and C typology is well reflected in the structure of environmental risk factors, suggesting that environmental experiences may be responsible for the tendency of cluster A

  9. Communication of Information about Genetic Risks: Putting Families at the Center.

    Science.gov (United States)

    Mendes, Álvaro; Metcalfe, Alison; Paneque, Milena; Sousa, Liliana; Clarke, Angus J; Sequeiros, Jorge

    2017-07-16

    Genetic information is a family affair. With the expansion of genomic technologies, many new causal genes and variants have been established and the potential for molecular diagnoses increased, with implications not only for patients but also their relatives. The need for genetic counseling and intrafamilial circulation of information on genetic risks grew accordingly. Also, the amount and, particularly, the complexity of the information to convey multiplied. Sharing information about genetic risks with family members, however, has never been an easy matter and often becomes a source of personal and familial conflicts and distress. Ethical requisites generally prevent healthcare professionals from directly contacting their consultands' relatives (affected or still at risk), who often feel unsupported throughout that process. We discuss here the communication of genetic risks to family members. We first consider genomic testing as a basis for family-centered health care, as opposed to a predominant focus on the individual. We reviewed the literature on sharing genetic risk information with family members, and the associated ethical issues for professionals. Some clinical cases are presented and discussed, and key issues for meeting the needs of individuals and families are addressed. We argue that genetic information is inextricably linked to the family and that communicating about genetic risks is a process grounded within the broader milieu of family relationships and functioning. We conclude for the need for a more family-centered approach and interventions that can promote sensitive attitudes to the provision of genetic information to and within the family, as well as its inclusion in educational and training programmes for genetic healthcare professionals. © 2017 Family Process Institute.

  10. Concerns about Genetic Testing for Schizophrenia among Young Adults at Clinical High Risk for Psychosis.

    Science.gov (United States)

    Lawrence, Ryan E; Friesen, Phoebe; Brucato, Gary; Girgis, Ragy R; Dixon, Lisa

    Genetic tests for schizophrenia may introduce risks and benefits. Among young adults at clinical high-risk for psychosis, little is known about their concerns and how they assess potential risks. We conducted semi-structured interviews with 15 young adults at clinical high-risk for psychosis to ask about their concerns. Participants expressed concerns about test reliability, data interpretation, stigma, psychological harm, family planning, and privacy. Participants' responses showed some departure from the ethics literature insofar as participants were primarily interested in reporting their results to people to whom they felt emotionally close, and expressed little consideration of biological closeness. Additionally, if tests showed an increased genetic risk for schizophrenia, four clinical high-risk persons felt obligated to tell an employer and another three would "maybe" tell an employer, even in the absence of clinical symptoms. These findings suggest opportunities for clinicians and genetic counselors to intervene with education and support.

  11. Genetic Vulnerability as a Distal Risk Factor for Suicidal Behaviour: Historical Perspective and Current Knowledge.

    Science.gov (United States)

    Andriessen, Karl; Videtic-Paska, Alja

    2015-09-01

    Suicide is a multidimensional problem. Observations of family history of suicide suggest the existence of a genetic vulnerability to suicidal behaviour. Starting with a historical perspective, the article reviews current knowledge of a genetic vulnerability to suicidal behaviour, distinct from the genetic vulnerability to psychiatric disorders, focused on clinical and population-based studies, and findings from recent molecular genetics association studies. The review includes peer-reviewed research articles and review papers from the professional literature in English language, retrieved from PubMed/Medline and PsycINFO. The research literature confirms a existence of a genetic vulnerability to suicidal behaviour. Even though the results of individual studies are difficult to compare, genetic influences could explain up to half of the variance of the occurrence of suicide. Genetic vulnerability could be a distal risk factor for suicide, which helps us to understand the occurrence of suicide among vulnerable people. Ethical implications of such vulnerability are highlighted.

  12. Reprogenetics, Genetic Tools and Reproductive Risk: Attitudes and Understanding Among Ethnic Groups in Israel.

    Science.gov (United States)

    Simonstein, Frida; Mashiach-Eizenberg, Michal

    2016-02-01

    The present study investigated a possible relationship between the attitudes toward genetic technologies and the understanding of genetics, reproduction, and reproductive risk among Israeli Arabs and Israeli Jews. The study included 203 respondents, who answered a structured self-report questionnaire. They were recruited using a snowball method, which increased the participation of Israeli Arabs in the sample, although the sample was not representative of the Israeli population as a whole (there were more Arabs and fewer men). The respondents in this study expressed a positive attitude toward genetic technologies, but were less in favor of using genetic tools for non-medical purposes. Respondents of both groups were not knowledgeable of genetics; however, they scored higher on the items related to reproductive risk, which suggests that some awareness about genetic risk exists in both sectors of the Israeli population. Nevertheless, Israeli Arabs were less positive than Israeli Jews regarding the application of genetic tools. Moreover, although an understanding of genetics correlated positively with the attitude among Arabs, it did not affect the attitude of Jews, who remained very positive, regardless of their level of understanding. This result suggests that other social and cultural factors, besides understanding, might be at work among these two major ethnic sectors. Further studies that integrate educational, social, and cultural aspects among ethnic sectors of the population are required to improve health services and genetic counselling in Israel and in other countries.

  13. Measurement and Associations of Pregnancy Risk Factors with Genetic Influences, Postnatal Environmental Influences, and Toddler Behavior

    Science.gov (United States)

    Marceau, Kristine; Hajal, Nastassia; Leve, Leslie D.; Reiss, David; Shaw, Daniel S.; Ganiban, Jody M.; Mayes, Linda C.; Neiderhiser, Jenae M.

    2013-01-01

    This study demonstrates the unique contributions of perinatal risk and genetic and environmental influences on child behavior using data from 561 domestic US adoption triads (birth mothers, adopted child, and adoptive parents). Findings show distinct patterns of associations among genetic (birth mother psychopathology), prenatal (six maternal…

  14. A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering

    NARCIS (Netherlands)

    Leusink, Maarten; Maitland-van der Zee, Anke H.; Ding, Bo; Drenos, Fotios; van Iperen, Erik Pa; Warren, Helen R.; Caulfield, Mark J.; Cupples, L. Adrienne; Cushman, Mary; Hingorani, Aroon D.; Hoogeveen, Ron C.; Hovingh, G. Kees; Kumari, Meena; Lange, Leslie A.; Munroe, Patricia B.; Nyberg, Fredrik; Schreiner, Pamela J.; Sivapalaratnam, Suthesh; de Bakker, Paul Iw; de Boer, Anthonius; Keating, Brendan J.; Asselbergs, Folkert W.; Onland-Moret, N. Charlotte

    2016-01-01

    To find new genetic loci associated with statin response, and to investigate the association of a genetic risk score (GRS) with this outcome. In a discovery meta-analysis (five studies, 1991 individuals), we investigated the effects of approximately 50000 single nucleotide polymorphisms on statin

  15. Genetic Predisposition to Central Obesity and Risk of Type 2 Diabetes: Two Independent Cohort Studies.

    Science.gov (United States)

    Huang, Tao; Qi, Qibin; Zheng, Yan; Ley, Sylvia H; Manson, JoAnn E; Hu, Frank B; Qi, Lu

    2015-07-01

    Abdominal obesity is a major risk factor for type 2 diabetes (T2D). We aimed to examine the association between the genetic predisposition to central obesity, assessed by the waist-to-hip ratio (WHR) genetic score, and T2D risk. The current study included 2,591 participants with T2D and 3,052 participants without T2D of European ancestry from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Genetic predisposition to central obesity was estimated using a genetic score based on 14 established loci for the WHR. We found that the central obesity genetic score was linearly related to higher T2D risk. Results were similar in the NHS (women) and HPFS (men). In combined results, each point of the central obesity genetic score was associated with an odds ratio (OR) of 1.04 (95% CI 1.01-1.07) for developing T2D, and the OR was 1.24 (1.03-1.45) when comparing extreme quartiles of the genetic score after multivariate adjustment. The data indicate that genetic predisposition to central obesity is associated with higher T2D risk. This association is mediated by central obesity. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  16. A risk assessment framework for irrigated agriculture under climate change

    Science.gov (United States)

    Ronco, P.; Zennaro, F.; Torresan, S.; Critto, A.; Santini, M.; Trabucco, A.; Zollo, A. L.; Galluccio, G.; Marcomini, A.

    2017-12-01

    In several regions, but especially in semi-arid areas, raising frequency, duration and intensity of drought events, mainly driven by climate change dynamics, are expected to dramatically reduce the current stocks of freshwater resources, limiting crop development and yield especially where agriculture largely depends on irrigation. The achievement of an affordable and sustainable equilibrium between available water resources and irrigation demand is essentially related to the planning and implementation of evidence-based adaptation strategies and actions. The present study proposed a state-of-the art conceptual framework and computational methodology to assess the potential water scarcity risk, due to changes in climate trends and variability, on irrigated croplands. The model has been tested over the irrigated agriculture of Puglia Region, a semi-arid territory with the largest agricultural production in Southern Italy. The methodology, based on the Regional Risk Assessment (RRA) approach, has been applied within a scenario-based hazard framework. Regional climate projections, under alternative greenhouse gas concentration scenarios (RCP4.5 and RCP8.5) and for two different timeframes, 2021-2050 and 2041-2070 compared to the baseline 1976-2005 period, have been used to drive hydrological simulations of river inflow to the most important reservoirs serving irrigation purposes in Puglia. The novelty of the proposed RRA-based approach does not simply rely on the concept of risk as combination of hazard, exposure and vulnerability, but rather elaborates detailed (scientific and conceptual) framing and computational description of these factors, to produce risk spatial pattern maps and related statistics distinguishing the most critical areas (risk hot spots).. The application supported the identification of the most affected areas (i.e. Capitanata Reclamation Consortia under RCP8.5 2041-2070 scenario), crops (fruit trees and vineyards), and, finally, the vulnerability

  17. COMPARATIVE EVALUATION OF RISK FACTORS FOR CARDIOVASCULAR DISEASE (CVD) IN GENETICALLY PREDISPOSED RATS

    Science.gov (United States)

    Rodent CVD models are increasingly used for understanding individual differences in susceptibility to environmental stressors such as air pollution. We characterized pathologies and a number of known human risk factors of CVD in genetically predisposed, male young adult Spontaneo...

  18. Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese

    NARCIS (Netherlands)

    S.A. Lubitz (Steven); K.L. Lunetta (Kathryn); H. Lin (Honghuang); D.E. Arking (Dan); S. Trompet (Stella); G. Li (Guo); B.P. Krijthe (Bouwe); D.I. Chasman (Daniel); J. Barnard (John); M.E. Kleber (Marcus); M. Dörr (Marcus); Y. Ozaki (Yukio); G.D. Smith; M. Müller-Nurasyid (Martina); S. Walter (Stefan); S.K. Agarwal (Sunil); J.C. Bis (Joshua); J. Brody (Jennifer); L. Chen (Lin); B.M. Everett (Brendan); I. Ford (Ian); O.H. Franco (Oscar); T.B. Harris (Tamara); A. Hofman (Albert); S. Kääb (Stefan); S. Mahida (Saagar); S. Kathiresan (Sekar); M. Kubo (Michiaki); L.J. Launer (Lenore); P.W. MacFarlane (Peter); J.W. Magnani (Jared); B. McKnight (Barbara); D.D. McManus (David); A. Peters (Annette); B.M. Psaty (Bruce); L.M. Rose (Lynda); J.I. Rotter (Jerome); G. Silbernagel (Günther); J.D. Smith (Jonathan); N. Sotoodehnia (Nona); D.J. Stott (David. J.); K.D. Taylor (Kent); A. Tomaschitz (Andreas); T. Tsunoda (Tatsuhiko); A.G. Uitterlinden (André); D.R. van Wagoner (David); U. Völker (Uwe); H. Völzke (Henry); J. Murabito (Joanne); M.F. Sinner (Moritz); V. Gudnason (Vilmundur); S.B. Felix (Stephan); W. März (Winfried); M.K. Chung (Mina); C.M. Albert (Christine); B.H.Ch. Stricker (Bruno); T. Tanaka (Toshihiro); S.R. Heckbert (Susan); J.W. Jukema (Jan Wouter); A. Alonso (Alvaro); E.J. Benjamin (Emelia); P.T. Ellinor (Patrick)

    2014-01-01

    textabstractObjectives This study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk. Background AF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple

  19. DEVELOPMENT OF AQUATIC MODELS FOR TESTING THE RELATIONSHIP BETWEEN GENETIC DIVERSITY AND POPULATION EXTINCTION RISK

    Science.gov (United States)

    The relationship between population adaptive potential and extinction risk in a changing environment is not well understood. Although the expectation is that genetic diversity is directly related to the capacity of populations to adapt, the statistical and predictive aspects of ...

  20. The association of XRCC3 Thr241Met genetic variant with risk of ...

    African Journals Online (AJOL)

    complementing group 3 gene (XRCC3) Thr241Met genetic variant could be potentially associated with the risk of prostate cancer. However, results from these published studies were conflicting rather than conclusive. Objectives:This meta-analysis ...

  1. Genetic and environmental influences on cardiovascular risk factors and cognitive function

    DEFF Research Database (Denmark)

    Xu, Chunsheng; Tian, Xiaocao; Sun, Jianping

    2018-01-01

    AIM: To explore the genetic and environmental influences on cardiovascular risk factors (CVRF) and cognitive function in the world's largest and rapidly aging Chinese population. METHODS: Cognitive function and CVRF, including body mass index, systolic blood pressure, diastolic blood pressure...

  2. Microarray Technology to Study the Role of Genetic Polymorphisms in Breast Cancer Risk

    National Research Council Canada - National Science Library

    Ozcelik, Hilmi

    2004-01-01

    .... In this study we took the candidate gene approach to study the association of 19 different genetic polymorphisms with breast cancer risk in a population-based sample using a high-throughput genotyping technology...

  3. Genetic variants in hormone-related genes and risk of breast cancer.

    Directory of Open Access Journals (Sweden)

    Tess Clendenen

    Full Text Available Sex hormones play a key role in the development of breast cancer. Certain polymorphic variants (SNPs and repeat polymorphisms in hormone-related genes are associated with sex hormone levels. However, the relationship observed between these genetic variants and breast cancer risk has been inconsistent. We conducted a case-control study nested within two prospective cohorts to assess the relationship between specific genetic variants in hormone-related genes and breast cancer risk. In total, 1164 cases and 2111 individually-matched controls were included in the study. We did not observe an association between potential functional genetic polymorphisms in the estrogen pathway, SHBG rs6259, ESR1 rs2234693, CYP19 rs10046 and rs4775936, and UGT1A1 rs8175347, or the progesterone pathway, PGR rs1042838, with the risk of breast cancer. Our results suggest that these genetic variants do not have a strong effect on breast cancer risk.

  4. Gestational age at birth and risk of intellectual disability without a common genetic cause.

    Science.gov (United States)

    Heuvelman, Hein; Abel, Kathryn; Wicks, Susanne; Gardner, Renee; Johnstone, Edward; Lee, Brian; Magnusson, Cecilia; Dalman, Christina; Rai, Dheeraj

    2017-12-06

    Preterm birth is linked to intellectual disability and there is evidence to suggest post-term birth may also incur risk. However, these associations have not yet been investigated in the absence of common genetic causes of intellectual disability, where risk associated with late delivery may be preventable. We therefore aimed to examine risk of intellectual disability without a common genetic cause across the entire range of gestation, using a matched-sibling design to account for unmeasured confounding by shared familial factors. We conducted a population-based retrospective study using data from the Stockholm Youth Cohort (n = 499,621) and examined associations in a nested cohort of matched outcome-discordant siblings (n = 8034). Risk of intellectual disability was greatest among those born extremely early (adjusted OR 24 weeks  = 14.54 [95% CI 11.46-18.44]), lessening with advancing gestational age toward term (aOR 32 weeks  = 3.59 [3.22-4.01]; aOR 37 weeks  = 1.50 [1.38-1.63]); aOR 38 weeks  = 1.26 [1.16-1.37]; aOR 39 weeks = 1.10 [1.04-1.17]) and increasing with advancing gestational age post-term (aOR 42 weeks  = 1.16 [1.08-1.25]; aOR 43 weeks  = 1.41 [1.21-1.64]; aOR 44 weeks  = 1.71 [1.34-2.18]; aOR 45 weeks  = 2.07 [1.47-2.92]). Associations persisted in a cohort of matched siblings suggesting they were robust against confounding by shared familial traits. Risk of intellectual disability was greatest among children showing evidence of fetal growth restriction, especially when birth occurred before or after term. Birth at non-optimal gestational duration may be linked causally with greater risk of intellectual disability. The mechanisms underlying these associations need to be elucidated as they are relevant to clinical practice concerning elective delivery around term and mitigation of risk in post-term children.

  5. Capital Structure Arbitrage under a Risk-Neutral Calibration

    Directory of Open Access Journals (Sweden)

    Peter J. Zeitsch

    2017-01-01

    Full Text Available By reinterpreting the calibration of structural models, a reassessment of the importance of the input variables is undertaken. The analysis shows that volatility is the key parameter to any calibration exercise, by several orders of magnitude. To maximize the sensitivity to volatility, a simple formulation of Merton’s model is proposed that employs deep out-of-the-money option implied volatilities. The methodology also eliminates the use of historic data to specify the default barrier, thereby leading to a full risk-neutral calibration. Subsequently, a new technique for identifying and hedging capital structure arbitrage opportunities is illustrated. The approach seeks to hedge the volatility risk, or vega, as opposed to the exposure from the underlying equity itself, or delta. The results question the efficacy of the common arbitrage strategy of only executing the delta hedge.

  6. Eating disorder-specific risk factors moderate the relationship between negative urgency and binge eating: A behavioral genetic investigation.

    Science.gov (United States)

    Racine, Sarah E; VanHuysse, Jessica L; Keel, Pamela K; Burt, S Alexandra; Neale, Michael C; Boker, Steven; Klump, Kelly L

    2017-07-01

    Theoretical models of binge eating and eating disorders include both transdiagnostic and eating disorder-specific risk factors. Negative urgency (i.e., the tendency to act impulsively when distressed) is a critical transdiagnostic risk factor for binge eating, but limited research has examined interactions between negative urgency and disorder-specific variables. Investigating these interactions can help identify the circumstances under which negative urgency is most strongly associated with binge eating. We examined whether prominent risk factors (i.e., appearance pressures, thin-ideal internalization, body dissatisfaction, dietary restraint) specified in well-established etiologic models of eating disorders moderate negative urgency-binge eating associations. Further, we investigated whether phenotypic moderation effects were due to genetic and/or environmental associations between negative urgency and binge eating. Participants were 988 female twins aged 11-25 years from the Michigan State University Twin Registry. Appearance pressures, thin-ideal internalization, and body dissatisfaction, but not dietary restraint, significantly moderated negative urgency-binge eating associations, with high levels of these risk factors and high negative urgency associated with the greatest binge eating. Twin moderation models revealed that genetic, but not environmental, sharing between negative urgency and binge eating was enhanced at higher levels of these eating disorder-specific variables. Future longitudinal research should investigate whether eating disorder risk factors shape genetic influences on negative urgency into manifesting as binge eating. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  7. A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0529 TITLE: A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk PRINCIPAL INVESTIGATOR...reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215...AND SUBTITLE A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1

  8. The relevance of animal experimental results for the assessment of radiation genetic risks in man

    International Nuclear Information System (INIS)

    Stephan, G.

    1981-01-01

    No suitable data are available from man for the quantitative assessment of genetic radiation risk. Therefore, the results from experiments on animals must be utilized. Two hypotheses are presented here in drawing analogical conclusions from one species to another. Although the extrapolation of results from animal experiments remains an open question, the use of experimental results from mice seems to be justified for an assessment of the genetic radiation risk in man. (orig.) [de

  9. Transparency of chemical risk assessment data under REACH.

    Science.gov (United States)

    Ingre-Khans, Ellen; Ågerstrand, Marlene; Beronius, Anna; Rudén, Christina

    2016-12-08

    The REACH regulation requires EU manufacturers and importers of substances to register information on the hazard and risk of their substances with the European Chemicals Agency (ECHA). Risk management of the substances is based on the provided information. It is known that conclusions on hazard and risk are influenced by expert judgements as well as potential conflict of interests. Thus, it is important that hazard and risk assessments are transparent and can be evaluated by a third party. The aim of this study is to scrutinize the transparency, i.e. the accessibility and comprehensibility, of information on substances registered under REACH. Data on repeated dose toxicity and hazard assessment conclusions were extracted for 60 substances from the REACH registration database available on the ECHA website. The data were compiled in a database for systematically evaluating the transparency of information related to the conclusions on hazard or risk. In addition, chemical safety reports (CSR) were requested from ECHA for five substances. The transparency of information on the hazard and risk of substances was found to be limited for several reasons. First, certain information was removed due to confidentiality and certain fields were not published because they could contain confidential information although the information had not been claimed confidential. Also, the extent to which registrants reported information varied, and the presentation of some data and certain terminology required further clarification. In addition, the data source for the majority of the key and supporting studies could not be identified due to confidentiality. Since registrants are only required to summarise studies, it cannot be verified whether all relevant information from non-public industry reports have been reported. Lastly, certain information related to the hazard and risk assessment were only reported in the CSR which is only available upon request; a time-consuming and work

  10. Worst-Case Portfolio Optimization under Stochastic Interest Rate Risk

    Directory of Open Access Journals (Sweden)

    Tina Engler

    2014-12-01

    Full Text Available We investigate a portfolio optimization problem under the threat of a market crash, where the interest rate of the bond is modeled as a Vasicek process, which is correlated with the stock price process. We adopt a non-probabilistic worst-case approach for the height and time of the market crash. On a given time horizon [0; T], we then maximize the investor’s expected utility of terminal wealth in the worst-case crash scenario. Our main result is an explicit characterization of the worst-case optimal portfolio strategy for the class of HARA (hyperbolic absolute risk aversion utility functions.

  11. Optimal natural resources management under uncertainty with catastrophic risk

    International Nuclear Information System (INIS)

    Motoh, Tsujimura

    2004-01-01

    We examine an optimal natural resources management problem under uncertainty with catastrophic risk and investigate the optimal rate of use of a natural resource. For this purpose, we use stochastic control theory. We assume that, until a catastrophic event occurs, the stock of the natural resource is governed by a stochastic differential equation. We describe the catastrophic phenomenon as a Poisson process. From this analysis, we show the optimal rate of use of the natural resource in explicit form. Furthermore, we present comparative static results for the optimal rate of use of the natural resource

  12. [Genetically modified organisms in food--production, detection and risks].

    Science.gov (United States)

    Zeljezić, Davor

    2004-11-01

    The first genetically modified plant (GMP) was a tobacco resistant to antibiotics in 1983. In 1996, the first genetically altered crop, a delayed-ripening tomato was commercially released. In the year 2003, the estimated global area of GM crops for was 67.7 million hectares. To produce such a plant a gene of interest has to be isolated from the donor. Together with a promoter, terminator sequence and marker gene it has to be introduced into the plant cell which is then stimulated to generate a whole GMP expressing new characteristics (herbicide/insect resistance, delayed ripening). The last few months have seen a strong public debate over genetically modified organisms which has raised scientific, economic, political, and ethical issues. Some questions concerning the safety of GMPs are still to be answered, and decisions about their future should be based on scientifically validated information.

  13. Network dysfunction of emotional and cognitive processes in those at genetic risk of bipolar disorder.

    Science.gov (United States)

    Breakspear, Michael; Roberts, Gloria; Green, Melissa J; Nguyen, Vinh T; Frankland, Andrew; Levy, Florence; Lenroot, Rhoshel; Mitchell, Philip B

    2015-11-01

    The emotional and cognitive vulnerabilities that precede the development of bipolar disorder are poorly understood. The inferior frontal gyrus-a key cortical hub for the integration of cognitive and emotional processes-exhibits both structural and functional changes in bipolar disorder, and is also functionally impaired in unaffected first-degree relatives, showing diminished engagement during inhibition of threat-related emotional stimuli. We hypothesized that this functional impairment of the inferior frontal gyrus in those at genetic risk of bipolar disorder reflects the dysfunction of broader network dynamics underlying the coordination of emotion perception and cognitive control. To test this, we studied effective connectivity in functional magnetic resonance imaging data acquired from 41 first-degree relatives of patients with bipolar disorder, 45 matched healthy controls and 55 participants with established bipolar disorder. Dynamic causal modelling was used to model the neuronal interaction between key regions associated with fear perception (the anterior cingulate), inhibition (the left dorsolateral prefrontal cortex) and the region upon which these influences converge, namely the inferior frontal gyrus. Network models that embodied non-linear, hierarchical relationships were the most strongly supported by data from our healthy control and bipolar participants. We observed a marked difference in the hierarchical influence of the anterior cingulate on the effective connectivity from the dorsolateral prefrontal cortex to the inferior frontal gyrus that is unique to the at-risk cohort. Non-specific, non-hierarchical mechanisms appear to compensate for this network disturbance. We thus establish a specific network disturbance suggesting dysfunction in the processes that support hierarchical relationships between emotion and cognitive control in those at high genetic risk for bipolar disorder. © The Author (2015). Published by Oxford University Press on behalf

  14. The risk for cancer and genetic abnormalities after radioiodine treatment of hyperthyroidism

    International Nuclear Information System (INIS)

    Reiners, C.

    1997-01-01

    According to recent studies, the risk for thyroid cancer is not increased after radioiodine treatment in patients with hyperthyroidism. Only the risk of cancer of the stomach seems to be increased slightly in patents treated with I-131 because of functional autonomy. However, the risk for gastric cancer is not increased after higher activities of I-131 because of thyroid cancer. There is no increased risk for genetic abnormalities after radioiodine treatment of hyperthyroidism. (orig.) [de

  15. Congenital and genetic cerebrovascular anomalies as risk factors for stroke in Saudi Arabia

    International Nuclear Information System (INIS)

    Salih, Mustafa A.; Al-Jarallah, Ahmed A.; Kentab, Amal Y.; Murshid, Waleed R.; Zahraa, Jihad N.; Abdel-Gader, Abdel-Galil M.; Alorainy, Ibrahim A.; Hassan, Hamdy H.; Tjan, G. T.

    2006-01-01

    To explore the role of and report congenital and genetic cerebrovascular anomalies as risk factors for stroke in a prospective and retrospective cohort of Saudi children. Children with stroke were evaluated at the Division of Pediatric Neurology (Dpn), or were seen as inpatients in the Pediatric Wards at King Khalid University Hospital (KKUH), Riyadh, Kingdom of Saudi Arabia during the periods July 1992 to February 2001 (retrospective study) and February 2001 to March 2003 (prospective study). Stroke work-up for each suspected case included hemostatic assays, serological, biochemical and neurophysiological tests. Neuroimaging modalities included routine skill x-rays, CT, MRI, magnetic resonance angiography (MRA) and conventional cerebral angiography. Of 104 children with stroke, congenital and genetic cerebrovascular anomalies were the underlying risk factor in 7 (6.7%). The patients were evaluated at the DPN at a mean age of 66 months (range = 8 months to 11 years, median = 6 years); and they had stroke at a mean age of 48 months (range = 2 months to 10 years, median = 8 months). Four patients had stroke in association with neurocutaneous syndromes. Two had Sturge-Weber syndrome (SWS), one had Klippel-Trenaunay syndrome associated with SWS, and the fourth had neurofibromatosis type 1. Two patients had intracranial hemorrhage secondary to ruptured aneurysm. A girl (aged 9 years and 4 months) had left posterior cerebral artery aneurysm. She was diagnosed to have autosomal dominant polycystic kidney disease following renal ultrasonography. She died 5 months later despite surgical intervention (clipping of aneurysm). The second child was an 8-months-old boy who presented with subarachnoid and intraventricular hemorrhage (IVH) following ruptured anterior communicating artery aneurysm. He recovered with no residual symptoms following successful clipping of the aneurysm. Arteriovenous malformation (AVM) caused IVH in a 7-year-old boy who reported to hospital 5 hours

  16. Optimal CO2 mitigation under damage risk valuation

    Science.gov (United States)

    Crost, Benjamin; Traeger, Christian P.

    2014-07-01

    The current generation has to set mitigation policy under uncertainty about the economic consequences of climate change. This uncertainty governs both the level of damages for a given level of warming, and the steepness of the increase in damage per warming degree. Our model of climate and the economy is a stochastic version of a model employed in assessing the US Social Cost of Carbon (DICE). We compute the optimal carbon taxes and CO2 abatement levels that maximize welfare from economic consumption over time under different risk states. In accordance with recent developments in finance, we separate preferences about time and risk to improve the model's calibration of welfare to observed market interest. We show that introducing the modern asset pricing framework doubles optimal abatement and carbon taxation. Uncertainty over the level of damages at a given temperature increase can result in a slight increase of optimal emissions as compared to using expected damages. In contrast, uncertainty governing the steepness of the damage increase in temperature results in a substantially higher level of optimal mitigation.

  17. Genetically predicted high body mass index is associated with increased gastric cancer risk.

    Science.gov (United States)

    Mao, Yingying; Yan, Caiwang; Lu, Qun; Zhu, Meng; Yu, Fei; Wang, Cheng; Dai, Juncheng; Ma, Hongxia; Hu, Zhibin; Shen, Hongbing; Jin, Guangfu

    2017-09-01

    Epidemiological studies have linked body mass index (BMI) with risk of gastrointestinal cancers. However, for gastric cancer, the relationship is more controversial. In particular, it is unclear whether the observed association is due to confounding or bias inherent in conventional observational studies. To investigate whether BMI is causally associated with gastric cancer risk, we applied Mendelian randomization using individual-level data from 2631 gastric cancer cases and 4373 cancer-free controls. We derived a weighted genetic risk score (wGRS) using 37 BMI-associated genetic variants as an instrumental variable. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between genetically predicted BMI and gastric cancer risk. We observed that higher genetically determined BMI was associated with increased gastric cancer risk (per standard deviation (SD) increase in the wGRS: OR=1.07, 95% CI: 1.02-1.13, P=4.94 × 10 -3 ). Compared with individuals in the bottom tertile of the BMI wGRS, those in the top tertile had 1.14-fold (95% CI: 1.01-1.29) increased risk of developing gastric cancer. Sensitivity analyses using alternative causal inference measures demonstrated consistent association. Our study indicated that genetically high BMI was associated with increased gastric cancer risk, suggesting that high BMI may have a causal role in the etiology of gastric cancer.

  18. Risks and benefits of genetically modified foods | Amin | African ...

    African Journals Online (AJOL)

    There are claims that fear towards new technology has been caused by the lack of information and education on the subject to the public. Modern biotechnology and its applications have been receiving the same criticism. Thus, the objective of this study is to analyze the trends and coverage of genetically modified food ...

  19. Assessing ecological risks and benefits of genetically modified crops

    OpenAIRE

    Bošković Jelena V.; Isajev Vasilije V.; Prijić Željana S.; Zečević Veselinka M.; Hojka Zdravko M.; Dozet Gordana K.

    2010-01-01

    Genetically modified (GM) crops and biotechnology are providing new opportunities for increasing crop productivity and tackling agriculture problems, such as diseases, pests and weeds, abiotic stress and nutritional limitations of staple food crops. As GM crops are being adopted in various locations with different ecosystems, a scientifically based understanding of the environmental effects of cultivations of GM crops would assist decision makers worldwide ...

  20. On structural design optimization under uncertainty and risk

    International Nuclear Information System (INIS)

    Teofilo Beck, Andre; Santana Gomes, Wellison Jose de

    2010-01-01

    In this paper, the effects of uncertainty and risk on structural design optimization are investigated, by comparing results of Deterministic Design Optimization (DDO), Reliability-based Design Optimization (RBDO) and Reliability-based Risk Optimization (RBRO). DDO yields a structural topology (or shape) which is optimum in terms of mechanics, but does not explicitly address parameter uncertainties and their effects on structural safety. RBDO properly models safety-under-uncertainty, allowing the optimum structure to maintain an acceptable level of safety. Results, however, are dependent on the failure probability used as constraint. Risk optimization (RBRO) increases the scope of the problem, by addressing the compromising goals of economy and safety. This is accomplished by quantifying the costs associated to construction, operation and maintenance, as well as the monetary consequences of failure. RBRO yields the optimum topology and the optimum point of balance between economy and safety. Results are compared for some example problems. The broader RBRO solution is found first, and optimum results are used as constraints in DDO and RBDO. Results show that even when the optimum safety coefficients are used as constraint in DDO, the formulation leads to optimum configurations which respect these design constraints, reduce manufacturing costs but increase total expected costs (including expected cost of failure). If the (optimum) system failure probability is used as constraint in RBDO, the optimum solution reduces manufacturing costs, but by increasing total expected costs. This happens when the costs associated to different failure modes are distinct.

  1. AFLPs reveal different population genetic structure under contrasting environments in the marine snail Nucella lapillus L.

    Directory of Open Access Journals (Sweden)

    Belén Carro

    Full Text Available Dispersal has received growing attention in marine ecology, particularly since evidence obtained with up-to-date techniques challenged the traditional view. The dogwhelk Nucella lapillus L., a sedentary gastropod with direct development, is a good example: dispersal was traditionally assumed to be limited until studies with microsatellites disputed this idea. To shed some light on this controversy, the genetic structure of dogwhelk populations in northwest Spain was investigated with highly polymorphic AFLP markers giving special attention to the influence of hydrodynamic stress. In agreement with the expectations for a poor disperser, our results show a significant genetic structure at regional (<200 km and areal scales (<15 km. However, the spatial genetic structure varied with wave-exposure in the present case study: IBD was evident under sheltered conditions but absent from the exposed area where genetic differentiation was stronger. Our results provide evidence that differences in wave-exposure can exert a detectable influence on the genetic structure of coastal organisms, even in species without a planktonic larva.

  2. Barriers and Facilitators to BRCA Genetic Counseling Among At-Risk Latinas in New York City

    Science.gov (United States)

    Sussner, Katarina M.; Jandorf, Lina; Thompson, Hayley S.; Valdimarsdottir, Heiddis B.

    2012-01-01

    Objective Despite underuse of genetic services for hereditary breast and/or ovarian cancer risk among Latinas (including counseling and testing for BRCA mutations), there is little known about the barriers and facilitators to BRCA genetic counseling among this group. It is imperative to first understand factors that may impede Latinas seeking BRCA genetic counseling, as it is considered a prerequisite to testing. Methods Quantitative telephone interviews (N=120) were conducted with at-risk Latinas in New York City to investigate interest, barriers and beliefs about BRCA genetic counseling. Statistical analyses examined predictors of intention to undergo BRCA genetic counseling. Results Despite moderate levels of awareness, Latinas held largely positive beliefs, attitudes and knowledge about BRCA genetic counseling. Perceived barriers included logistic concerns (e.g., where to go, cost/health insurance coverage), emotional concerns (e.g., fear, distress) and competing life concerns (e.g, too many other things to worry about, too busy taking care of children or family members). Multivariate results showed that the strongest predictor of intention to undergo BRCA genetic counseling was competing life concerns; Latinas with more competing life concerns were less likely to intend to undergo BRCA genetic counseling (p=0.0002). Other significant predictors of intention included perceived risk of carrying a BRCA mutation (p=0.01) and referral by their physician (p=0.02). Conclusion Educational efforts to promote BRCA genetic counseling among at-risk Latinas and increase referrals by their physicians should incorporate discussion of perceived barriers to counseling, such as competing life concerns that Latinas may need to overcome in order to seek genetic counseling. PMID:22987526

  3. Provider Discussions of Genetic Tests With U.S. Women at Risk for a BRCA Mutation.

    Science.gov (United States)

    Hull, Leland E; Haas, Jennifer S; Simon, Steven R

    2018-02-01

    The U.S. Preventive Services Task Force recommends that primary care providers screen unaffected women with a family history of BRCA mutation-associated cancers, but without a personal history of BRCA-related cancer, for referral to genetic counseling and potential genetic testing. The 2015 National Health Interview Survey was analyzed in January 2017 to determine the rates at which unaffected adult women with a positive family history of BRCA-related cancers, assessed using the Family History Screen-7, reported discussing genetic testing with a provider, using genetic counseling services, and having genetic testing for increased cancer risk. Clinical correlates associated with these outcomes were assessed using multivariable logistic regression (AOR with 95% CI). Among unaffected Family History Screen-7 screen-positive women, 9.5% reported discussing genetic testing with a provider, 5.1% reported genetic counseling, and 2.7% reported uptake of genetic testing. Younger women (aged 18-39 and 40-49 years) were more likely to discuss genetic testing than women aged ≥60 years (AOR=1.50, 95% CI=1.09, 2.06 and AOR=1.64, 95% CI=1.15, 2.33, respectively). Women of black race (AOR=1.50, 95% CI=1.09, 2.07) and women with greater than a high school education (AOR=1.85, 95% CI=1.41, 2.43) were more likely to discuss genetic testing than women of white race and women with a high school education or less, respectively. Among a higher risk subgroup with an even stronger family history of BRCA-associated cancers, 18.5% of women reported discussions. Despite a decade-old U.S. Preventive Services Task Force recommendation, few unaffected women at risk for BRCA-associated cancer report discussing genetic testing with a provider. Published by Elsevier Inc.

  4. Genetic Adaptation to Growth Under Laboratory Conditions in Escherichia coli and Salmonella enterica

    Directory of Open Access Journals (Sweden)

    Anna Knöppel

    2018-04-01

    Full Text Available Experimental evolution under controlled laboratory conditions is becoming increasingly important to address various evolutionary questions, including, for example, the dynamics and mechanisms of genetic adaptation to different growth and stress conditions. In such experiments, mutations typically appear that increase the fitness under the conditions tested (medium adaptation, but that are not necessarily of interest for the specific research question. Here, we have identified mutations that appeared during serial passage of E. coli and S. enterica in four different and commonly used laboratory media and measured the relative competitive fitness and maximum growth rate of 111 genetically re-constituted strains, carrying different single and multiple mutations. Little overlap was found between the mutations that were selected in the two species and the different media, implying that adaptation occurs via different genetic pathways. Furthermore, we show that commonly occurring adaptive mutations can generate undesired genetic variation in a population and reduce the accuracy of competition experiments. However, by introducing media adaptation mutations with large effects into the parental strain that was used for the evolution experiment, the variation (standard deviation was decreased 10-fold, and it was possible to measure fitness differences between two competitors as small as |s| < 0.001.

  5. The myth of natural barriers. Is transgene introgression by genetically modified crops an environmental risk?

    Science.gov (United States)

    Guarnieri, Vincenzo; Benessia, Alice; Camino, Elena; Barbiero, Giuseppe

    2008-01-01

    Genetically modified (GM) crops under open field conditions are a complex and controversial issue. Ecologists are discussing about the possibility that a transgene belonging to GM plants could spread to native populations through a process known as introgression the stable incorporation of a gene in the host genome able to generate a differentiated population. The ecological consequences of a transgene introgression in plants or bacteria are not yet well understood, but could be significant. In this critical review we consider vertical and horizontal introgression. We analyse the biochemical and genetic constraints, and environmental factors that limit the possibility of transgene spread; meanwhile we show cases in which the natural barriers are overcome. Then we discuss the overall management of GM crops, noting the shortcomings and approximations of risk assessment based on linear thinking typical of the biomolecular approach. Finally we suggest to explicitly weight facts together with values and we encourage the undertaking of an ecological perspective, encompassing the complexity of (non-linear) relations between organisms and the environment.

  6. Development of a construct-based risk assessment framework for genetic engineered crops.

    Science.gov (United States)

    Beker, M P; Boari, P; Burachik, M; Cuadrado, V; Junco, M; Lede, S; Lema, M A; Lewi, D; Maggi, A; Meoniz, I; Noé, G; Roca, C; Robredo, C; Rubinstein, C; Vicien, C; Whelan, A

    2016-10-01

    Experience gained in the risk assessment (RA) of genetically engineered (GE) crops since their first experimental introductions in the early nineties, has increased the level of familiarity with these breeding methodologies and has motivated several agencies and expert groups worldwide to revisit the scientific criteria underlying the RA process. Along these lines, the need to engage in a scientific discussion for the case of GE crops transformed with similar constructs was recently identified in Argentina. In response to this need, the Argentine branch of the International Life Sciences Institute (ILSI Argentina) convened a tripartite working group to discuss a science-based evaluation approach for transformation events developed with genetic constructs which are identical or similar to those used in previously evaluated or approved GE crops. This discussion considered new transformation events within the same or different species and covered both environmental and food safety aspects. A construct similarity concept was defined, considering the biological function of the introduced genes. Factors like environmental and dietary exposure, familiarity with both the crop and the trait as well as the crop biology, were identified as key to inform a construct-based RA process.

  7. Flood Risk in the Danube basin under climate change

    Science.gov (United States)

    Schröter, Kai; Wortmann, Michel; del Rocio Rivas Lopez, Maria; Liersch, Stefan; Viet Nguyen, Dung; Hardwick, Stephen; Hattermann, Fred

    2017-04-01

    The projected increase in temperature is expected to intensify the hydrological cycle, and thus more intense precipitation is likely to increase hydro-meteorological extremes and flood hazard. However to assess the future dynamics of hazard and impact induced by these changes it is necessary to consider extreme events and to take a spatially differentiated perspective. The Future Danube Model is a multi-hazard and risk model suite for the Danube region which has been developed in the OASIS project. The model comprises modules for estimating potential perils from heavy precipitation, heat-waves, floods, droughts, and damage risk considering hydro-climatic extremes under current and climate change conditions. Web-based open Geographic Information Systems (GIS) technology allows customers to graphically analyze and overlay perils and other spatial information such as population density or assets exposed. The Future Danube Model combines modules for weather generation, hydrological and hydrodynamic processes, and supports risk assessment and adaptation planning support. This contribution analyses changes in flood hazard in the Danube basin and in flood risk for the German part of the Danube basin. As climate change input, different regionalized climate ensemble runs of the newest IPCC generation are used, the so-called Representative Concentration Pathways (RCPs). They are delivered by the CORDEX initiative (Coordinated Downscaling Experiments). The CORDEX data sample is extended using the statistical weather generator (IMAGE) in order to also consider extreme events. Two time slices are considered: near future 2020-2049 and far future 2050-2079. This data provides the input for the hydrological, hydraulic and flood loss model chain. Results for RCP4.5 and RCP8.5 indicate an increase in intensity and frequency of peak discharges and thus in flood hazard for many parts of the Danube basin.

  8. Risk perception among women receiving genetic counseling: a population-based follow-up study

    DEFF Research Database (Denmark)

    Mikkelsen, Ellen M; Sunde, Lone; Johansen, Christoffer

    2007-01-01

    BACKGROUND: We aimed to explore the impact of genetic counseling on perceived personal lifetime risk of breast cancer, the accuracy of risk perception, and possible predictors of inaccurate risk perception 1 year following counseling. METHODS: We conducted a population-based prospective follow...... counseling, compared to a reduction of 5% (p=0.03) and 2% (p=0.01) in Reference Groups I and II, respectively. Risk communicated only in words, inaccurate risk perception at baseline, and presence of a familial mutation appeared to be predictors of inaccurate risk perception 12 months after counseling...

  9. Entangled local biologies: genetic risk, bodies and inequities in Brazilian cancer genetics.

    Science.gov (United States)

    Gibbon, Sahra

    2017-08-01

    Engaging recent social science work examining the truth making claims of science and biomedicine, this paper explores how biology is being localised in Brazilian cancer genetics. It draws from ethnographic fieldwork in urban regions of southern Brazil working with and alongside patients, families and practitioners in cancer genetic clinics. It examines how different sorts of 'local biologies' are articulated in the context of research, clinical practice and among implicated patient communities and the way these can 'recursively' move across different spheres and scales of social action to extend and transform the meaning of the biological. It shows how the mattering of the biological in Brazilian cancer genetics is fundamentally informed by questions of inequity and care, even while multiple local biologies may obscure rather than reveal the biopolitics of cancer. In an era of epigenetics this raises new opportunities and challenges for anthropological analysis as intervention.

  10. Diffusion-weighted MRI for detecting prostate tumour in men at increased genetic risk

    International Nuclear Information System (INIS)

    Souza, Nandita M. de; Morgan, Veronica A.; Bancroft, Elizabeth; Sohaib, S. Aslam; Giles, Sharon L.; Kote-Jarai, Zsofia; Castro, Elena; Hazell, Steven; Jafar, Maysam; Eeles, Rosalind

    2014-01-01

    •Endorectal T2W + DW-MRI is potentially useful for prostate cancer screening.•MRI is specific for detecting prostate cancer in men with increased genetic risk.•Detection of prostate cancer in men at genetically low risk with MRI is limited. Endorectal T2W + DW-MRI is potentially useful for prostate cancer screening. MRI is specific for detecting prostate cancer in men with increased genetic risk. Detection of prostate cancer in men at genetically low risk with MRI is limited. Diffusion-weighted (DW)-MRI is invaluable in detecting prostate cancer. We determined its sensitivity and specificity and established interobserver agreement for detecting tumour in men with a family history of prostate cancer stratified by genetic risk. 51 men with a family history of prostate cancer underwent T2-W + DW-endorectal MRI at 3.0 T. Presence of tumour was noted at right and left apex, mid and basal prostate sextants by 2 independent observers, 1 experienced and the other inexperienced in endorectal MRI. Sensitivity and specificity against a 10-core sampling technique (lateral and medial cores at each level considered together) in men with >2× population risk based on 71 SNP analysis versus those with lower genetic risk scores was established. Interobserver agreement was determined at a subject level. Biopsies indicated cancer in 28 sextants in 13/51 men; 32 of 51 men had twice the population risk (>0.25) based on 71 SNP profiling. Sensitivity/specificity per-subject for patients was 90.0%/86.4% (high-risk) vs. 66.7%/100% (low-risk, observer 1) and 60.0%/86.3% (high-risk) vs. 33.3%/93.8% (low-risk, observer 2) with moderate overall inter-observer agreement (kappa = 0.42). Regional sensitivities/specificities for high-risk vs. low-risk for observer 1 apex 72.2%/100% [33.3%/100%], mid 100%/93.1% [100%/97.3%], base 16.7%/98.3% [0%/100%] and for observer 2 apex 36.4%/98.1% [0%/100%], mid 28.6%/96.5% [100%/100%], base 20%/100% [0%/97.3%] were poorer as they failed to detect

  11. Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017.

    Science.gov (United States)

    Giri, Veda N; Knudsen, Karen E; Kelly, William K; Abida, Wassim; Andriole, Gerald L; Bangma, Chris H; Bekelman, Justin E; Benson, Mitchell C; Blanco, Amie; Burnett, Arthur; Catalona, William J; Cooney, Kathleen A; Cooperberg, Matthew; Crawford, David E; Den, Robert B; Dicker, Adam P; Eggener, Scott; Fleshner, Neil; Freedman, Matthew L; Hamdy, Freddie C; Hoffman-Censits, Jean; Hurwitz, Mark D; Hyatt, Colette; Isaacs, William B; Kane, Christopher J; Kantoff, Philip; Karnes, R Jeffrey; Karsh, Lawrence I; Klein, Eric A; Lin, Daniel W; Loughlin, Kevin R; Lu-Yao, Grace; Malkowicz, S Bruce; Mann, Mark J; Mark, James R; McCue, Peter A; Miner, Martin M; Morgan, Todd; Moul, Judd W; Myers, Ronald E; Nielsen, Sarah M; Obeid, Elias; Pavlovich, Christian P; Peiper, Stephen C; Penson, David F; Petrylak, Daniel; Pettaway, Curtis A; Pilarski, Robert; Pinto, Peter A; Poage, Wendy; Raj, Ganesh V; Rebbeck, Timothy R; Robson, Mark E; Rosenberg, Matt T; Sandler, Howard; Sartor, Oliver; Schaeffer, Edward; Schwartz, Gordon F; Shahin, Mark S; Shore, Neal D; Shuch, Brian; Soule, Howard R; Tomlins, Scott A; Trabulsi, Edouard J; Uzzo, Robert; Vander Griend, Donald J; Walsh, Patrick C; Weil, Carol J; Wender, Richard; Gomella, Leonard G

    2018-02-01

    Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease.

  12. Height, selected genetic markers and prostate cancer risk

    DEFF Research Database (Denmark)

    Lophatananon, Artitaya; Stewart-Brown, Sarah; Kote-Jarai, Zsofia

    2017-01-01

    BACKGROUND: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. METHODS: We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases ...

  13. Height, selected genetic markers and prostate cancer risk

    DEFF Research Database (Denmark)

    Lophatananon, Artitaya; Stewart-Brown, Sarah; Kote-Jarai, Zsofia

    2017-01-01

    Background:Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer.Methods:We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and...

  14. Genetic association of telomere length with hepatocellular carcinoma risk: A Mendelian randomization analysis.

    Science.gov (United States)

    Cheng, Yue; Yu, Chengxiao; Huang, Mingtao; Du, Fangzhi; Song, Ci; Ma, Zijian; Zhai, Xiangjun; Yang, Yuan; Liu, Jibin; Bei, Jin-Xin; Jia, Weihua; Jin, Guangfu; Li, Shengping; Zhou, Weiping; Liu, Jianjun; Dai, Juncheng; Hu, Zhibin

    2017-10-01

    Observational studies show an association between telomere length and Hepatocellular carcinoma (HCC) risk, but the relationship is controversial. Particularly, it remains unclear whether the association is due to confounding or biases inherent in conventional epidemiological studies. Here, we applied Mendelian randomization approach to evaluate whether telomere length is causally associated with HCC risk. Individual-level data were from HBV-related HCC Genome-wide association studies (1,538 HBV positive HCC patients and 1,465 HBV positive controls). Genetic risk score, as proxy for actual measured telomere length, derived from nine telomere length-associated genetic variants was used to evaluate the effect of telomere length on HCC risk. We observed a significant risk signal between genetically increased telomere length and HBV-related HCC risk (OR=2.09, 95% CI 1.32-3.31, P=0.002). Furthermore, a U-shaped curve was fitted by the restricted cubic spline curve, which indicated that either short or long telomere length would increase HCC risk (P=0.0022 for non-linearity test). Subgroup analysis did not reveal significant heterogeneity between different age, gender, smoking status and drinking status groups. Our results indicated that a genetic background that favors longer or shorter telomere length may increase HBV-related HCC risk-a U-shaped association. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. The potential of large studies for building genetic risk prediction models

    Science.gov (United States)

    NCI scientists have developed a new paradigm to assess hereditary risk prediction in common diseases, such as prostate cancer. This genetic risk prediction concept is based on polygenic analysis—the study of a group of common DNA sequences, known as singl

  16. Genetic modifiers of CHEK2*1100delC-associated breast cancer risk

    DEFF Research Database (Denmark)

    Muranen, Taru A; Greco, Dario; Blomqvist, Carl

    2017-01-01

    PURPOSE: CHEK2*1100delC is a founder variant in European populations that confers a two- to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion...

  17. Prediction of breast cancer risk based on profiling with common genetic variants

    DEFF Research Database (Denmark)

    Mavaddat, Nasim; Pharoah, Paul D P; Michailidou, Kyriaki

    2015-01-01

    BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. M...

  18. Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population

    DEFF Research Database (Denmark)

    Robinson, Elise B; St Pourcain, Beate; Anttila, Verneri

    2016-01-01

    Almost all genetic risk factors for autism spectrum disorders (ASDs) can be found in the general population, but the effects of this risk are unclear in people not ascertained for neuropsychiatric symptoms. Using several large ASD consortium and population-based resources (total n > 38,000), we...

  19. Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk

    DEFF Research Database (Denmark)

    Rudolph, Anja; Hein, Rebecca; Lindström, Sara

    2013-01-01

    Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case...

  20. Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease

    NARCIS (Netherlands)

    Gutierrez-Achury, Javier; Zhernakova, Alexandra; Pulit, Sara L.; Trynka, Gosia; Hunt, Karen A.; Romanos, Jihane; Raychaudhuri, Soumya; van Heel, David A.; Wijmenga, Cisca; de Balcker, Paul I. W.

    Although dietary gluten is the trigger for celiac disease, risk is strongly influenced by genetic variation in the major histocompatibility complex (MHC) region. We fine mapped the MHC association signal to identify additional risk factors independent of the HLA-DQA1 and HLA-DQB1 alleles and

  1. DTREEv2, a computer-based support system for the risk assessment of genetically modified plants

    NARCIS (Netherlands)

    Pertry, I.; Nothegger, C.; Sweet, J.; Kuiper, H.A.; Davies, H.; Iserentant, D.; Hull, R.; Mezzetti, B.; Messens, K.; Loose, De M.; Oliveira, de D.; Burssens, S.; Gheysen, G.; Tzotzos, G.

    2014-01-01

    Risk assessment of genetically modified organisms (GMOs) remains a contentious area and a major factor influencing the adoption of agricultural biotech. Methodologically, in many countries, risk assessment is conducted by expert committees with little or no recourse to databases and expert systems

  2. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease

    Science.gov (United States)

    The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CA...

  3. Prediction of breast cancer risk based on profiling with common genetic variants

    NARCIS (Netherlands)

    N. Mavaddat (Nasim); P.D.P. Pharoah (Paul); K. Michailidou (Kyriaki); J.P. Tyrer (Jonathan); M.N. Brook (Mark N.); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); A.M. Dunning (Alison); M. Shah (Mitul); R.N. Luben (Robert); J. Brown (Judith); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune F.); H. Flyger (Henrik); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); J. Peto (Julian); I. dos Santos Silva (Isabel); F. Dudbridge (Frank); N. Johnson (Nichola); M.K. Schmidt (Marjanka); A. Broeks (Annegien); S. Verhoef; E.J. Rutgers (Emiel J.); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); L.A. Brinton (Louise); J. Lissowska (Jolanta); F.J. Couch (Fergus); J.E. Olson (Janet); C. Vachon (Celine); V.S. Pankratz (Shane); D. Lambrechts (Diether); H. Wildiers (Hans); C. van Ongeval (Chantal); E. van Limbergen (Erik); V. Kristensen (Vessela); G. Grenaker Alnæs (Grethe); S. Nord (Silje); A.-L. Borresen-Dale (Anne-Lise); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P.A. Fasching (Peter); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias); B. Burwinkel (Barbara); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); A. Trentham-Dietz (Amy); P. Newcomb (Polly); L. Titus (Linda); K.M. Egan (Kathleen M.); D. Hunter (David); S. Lindstrom (Stephen); R. Tamimi (Rulla); P. Kraft (Peter); N. Rahman (Nazneen); C. Turnbull (Clare); A. Renwick (Anthony); S. Seal (Sheila); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); P. Menéndez (Primitiva); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); T. Dörk (Thilo); H. Anton-Culver (Hoda); S.L. Neuhausen (Susan); A. Ziogas (Argyrios); L. Bernstein (Leslie); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); E.K. Khusnutdinova (Elza); M. Bermisheva (Marina); D. Prokofyeva (Darya); Z. Takhirova (Zalina); A. Meindl (Alfons); R.K. Schmutzler (Rita); C. Sutter (Christian); R. Yang (Rongxi); P. Schürmann (Peter); M. Bremer (Michael); H. Christiansen (Hans); T.-W. Park-Simon; P. Hillemanns (Peter); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); M. Sanchez (Marie); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); V. Pensotti (Valeria); J. Hopper (John); H. Tsimiklis (Helen); C. Apicella (Carmel); M.C. Southey (Melissa); H. Brauch (Hiltrud); T. Brüning (Thomas); Y.-D. Ko (Yon-Dschun); A.J. Sigurdson (Alice); M.M. Doody (Michele M.); U. Hamann (Ute); D. Torres (Diana); H.U. Ulmer (Hans); A. Försti (Asta); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A. Marie Mulligan (Anna); G. Chenevix-Trench (Georgia); R. Balleine (Rosemary); G.G. Giles (Graham); R.L. Milne (Roger); C.A. McLean (Catriona Ann); A. Lindblom (Annika); S. Margolin (Sara); C.A. Haiman (Christopher); B.E. Henderson (Brian); F. Schumacher (Fredrick); L. Le Marchand (Loic); U. Eilber (Ursula); S. Wang-Gohrke (Shan); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A.M.W. van den Ouweland (Ans); L.B. Koppert (Lisa); J. Carpenter (Jane); C. Clarke (Christine); R.J. Scott (Rodney J.); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); H. Brenner (Hermann); V. Arndt (Volker); C. Stegmaier (Christa); A. Karina Dieffenbach (Aida); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); K. Offit (Kenneth); J. Vijai (Joseph); M. Robson (Mark); R. Rau-Murthy (Rohini); M. Dwek (Miriam); R. Swann (Ruth); K. Annie Perkins (Katherine); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); D. Eccles (Diana); W. Tapper (William); M. Rafiq (Meena); E.M. John (Esther M.); A.S. Whittemore (Alice); S. Slager (Susan); D. Yannoukakos (Drakoulis); A.E. Toland (Amanda); S. Yao (Song); W. Zheng (Wei); S.L. Halverson (Sandra L.); A. González-Neira (Anna); G. Pita (G.); M. Rosario Alonso; N. Álvarez (Nuria); D. Herrero (Daniel); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); M. Maranian (Melanie); S. Healey (Sue); J. Simard (Jacques); P. Hall (Per); D.F. Easton (Douglas); M. García-Closas (Montserrat)

    2015-01-01

    textabstractBackground: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is

  4. Genetic variation in adipokine genes and risk of colorectal cancer

    Czech Academy of Sciences Publication Activity Database

    Pechlivanis, S.; Bermejo, J. L.; Pardini, Barbara; Naccarati, Alessio; Vodičková, Ludmila; Novotný, J.; Hemminki, K.; Vodička, Pavel; Försti, A.

    2009-01-01

    Roč. 160, č. 6 (2009), s. 933-940 ISSN 0804-4643 R&D Projects: GA ČR GA310/07/1430; GA MZd NR8563 Grant - others:EU(SE) LSHC-CT-2004-503465 Institutional research plan: CEZ:AV0Z50390512 Keywords : colorectal cancer * diabetes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.539, year: 2009

  5. 42 CFR 438.812 - Costs under risk and nonrisk contracts.

    Science.gov (United States)

    2010-10-01

    ... Participation § 438.812 Costs under risk and nonrisk contracts. (a) Under a risk contract, the total amount the State agency pays for carrying out the contract provisions is a medical assistance cost. (b) Under a... 42 Public Health 4 2010-10-01 2010-10-01 false Costs under risk and nonrisk contracts. 438.812...

  6. The value of genetic information for diabetes risk prediction - differences according to sex, age, family history and obesity.

    Directory of Open Access Journals (Sweden)

    Kristin Mühlenbruch

    Full Text Available BACKGROUND: Genome-wide association studies have identified numerous single nucleotide polymorphisms associated with type 2 diabetes through the past years. In previous studies, the usefulness of these genetic markers for prediction of diabetes was found to be limited. However, differences may exist between substrata of the population according to the presence of major diabetes risk factors. This study aimed to investigate the added predictive value of genetic information (42 single nucleotide polymorphisms in subgroups of sex, age, family history of diabetes, and obesity. METHODS: A case-cohort study (random subcohort N = 1,968; incident cases: N = 578 within the European Prospective Investigation into Cancer and Nutrition Potsdam study was used. Prediction models without and with genetic information were evaluated in terms of the area under the receiver operating characteristic curve and the integrated discrimination improvement. Stratified analyses included subgroups of sex, age (<50 or ≥50 years, family history (positive if either father or mother or a sibling has/had diabetes, and obesity (BMI< or ≥30 kg/m(2. RESULTS: A genetic risk score did not improve prediction above classic and metabolic markers, but - compared to a non-invasive prediction model - genetic information slightly improved the area under the receiver operating characteristic curve (difference [95%-CI]: 0.007 [0.002-0.011]. Stratified analyses showed stronger improvement in the older age group (0.010 [0.002-0.018], the group with a positive family history (0.012 [0.000-0.023] and among obese participants (0.015 [-0.005-0.034] compared to the younger participants (0.005 [-0.004-0.014], participants with a negative family history (0.003 [-0.001-0.008] and non-obese (0.007 [0.000-0.014], respectively. No difference was found between men and women. CONCLUSION: There was no incremental value of genetic information compared to standard non-invasive and metabolic

  7. Genetic risk scores and family history as predictors of schizophrenia in Nordic registers

    DEFF Research Database (Denmark)

    Lu, Y.; Pouget, J. G.; Andreassen, O. A.

    2017-01-01

    Background: Family history is a long-standing and readily obtainable risk factor for schizophrenia (SCZ). Low-cost genotyping technologies have enabled large genetic studies of SCZ, and the results suggest the utility of genetic risk scores (GRS, direct assessments of inherited common variant risk...... through the quality control procedures used by the Psychiatric Genomics Consortium. Using external training data, GRS were estimated for SCZ, bipolar disorder (BIP), major depression, autism, educational attainment, and body mass index. Multivariable modeling was used to estimate effect sizes. Results...

  8. Risks associated with genetic testing: health insurance discrimination or simply business as usual?

    Science.gov (United States)

    Steinberg, K K

    2000-01-01

    Doctors can test patients for mutations that put them at high risk for hereditary forms of such diseases as breast and ovarian cancer. Even though the opportunities for disease prevention using genetic testing will increase with time, the risks of testing, which include insurance loss and employment discrimination, currently make testing problematic. Some have proposed making use of genetic information in health insurance underwriting illegal. But in the current system of risk-based underwriting, it is hard to imagine that insurance companies will willingly forego access to a growing body of information on risk. If the American public chooses to limit the use of genetic information, a reassessment of current laws or methods of paying for health care will be needed.

  9. Psychological factors associated with emotional responses to receiving genetic risk information.

    Science.gov (United States)

    Bennett, Paul; Wilkinson, Clare; Turner, Jim; Brain, Kate; Edwards, Rhiannon Tudor; Griffith, Gethin; France, Barbara; Gray, Jonathon

    2008-06-01

    This study identified levels of distress, and predictors of levels of distress, in women undergoing assessment for genetic risk of breast/ovarian cancer based on their family history. It comprised a cohort study following 154 women who completed questionnaires at entry into a cancer genetic assessment programme and following risk provision. Independent significant associates of anxiety following risk provision were age, neuroticism, feeling hopeless about developing cancer, a perceived lack of control over developing cancer, lack of a social confidant, and a coping response involving acceptance/resignation. Depression was associated with age, neuroticism, feeling hopeless about developing cancer, lack of social confidant, and a coping response involving acceptance/resignation. To avoid high levels of psychological morbidity in future cohorts undergoing cancer genetic risk assessment, information should be given that emphasises that some degree of control over health outcomes through behaviour change or increased surveillance is possible.

  10. Issues of the economic risks theory under direct taxation

    Directory of Open Access Journals (Sweden)

    Vyacheslav Aleksandrovich Slavin

    2015-09-01

    perturbation described by periodic functions of time their frequency equal to the frequency of technological cycles of the firm production units. The work states a number of correlations between the indicators of production processes and taxation processes. The effect of progressive taxation on the company is described. Scientific novelty for the first time the aricle demonstrates the possibility to theoretically describe the economic risks of the taxation company and to establish the economic nature of their essential characteristics. Practical significance the obtained results allow to form a complex of practical programs aimed at the optimization of the company performance indicators for the purpose of reducing the probability its assets of loss under taxation. nbsp

  11. CoaSim: A Flexible Environment for Simulating Genetic Data under Coalescent Models

    DEFF Research Database (Denmark)

    Mailund; Schierup, Mikkel Heide; Pedersen, Christian Nørgaard Storm

    2005-01-01

    Background Coalescent simulations are playing a large role in interpreting large scale intra- polymorphism surveys and for planning and evaluating association studies. Coalescent of data sets under different models can be compared to the actual data to test different evolutionary factors and thus...... get insight into these. Results We have created the CoaSim application as a flexible environment for Monte various types of genetic data under equilibrium and non-equilibrium coalescent variety of applications. Interaction with the tool is through the Guile version scripting language. Scheme scripts...

  12. Sexually antagonistic selection on genetic variation underlying both male and female same-sex sexual behavior.

    Science.gov (United States)

    Berger, David; You, Tao; Minano, Maravillas R; Grieshop, Karl; Lind, Martin I; Arnqvist, Göran; Maklakov, Alexei A

    2016-05-13

    Intralocus sexual conflict, arising from selection for different alleles at the same locus in males and females, imposes a constraint on sex-specific adaptation. Intralocus sexual conflict can be alleviated by the evolution of sex-limited genetic architectures and phenotypic expression, but pleiotropic constraints may hinder this process. Here, we explored putative intralocus sexual conflict and genetic (co)variance in a poorly understood behavior with near male-limited expression. Same-sex sexual behaviors (SSBs) generally do not conform to classic evolutionary models of adaptation but are common in male animals and have been hypothesized to result from perception errors and selection for high male mating rates. However, perspectives incorporating sex-specific selection on genes shared by males and females to explain the expression and evolution of SSBs have largely been neglected. We performed two parallel sex-limited artificial selection experiments on SSB in male and female seed beetles, followed by sex-specific assays of locomotor activity and male sex recognition (two traits hypothesized to be functionally related to SSB) and adult reproductive success (allowing us to assess fitness consequences of genetic variance in SSB and its correlated components). Our experiments reveal both shared and sex-limited genetic variance for SSB. Strikingly, genetically correlated responses in locomotor activity and male sex-recognition were associated with sexually antagonistic fitness effects, but these effects differed qualitatively between male and female selection lines, implicating intralocus sexual conflict at both male- and female-specific genetic components underlying SSB. Our study provides experimental support for the hypothesis that widespread pleiotropy generates pervasive intralocus sexual conflict governing the expression of SSBs, suggesting that SSB in one sex can occur due to the expression of genes that carry benefits in the other sex.

  13. Ecological Risk Assessment of Genetically Modified Higher Plants (GMHP)

    DEFF Research Database (Denmark)

    Kjær, C.; Damgaard, C.; Kjellsson, G.

    assessment of GM plants when application for placing on the market is made. It is our hope that both the scientific community, the biotechnological industry and the regulatory bodies will participate in the process of improving the present draft, so that it can develop into a useful tool for both...... and establishment of the modified plant in natural habitats; risk of introgression of the inserted or modified traits to other plant species; and the risk of adverse effects on non-target organisms. The guidance paper considers only aspects of ecological risk assessment. Possible risks to human health, livestock...... for reproduction of the GMHP B. Identification of possible effects on non-target organisms C. Detection of potential hybridisation, and assessment of the selective force acting on the inserted gene in a natural plant population Tier III. Laboratory measurements and small scale trials on the GMHP A. Test of changes...

  14. Stress and Coping in Genetic Testing for Cancer Risk

    National Research Council Canada - National Science Library

    Coyne, James

    1997-01-01

    .... In the absence of a large body of relevant prior research, we are faced with an urgent need for basic descriptive data concerning women at high-risk for early onset breast cancer and their families...

  15. Genetically elevated bilirubin and risk of ischaemic heart disease

    DEFF Research Database (Denmark)

    Stender, Stefan; Frikke-Schmidt, R; Nordestgaard, B G

    2013-01-01

    Elevated plasma levels of bilirubin, an endogenous antioxidant, have been associated with reduced risk of ischaemic heart disease (IHD) and myocardial infarction (MI). Whether this is a causal relationship remains unclear....

  16. Meeting Report: Risk Assessment of Tamiflu Use Under Pandemic Conditions

    Science.gov (United States)

    Singer, Andrew C.; Howard, Bruce M.; Johnson, Andrew C.; Knowles, Chris J.; Jackman, Simon; Accinelli, Cesare; Caracciolo, Anna Barra; Bernard, Ian; Bird, Stephen; Boucard, Tatiana; Boxall, Alistair; Brian, Jayne V.; Cartmell, Elise; Chubb, Chris; Churchley, John; Costigan, Sandra; Crane, Mark; Dempsey, Michael J.; Dorrington, Bob; Ellor, Brian; Fick, Jerker; Holmes, John; Hutchinson, Tom; Karcher, Franz; Kelleher, Samuel L.; Marsden, Peter; Noone, Gerald; Nunn, Miles A.; Oxford, John; Rachwal, Tony; Roberts, Noel; Roberts, Mike; Saccà, Maria Ludovica; Sanders, Matthew; Straub, Jürg Oliver; Terry, Adrian; Thomas, Dean; Toovey, Stephen; Townsend, Rodney; Voulvoulis, Nikolaos; Watts, Chris

    2008-01-01

    On 3 October 2007, 40 participants with diverse expertise attended the workshop Tamiflu and the Environment: Implications of Use under Pandemic Conditions to assess the potential human health impact and environmental hazards associated with use of Tamiflu during an influenza pandemic. Based on the identification and risk-ranking of knowledge gaps, the consensus was that oseltamivir ethylester-phosphate (OE-P) and oseltamivir carboxylate (OC) were unlikely to pose an ecotoxicologic hazard to freshwater organisms. OC in river water might hasten the generation of OC-resistance in wildfowl, but this possibility seems less likely than the potential disruption that could be posed by OC and other pharmaceuticals to the operation of sewage treatment plants. The work-group members agreed on the following research priorities: a) available data on the ecotoxicology of OE-P and OC should be published; b) risk should be assessed for OC-contaminated river water generating OC-resistant viruses in wildfowl; c) sewage treatment plant functioning due to microbial inhibition by neuraminidase inhibitors and other antimicrobials used during a pandemic should be investigated; and d) realistic worst-case exposure scenarios should be developed. Additional modeling would be useful to identify localized areas within river catchments that might be prone to high pharmaceutical concentrations in sewage treatment plant effluent. Ongoing seasonal use of Tamiflu in Japan offers opportunities for researchers to assess how much OC enters and persists in the aquatic environment. PMID:19057712

  17. Selection of risk reduction portfolios under interval-valued probabilities

    International Nuclear Information System (INIS)

    Toppila, Antti; Salo, Ahti

    2017-01-01

    A central problem in risk management is that of identifying the optimal combination (or portfolio) of improvements that enhance the reliability of the system most through reducing failure event probabilities, subject to the availability of resources. This optimal portfolio can be sensitive with regard to epistemic uncertainties about the failure events' probabilities. In this paper, we develop an optimization model to support the allocation of resources to improvements that mitigate risks in coherent systems in which interval-valued probabilities defined by lower and upper bounds are employed to capture epistemic uncertainties. Decision recommendations are based on portfolio dominance: a resource allocation portfolio is dominated if there exists another portfolio that improves system reliability (i) at least as much for all feasible failure probabilities and (ii) strictly more for some feasible probabilities. Based on non-dominated portfolios, recommendations about improvements to implement are derived by inspecting in how many non-dominated portfolios a given improvement is contained. We present an exact method for computing the non-dominated portfolios. We also present an approximate method that simplifies the reliability function using total order interactions so that larger problem instances can be solved with reasonable computational effort. - Highlights: • Reliability allocation under epistemic uncertainty about probabilities. • Comparison of alternatives using dominance. • Computational methods for generating the non-dominated alternatives. • Deriving decision recommendations that are robust with respect to epistemic uncertainty.

  18. Genetic polymorphisms associated with smoking behaviour predict the risk of surgery in patients with Crohn's disease.

    Science.gov (United States)

    Lang, B M; Biedermann, L; van Haaften, W T; de Vallière, C; Schuurmans, M; Begré, S; Zeitz, J; Scharl, M; Turina, M; Greuter, T; Schreiner, P; Heinrich, H; Kuntzen, T; Vavricka, S R; Rogler, G; Beerenwinkel, N; Misselwitz, B

    2018-01-01

    Smoking is a strong environmental factor leading to adverse outcomes in Crohn's disease, but a more benign course in ulcerative colitis. Several single nucleotide polymorphisms (SNPs) are associated with smoking quantity and behaviour. To assess whether smoking-associated SNPs interact with smoking to influence the clinical course of inflammatory bowel diseases. Genetic and prospectively obtained clinical data from 1434 Swiss inflammatory bowel disease cohort patients (821 Crohn's disease and 613 ulcerative colitis) were analysed. Six SNPs associated with smoking quantity and behaviour (rs588765, rs1051730, rs1329650, rs4105144, rs6474412 and rs3733829) were combined to form a risk score (range: 0-12) by adding the number of risk alleles. We calculated multivariate models for smoking, risk of surgery, fistula, Crohn's disease location and ulcerative colitis disease extent. In Crohn's disease patients who smoke, the number of surgeries was associated with the genetic risk score. This translates to a predicted 3.5-fold (95% confidence interval: 2.4- to 5.7-fold, Prisk alleles than individuals with the lowest risk. Patients with a risk score >7 had a significantly shorter time to first intestinal surgery. The genetic risk score did not predict surgery in ulcerative colitis or occurrence of fistulae in Crohn's disease. SNP rs6265 was associated with ileal disease in Crohn's disease (Prisk for surgery in Crohn's disease patients who smoke. Our data provide an example of genetics interacting with the environment to influence the disease course of inflammatory bowel disease. © 2017 John Wiley & Sons Ltd.

  19. Prostate cancer screening using risk stratification based on a multi-state model of genetic variants.

    Science.gov (United States)

    Yen, Amy Ming-Fang; Auvinen, Anssi; Schleutker, Johanna; Wu, Yi-Ying; Fann, Jean Ching-Yuan; Tammela, Teuvo; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Chen, Hsiu-Hsi

    2015-06-01

    Risk-stratified screening for prostate cancer (PCa) with prostate-specific antigen (PSA) testing incorporating genetic variants has received some attention but has been scarcely investigated. We developed a model to stratify the Finnish population by different risk profiles related to genetic variants to optimize the screening policy. Data from the Finnish randomized controlled trial on screening for PCa with PSA testing were used to estimate a six-state Markov model of disease progression. Blood samples from Finnish men were used to assess the risk of PCa related to three genetic variants (rs4242382, rs138213197, and rs200331695). A risk score-based approach combined with a series of computer simulation models was applied to optimize individual screening policies. The 10-year risk of having progressive prostate cancer detected ranged from 43% in the top 5% risk group to approximately 11% in the bottom half of the population. Using the median group, with screening every four years beginning at 55 years-old, as the reference group, the recommended age beginning screening was approximately 47 years-old for the top 5% risk group and 55 years-old for those in the lower 60% risk group. The recommended interscreening interval has been shortened for individuals in the high risk group. The increased availability of genomic information allows the proposed multistate model to be more discriminating with respect to risk stratification and the suggested screening policy, particularly for the lowest risk groups-. -- A multi-state genetic variant-based model was developed for further application to population risk stratification to optimize the interscreening interval and the age at which to begin screening for PSA. A small sub-group of the population is likely to benefit from more intensive screening with early start and short interval, while half of the population is unlikely to benefit from such protocol (compared with four-year interval after age 55 years). © 2015 Wiley

  20. Mapping autism risk loci using genetic linkage and chromosomal rearrangements

    Science.gov (United States)

    Szatmari, Peter; Paterson, Andrew; Zwaigenbaum, Lonnie; Roberts, Wendy; Brian, Jessica; Liu, Xiao-Qing; Vincent, John; Skaug, Jennifer; Thompson, Ann; Senman, Lili; Feuk, Lars; Qian, Cheng; Bryson, Susan; Jones, Marshall; Marshall, Christian; Scherer, Stephen; Vieland, Veronica; Bartlett, Christopher; Mangin, La Vonne; Goedken, Rhinda; Segre, Alberto; Pericak-Vance, Margaret; Cuccaro, Michael; Gilbert, John; Wright, Harry; Abramson, Ruth; Betancur, Catalina; Bourgeron, Thomas; Gillberg, Christopher; Leboyer, Marion; Buxbaum, Joseph; Davis, Kenneth; Hollander, Eric; Silverman, Jeremy; Hallmayer, Joachim; Lotspeich, Linda; Sutcliffe, James; Haines, Jonathan; Folstein, Susan; Piven, Joseph; Wassink, Thomas; Sheffield, Val; Geschwind, Daniel; Bucan, Maja; Brown, Ted; Cantor, Rita; Constantino, John; Gilliam, Conrad; Herbert, Martha; Lajonchere, Clara; Ledbetter, David; Lese-Martin, Christa; Miller, Janet; Nelson, Stan; Samango-Sprouse, Carol; Spence, Sarah; State, Matthew; Tanzi, Rudolph; Coon, Hilary; Dawson, Geraldine; Devlin, Bernie; Estes, Annette; Flodman, Pamela; Klei, Lambertus; Mcmahon, William; Minshew, Nancy; Munson, Jeff; Korvatska, Elena; Rodier, Patricia; Schellenberg, Gerard; Smith, Moyra; Spence, Anne; Stodgell, Chris; Tepper, Ping Guo; Wijsman, Ellen; Yu, Chang-En; Rogé, Bernadette; Mantoulan, Carine; Wittemeyer, Kerstin; Poustka, Annemarie; Felder, Bärbel; Klauck, Sabine; Schuster, Claudia; Poustka, Fritz; Bölte, Sven; Feineis-Matthews, Sabine; Herbrecht, Evelyn; Schmötzer, Gabi; Tsiantis, John; Papanikolaou, Katerina; Maestrini, Elena; Bacchelli, Elena; Blasi, Francesca; Carone, Simona; Toma, Claudio; Van Engeland, Herman; De Jonge, Maretha; Kemner, Chantal; Koop, Frederieke; Langemeijer, Marjolein; Hijmans, Channa; Staal, Wouter; Baird, Gillian; Bolton, Patrick; Rutter, Michael; Weisblatt, Emma; Green, Jonathan; Aldred, Catherine; Wilkinson, Julie-Anne; Pickles, Andrew; Le Couteur, Ann; Berney, Tom; Mcconachie, Helen; Bailey, Anthony; Francis, Kostas; Honeyman, Gemma; Hutchinson, Aislinn; Parr, Jeremy; Wallace, Simon; Monaco, Anthony; Barnby, Gabrielle; Kobayashi, Kazuhiro; Lamb, Janine; Sousa, Ines; Sykes, Nuala; Cook, Edwin; Guter, Stephen; Leventhal, Bennett; Salt, Jeff; Lord, Catherine; Corsello, Christina; Hus, Vanessa; Weeks, Daniel; Volkmar, Fred; Tauber, Maïté; Fombonne, Eric; Shih, Andy; Meyer, Kacie

    2007-01-01

    Autism spectrum disorders (ASD) are common, heritable neurodevelopmental conditions. The genetic architecture of ASD is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASD by using Affymetrix 10K single nucleotide polymorphism (SNP) arrays and 1168 families with ≥ 2 affected individuals to perform the largest linkage scan to date, while also analyzing copy number variation (CNV) in these families. Linkage and CNV analyses implicate chromosome 11p12-p13 and neurexins, respectively, amongst other candidate loci. Neurexins team with previously-implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for ASD. PMID:17322880

  1. Risk assessment: the importance of genetic polymorphisms in man

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Loft, S H; Autrup, H

    2001-01-01

    of 2. Some polymorphisms are effect modifiers, i.e. without exposure they have no consequence and the effect of exposure can appear independent of the genotype. Genetic polymorphisms in metabolism of environmental toxicants plays a significant role in exposures to traffic generated air pollution...... in Copenhagen, revealing statistically significant higher levels of chromosomal aberrations in non-smoking bus drivers with glutathion-S-transferase M1, GSTM1 null and N-acetyltransferase 2, NAT2 slow genotypes. Combined with cohort studies showing positive associations between high chromosomal levels...

  2. Risks assessment - role of pre-existing genetic variation

    International Nuclear Information System (INIS)

    Unrau, P.; Doerffer, K.

    1996-01-01

    Previously published research on the epidemiology and molecular basis of genetic or congenital diseases and their occurrence in certain 'ethnic' or isolated populations is discussed to show the significance of consanguinity and 'ethnicity' as contributing factors. A statistical study aiming to correlate malformations with absolutely any environmental factor may miss the significance of defects in a gene pool. This consideration has an obvious significance for the nuclear industry. For example, carriers of Fanconi's anemia appear to have an increased tendency to develop acute myelogenous leukemia. The authors indicate the difficulty in finding a definite molecular basis even for simple Mendelian monogenic disorders such as Tay-Sachs disease. 12 refs., 4 tabs

  3. Novel genetic loci underlying human intracranial volume identified through genome-wide association

    Science.gov (United States)

    Adams, Hieab HH; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura ME; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher RK; Cuellar-Partida, Gabriel; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David CM; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Olde Loohuis, Loes M; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein MJ; Van Eijk, Kristel R; Van Erp, Theo GM; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco JC; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald HH; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, WT; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W

    2016-01-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth. PMID:27694991

  4. Determination of the Genetic Architecture Underlying Short Wavelength Sensitivity in Lake Malawi Cichlids.

    Science.gov (United States)

    Nandamuri, Sri Pratima; Dalton, Brian E; Carleton, Karen L

    2017-06-01

    African cichlids are an exemplary system to study organismal diversity and rapid speciation. Species differ in external morphology including jaw shape and body coloration, but also differ in sensory systems including vision. All cichlids have 7 cone opsin genes with species differing broadly in which opsins are expressed. The differential opsin expression results in closely related species with substantial differences in spectral sensitivity of their photoreceptors. In this work, we take a first step in determining the genetic basis of opsin expression in cichlids. Using a second generation cross between 2 species with different opsin expression patterns, we make a conservative estimate that short wavelength opsin expression is regulated by a few loci. Genetic mapping in 96 F2 hybrids provides clear evidence of a cis-regulatory region for SWS1 opsin that explains 34% of the variation in expression between the 2 species. Additionally, in situ hybridization has shown that SWS1 and SWS2B opsins are coexpressed in individual single cones in the retinas of F2 progeny. Results from this work will contribute to a better understanding of the genetic architecture underlying opsin expression. This knowledge will help answer long-standing questions about the evolutionary processes fundamental to opsin expression variation and how this contributes to adaptive cichlid divergence. © The American Genetic Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Genetic variants associated with earlier age at menopause increase the risk of cardiovascular events in women.

    Science.gov (United States)

    Sarnowski, Chloé; Kavousi, Maryam; Isaacs, Steve; Demerath, Ellen W; Broer, Linda; Muka, Taulant; Franco, Oscar H; Ikram, Mohammad Arfan; Uitterlinden, André; Franceschini, Nora; Lunetta, Kathryn L; Murabito, Joanne M

    2018-04-01

    To better understand the relationship between cardiovascular disease risk and age-at-natural menopause using genetic data. Early menopause is associated with cardiovascular disease risk. We constructed a genetic risk score comprising 56 age-at-natural menopause decreasing alleles in men and women from the Framingham Heart Study, the Atherosclerosis Risk in Communities Study, and the Rotterdam Study. If the genetic predisposition to earlier age-at-natural menopause is associated with increased cardiovascular disease risk, it is reasonable to ask whether the risk is shared by men carrying the alleles, despite not experiencing menopause. We estimated the hazard ratio for the score for time to first cardiovascular event. To investigate the possible genetic pleiotropy between age-at-natural menopause and cardiovascular disease, we performed cross-trait linkage disequilibrium score regressions between age-at-natural menopause and cardiovascular disease and risk factors using genome-wide association studies. Twenty-two thousand five hundred and sixty-eight cardiovascular disease-free participants at baseline were analyzed (9,808 men, 12,760 women). Each additional unit of the genetic propensity to earlier age-at-natural menopause increased the hazard of both cardiovascular disease and cardiac death in women (cardiovascular disease: hazard ratio 1.10 [1.04-1.16], P = 9.7 × 10; cardiac death: 1.12 [1.02-1.24], P = 0.03), whereas no effect was observed for either outcome in men (hazard ratio 0.99 [0.95-1.04], P = 0.71; 1.05 [0.94-1.16], P = 0.34). We found significant negative genetic correlations in women, but not men, between age-at-natural menopause and cardiovascular disease and risk factors. Genetic variants associated with earlier age-at-natural menopause are associated with increased cardiovascular disease risk in women, but not men, suggesting sex-specific genetic effects on cardiovascular disease risk.

  6. Genetic vulnerability to diabetes and obesity: does education offset the risk?

    Science.gov (United States)

    Liu, S Y; Walter, S; Marden, J; Rehkopf, D H; Kubzansky, L D; Nguyen, T; Glymour, M M

    2015-02-01

    The prevalence of type 2 diabetes (T2D) and obesity has recently increased dramatically. These common diseases are likely to arise from the interaction of multiple genetic, socio-demographic and environmental risk factors. While previous research has found genetic risk and education to be strong predictors of these diseases, few studies to date have examined their joint effects. This study investigates whether education modifies the association between genetic background and risk for type 2 diabetes (T2D) and obesity. Using data from non-Hispanic Whites in the Health and Retirement Study (HRS, n = 8398), we tested whether education modifies genetic risk for obesity and T2D, offsetting genetic effects; whether this effect is larger for individuals who have high risk for other (unobserved) reasons, i.e., at higher quantiles of HbA1c and BMI; and whether effects differ by gender. We measured T2D risk using Hemoglobin A1c (HbA1c) level, and obesity risk using body-mass index (BMI). We constructed separate genetic risk scores (GRS) for obesity and diabetes respectively based on the most current available information on the single nucleotide polymorphism (SNPs) confirmed as genome-wide significant predictors for BMI (29 SNPs) and diabetes risk (39 SNPs). Linear regression models with years of schooling indicate that the effect of genetic risk on HbA1c is smaller among people with more years of schooling and larger among those with less than a high school (HS) degree compared to HS degree-holders. Quantile regression models show that the GRS × education effect systematically increased along the HbA1c outcome distribution; for example the GRS × years of education interaction coefficient was -0.01 (95% CI = -0.03, 0.00) at the 10th percentile compared to -0.03 (95% CI = -0.07, 0.00) at the 90th percentile. These results suggest that education may be an important socioeconomic source of heterogeneity in responses to genetic vulnerability to T2D. Copyright

  7. Estimating the predictive ability of genetic risk models in simulated data based on published results from genome-wide association studies.

    Science.gov (United States)

    Kundu, Suman; Mihaescu, Raluca; Meijer, Catherina M C; Bakker, Rachel; Janssens, A Cecile J W

    2014-01-01

    There is increasing interest in investigating genetic risk models in empirical studies, but such studies are premature when the expected predictive ability of the risk model is low. We assessed how accurately the predictive ability of genetic risk models can be estimated in simulated data that are created based on the odds ratios (ORs) and frequencies of single-nucleotide polymorphisms (SNPs) obtained from genome-wide association studies (GWASs). We aimed to replicate published prediction studies that reported the area under the receiver operating characteristic curve (AUC) as a measure of predictive ability. We searched GWAS articles for all SNPs included in these models and extracted ORs and risk allele frequencies to construct genotypes and disease status for a hypothetical population. Using these hypothetical data, we reconstructed the published genetic risk models and compared their AUC values to those reported in the original articles. The accuracy of the AUC values varied with the method used for the construction of the risk models. When logistic regression analysis was used to construct the genetic risk model, AUC values estimated by the simulation method were similar to the published values with a median absolute difference of 0.02 [range: 0.00, 0.04]. This difference was 0.03 [range: 0.01, 0.06] and 0.05 [range: 0.01, 0.08] for unweighted and weighted risk scores. The predictive ability of genetic risk models can be estimated using simulated data based on results from GWASs. Simulation methods can be useful to estimate the predictive ability in the absence of empirical data and to decide whether empirical investigation of genetic risk models is warranted.

  8. Differential Effects of Estrogen and Progesterone on Genetic and Environmental Risk for Emotional Eating in Women

    Science.gov (United States)

    Klump, Kelly L.; O’Connor, Shannon M.; Hildebrandt, Britny A.; Keel, Pamela K.; Neale, Michael; Sisk, Cheryl L.; Boker, Steven; Burt, S. Alexandra

    2016-01-01

    Recent data show shifts in genetic and environmental influences on emotional eating across the menstrual cycle, with significant shared environmental influences during pre-ovulation, and primarily genetic effects during post-ovulation. Factors driving differential effects are unknown, although increased estradiol during pre-ovulation and increased progesterone during post-ovulation are thought to play a role. We indirectly investigated this possibility by examining whether overall levels of estradiol and progesterone differentially impact genetic and environmental risk for emotional eating in adult female twins (N = 571) drawn from the MSU Twin Registry. Emotional eating, estradiol levels, and progesterone levels were assessed daily and then averaged to create aggregate measures for analysis. As predicted, shared environmental influences were significantly greater in twins with high estradiol levels, whereas additive genetic effects increased substantially across low versus high progesterone groups. Results highlight significant and differential effects of ovarian hormones on etiologic risk for emotional eating in adulthood. PMID:27747142

  9. Structure of genetic and environmental risk factors for dimensional representations of DSM–IV anxiety disorders

    Science.gov (United States)

    Tambs, Kristian; Czajkowsky, Nikolai; Røysamb, Espen; Neale, Michael C.; Reichborn-Kjennerud, Ted; Aggen, Steven H.; Harris, Jennifer R.; Ørstavik, Ragnhild E.; Kendler, Kenneth S.

    2010-01-01

    Background Twin data permit decomposition of comorbidity into genetically and environmentally derived correlations. No previous twin study includes all major forms of anxiety disorder. Aims To estimate the degree to which genetic and environmental risk factors are shared rather than unique to dimensionally scored panic disorder, generalised anxiety disorder, phobias, obsessive–compulsive disorder and post-traumatic stress disorder. Method Data obtained from 2801 young-adult Norwegian twins by means of the Composite International Diagnostic Interview were analysed with the Mx program. Results A multivariate common factor model fitted best. The latent liability to all anxiety disorders was substantially more heritable (54%) than the individual disorders (23% to 40%). Most of the genetic effect was common to the disorders. Genes contributed just over 50% to the covariance between liabilities. Conclusions The five anxiety disorders all share genetic and environmental risk factors. This has implications for the revision of the anxiety disorder section in DSM–V. PMID:19794197

  10. Use of doubling doses for the estimation of genetic risks

    International Nuclear Information System (INIS)

    Searle, A.G.

    1977-01-01

    Doubling dose estimates derived from radiation experiments in mice are proving of great value for the assessment of genetic hazards to man from extra radiation exposure because they allow the latest information on mutation frequencies and the incidence of genetic disease in man to be used in the assessment process. The similarity in spectra of 'spontaneous' and induced mutations increases coincidence in the validity of this approach. Data on rates of induction of dominant and recessive mutations, translocations and X-chromosome loss are used to derive doubling doses for chronic exposures to both low and high-LET radiations. Values for γ and X-rays, derived from both male and female germ-cells, fall inside a fairly small range and it is felt that the use of an overall figure of 100 rads is justifiable for protection purposes. Values for neutrons and α-particles, obtained from male germ-cells, varied according to neutron energy etc. but clustered around a value of 5 rads for fission neutrons

  11. Comparative proteomic analysis of genetically modified maize grown under different agroecosystems conditions in Brazil

    Science.gov (United States)

    2013-01-01

    Background Profiling technologies allow the simultaneous measurement and comparison of thousands of cell components without prior knowledge of their identity. In the present study, we used two-dimensional gel electrophoresis combined with mass spectrometry to evaluate protein expression of Brazilian genetically modified maize hybrid grown under different agroecosystems conditions. To this effect, leaf samples were subjected to comparative analysis using the near-isogenic non-GM hybrid as the comparator. Results In the first stage of the analysis, the main sources of variation in the dataset were identified by using Principal Components Analysis which correlated most of the variation to the different agroecosystems conditions. Comparative analysis within each field revealed a total of thirty two differentially expressed proteins between GM and non-GM samples that were identified and their molecular functions were mainly assigned to carbohydrate and energy metabolism, genetic information processing and stress response. Conclusions To the best of our knowledge this study represents the first evidence of protein identities with differentially expressed isoforms in Brazilian MON810 genetic background hybrid grown under field conditions. As global databases on outputs from “omics” analysis become available, these could provide a highly desirable benchmark for safety assessments. PMID:24304660

  12. Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry

    DEFF Research Database (Denmark)

    Zhao, Zhiguo; Wen, Wanqing; Michailidou, Kyriaki

    2016-01-01

    PURPOSE: Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. METHODS: We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D suscept...

  13. Non-genetic risk factors and their influence on the management of patients in the clinic.

    Science.gov (United States)

    Álvarez, Teresa; Soto, Immaculada; Astermark, Jan

    2015-02-01

    The development of inhibitors is the most serious iatrogenic complication affecting patients with haemophilia. This complication is associated with impaired vital or functional prognosis, reduced quality of life and increased cost of treatment. The reasons why some patients develop antibodies to factor replacement and others do not remain unclear. It is however clear that inhibitor development results from a complex multifactorial interaction between genetic and non-genetic risk factors. Environmental influences implicated in increasing the risk of inhibitor formation can be viewed as modifiable risk factors. Therefore, identification of the non-genetic risk factors may offer the possibility of personalising haemophilia therapy by modifying treatment strategies in high-risk patients in the critical early phase of factor VIII exposure. In this article, we review the non-genetic factors reported as well as the potential impact of danger signals and the different scores for inhibitor development risk stratification. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Comparative analyses of genetic risk prediction methods reveal ...

    Indian Academy of Sciences (India)

    2015-03-12

    Mar 12, 2015 ... where it is related to modern lifestyle with additional com- plication due to rising incidence of type 2 diabetes melli- tus (DM) and obesity (Angulo and ..... is rapidly becoming a health burden in western and develop- ing countries. In this study we defined a model of disease risk score prediction for different ...

  15. Risk Management of the Natural Gas Consumption using Genetic Algorithms

    Czech Academy of Sciences Publication Activity Database

    Pelikán, Emil; Šimůnek, Milan

    2005-01-01

    Roč. 15, - (2005), s. 425-436 ISSN 1210-0552 R&D Projects: GA AV ČR 1ET400300513 Institutional research plan: CEZ:AV0Z10300504 Keywords : forecasting * risk-management * energy consumption Subject RIV: BB - Applied Statistics, Operational Research

  16. Interaction between 5 genetic variants and allergy in glioma risk

    DEFF Research Database (Denmark)

    Schoemaker, Minouk J; Robertson, Lindsay; Wigertz, Annette

    2010-01-01

    .047), and between "any allergy" and rs6010620 (greater protective effect; interaction OR = 0.70, P = 0.017). Case-only analyses provided further support for atopy interactions for rs4977756 and rs498872. This study provides evidence for possible gene-environment interactions in glioma development......., CDKN2A-CDKN2B), 11q23.3 (rs498872, PHLDB1), and 20q13.33 (rs6010620, RTEL1) as determinants of glioma risk. The authors investigated whether there is interaction between the effects of allergy and these 5 variants on glioma risk. Data from 5 case-control studies carried out in Denmark, Finland, Sweden......, and the United Kingdom (2000-2004) were used, totaling 1,029 cases and 1,668 controls. Risk was inversely associated with asthma, hay fever, eczema, and "any allergy," significantly for each factor except asthma, and was significantly positively associated with number of risk alleles for each of the 5 single...

  17. Managing genetic tests, surveillance, and preventive medicine under a public health insurance system.

    Science.gov (United States)

    Filipova-Neumann, Lilia; Hoy, Michael

    2014-03-01

    There is a prospect in the medium to long term future of substantial advancements in the understanding of the relationship between disease and genetics. We consider the implications of increased information from genetic tests about predisposition to diseases from the perspective of managing health care provision under a public health insurance scheme. In particular, we consider how such information may potentially improve the targeting of medical surveillance (or prevention) activities to improve the chances of early detection of disease onset. We show that the moral hazard implications inherent in surveillance and prevention decisions that are chosen to be privately rather than socially optimal may be exacerbated by increased information about person-specific predisposition to disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Exploring the genetics underlying autoimmune diseases with network analysis and link prediction

    KAUST Repository

    Alanis Lobato, Gregorio

    2014-02-01

    Ever since the first Genome Wide Association Study (GWAS) was carried out we have seen an important number of discoveries of biological and clinical relevance. However, there are some scientists that consider that these research outcomes and their utility are far from what was expected from this experimental design. We instead believe that the thousands of genetic variants associated with complex disorders by means of GWASs are an extremely valuable source of information that needs to be mined in a different way. Based on this philosophy, we followed a holistic perspective to analyze GWAS data and explored the structural properties of the network representation of one of these datasets with the aim to advance our understanding of the genetic intricacies underlying autoimmune human diseases. The simplicity, computational efficiency and precision of the tools proposed in this paper represent a new means to address GWAS data and contribute to the better exploitation of these rich sources of information. © 2014 IEEE.

  19. Identical twins in forensic genetics - Epidemiology and risk based estimation of weight of evidence.

    Science.gov (United States)

    Tvedebrink, Torben; Morling, Niels

    2015-12-01

    The increase in the number of forensic genetic loci used for identification purposes results in infinitesimal random match probabilities. These probabilities are computed under assumptions made for rather simple population genetic models. Often, the forensic expert reports likelihood ratios, where the alternative hypothesis is assumed not to encompass close relatives. However, this approach implies that important factors present in real human populations are discarded. This approach may be very unfavourable to the defendant. In this paper, we discuss some important aspects concerning the closest familial relationship, i.e., identical (monozygotic) twins, when reporting the weight of evidence. This can be done even when the suspect has no knowledge of an identical twin or when official records hold no twin information about the suspect. The derived expressions are not original as several authors previously have published results accounting for close familial relationships. However, we revisit the discussion to increase the awareness among forensic genetic practitioners and include new information on medical and societal factors to assess the risk of not considering a monozygotic twin as the true perpetrator. If accounting for a monozygotic twin in the weight of evidence, it implies that the likelihood ratio is truncated at a maximal value depending on the prevalence of monozygotic twins and the societal efficiency of recognising a monozygotic twin. If a monozygotic twin is considered as an alternative proposition, then data relevant for the Danish society suggests that the threshold of likelihood ratios should approximately be between 150,000 and 2,000,000 in order to take the risk of an unrecognised identical, monozygotic twin into consideration. In other societies, the threshold of the likelihood ratio in crime cases may reach other, often lower, values depending on the recognition of monozygotic twins and the age of the suspect. In general, more strictly kept

  20. Germline genetic variants with implications for disease risk and therapeutic outcomes.

    Science.gov (United States)

    Pasternak, Amy L; Ward, Kristen M; Luzum, Jasmine A; Ellingrod, Vicki L; Hertz, Daniel L

    2017-10-01

    Genetic testing has multiple clinical applications including disease risk assessment, diagnosis, and pharmacogenomics. Pharmacogenomics can be utilized to predict whether a pharmacologic therapy will be effective or to identify patients at risk for treatment-related toxicity. Although genetic tests are typically ordered for a distinct clinical purpose, the genetic variants that are found may have additional implications for either disease or pharmacology. This review will address multiple examples of germline genetic variants that are informative for both disease and pharmacogenomics. The discussed relationships are diverse. Some of the agents are targeted for the disease-causing genetic variant, while others, although not targeted therapies, have implications for the disease they are used to treat. It is also possible that the disease implications of a genetic variant are unrelated to the pharmacogenomic implications. Some of these examples are considered clinically actionable pharmacogenes, with evidence-based, pharmacologic treatment recommendations, while others are still investigative as areas for additional research. It is important that clinicians are aware of both the disease and pharmacogenomic associations of these germline genetic variants to ensure patients are receiving comprehensive personalized care. Copyright © 2017 the American Physiological Society.

  1. Sex differences in genetic and environmental risk factors for irrational fears and phobias.

    Science.gov (United States)

    Kendler, K S; Jacobson, K C; Myers, J; Prescott, C A

    2002-02-01

    For irrational fears and their associated phobias, epidemiological studies suggest sex differences in prevalence and twin studies report significant genetic effects. How does sex impact on the familial transmission of liability to fears and phobias? In personal interviews with over 3000 complete pairs (of whom 1058 were opposite-sex dizygotic pairs), ascertained from a population-based registry, we assessed the lifetime prevalence of five phobias and their associated irrational fears analysed using a multiple threshold model. Twin resemblance was assessed by polychoric correlations and biometrical model-fitting incorporating sex-specific effects. For agoraphobia, situational and blood/injury fear/phobia, the best fit model suggested equal heritability in males and females and genetic correlations between the sexes of less than +0.50. For animal fear/phobias by contrast, the best fit model suggested equal heritability in males and females and a genetic correlation of unity. No evidence was found for an impact of family environment on liability to these fears or phobias. For social phobias, twin resemblance in males was explained by genetic factors and in females by familial-environmental factors. The impact of sex on genetic risk may differ meaningfully across phobia subtypes. Sex-specific genetic risk factors may exist for agoraphobia, social, situational and blood-injury phobias but not for animal fear/phobia. These results should be interpreted in the context of the limited power of twin studies, even with large sample sizes, to resolve sex-specific genetic effects.

  2. Genetic risk scores link body fat distribution with specific cardiometabolic profiles

    DEFF Research Database (Denmark)

    Svendstrup, Mathilde; Sandholt, Camilla H; Andersson Galijatovic, Ehm Astrid

    2016-01-01

    OBJECTIVE: Forty-nine known single nucleotide polymorphisms (SNPs) associating with body mass index (BMI)-adjusted waist-hip-ratio (WHR) (WHRadjBMI) were recently suggested to cluster into three groups with different associations to cardiometabolic traits. Genetic risk scores of the clusters...... on the risk of incident diabetes and associations with detailed cardiometabolic phenotypes were tested. METHODS: In a prospective study of 6,121 Inter99 individuals, the risk of incident diabetes using Cox proportional hazards regression was evaluated. Using linear regession, the associations between genetic...... risk scores and anthropometry and blood samples at fasting and during an oral glucose tolerance test were tested. Analyses were adjusted for age, sex, and BMI. RESULTS: Cluster 1 associated with an increased risk of diabetes (HR = 1.05, P = 2.74 × 10(-) (4) ) and with a poor metabolic profile...

  3. Risk assesment in the context of EC directives on genetically modified organisms

    International Nuclear Information System (INIS)

    Meer, P.J. van der

    1992-01-01

    The introduction of these new molecular technologies initiated an international discussion on the safety in biotechnology. In 1974 one of the pioneers of this new technology, Paul Berg, expressed his view on the potential risks of recombinant DNA applications in the famous 'Berg letter', leading to a self-imposed moratorium on certain experiments. Following the Berg letter and the Asilomar convention, much international attention has been given to the question of safety in biotechnology. This attention resulted in hundreds of documents, research programmes, guidelines and regulations. This resulted, among others, in two EC Directives on genetically modified organisms: the EC Directive 90/219/EEC on the contained use of genetically modified micro-organisms, and Directive 90/220/EEC on the release of genetically modified organisms. These directives lay down a system for harmonization of risk assessment and risk management with regard to the safety for human health and the environment

  4. Prediction of individual genetic risk to prostate cancer using a polygenic score

    DEFF Research Database (Denmark)

    Szulkin, Robert; Whitington, Thomas; Eklund, Martin

    2015-01-01

    BACKGROUND: Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate...... prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. RESULTS...... regions established as associated with prostate cancer risk. CONCLUSIONS: Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction....

  5. The joint regulation of genetic gain and inbreeding under mate selection.

    Science.gov (United States)

    Klieve, H M; Kinghorn, B P; Barwick, S A

    1994-01-12

    Stochastic simulation was used to evaluate a range of selection strategies with respect to both additive genetic response and inbreeding. Strategies involving selection on BLUP ebvs or individual phenotype, followed by random mating, were compared with mate selection strategies which used portfolio analysis to give joint consideration to genetic merit and inbreeding. An adapted Mean Of Total Absolute Deviations (MOTAD) method was used in a mate selection model to define optimal matings with regard to aggregate genetic merit and inbreeding for a base population h(2) of 0.2. Compared with random mating following selection on BLUP ebvs, inbreeding levels after 10 years of selection were able to be reduced under BLUP plus mate selection from ∼.23 to as little as .11. Additive genetic gain was either little compromised or increased. The results suggest that information linking expected levels of genetic merit and inbreeding can be used to find the preferred selection strategy. ZUSAMMENFASSUNG: Gemeinsame Kontrolle von Zuchtfortschritt und Inzucht bei Partnerselektion Es wurde stochastische Simulation zur Auswertung einer Reihe von Selektionsstrategien hinsichtlich Zuchtwertzuwachs und Inzucht verwendet. Strategien mit Selektion auf der Basis von BLUP ebvs oder individuellem Phänotyp mit nachfolgender Zufallspaarung wurden mit Partnerselektionsstrategien verglichen, die Portfolioanalyse zur gemeinsamen Beachtung von Zuchtwert und Inzucht verwendeten. Eine Methode adaptierter MITTELWERTE TOTALER ABSOLUTER ABWEICHUNGEN (MOTAD) Methode wurde beim Partnerselektionsmodell zur Definition optimaler Paarungen in Hinblick auf Gesamtzuchtwert und Inzucht bei einer Populationsheritabilität von 0,2 verwendet. Verglichen mit Zufallspaarung nach Selektion auf BLUP ebvs waren die Inzuchtgrade nach 10 Selektionsjahren von 0,23 auf 0,11 reduziert und additiver Zuchtfortschritt war dabei wenig beeinträchtigt oder nahm sogar zu. Die Ergebnisse weisen darauf hin, daß Information, die

  6. Evaluating investments in renewable energy under policy risks

    International Nuclear Information System (INIS)

    Gatzert, Nadine; Vogl, Nikolai

    2016-01-01

    The considerable amount of required infrastructure and renewable energy investments expected in the forthcoming years also implies an increasingly relevant contribution of private and institutional investors. In this context, especially regulatory and policy risks have been shown to play a major role for investors when evaluating investments in renewable energy and should thus also be taken into account in risk assessment and when deriving risk-return profiles. In this paper, we provide a stochastic model framework to quantify policy risks associated with renewable energy investments (e.g. a retrospective reduction of a feed-in tariff), thereby also taking into account energy price risk, resource risk, and inflation risk. The model is illustrated by means of simulations and scenario analyses, and it makes use of expert estimates and fuzzy set theory for quantifying policy risks. Our numerical results for a portfolio of onshore wind farms in Germany and France show that policy risk can strongly impact risk-return profiles, and that cross-country diversification effects can considerably decrease the overall risk for investors. - Highlights: •Quantification of policy risks associated with renewable energy investments. •Results emphasize that policy risk has a major impact on risk and return. •Study of the cross-country diversification potential. •Cross-country diversification can considerably decrease the risk for an investor.

  7. Interaction between common breast cancer susceptibility variants, genetic ancestry, and nongenetic risk factors in Hispanic women.

    Science.gov (United States)

    Fejerman, Laura; Stern, Mariana C; John, Esther M; Torres-Mejía, Gabriela; Hines, Lisa M; Wolff, Roger K; Baumgartner, Kathy B; Giuliano, Anna R; Ziv, Elad; Pérez-Stable, Eliseo J; Slattery, Martha L

    2015-11-01

    Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population. We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions. We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74-1.20), 1.20 (0.94-1.53), and 1.49 (1.28-1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72-1.42), 1.19 (0.98-1.45), and 1.69 (1.26-2.26) for never, 12 months breastfeeding, respectively, Pinteraction 0.014]. The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women. These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk. ©2015 American Association for Cancer Research.

  8. Portrayal of genetic risk for breast cancer in ethnic and non-ethnic newspapers.

    Science.gov (United States)

    Donelle, L; Hoffman-Goetz, L; Clarke, J N

    2004-01-01

    There has been enormous attention paid to the genetics of breast cancer in this era of genomic medicine. A great deal of the interest has been generated through discourse in the public mass media. However, genetic risk is a probabilistic concept and one that requires adequate numeracy skills. The purpose of this qualitative content analysis was to describe and evaluate the portrayal of genetic risk for breast cancer in mass print media. Mass print newspapers targeting high (Ashkenazi Jews) and low (general Canadian population) genetic risk audiences and published at least monthly, available in English and accessible through public archives at the National Library of Canada, were identified and hand searched for articles on breast cancer. Approximately 47% of breast cancer articles in 6 Jewish newspapers and published between 1996-2000 identified genetics in the title, first or last paragraph compared with 17% of 145 articles in 6 provincial newspapers published in 2000. The description of breast cancer risk was equally problematic in print media targeting high and low risk audiences. Statistics were presented in complex and contradictory ways, with, for example, the confounding of individual and population based risk estimates. Inconsistent messages about the value of genetic screening for breast cancer characterized articles in both ethnic and non-ethnic newspapers. Deciphering the information into a comprehensible form is likely challenging, particularly in light of widespread numeric-literacy limitations. The publication of discrepant research findings and the perplexing statistical information consequently brought into question the credibility of the scientific process and the recommendations of health care professionals.

  9. Genetic Parameter Estimates of Carcass Traits under National Scale Breeding Scheme for Beef Cattle

    Directory of Open Access Journals (Sweden)

    ChangHee Do

    2016-08-01

    productivity and carcass quality could be obtained under the national scale breeding scheme of Korea for Hanwoo and that continuous efforts to improve the breeding scheme should be made to increase genetic progress.

  10. Delimiting genetic units in Neotropical toads under incomplete lineage sorting and hybridization

    Directory of Open Access Journals (Sweden)

    Thomé Maria Tereza C

    2012-12-01

    Full Text Available Abstract Background Delimiting genetic units is useful to enhance taxonomic discovery and is often the first step toward understanding evolutionary mechanisms generating diversification. The six species within the Rhinella crucifer group of toads were defined under morphological criteria alone. Previous data suggest limited correspondence of these species to mitochondrial lineages, and morphological intergradation at transitions between forms suggests hybridization. Here we extensively sampled populations throughout the geographic distribution of the group and analyzed mitochondrial and nuclear sequence data to delimit genetic units using tree–based and allele frequency–based approaches. Results These approaches yielded complementary results, with allele frequency-based methods performing unexpectedly well given the limited number of loci examined. Both mitochondrial and nuclear markers supported a genetic structure of five units within the group, with three of the inferred units distributed within its main range, while two other units occur in separate isolates. The inferred units are mostly discordant with currently described forms: unequivocal association exists for only two of the six species in the group. Genetic evidence for hybridization exists for two pairs of units, with clear cyto–nuclear allele mixing observed in one case. Conclusions Our results confirmed that current taxonomy does not represent evolutionary units in the Rhinella crucifer group. Correspondence between genetically distinguishable units and the currently recognized species is only possible for Rhinella henseli and R. inopina. The recognition of other species relies on the reassessment of the geographic range of R. crucifer, the examination of the type series of R. ornata for hybrids, and on the use of additional markers to verify the genetic distinctiveness of R. abei. We state that R. pombali should not remain a valid species since its description appears to be

  11. Risk adjustment model of credit life insurance using a genetic algorithm

    Science.gov (United States)

    Saputra, A.; Sukono; Rusyaman, E.

    2018-03-01

    In managing the risk of credit life insurance, insurance company should acknowledge the character of the risks to predict future losses. Risk characteristics can be learned in a claim distribution model. There are two standard approaches in designing the distribution model of claims over the insurance period i.e, collective risk model and individual risk model. In the collective risk model, the claim arises when risk occurs is called individual claim, accumulation of individual claim during a period of insurance is called an aggregate claim. The aggregate claim model may be formed by large model and a number of individual claims. How the measurement of insurance risk with the premium model approach and whether this approach is appropriate for estimating the potential losses occur in the future. In order to solve the problem Genetic Algorithm with Roulette Wheel Selection is used.

  12. Genetic ancestry modifies the association between genetic risk variants and breast cancer risk among Hispanic and non-Hispanic white women.

    Science.gov (United States)

    Fejerman, Laura; Stern, Mariana C; Ziv, Elad; John, Esther M; Torres-Mejia, Gabriela; Hines, Lisa M; Wolff, Roger; Wang, Wei; Baumgartner, Kathy B; Giuliano, Anna R; Slattery, Martha L

    2013-08-01

    Hispanic women in the USA have lower breast cancer incidence than non-Hispanic white (NHW) women. Genetic factors may contribute to this difference. Breast cancer genome-wide association studies (GWAS) conducted in women of European or Asian descent have identified multiple risk variants. We tested the association between 10 previously reported single nucleotide polymorphisms (SNPs) and risk of breast cancer in a sample of 4697 Hispanic and 3077 NHW women recruited as part of three population-based case-control studies of breast cancer. We used stratified logistic regression analyses to compare the associations with different genetic variants in NHWs and Hispanics classified by their proportion of Indigenous American (IA) ancestry. Five of 10 SNPs were statistically significantly associated with breast cancer risk. Three of the five significant variants (rs17157903-RELN, rs7696175-TLR1 and rs13387042-2q35) were associated with risk among Hispanics but not in NHWs. The odds ratio (OR) for the heterozygous at 2q35 was 0.75 [95% confidence interval (CI) = 0.50-1.15] for low IA ancestry and 1.38 (95% CI = 1.04-1.82) for high IA ancestry (P interaction 0.02). The ORs for association at RELN were 0.87 (95% CI = 0.59-1.29) and 1.69 (95% CI = 1.04-2.73), respectively (P interaction 0.03). At the TLR1 locus, the ORs for women homozygous for the rare allele were 0.74 (95% CI = 0.42-1.31) and 1.73 (95% CI = 1.19-2.52) (P interaction 0.03). Our results suggest that the proportion of IA ancestry modifies the magnitude and direction of the association of 3 of the 10 previously reported variants. Genetic ancestry should be considered when assessing risk in women of mixed descent and in studies designed to discover causal mutations.

  13. Internal modelling under Risk-Based Capital (RBC) framework

    Science.gov (United States)

    Ling, Ang Siew; Hin, Pooi Ah

    2015-12-01

    Very often the methods for the internal modelling under the Risk-Based Capital framework make use of the data which are in the form of run-off triangle. The present research will instead extract from a group of n customers, the historical data for the sum insured si of the i-th customer together with the amount paid yij and the amount aij reported but not yet paid in the j-th development year for j = 1, 2, 3, 4, 5, 6. We model the future value (yij+1, aij+1) to be dependent on the present year value (yij, aij) and the sum insured si via a conditional distribution which is derived from a multivariate power-normal mixture distribution. For a group of given customers with different original purchase dates, the distribution of the aggregate claims liabilities may be obtained from the proposed model. The prediction interval based on the distribution for the aggregate claim liabilities is found to have good ability of covering the observed aggregate claim liabilities.

  14. Sustainable and Resilient Supply Chain Network Design under Disruption Risks

    Directory of Open Access Journals (Sweden)

    Sonia Irshad Mari

    2014-09-01

    Full Text Available Sustainable supply chain network design is a rich area for academic research that is still in its infancy and has potential to affect supply chain performance. Increasing regulations for carbon and waste management are forcing firms to consider their supply chains from ecological and social objectives, but in reality, however, facilities and the links connecting them are disrupted from time to time, due to poor weather, natural or manmade disasters or a combination of any other factors. Supply chain systems drop their sustainability objectives while coping with these unexpected disruptions. Hence, the new challenges for supply chain managers are to design an efficient and effective supply chain network that will be resilient enough to bounce back from any disruption and that also should have sufficient vigilance to offer same sustainability under a disruption state. This paper focuses on ecological sustainability, because an environmental focus in a supply chain system is more important and also links with other pillars of sustainability, as the products need to be produced, packed and transported in an ethical way, which should not harm social balance and the environment. Owing to importance of the considered issue, this paper attempts to introduce a network optimization model for a sustainable and resilient supply chain network by incorporating (1 sustainability via carbon emissions and embodied carbon footprints and (2 resilience by incorporating location-specific risks. The proposed goal programming (GP model optimizes the total cost, while considering the resilience and sustainability of the supply chain network.

  15. Genetic toxicology at the crossroads-from qualitative hazard evaluation to quantitative risk assessment.

    Science.gov (United States)

    White, Paul A; Johnson, George E

    2016-05-01

    Applied genetic toxicology is undergoing a transition from qualitative hazard identification to quantitative dose-response analysis and risk assessment. To facilitate this change, the Health and Environmental Sciences Institute (HESI) Genetic Toxicology Technical Committee (GTTC) sponsored a workshop held in Lancaster, UK on July 10-11, 2014. The event included invited speakers from several institutions and the contents was divided into three themes-1: Point-of-departure Metrics for Quantitative Dose-Response Analysis in Genetic Toxicology; 2: Measurement and Estimation of Exposures for Better Extrapolation to Humans and 3: The Use of Quantitative Approaches in Genetic Toxicology for human health risk assessment (HHRA). A host of pertinent issues were discussed relating to the use of in vitro and in vivo dose-response data, the development of methods for in vitro to in vivo extrapolation and approaches to use in vivo dose-response data to determine human exposure limits for regulatory evaluations and decision-making. This Special Issue, which was inspired by the workshop, contains a series of papers that collectively address topics related to the aforementioned themes. The Issue includes contributions that collectively evaluate, describe and discuss in silico, in vitro, in vivo and statistical approaches that are facilitating the shift from qualitative hazard evaluation to quantitative risk assessment. The use and application of the benchmark dose approach was a central theme in many of the workshop presentations and discussions, and the Special Issue includes several contributions that outline novel applications for the analysis and interpretation of genetic toxicity data. Although the contents of the Special Issue constitutes an important step towards the adoption of quantitative methods for regulatory assessment of genetic toxicity, formal acceptance of quantitative methods for HHRA and regulatory decision-making will require consensus regarding the

  16. Genetic Testing for Sports Performance, Responses to Training and Injury Risk: Practical and Ethical Considerations.

    Science.gov (United States)

    Williams, Alun G; Wackerhage, Henning; Day, Stephen H

    2016-01-01

    This paper addresses practical and ethical considerations regarding genetic tests to predict performance and/or risk of exercise-related injury or illness. Various people might wish to conduct sport-related genetic tests for a variety of reasons. For example, an individual might seek personal genetic information to help guide their own sport participation. A sports coach might wish to test young athletes to aid team selection or individualize training. A physician might want to predict the risk of injury or illness in athletes and advise regarding selection or preventative measures. An insurance company might seek to estimate the risk of career-threatening injury for athletes based partly on genetic information. Whilst this information is, in part, encoded in our DNA sequence, the available tests allow generally only a poor prediction of the aforementioned variables. In other words, the current genetic tests and analysis methods are not powerful enough to inform important decisions in sport to a substantial degree. It is particularly disappointing that more than half of the commercially available genetic tests related to exercise and sport do not appear to identify publicly the genetic variants they assess, making scrutiny by academic scholars and consumers (or their representatives) impossible. There are also challenging ethical issues to consider. For example, the imposition of genetic tests on individuals (especially young people) by third parties is potentially susceptible to abuse. Scientists and practitioners should understand the limitations of the tests currently available, the ethical concerns and the importance of counselling before and after testing so that they are only used in a responsible manner. © 2016 S. Karger AG, Basel.

  17. Neural Correlates of Feedback Processing in Decision Making under Risk

    Directory of Open Access Journals (Sweden)

    Beate eSchuermann

    2012-07-01

    Full Text Available Introduction. Event-related brain potentials (ERP provide important information about the sensitivity of the brain to process varying risks. The aim of the present study was to determine how different risk levels are reflected in decision-related ERPs, namely the feedback-related negativity (FRN and the P300. Material and Methods. 20 participants conducted a probabilistic two-choice gambling task while an electroencephalogram was recorded. Choices were provided between a low-risk option yielding low rewards and low losses and a high-risk option yielding high rewards and high losses. While options differed in expected risks, they were equal in expected values and in feedback probabilities. Results. At the behavioral level, participants were generally risk-averse but modulated their risk-taking behavior according to reward history. An early positivity (P200 was enhanced on negative feedbacks in high-risk compared to low-risk options. With regard to the FRN, there were significant amplitude differences between positive and negative feedbacks in high-risk options, but not in low-risk options. While the FRN on negative feedbacks did not vary with decision riskiness, reduced amplitudes were found for positive feedbacks in high-risk relative to low-risk choices. P300 amplitudes were larger in high-risk decisions, and in an additive way, after negative compared to positive feedback. Discussion. The present study revealed significant influences of risk and valence processing on ERPs. FRN findings suggest that the reward prediction error signal is increased after high-risk decisions. The increased P200 on negative feedback in risky decisions suggests that large negative prediction errors are processed as early as in the P200 time range. The later P300 amplitude is sensitive to feedback valence as well as to the risk of a decision. Thus, the P300 carries additional information for reward processing, mainly the enhanced motivational significance of risky

  18. Changes in genetic risk for emotional eating across the menstrual cycle: a longitudinal study.

    Science.gov (United States)

    Klump, K L; Hildebrandt, B A; O'Connor, S M; Keel, P K; Neale, M; Sisk, C L; Boker, S; Burt, S A

    2015-11-01

    Previous studies have shown significant within-person changes in binge eating and emotional eating across the menstrual cycle, with substantial increases in both phenotypes during post-ovulation. Increases in both estradiol and progesterone levels appear to account for these changes in phenotypic risk, possibly via increases in genetic effects. However, to date, no study has examined changes in genetic risk for binge phenotypes (or any other phenotype) across the menstrual cycle. The goal of the present study was to examine within-person changes in genetic risk for emotional eating scores across the menstrual cycle. Participants were 230 female twin pairs (460 twins) from the Michigan State University Twin Registry who completed daily measures of emotional eating for 45 consecutive days. Menstrual cycle phase was coded based on dates of menstrual bleeding and daily ovarian hormone levels. Findings revealed important shifts in genetic and environmental influences, where estimates of genetic influences were two times higher in post- as compared with pre-ovulation. Surprisingly, pre-ovulation was marked by a predominance of environmental influences, including shared environmental effects which have not been previously detected for binge eating phenotypes in adulthood. Our study was the first to examine within-person shifts in genetic and environmental influences on a behavioral phenotype across the menstrual cycle. Results highlight a potentially critical role for these shifts in risk for emotional eating across the menstrual cycle and underscore the need for additional, large-scale studies to identify the genetic and environmental factors contributing to menstrual cycle effects.

  19. The role of genetics in stroke risk factors; the discussion of two rare genetic syndroms associated with stroke and review of the literature

    Directory of Open Access Journals (Sweden)

    Eda Kılıç Çoban

    2015-09-01

    Full Text Available Stroke is defined as a focal or at times global neurological impairment of sudden onset, that lasts more than 24 hours or that leads to death. The nonmodifiable risk factors for stroke include age, race, gender and acquired risk factors include smoking, hypertension, diabetes and obesity. Previous studies have shown that these mentioned risk factors might be responsible for approximately 50% of patients presenting stroke. However for the remaining half of the stroke patients no risk factors could be detected and genetics might be responsible for this group. In this manuscript we would like to present 2 cases who were being followed-up with the rare genetic syndromes as Marfan syndrome and Robinow syndrome respectively. These patients presented to our clinic with stroke and no identifiable risk factors other than these genetic syndromes could be detected. By this case-series we would like to further discuss the relationship between genetic syndromes and stroke.

  20. The media and genetically modified foods: evidence in support of social amplification of risk.

    Science.gov (United States)

    Frewer, Lynn J; Miles, Susan; Marsh, Roy

    2002-08-01

    Empirical examinations of the "social amplification of risk" framework are rare, partly because of the difficulties in predicting when conditions likely to result in amplification effects will occur. This means that it is difficult to examine changes in risk perception that are contemporaneous with increases and/or decreases in social or media discussion of the risks associated with a particular risk event. However, the collection of attitude data before, during, and after the increased reporting of the risks of genetically modified food in the United Kingdom (spring 1999) has demonstrated that people's risk perceptions do increase and decrease in line with what might be expected upon examination of the amplification and attenuation mechanisms integral to the framework. Perceptions of benefit, however, appeared to be permanently depressed by negative reporting about genetically modified food. Trust in regulatory institutions with responsibility for protecting the public was not affected. It was concluded that the social amplification of risk framework is a useful framework for beginning to explain the potential impact on risk perceptions of a risk event, particularly if that risk event is presented to the public as a new hazard occurring in a crisis context.

  1. Ethnic background and genetic variation in the evaluation of cancer risk: a systematic review.

    Directory of Open Access Journals (Sweden)

    Lijun Jing

    Full Text Available The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort's ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be

  2. Effect of Alzheimer disease genetic risk disclosure on dietary supplement use.

    Science.gov (United States)

    Vernarelli, Jacqueline A; Roberts, J Scott; Hiraki, Susan; Chen, Clara A; Cupples, L Adrienne; Green, Robert C

    2010-05-01

    Genetic susceptibility testing for Alzheimer disease (AD) with APOE genotype disclosure is not recommended for clinical use but is available through direct-to-consumer (DTC) genetic testing companies. Little is known about whether APOE genotype disclosure would actually prompt changes in nutrition behaviors among at-risk individuals. We studied the effect of APOE genotype disclosure for AD risk assessment on dietary supplement use in adults with a family history of AD. As part of a secondary analysis of data from the second Risk Evaluation and Education for Alzheimer's Disease Study, we examined the effect of genotype disclosure on health-behavior changes among 272 unaffected first-degree relatives of persons with AD. Overall, 16% of all participants reported a change in dietary supplement use after AD risk assessment. Participants who learned that they had at least one copy of the risk-increasing epsilon4 allele (epsilon4+) had 4.75 times the odds of reporting a change in dietary supplement use than did their counterparts who had an absence of the risk-increasing epsilon4 allele (epsilon4-) (95% CI: 2.23, 10.10; P exercise, or medications. In this sample of first-degree relatives receiving genetic susceptibility testing for AD, an APOE epsilon4+ genotype status was positively associated with dietary supplement use after risk disclosure. Such changes occurred despite the absence of evidence that supplement use reduces the risk of AD. Given the expansion of DTC genetic tests, this study highlights the need for future studies in disease risk communication.

  3. Genetics University of Toronto Thrombophilia Study in Women (GUTTSI: genetic and other risk factors for venous thromboembolism in women

    Directory of Open Access Journals (Sweden)

    Evrovski Jovan

    2001-05-01

    Full Text Available Abstract Background Women may be at increased risk for venous thromboembolism (VTE as compared with men. We studied the effects of genetic and biochemical markers of thrombophilia in women, in conjunction with other established risk factors for VTE. Method The present retrospective case-control study was conducted in a thrombosis treatment programme at a large Toronto hospital. The cases were 129 women aged 16-79 years with objectively confirmed VTE. Age-matched control individuals were women who were free of venous thrombosis. Neither cases nor control individuals had known cardiovascular disease. Participants were interviewed regarding personal risk factors for VTE, including smoking, history of malignancy, pregnancy, and oestrogen or oral contraceptive use. Blood specimens were analyzed for common single nucleotide polymorphisms of prothrombin, factor V and methylenetetrahydrofolate reductase (MTHFR; C677T, A1298C and T1317C, and the A66G polymorphism for methionine synthase reductase (MTRR.Fasting plasma homocysteine was also analyzed. Results Women with VTE were significantly more likely than female control individuals to carry the prothrombin polymorphism and the factor V polymorphism, or to have fasting hyperhomocysteinaemia. Homozygosity for the C677T MTHFR gene was not a significant risk factor for VTE, or were the A1298C or T1317C MTHFR homozygous variants. Also, the A66G MTRR homozygous state did not confer an increased risk for VTE. Conclusion Prothrombin and factor V polymorphisms increased the risk for VTE in women, independent from other established risk factors. Although hyperhomocysteinaemia also heightens this risk, common polymorphisms in two genes that are responsible for homocysteine remethylation do not. These findings are consistent with previous studies that included both men and women.

  4. Micro-social risk factors and genetic predisposition to micro-social risk factors and genetic predisposition to digestive diseases among adolescents living in georgia.

    Science.gov (United States)

    Chikava, M; Bakradze, M; Varsimashvili, M

    2013-02-01

    The purpose of the study was to analyse the genetic predisposition to digestive diseases, micro-social stressors and other risk factors among adolescents and compare them to each other by strength of association with Chronic Digestive Diseases (CDD). One phase epidemiological research was conducted in population of adolescents aged 14-21 years, living in Georgia. The representative contigent - 430 adolescents were selected by the method of simple randomization. The two groups were separated from the research contingent: 84 adolescents with the CDD (the experimental group) and 346 condtionally healthy adolescents (the control group). The degree of relationship between the defined risk factor and CDD among adolescents was studied through case-control study method. Statistical processing of the obtained data was provided through SPSS v.11,5. The risk factors ranking was held according to decrease of OR values. Analysis of micro-social and hereditary risk factors showed that the associations between CDD and the combination of chronic psychological overloads, calculated together, is stronger (OR=15,3 (95% CI: 9,06-37,8)), than with genetic predisposition to digestive diseases (OR=11,5). From chronic psychological overloads, the most strong relationship with CDD have adolescents study overloads (OR=7,1) and conflict situations at the family (OR=6,0), as well as adolescents bad habits (OR=5,14) and unsatisfactory living conditions (OR=3,74). The listed above OR indicies may be used for planning preventive measures, needed for decrease CDD prevalence among adolescents.

  5. Interspecific Hybridization in Pilot Whales and Asymmetric Genetic Introgression in Northern Globicephala melas under the Scenario of Global Warming.

    Science.gov (United States)

    Miralles, Laura; Oremus, Marc; Silva, Mónica A; Planes, Serge; Garcia-Vazquez, Eva

    2016-01-01

    Pilot whales are two cetacean species (Globicephala melas and G. macrorhynchus) whose distributions are correlated with water temperature and partially overlap in some areas like the North Atlantic Ocean. In the context of global warming, distribution range shifts are expected to occur in species affected by temperature. Consequently, a northward displacement of the tropical pilot whale G. macrorynchus is expected, eventually leading to increased secondary contact areas and opportunities for interspecific hybridization. Here, we describe genetic evidences of recurrent hybridization between pilot whales in northeast Atlantic Ocean. Based on mitochondrial DNA sequences and microsatellite loci, asymmetric introgression of G. macrorhynchus genes into G. melas was observed. For the latter species, a significant correlation was found between historical population growth rate estimates and paleotemperature oscillations. Introgressive hybridization, current temperature increases and lower genetic variation in G. melas suggest that this species could be at risk in its northern range. Under increasing environmental and human-mediated stressors in the North Atlantic Ocean, it seems recommendable to develop a conservation program for G. melas.

  6. Newsvendor problem with random shortage cost under a risk criterion

    NARCIS (Netherlands)

    Wu, Meng; Zhu, Stuart X.; Teunter, Ruud H.

    2013-01-01

    We study profit maximization vs risk approaches for the standard newsvendor problem with uncertainty in demand as well as a generalized version with uncertainty in the shortage cost (as often applies in practice). We consider two well-known risk approaches: Value-at-Risk (VaR) included as a

  7. Genetic variability of garlic accessions as revealed by agro-morphological traits evaluated under different environments.

    Science.gov (United States)

    Hoogerheide, E S S; Azevedo Filho, J A; Vencovsky, R; Zucchi, M I; Zago, B W; Pinheiro, J B

    2017-05-31

    The cultivated garlic (Allium sativum L.) displays a wide phenotypic diversity, which is derived from natural mutations and phenotypic plasticity, due to dependence on soil type, moisture, latitude, altitude and cultural practices, leading to a large number of cultivars. This study aimed to evaluate the genetic variability shown by 63 garlic accessions belonging to Instituto Agronômico de Campinas and the Escola Superior de Agricultura "Luiz de Queiroz" germplasm collections. We evaluated ten quantitative characters in experimental trials conducted under two localities of the State of São Paulo: Monte Alegre do Sul and Piracicaba, during the agricultural year of 2007, in a randomized blocks design with five replications. The Mahalanobis distance was used to measure genetic dissimilarities. The UPGMA method and Tocher's method were used as clustering procedures. Results indicated significant variation among accessions (P < 0.01) for all evaluated characters, except for the percentage of secondary bulb growth in MAS, indicating the existence of genetic variation for bulb production, and germplasm evaluation considering different environments is more reliable for the characterization of the genotypic variability among garlic accessions, since it diminishes the environmental effects in the clustering of genotypes.

  8. Novel genetic loci underlying human intracranial volume identified through genome-wide association.

    Science.gov (United States)

    Adams, Hieab H H; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura M E; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; Braber, Anouk Den; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco J C; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, W T; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic J A; Van Duijn, Cornelia M; Van Haren, Neeltje E M; Van T Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton J M; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

    2016-12-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρ genetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

  9. Sardinians genetic background explained by runs of homozygosity and genomic regions under positive selection.

    Science.gov (United States)

    Di Gaetano, Cornelia; Fiorito, Giovanni; Ortu, Maria Francesca; Rosa, Fabio; Guarrera, Simonetta; Pardini, Barbara; Cusi, Daniele; Frau, Francesca; Barlassina, Cristina; Troffa, Chiara; Argiolas, Giuseppe; Zaninello, Roberta; Fresu, Giovanni; Glorioso, Nicola; Piazza, Alberto; Matullo, Giuseppe

    2014-01-01

    The peculiar position of Sardinia in the Mediterranean sea has rendered its population an interesting biogeographical isolate. The aim of this study was to investigate the genetic population structure, as well as to estimate Runs of Homozygosity and regions under positive selection, using about 1.2 million single nucleotide polymorphisms genotyped in 1077 Sardinian individuals. Using four different methods--fixation index, inflation factor, principal component analysis and ancestry estimation--we were able to highlight, as expected for a genetic isolate, the high internal homogeneity of the island. Sardinians showed a higher percentage of genome covered by RoHs>0.5 Mb (F(RoH%0.5)) when compared to peninsular Italians, with the only exception of the area surrounding Alghero. We furthermore identified 9 genomic regions showing signs of positive selection and, we re-captured many previously inferred signals. Other regions harbor novel candidate genes for positive selection, like TMEM252, or regions containing long non coding RNA. With the present study we confirmed the high genetic homogeneity of Sardinia that may be explained by the shared ancestry combined with the action of evolutionary forces.

  10. The association between a genetic risk score for allergy and the risk of developing allergies in childhood-Results of the WHISTLER cohort

    NARCIS (Netherlands)

    Arabkhazaeli, Ali; Ahmadizar, Fariba; Leusink, Maarten; Arets, Hubertus G. M.; Raaijmakers, Jan A. M.; Uiterwaal, Cuno S. P. M.; van der Ent, Cornelis K.; Maitland-van der Zee, Anke-Hilse; Vijverberg, Susanne J. H.

    2018-01-01

    Several genetic variants have been associated with the susceptibility to allergic disease in adults, but it remains unclear whether these genetic variants are also associated with the onset of allergic disease early in life. The aim of this study was to develop a genetic risk score (GRS) for allergy

  11. The association between a genetic risk score for allergy and the risk of developing allergies in childhood-Results of the WHISTLER cohort

    NARCIS (Netherlands)

    Arabkhazaeli, Ali; Ahmadizar, Fariba; Leusink, Maarten; Arets, Hubertus G. M.; Raaijmakers, Jan A. M.; Uiterwaal, Cuno S. P. M.; van der Ent, Cornelis K.; Maitland-van der Zee, Anke-Hilse; Vijverberg, Susanne J. H.

    2018-01-01

    Background: Several genetic variants have been associated with the susceptibility to allergic disease in adults, but it remains unclear whether these genetic variants are also associated with the onset of allergic disease early in life. The aim of this study was to develop a genetic risk score (GRS)

  12. Meat, vegetables and genetic polymorphisms and the risk of colorectal carcinomas and adenomas

    International Nuclear Information System (INIS)

    Skjelbred, Camilla F; Sæbø, Mona; Hjartåker, Anette; Grotmol, Tom; Hansteen, Inger-Lise; Tveit, Kjell M; Hoff, Geir; Kure, Elin H

    2007-01-01

    The risk of sporadic colorectal cancer (CRC) is mainly associated with lifestyle factors, particularly dietary factors. Diets high in red meat and fat and low in fruit and vegetables are associated with an increased risk of CRC. The dietary effects may be modulated by genetic polymorphisms in biotransformation genes. In this study we aimed to evaluate the role of dietary factors in combination with genetic factors in the different stages of colorectal carcinogenesis in a Norwegian population. We used a case-control study design (234 carcinomas, 229 high-risk adenomas, 762 low-risk adenomas and 400 controls) to test the association between dietary factors (meat versus fruit, berries and vegetables) genetic polymorphisms in biotransformation genes (GSTM1, GSTT1, GSTP1 Ile 105 Val, EPHX1 Tyr 113 His and EPHX1 His 139 Arg), and risk of colorectal carcinomas and adenomas. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression. A higher ratio of total meat to total fruit, berry and vegetable intake was positively associated with both high and low-risk adenomas, with approximately twice the higher risk in the 2 nd quartile compared to the lowest quartile. For the high-risk adenomas this positive association was more obvious for the common allele (Tyr allele) of the EPHX1 codon 113 polymorphism. An association was also observed for the EPHX1 codon 113 polymorphism in the low-risk adenomas, although not as obvious. Although, the majority of the comparison groups are not significant, our results suggest an increased risk of colorectal adenomas in individuals for some of the higher ratios of total meat to total fruit, berry and vegetable intake. In addition the study supports the notion that the biotransformation enzymes GSTM1, GSTP1 and EPHX1 may modify the effect of dietary factors on the risk of developing colorectal carcinoma and adenoma

  13. Simulated Annealing Genetic Algorithm Based Schedule Risk Management of IT Outsourcing Project

    Directory of Open Access Journals (Sweden)

    Fuqiang Lu

    2017-01-01

    Full Text Available IT outsourcing is an effective way to enhance the core competitiveness for many enterprises. But the schedule risk of IT outsourcing project may cause enormous economic loss to enterprise. In this paper, the Distributed Decision Making (DDM theory and the principal-agent theory are used to build a model for schedule risk management of IT outsourcing project. In addition, a hybrid algorithm combining simulated annealing (SA and genetic algorithm (GA is designed, namely, simulated annealing genetic algorithm (SAGA. The effect of the proposed model on the schedule risk management problem is analyzed in the simulation experiment. Meanwhile, the simulation results of the three algorithms GA, SA, and SAGA show that SAGA is the most superior one to the other two algorithms in terms of stability and convergence. Consequently, this paper provides the scientific quantitative proposal for the decision maker who needs to manage the schedule risk of IT outsourcing project.

  14. Observationally and Genetically High YKL-40 and Risk of Venous Thromboembolism in the General Population

    DEFF Research Database (Denmark)

    Kjaergaard, Alisa D; Johansen, Julia S; Bojesen, Stig E

    2016-01-01

    OBJECTIVE: High baseline YKL-40 is associated with later development of ischemic stroke, but not with myocardial infarction. Whether high YKL-40 levels are associated with increased risk of venous thromboembolism is presently unknown. We tested the hypothesis that observationally and genetically...... high YKL-40 is associated with increased risk of venous thromboembolism in the general population. APPROACH AND RESULTS: Cohort and Mendelian randomization studies in 96 110 individuals from the Danish general population, with measured plasma levels of YKL-40 (N=21 647) and CHI3L1 rs4950928 genotype (N...... levels, but not with risk of venous thromboembolism. A doubling in YKL-40 was associated with a multifactorially adjusted observational hazard ratio for pulmonary embolism of 1.17 (1.00-1.38) and a genetic odds ratio of 0.97 (0.76-1.23). Corresponding risk estimates were 1.28 (1.12-1.47) observationally...

  15. Lifestyle modifies obesity-associated risk of cardiovascular disease in a genetically homogeneous population

    DEFF Research Database (Denmark)

    Jørgensen, Marit E; Borch-Johnsen, Knut; Bjerregaard, Peter

    2006-01-01

    BACKGROUND: The association between obesity and cardiovascular disease risk differs across populations. Whether such differences in obesity-related risk factors exist within population groups of the same genetic origin but with differences in lifestyle remains to be determined. OBJECTIVE: The aim...... was to analyze whether obesity was associated with the same degree of metabolic disturbances in 2 groups of genetically homogeneous Inuit who were exposed to considerable differences in lifestyle. DESIGN: We studied obesity and cardiovascular disease risk factors in a cross-sectional population survey of 2311...... groups of Inuit living in Greenland and Inuit migrants living in Denmark. The findings indicate that lifestyle factors modify the cardiovascular disease risk associated with obesity....

  16. Genetic predisposition to coronary heart disease and stroke using an additive genetic risk score: a population-based study in Greece

    Science.gov (United States)

    Objective: To determine the extent to which the risk for incident coronary heart disease (CHD) increases in relation to a genetic risk score (GRS) that additively integrates the influence of high-risk alleles in nine documented single nucleotide polymorphisms (SNPs) for CHD, and to examine whether t...

  17. Genetic Testing and Neuroimaging: Trading off Benefit and Risk for Youth with Mental Illness.

    Science.gov (United States)

    Lee, Grace; Mizgalewicz, Ania; Borgelt, Emily; Illes, Judy

    According to the World Health Organization, mental illness is one of the leading causes of disability worldwide. The first onset of mental illness usually occurs during childhood or adolescence. Neuroimaging and genetic testing have been invaluable in research on behavioral and intentional disorders, particularly with their potential to lead to improved diagnostic and predictive capabilities and to decrease the associated burdens of disease. The present study focused specifically the perspectives of mental health providers on the role of neuroimaging and genetic testing in clinical practice with children and adolescents. We interviewed 38 psychiatrists, psychologists, and allied mental health professionals who work primarily with youth about their receptivity towards either the use of neuroimaging or genetic testing. Interviews probed the role they foresee for these modalities for prediction, diagnosis, and treatment planning, and the benefits and risks they anticipate. Practitioners anticipated three major benefits associated with clinical introduction of imaging and genetic testing in the mental health care for youth: (1) improved understanding of illness, (2) more accurate diagnosis than available through conventional clinical examination, and (3) validation of treatment plans. They also perceived three major risks: (1) potential adverse impacts on employment and insurance as adolescents reach adulthood, (2) misuse or misinterpretation of the imaging or genetic data, and (3) infringements on self-esteem or self-motivation. Movement of brain imaging and genetic testing into clinical care will require a delicate balance of biology and respect for autonomy in the still-evolving cognitive and affective world of young individuals.

  18. The Total Risk Analysis of Large Dams under Flood Hazards

    Directory of Open Access Journals (Sweden)

    Yu Chen

    2018-02-01

    Full Text Available Dams and reservoirs are useful systems in water conservancy projects; however, they also pose a high-risk potential for large downstream areas. Flood, as the driving force of dam overtopping, is the main cause of dam failure. Dam floods and their risks are of interest to researchers and managers. In hydraulic engineering, there is a growing tendency to evaluate dam flood risk based on statistical and probabilistic methods that are unsuitable for the situations with rare historical data or low flood probability, so a more reasonable dam flood risk analysis method with fewer application restrictions is needed. Therefore, different from previous studies, this study develops a flood risk analysis method for large dams based on the concept of total risk factor (TRF used initially in dam seismic risk analysis. The proposed method is not affected by the adequacy of historical data or the low probability of flood and is capable of analyzing the dam structure influence, the flood vulnerability of the dam site, and downstream risk as well as estimating the TRF of each dam and assigning corresponding risk classes to each dam. Application to large dams in the Dadu River Basin, Southwestern China, demonstrates that the proposed method provides quick risk estimation and comparison, which can help local management officials perform more detailed dam safety evaluations for useful risk management information.

  19. The flowering repressor SVP underlies a novel Arabidopsis thaliana QTL interacting with the genetic background.

    Science.gov (United States)

    Méndez-Vigo, Belén; Martínez-Zapater, José M; Alonso-Blanco, Carlos

    2013-01-01

    The timing of flowering initiation is a fundamental trait for the adaptation of annual plants to different environments. Large amounts of intraspecific quantitative variation have been described for it among natural accessions of many species, but the molecular and evolutionary mechanisms underlying this genetic variation are mainly being determined in the model plant Arabidopsis thaliana. To find novel A. thaliana flowering QTL, we developed introgression lines from the Japanese accession Fuk, which was selected based on the substantial transgression observed in an F(2) population with the reference strain Ler. Analysis of an early flowering line carrying a single Fuk introgression identified Flowering Arabidopsis QTL1 (FAQ1). We fine-mapped FAQ1 in an 11 kb genomic region containing the MADS transcription factor gene SHORT VEGETATIVE PHASE (SVP). Complementation of the early flowering phenotype of FAQ1-Fuk with a SVP-Ler transgen demonstrated that FAQ1 is SVP. We further proved by directed mutagenesis and transgenesis that a single amino acid substitution in SVP causes the loss-of-function and early flowering of Fuk allele. Analysis of a worldwide collection of accessions detected FAQ1/SVP-Fuk allele only in Asia, with the highest frequency appearing in Japan, where we could also detect a potential ancestral genotype of FAQ1/SVP-Fuk. In addition, we evaluated allelic and epistatic interactions of SVP natural alleles by analysing more than one hundred transgenic lines carrying Ler or Fuk SVP alleles in five genetic backgrounds. Quantitative analyses of these lines showed that FAQ1/SVP effects vary from large to small depending on the genetic background. These results support that the flowering repressor SVP has been recently selected in A. thaliana as a target for early flowering, and evidence the relevance of genetic interactions for the intraspecific evolution of FAQ1/SVP and flowering time.

  20. The flowering repressor SVP underlies a novel Arabidopsis thaliana QTL interacting with the genetic background.

    Directory of Open Access Journals (Sweden)

    Belén Méndez-Vigo

    Full Text Available The timing of flowering initiation is a fundamental trait for the adaptation of annual plants to different environments. Large amounts of intraspecific quantitative variation have been described for it among natural accessions of many species, but the molecular and evolutionary mechanisms underlying this genetic variation are mainly being determined in the model plant Arabidopsis thaliana. To find novel A. thaliana flowering QTL, we developed introgression lines from the Japanese accession Fuk, which was selected based on the substantial transgression observed in an F(2 population with the reference strain Ler. Analysis of an early flowering line carrying a single Fuk introgression identified Flowering Arabidopsis QTL1 (FAQ1. We fine-mapped FAQ1 in an 11 kb genomic region containing the MADS transcription factor gene SHORT VEGETATIVE PHASE (SVP. Complementation of the early flowering phenotype of FAQ1-Fuk with a SVP-Ler transgen demonstrated that FAQ1 is SVP. We further proved by directed mutagenesis and transgenesis that a single amino acid substitution in SVP causes the loss-of-function and early flowering of Fuk allele. Analysis of a worldwide collection of accessions detected FAQ1/SVP-Fuk allele only in Asia, with the highest frequency appearing in Japan, where we could also detect a potential ancestral genotype of FAQ1/SVP-Fuk. In addition, we evaluated allelic and epistatic interactions of SVP natural alleles by analysing more than one hundred transgenic lines carrying Ler or Fuk SVP alleles in five genetic backgrounds. Quantitative analyses of these lines showed that FAQ1/SVP effects vary from large to small depending on the genetic background. These results support that the flowering repressor SVP has been recently selected in A. thaliana as a target for early flowering, and evidence the relevance of genetic interactions for the intraspecific evolution of FAQ1/SVP and flowering time.

  1. Genetic Markers Enhance Coronary Risk Prediction in Men: The MORGAM Prospective Cohorts

    Science.gov (United States)

    Hughes, Maria F.; Saarela, Olli; Stritzke, Jan; Kee, Frank; Silander, Kaisa; Klopp, Norman; Kontto, Jukka; Karvanen, Juha; Willenborg, Christina; Salomaa, Veikko; Virtamo, Jarmo; Amouyel, Phillippe; Arveiler, Dominique; Ferrières, Jean; Wiklund, Per-Gunner; Baumert, Jens; Thorand, Barbara; Diemert, Patrick; Trégouët, David-Alexandre; Hengstenberg, Christian; Peters, Annette; Evans, Alun; Koenig, Wolfgang; Erdmann, Jeanette; Samani, Nilesh J.

    2012-01-01

    Background More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design. Methods Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5–18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived. Results Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50–59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events. Conclusions Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men. PMID:22848412

  2. The neural bases underlying social risk perception in purchase decisions.

    Science.gov (United States)

    Yokoyama, Ryoichi; Nozawa, Takayuki; Sugiura, Motoaki; Yomogida, Yukihito; Takeuchi, Hikaru; Akimoto, Yoritaka; Shibuya, Satoru; Kawashima, Ryuta

    2014-05-01

    Social considerations significantly influence daily purchase decisions, and the perception of social risk (i.e., the anticipated disapproval of others) is crucial in dissuading consumers from making purchases. However, the neural basis for consumers' perception of social risk remains undiscovered, and this novel study clarifies the relevant neural processes. A total of 26 volunteers were scanned while they evaluated purchase intention of products (purchase intention task) and their anticipation of others' disapproval for possessing a product (social risk task), using functional magnetic resonance imaging (fMRI). The fMRI data from the purchase intention task was used to identify the brain region associated with perception of social risk during purchase decision making by using subjective social risk ratings for a parametric modulation analysis. Furthermore, we aimed to explore if there was a difference between participants' purchase decisions and their explicit evaluations of social risk, with reference to the neural activity associated with social risk perception. For this, subjective social risk ratings were used for a parametric modulation analysis on fMRI data from the social risk task. Analysis of the purchase intention task revealed a significant positive correlation between ratings of social risk and activity in the anterior insula, an area of the brain that is known as part of the emotion-related network. Analysis of the social risk task revealed a significant positive correlation between ratings of social risk and activity in the temporal parietal junction and the medial prefrontal cortex, which are known as theory-of-mind regions. Our results suggest that the anterior insula processes consumers' social risk implicitly to prompt consumers not to buy socially unacceptable products, whereas ToM-related regions process such risk explicitly in considering the anticipated disapproval of others. These findings may prove helpful in understanding the mental

  3. Avoiding Drought Risks and Social Conflict Under Climate Change

    Science.gov (United States)

    Towler, E.; Lazrus, H.; Paimazumder, D.

    2014-12-01

    Traditional drought research has mainly focused on physical drought risks and less on the cultural processes that also contribute to how drought risks are perceived and managed. However, as society becomes more vulnerable to drought and climate change threatens to increase water scarcity, it is clear that drought research would benefit from a more interdisciplinary approach. To assess avoided drought impacts from reduced climate change, drought risks need to be assessed in the context of both climate prediction as well as improved understanding of socio-cultural processes. To this end, this study explores a risk-based framework to combine physical drought likelihoods with perceived risks from stakeholder interviews. Results are presented from a case study on how stakeholders in south-central Oklahoma perceive drought risks given diverse cultural beliefs, water uses, and uncertainties in future drought prediction. Stakeholder interviews (n=38) were conducted in 2012 to understand drought risks to various uses of water, as well as to measure worldviews from the cultural theory of risk - a theory that explains why people perceive risks differently, potentially leading to conflict over management decisions. For physical drought risk, drought projections are derived from a large ensemble of future climates generated from two RCPs that represent higher and lower emissions trajectories (i.e., RCP8.5 and RCP4.5). These are used to develop a Combined Drought Risk Matrix (CDRM) that characterizes drought risks for different water uses as the products of both physical likelihood (from the climate ensemble) and risk perception (from the interviews). We use the CRDM to explore the avoided drought risks posed to various water uses, as well as to investigate the potential for reduction of conflict over water management.

  4. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

    DEFF Research Database (Denmark)

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti

    2011-01-01

    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown...... the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture...

  5. Omega-3 fatty acids and the genetic risk of early onset acute coronary syndrome.

    Science.gov (United States)

    Leung Yinko, S S L; Thanassoulis, G; Stark, K D; Avgil Tsadok, M; Engert, J C; Pilote, L

    2014-11-01

    Recent gene-environment interaction studies suggest that diet may influence an individual's genetic predisposition to cardiovascular risk. We evaluated whether omega-3 fatty acid intake may influence the risk for acute coronary syndrome (ACS) conferred by genetic polymorphisms among patients with early onset ACS. Our population consisted of 705 patients of white European descent enrolled in GENESIS-PRAXY, a multicenter cohort study of patients aged 18-55 years and hospitalized with ACS. We used a case-only design to investigate interactions between the omega-3 index (a validated biomarker of omega-3 fatty acid intake) and 30 single nucleotide polymorphisms (SNPs) robustly associated with ACS. We used logistic regression to assess the interaction between each SNP and the omega-3 index. Interaction was also assessed between the omega-3 index and a genetic risk score generated from the 30 SNPs. All models were adjusted for age and sex. An interaction for increased ACS risk was found between carriers of the chromosome 9p21 variant rs4977574 and low omega-3 index (OR 1.57, 95% CI 1.07-2.32, p = 0.02), but this was not significant after correction for multiple testing. Similar results were obtained in the adjusted model (OR 1.55, 95% CI 1.05-2.29, p = 0.03). We did not observe any interaction between the genetic risk score or any of the other SNPs and the omega-3 index. Our results suggest that omega-3 fatty acid intake may modify the genetic risk conferred by chromosome 9p21 variation in the development of early onset ACS and requires independent replication. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. The Effects of Coping Therapy on General Health of Pregnant Women with High Risk of Genetics Abnormalities in their Fetus

    Directory of Open Access Journals (Sweden)

    F Nazmiye

    2016-11-01

    Full Text Available Introduction: The physiological changes in pregnancy lead to the psychological pressures. Therefore, there is a need for applying cognitive behavioral and emotional confronting to encounter these problems. The present research investigated the effect of coping therapy on general health of pregnant women with high risk of genetic abnormalities in their fetus. Methods: The present study was a semi experimental research. Pre and post tests were used to investigate coping therapy between 30 pregnant women who were referred to Khatomolanbia Genetic Clinic, Yazd, Iran. All the women had pregnancy screening test with high risk of genetics abnormalities in their fetus. They were divided randomly into two groups of case and controls. The test of GHQ was performed in both groups, then the case groups went under 8 sessions of teaching coping therapy each lasting 120 min. After finishing the sessions, post test was performed and analyzing the data using descriptive statistical index and covariance analysis test. Results: Teaching coping therapy to case group caused improvement in their GHQ mark, and this change was significantly different from the change in the GHQ mark of control group. In addition, there was a significant decrease in anxiety, depression and physical signs and an improvement of social function in case group compare to the control group. Discussion: Teaching coping therapy can improve the general health of pregnant women with high risk of genetic abnormalities in their fetus. Therefore, presenting educational courses to the women can improve their general health indices in addition to preventing the probable effects of stress on fetus.

  7. Belief and disbelief in the existence of genetic risk factors for suicide: cross-cultural comparisons.

    Science.gov (United States)

    Voracek, Martin

    2007-12-01

    There is evidence for widespread disbelief in the genetics of suicide, despite recent research progress in this area and convergent evidence supporting a role for genetic factors. This study analyzed the beliefs held in 8 samples (total N = 1224) of various types (psychology, medical, and various undergraduates, psychology graduates, and the general population) from 6 countries located on 3 continents (Austria, Canada, Malaysia, Romania, United Kingdom, and the USA). Endorsement rates for the existence of genetic risk factors for suicide ranged from 26% and 30% (Austrian psychology undergraduates and general population) to around 50% (psychology undergraduates in the USA and United Kingdom). In the 8 samples, respondents' sex, age, religiosity, political orientation, and other demographic variables were, for the most part, unrelated, but overall knowledge about suicide throughout was related positively to endorsement rates. Consistent with previous research, across a considerable variety of sample types and cultural settings there was no evidence for a clear majority believing in genetic bases for suicide.

  8. Genetic variants demonstrating flip-flop phenomenon and breast cancer risk prediction among women of African ancestry.

    Science.gov (United States)

    Wang, Shengfeng; Qian, Frank; Zheng, Yonglan; Ogundiran, Temidayo; Ojengbede, Oladosu; Zheng, Wei; Blot, William; Nathanson, Katherine L; Hennis, Anselm; Nemesure, Barbara; Ambs, Stefan; Olopade, Olufunmilayo I; Huo, Dezheng

    2018-04-01

    Few studies have evaluated the performance of existing breast cancer risk prediction models among women of African ancestry. In replication studies of genetic variants, a change in direction of the risk association is a common phenomenon. Termed flip-flop, it means that a variant is risk factor in one population but protective in another, affecting the performance of risk prediction models. We used data from the genome-wide association study (GWAS) of breast cancer in the African diaspora (The Root consortium), which included 3686 participants of African ancestry from Nigeria, USA, and Barbados. Polygenic risk scores (PRSs) were constructed from the published odds ratios (ORs) of four sets of susceptibility loci for breast cancer. Discrimination capacity was measured using the area under the receiver operating characteristic curve (AUC). Flip-flop phenomenon was observed among 30~40% of variants across studies. Using the 34 variants with consistent directionality among previous studies, we constructed a PRS with AUC of 0.531 (95% confidence interval [CI]: 0.512-0.550), which is similar to the PRS using 93 variants and ORs from European ancestry populations (AUC = 0.525, 95% CI: 0.506-0.544). Additionally, we found the 34-variant PRS has good discriminative accuracy in women with family history of breast cancer (AUC = 0.586, 95% CI: 0.532-0.640). We found that PRS based on variants identified from prior GWASs conducted in women of European and Asian ancestries did not provide a comparable degree of risk stratification for women of African ancestry. Further large-scale fine-mapping studies in African ancestry populations are desirable to discover population-specific genetic risk variants.

  9. Does educational attainment shape reactions to genetic risk for Alzheimer's disease? Results from a national survey experiment.

    Science.gov (United States)

    Andersson, Matthew A; Gadarian, Shana Kushner; Almeling, Rene

    2017-05-01

    While higher education is associated with healthy lifestyles and health literacy, it remains unclear whether education shapes reactions to varying levels of genetic risk for Alzheimer's disease (AD). In this study, participants (N = 701) in the National Genetic Risk Survey Experiment (NGRISE) received a hypothetical genetic risk assessment for AD (ranging from 20 to 80% lifetime risk) and then completed items on their cognitive (perceived threat to health), emotional (general negative affect), and anticipated behavioral (seek information, improve health behaviors, engage in public or private civic action) reactions to this risk. Individuals with a college education showed reactions to increasing genetic risk approximately twice or several times as strong relative to those of individuals with lower (high school, HS) education. In fact, behavioral reactions do not significantly increase with AD risk among those with HS education. Some educational differences in risk response widen at older ages. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Reaching high-risk underserved individuals for cancer genetic counseling by video-teleconferencing.

    Science.gov (United States)

    Mette, Lindsey A; Saldívar, Anna Maria Pulido; Poullard, Natalie E; Torres, Ivette C; Seth, Sarah G; Pollock, Brad H; Tomlinson, Gail E

    2016-04-01

    Breast and colorectal cancers are common cancers for which genetic risk assessment and counseling are available. However, these services are often limited to metropolitan areas and are not readily accessible to underserved populations. Moreover, ethnic and racial disparities present additional obstacles to identifying and screening high-risk individuals and have a bearing on treatment outcomes. To provide cancer genetic risk assessment and counseling through telemedicine to the remote, underserved primarily Hispanic population of the Texas-Mexico border region. Program participants were mailed a questionnaire to assess their satisfaction with the program so that we could determine the acceptability of video-teleconferencing for cancer risk assessment. The overall level of satisfaction with the program was very high, demonstrating the acceptability of a cancer genetic risk assessment program that relied on telemedicine to reach and underserved minority community. Delivery model requires the availability of and access to communication technologies; trained staff are needed at remote sites for sample collection and patient handling. Video-teleconferencing is an acceptable method of providing cancer risk assessment in a remote, underserved population. ©2016 Frontline Medical Communications.

  11. Epigenomic strategies at the interface of genetic and environmental risk factors for autism.

    Science.gov (United States)

    LaSalle, Janine M

    2013-07-01

    Autism spectrum disorders (ASD) have been increasing in prevalence over the last two decades, primarily because of increased awareness and diagnosis. However, autism is clearly a complex human genetic disorder that involves interactions between genes and environment. Epigenetic mechanisms, such as DNA methylation, act at the interface of genetic and environmental risk and protective factors. Advancements in genome-wide sequencing has broadened the view of the human methylome and revealed the organization of the human genome into large-scale methylation domains that footprint over neurologically important genes involved in embryonic development. Future integrative epigenomic analyses of genetic risk factors with environmental exposures and methylome analyses are expected to be important for understanding the complex etiology of ASD.

  12. Unfolding an under-determined neutron spectrum using genetic algorithm based Monte Carlo

    International Nuclear Information System (INIS)

    Suman, V.; Sarkar, P.K.

    2011-01-01

    Spallation in addition to the other photon-neutron reactions in target materials and different components in accelerators may result in production of huge amount of energetic protons which further leads to the production of neutron and contributes to the main component of the total dose. For dosimetric purposes in accelerator facilities the detector measurements doesn't provide directly the actual neutron flux values but a cumulative picture. To obtain Neutron spectrum from the measured data, response functions of the measuring instrument together with the measurements are used into many unfolding techniques which are frequently used for unfolding the hidden spectral information. Here we discuss a genetic algorithm based unfolding technique which is in the process of development. Genetic Algorithm is a stochastic method based on natural selection, which mimics Darwinian theory of survival of the best. The above said method has been tested to unfold the neutron spectra obtained from a reaction carried out at an accelerator facility, with energetic carbon ions on thick silver target along with its respective neutron response of BC501A liquid scintillation detector. The problem dealt here is under-determined where the number of measurements is less than the required energy bin information. The results so obtained were compared with those obtained using the established unfolding code FERDOR, which unfolds data for completely determined problems. It is seen that the genetic algorithm based solution has a reasonable match with the results of FERDOR, when smoothening carried out by Monte Carlo is taken into consideration. This method appears to be a promising candidate for unfolding neutron spectrum in cases of under-determined and over-determined, where measurements are more. The method also has advantages of flexibility, computational simplicity and works well without need of any initial guess spectrum. (author)

  13. The structure of genetic and environmental risk factors for fears and phobias

    Science.gov (United States)

    Loken, E. K.; Hettema, J.M.; Aggen, S.H.; Kendler, K. S.

    2014-01-01

    Background Although prior genetic studies of interview-assessed fears and phobias have shown that genetic factors predispose individuals to fears and phobias, they have been restricted to the DSM-III to DSM-IV aggregated subtypes of phobias rather than to individual fearful and phobic stimuli. Method We examined the lifetime history of fears and/or phobias in response to 21 individual phobic stimuli in 4067 personally interviewed twins from same-sex pairs from the Virginia Adult Twin Study of Psychiatric and Substance Abuse Disorders (VATSPSUD). We performed multivariate statistical analyses using Mx and Mplus. Results The best-fitting model for the 21 phobic stimuli included four genetic factors (agora-social-acrophobia, animal phobia, blood-injection-illness phobia and claustrophobia) and three environmental factors (agora-social-hospital phobia, animal phobia, and situational phobia). Conclusions This study provides the first view of the architecture of genetic and environmental risk factors for phobic disorders and their subtypes. The genetic factors of the phobias support the DSM-IV and DSM-5 constructs of animal and blood-injection-injury phobias but do not support the separation of agoraphobia from social phobia. The results also do not show a coherent genetic factor for the DSM-IV and DSM-5 situational phobia. Finally, the patterns of co-morbidity across individual fears and phobias produced by genetic and environmental influences differ appreciably. PMID:24384457

  14. The structure of genetic and environmental risk factors for fears and phobias.

    Science.gov (United States)

    Loken, E K; Hettema, J M; Aggen, S H; Kendler, K S

    2014-08-01

    Although prior genetic studies of interview-assessed fears and phobias have shown that genetic factors predispose individuals to fears and phobias, they have been restricted to the DSM-III to DSM-IV aggregated subtypes of phobias rather than to individual fearful and phobic stimuli. We examined the lifetime history of fears and/or phobias in response to 21 individual phobic stimuli in 4067 personally interviewed twins from same-sex pairs from the Virginia Adult Twin Study of Psychiatric and Substance Abuse Disorders (VATSPSUD). We performed multivariate statistical analyses using Mx and Mplus. The best-fitting model for the 21 phobic stimuli included four genetic factors (agora-social-acrophobia, animal phobia, blood-injection-illness phobia and claustrophobia) and three environmental factors (agora-social-hospital phobia, animal phobia, and situational phobia). This study provides the first view of the architecture of genetic and environmental risk factors for phobic disorders and their subtypes. The genetic factors of the phobias support the DSM-IV and DSM-5 constructs of animal and blood-injection-injury phobias but do not support the separation of agoraphobia from social phobia. The results also do not show a coherent genetic factor for the DSM-IV and DSM-5 situational phobia. Finally, the patterns of co-morbidity across individual fears and phobias produced by genetic and environmental influences differ appreciably.

  15. Genetic liability, prenatal health, stress and family environment: risk factors in the Harvard Adolescent Family High Risk for schizophrenia study.

    Science.gov (United States)

    Walder, Deborah J; Faraone, Stephen V; Glatt, Stephen J; Tsuang, Ming T; Seidman, Larry J

    2014-08-01

    The familial ("genetic") high-risk (FHR) paradigm enables assessment of individuals at risk for schizophrenia based on a positive family history of schizophrenia in first-degree, biological relatives. This strategy presumes genetic transmission of abnormal traits given high heritability of the illness. It is plausible, however, that adverse environmental factors are also transmitted in these families. Few studies have evaluated both biological and environmental factors within a FHR study of adolescents. We conceptualize four precursors to psychosis pathogenesis: two biological (genetic predisposition, prenatal health issues (PHIs)) and two environmental (family environment, stressful life events (SLEs)). Participants assessed between 1998 and 2007 (ages 13-25) included 40 (20F/20M) adolescents at FHR for schizophrenia (FHRs) and 55 (31F/24M) community controls. 'Genetic load' indexed number of affected family members relative to pedigree size. PHI was significantly greater among FHRs, and family cohesion and expressiveness were less (and family conflict was higher) among FHRs; however, groups did not significantly differ in SLE indices. Among FHRs, genetic liability was significantly associated with PHI and family expressiveness. Prenatal and family environmental disruptions are elevated in families with a first-degree relative with schizophrenia. Findings support our proposed 'polygenic neurodevelopmental diathesis-stress model' whereby psychosis susceptibility (and resilience) involves the independent and synergistic confluence of (temporally-sensitive) biological and environmental factors across development. Recognition of biological and social environmental influences across critical developmental periods points to key issues relevant for enhanced identification of psychosis susceptibility, facilitation of more precise models of illness risk, and development of novel prevention strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Sugarcane production under smallholder farming systems: Farmers preferred traits, constraints and genetic resources

    Directory of Open Access Journals (Sweden)

    Esayas Tena

    2016-05-01

    Full Text Available Smallholder sugarcane production sector is under researched and underdeveloped with limited industrial link and support. The objectives of this study were to assess the current state of sugarcane production, farmers’ perceived production constraints and preferred traits, and to collect germplasm grown by smallholder farmers in southern Ethiopia for strategic breeding and conservation. The study was conducted across 16 administrative zones, 28 districts and 56 peasant associations involving 560 smallholder sugarcane growers in southern Ethiopia using a participatory rural appraisal (PRA approach. Sugarcane genetic resources were collected through structured sampling. Findings from this study indicated that monocropping was identified as the predominant sugarcane farming system. Respondent farmers prioritized drought tolerance (21%, increased cane yield (20%, early maturity (18%, marketability (17%, and high biomass (14% as the top preferred traits of sugarcane. Ninety diverse sugarcane landraces were collected from homesteads of smallholder farmers. Findings from this study would serve as baseline information towards sugarcane research and development emphasising the constraints and preferences of smallholder sugarcane growers in Ethiopia or similar agro-ecologies. This is the first study to report farmers preferred traits and constraints, and genetic resources of sugarcane under smallholder farming systems in Ethiopia.

  17. The association of XRCC3 Thr241Met genetic variant with risk of ...

    African Journals Online (AJOL)

    Background: Previous studies suggest that the X-ray repair cross-complementing group 3 gene (XRCC3) Thr241Met genetic variant could be potentially associated with the risk of prostate cancer. However, results from these published studies were conflicting rather than conclusive. Objectives:This meta-analysis aimed to ...

  18. Rhinovirus Wheezing Illness and Genetic Risk of Childhood-Onset Asthma

    DEFF Research Database (Denmark)

    Calışkan, Minal; Bochkov, Yury A; Kreiner-Møller, Eskil

    2013-01-01

    Background Both genetic variation at the 17q21 locus and virus-induced respiratory wheezing illnesses are associated with the development of asthma. Our aim was to determine the effects of these two factors on the risk of asthma in the Childhood Origins of Asthma (COAST) and the Copenhagen Prospe...

  19. The assessment of genetic risk of breast cancer : a set of GP guidelines

    NARCIS (Netherlands)

    de Bock, GH; Vlieland, TPMV; Hageman, GCHA; Oosterwijk, JC; Springer, MP; Kievit, J

    Background. Assessing a genetic risk for developing breast cancer is not an easy task for a GP. Current expert guidelines for referring and counselling women with a family history positive for breast cancer are complex and difficult to apply in general practice, and have only two strategies (to

  20. Genetic, behavioral, and sociodemographic risk factors for second eye progression in age-related macular degeneration

    NARCIS (Netherlands)

    Lechanteur, Y.T.; van de Ven, J.P.; Smailhodzic, D.; Boon, C.J.F.; Klevering, B.J.; Fauser, S.; Groenewoud, J.M.; Wilt, G.J. van der; Hollander, A.I. den; Hoyng, C.B.

    2012-01-01

    PURPOSE: This study was conducted to investigate the correlation of genetic, sociodemographic, and behavioral risk factors with second eye progression to end-stage AMD. METHODS: One hundred and eight patients with end-stage AMD in one or both eyes were included in a retrospective time-to-event

  1. Sudden infant death syndrome, childhood thrombosis, and presence of genetic risk factors for thrombosis

    DEFF Research Database (Denmark)

    Larsen, TB; Nørgaard-Pedersen, B; Lundemose, JB

    2000-01-01

    . The vulnerability of the infant brain stem to ischemia has been suggested to be a conceivable cause of sudden infant death syndrome. This is compatible with a hypothesis that genetic risk factors for cerebral thrombosis could cause microinfarction in the brain stem during the first month of life, affecting vital...

  2. Molecular genetic features and risk assessment in a series of 30 ...

    African Journals Online (AJOL)

    Background: The objective of the study was to investigate the relationship between molecular genetic features and the standard criteria of risk assessment in patients affected by gastrointestinal stromal tumours (GISTs). Methods: A review was conducted of a series of 30 patients, with a mean age of 67 years, who underwent ...

  3. Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer

    DEFF Research Database (Denmark)

    Nimptsch, Katharina; Song, Mingyang; Aleksandrova, Krasimira

    2017-01-01

    analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable...

  4. Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

    NARCIS (Netherlands)

    S. Reppe (Sjur); Y. Wang (Yunpeng); W.K. Thompson (Wesley K.); L.K. McEvoy (Linda K.); N.J. Schork (Nicholas); V. Zuber (Verena); M. Leblanc (Marissa); F. Bettella (Francesco); I.G. Mills (Ian G.); R.S. Desikan (Rahul S.); S. Djurovic (Srdjan); K.M. Gautvik (Kaare); A.M. Dale (Anders); O.A. Andreassen (Ole); K. Estrada Gil (Karol); U. Styrkarsdottir (Unnur); E. Evangelou (Evangelos); Y.-H. Hsu (Yi-Hsiang); E.L. Duncan (Emma); E.E. Ntzani (Evangelia); L. Oei (Ling); O.M.E. Albagha (Omar M.); N. Amin (Najaf); J.P. Kemp (John); D.L. Koller (Daniel); G. Li (Guo); C.-T. Liu (Ching-Ti); R.L. Minster (Ryan); A. Moayyeri (Alireza); L. Vandenput (Liesbeth); D. Willner (Dana); S.-M. Xiao (Su-Mei); L.M. Yerges-Armstrong (Laura); H.-F. Zheng (Hou-Feng); N. Alonso (Nerea); J. Eriksson (Joel); C.M. Kammerer (Candace); S. Kaptoge (Stephen); P.J. Leo (Paul); G. Thorleifsson (Gudmar); S.G. Wilson (Scott); J.F. Wilson (James F); V. Aalto (Ville); M. Alen (Markku); A.K. Aragaki (Aaron); T. Aspelund (Thor); J.R. Center (Jacqueline); Z. Dailiana (Zoe); C. Duggan; M. Garcia (Melissa); N. Garcia-Giralt (Natàlia); S. Giroux (Sylvie); G. Hallmans (Göran); L.J. Hocking (Lynne); L.B. Husted (Lise Bjerre); K. Jameson (Karen); R. Khusainova (Rita); G.S. Kim (Ghi Su); C. Kooperberg (Charles); T. Koromila (Theodora); M. Kruk (Marcin); M. Laaksonen (Marika); A.Z. Lacroix (Andrea Z.); S.H. Lee (Seung Hun); P.C. Leung (Ping C.); J.R. Lewis (Joshua); L. Masi (Laura); S. Mencej-Bedrac (Simona); T.V. Nguyen (Tuan); X. Nogues (Xavier); M.S. Patel (Millan); J. Prezelj (Janez); L.M. Rose (Lynda); S. Scollen (Serena); K. Siggeirsdottir (Kristin); G.D. Smith; O. Svensson (Olle); S. Trompet (Stella); O. Trummer (Olivia); N.M. van Schoor (Natasja); J. Woo (Jean); K. Zhu (Kun); S. Balcells (Susana); M.L. Brandi; B.M. Buckley (Brendan M.); S. Cheng (Sulin); C. Christiansen; C. Cooper (Charles); G.V. Dedoussis (George); I. Ford (Ian); M. Frost (Morten); D. Goltzman (David); J. González-Macías (Jesús); M. Kähönen (Mika); M. Karlsson (Magnus); E.K. Khusnutdinova (Elza); J.-M. Koh (Jung-Min); P. Kollia (Panagoula); B.L. Langdahl (Bente); W.D. Leslie (William D.); P. Lips (Paul); O. Ljunggren (Östen); R. Lorenc (Roman); J. Marc (Janja); D. Mellström (Dan); B. Obermayer-Pietsch (Barbara); D. Olmos (David); U. Pettersson-Kymmer (Ulrika); D.M. Reid (David); J.A. Riancho (José); P.M. Ridker (Paul); M.F. Rousseau (Francois); P.E. Slagboom (Eline); N.L.S. Tang (Nelson L.S.); R. Urreizti (Roser); W. Van Hul (Wim); J. Viikari (Jorma); M.T. Zarrabeitia (María); Y.S. Aulchenko (Yurii); M.C. Castaño Betancourt (Martha); E. Grundberg (Elin); L. Herrera (Lizbeth); T. Ingvarsson (Torvaldur); H. Johannsdottir (Hrefna); T. Kwan (Tony); R. Li (Rui); R.N. Luben (Robert); M.C. Medina-Gomez (Carolina); S.T. Palsson (Stefan Th); J.I. Rotter (Jerome I.); G. Sigurdsson (Gunnar); J.B.J. van Meurs (Joyce); D.J. Verlaan (Dominique); F.M. Williams (Frances); A.R. Wood (Andrew); Y. Zhou (Yanhua); T. Pastinen (Tomi); S. Raychaudhuri (Soumya); J.A. Cauley (Jane); D.I. Chasman (Daniel); G.R. Clark (Graeme); S.R. Cummings (Steven R.); P. Danoy (Patrick); E.M. Dennison (Elaine); R. Eastell (Richard); J.A. Eisman (John); V. Gudnason (Vilmundur); A. Hofman (Albert); R.D. Jackson (Rebecca); G. Jones (Graeme); J.W. Jukema (Jan Wouter); K.T. Khaw; T. Lehtimäki (Terho); Y. Liu (YongMei); M. Lorentzon (Mattias); E. McCloskey (Eugene); B.D. Mitchell (Braxton); K. Nandakumar (Kannabiran); G.C. Nicholson (Geoffrey); B.A. Oostra (Ben); M. Peacock (Munro); H.A.P. Pols (Huib); R.L. Prince (Richard); O. Raitakari (Olli); I.R. Reid (Ian); J. Robbins (John); P.N. Sambrook (Philip); P.C. Sham (Pak Chung); A.R. Shuldiner (Alan); F.A. Tylavsky (Frances); C.M. van Duijn (Cornelia); N.J. Wareham (Nicholas J.); L.A. Cupples (Adrienne); M.J. Econs (Michael); D.M. Evans (David); T.B. Harris (Tamara B.); A.W.C. Kung (Annie Wai Chee); B.M. Psaty (Bruce); J. Reeve (Jonathan); T.D. Spector (Timothy); E.A. Streeten (Elizabeth); M.C. Zillikens (Carola); U. Thorsteinsdottir (Unnur); C. Ohlsson (Claes); D. Karasik (David); J.B. Richards (Brent); M.A. Brown (Matthew); J-A. Zwart (John-Anker); A.G. Uitterlinden (André); S.H. Ralston (Stuart); J.P.A. Ioannidis (John P.A.); D.P. Kiel (Douglas P.); F. Rivadeneira Ramirez (Fernando)

    2015-01-01

    textabstractBone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown.

  5. An Underlying Common Factor, Influenced by Genetics and Unique Environment, Explains the Covariation Between Major Depressive Disorder, Generalized Anxiety Disorder, and Burnout: A Swedish Twin Study.

    Science.gov (United States)

    Mather, Lisa; Blom, Victoria; Bergström, Gunnar; Svedberg, Pia

    2016-12-01

    Depression and anxiety are highly comorbid due to shared genetic risk factors, but less is known about whether burnout shares these risk factors. We aimed to examine whether the covariation between major depressive disorder (MDD), generalized anxiety disorder (GAD), and burnout is explained by common genetic and/or environmental factors. This cross-sectional study included 25,378 Swedish twins responding to a survey in 2005-2006. Structural equation models were used to analyze whether the trait variances and covariances were due to additive genetics, non-additive genetics, shared environment, and unique environment. Univariate analyses tested sex limitation models and multivariate analysis tested Cholesky, independent pathway, and common pathway models. The phenotypic correlations were 0.71 (0.69-0.74) between MDD and GAD, 0.58 (0.56-0.60) between MDD and burnout, and 0.53 (0.50-0.56) between GAD and burnout. Heritabilities were 45% for MDD, 49% for GAD, and 38% for burnout; no statistically significant sex differences were found. A common pathway model was chosen as the final model. The common factor was influenced by genetics (58%) and unique environment (42%), and explained 77% of the variation in MDD, 69% in GAD, and 44% in burnout. GAD and burnout had additive genetic factors unique to the phenotypes (11% each), while MDD did not. Unique environment explained 23% of the variability in MDD, 20% in GAD, and 45% in burnout. In conclusion, the covariation was explained by an underlying common factor, largely influenced by genetics. Burnout was to a large degree influenced by unique environmental factors not shared with MDD and GAD.

  6. Autism risk assessment in siblings of affected children using sex-specific genetic scores

    Directory of Open Access Journals (Sweden)

    Carayol Jerome

    2011-10-01

    Full Text Available Abstract Background The inheritance pattern in most cases of autism is complex. The risk of autism is increased in siblings of children with autism and previous studies have indicated that the level of risk can be further identified by the accumulation of multiple susceptibility single nucleotide polymorphisms (SNPs allowing for the identification of a higher-risk subgroup among siblings. As a result of the sex difference in the prevalence of autism, we explored the potential for identifying sex-specific autism susceptibility SNPs in siblings of children with autism and the ability to develop a sex-specific risk assessment genetic scoring system. Methods SNPs were chosen from genes known to be associated with autism. These markers were evaluated using an exploratory sample of 480 families from the Autism Genetic Resource Exchange (AGRE repository. A reproducibility index (RI was proposed and calculated in all children with autism and in males and females separately. Differing genetic scoring models were then constructed to develop a sex-specific genetic score model designed to identify individuals with a higher risk of autism. The ability of the genetic scores to identify high-risk children was then evaluated and replicated in an independent sample of 351 affected and 90 unaffected siblings from families with at least 1 child with autism. Results We identified three risk SNPs that had a high RI in males, two SNPs with a high RI in females, and three SNPs with a high RI in both sexes. Using these results, genetic scoring models for males and females were developed which demonstrated a significant association with autism (P = 2.2 × 10-6 and 1.9 × 10-5, respectively. Conclusions Our results demonstrate that individual susceptibility associated SNPs for autism may have important differential sex effects. We also show that a sex-specific risk score based on the presence of multiple susceptibility associated SNPs allow for the identification of

  7. The discourse around usefulness, morality, risk and trust: a focus group study on prenatal genetic testing.

    Science.gov (United States)

    Pivetti, Monica; Montali, Lorenzo; Simonetti, Giorgia

    2012-12-01

    This study explores the underlying values and beliefs that guide women's reasoning on prenatal genetic test (PGT) uptake, as framed by their own words, during a group discussion, in a Catholic country such as Italy. Women's reasoning was explored by means of five focus group consisting of seven pregnant women and 13 new mothers. The focus group material content was analysed using the Nudist software. The discourse around PGT was rooted into four frames of reference: The usefulness dimension was used to express the positions in favour of PGT, whereas morality, risk and trust were used to express negative evaluations on such a technology. Participants advocated for themselves the choice of being tested, besides giving some credit to the partner's opinion. Moreover, participants reported little knowledge on PGT. The research shed some light on the frames of reference used by participants to build their positions on PGT uptake, confirming the public's ability to translate scientific accounts into personally meaningful information. A more complete understanding of the reasons for decisions to test would help counsellors to better communicate with women and couples, and to better assist them to make a better informed testing decision. © 2012 John Wiley & Sons, Ltd.

  8. Children's risk and resilience following a natural disaster: genetic vulnerability, posttraumatic stress, and depression.

    Science.gov (United States)

    La Greca, Annette M; Lai, Betty S; Joormann, Jutta; Auslander, Beth B; Short, Mary A

    2013-12-01

    We examined children's risk and resilience following a natural disaster, evaluating the role of stress, social support, and two genetic markers: the short allele of the serotonin transporter gene (5-HTTLPR), and the met allele of the Brain-Derived Neurotrophic Factor (BDNF).Under high levels of hurricane exposure or hurricane-related stressors, we expected children displaying the markers would report greater symptoms of posttraumatic stress disorder (PTSD) and depression than children without these markers. Social support was explored as an additional moderating variable. Eight months after Hurricane Ike, 116 children (M age=8.85 years, SD=.89; 54% girls) residing in Galveston, Texas, provided saliva samples and completed measures of hurricane exposure and stress, and symptoms of PTSD and depression; 80 also completed a social support measure. For BDNF, analyses revealed several Gene by Environment interactions; greater stress was related to more symptoms of PTSD and depression, and this effect was stronger for children with the met allele. No findings emerged for 5-HTTLPR. Stressors and social support also were associated with children's PTSD and depressive symptoms. Findings should be tempered by the relatively small sample, especially for analysis that included social support. The met allele (BDNF) may play a role in children's disaster reactions. Further research should consider the complex interplay between genes, stressors, support, and psychological outcomes over time. © 2013 Elsevier B.V. All rights reserved.

  9. The genetic landscape of high-risk neuroblastoma.

    Science.gov (United States)

    Pugh, Trevor J; Morozova, Olena; Attiyeh, Edward F; Asgharzadeh, Shahab; Wei, Jun S; Auclair, Daniel; Carter, Scott L; Cibulskis, Kristian; Hanna, Megan; Kiezun, Adam; Kim, Jaegil; Lawrence, Michael S; Lichenstein, Lee; McKenna, Aaron; Pedamallu, Chandra Sekhar; Ramos, Alex H; Shefler, Erica; Sivachenko, Andrey; Sougnez, Carrie; Stewart, Chip; Ally, Adrian; Birol, Inanc; Chiu, Readman; Corbett, Richard D; Hirst, Martin; Jackman, Shaun D; Kamoh, Baljit; Khodabakshi, Alireza Hadj; Krzywinski, Martin; Lo, Allan; Moore, Richard A; Mungall, Karen L; Qian, Jenny; Tam, Angela; Thiessen, Nina; Zhao, Yongjun; Cole, Kristina A; Diamond, Maura; Diskin, Sharon J; Mosse, Yael P; Wood, Andrew C; Ji, Lingyun; Sposto, Richard; Badgett, Thomas; London, Wendy B; Moyer, Yvonne; Gastier-Foster, Julie M; Smith, Malcolm A; Guidry Auvil, Jaime M; Gerhard, Daniela S; Hogarty, Michael D; Jones, Steven J M; Lander, Eric S; Gabriel, Stacey B; Getz, Gad; Seeger, Robert C; Khan, Javed; Marra, Marco A; Meyerson, Matthew; Maris, John M

    2013-03-01

    Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 affected individuals (cases) using a combination of whole-exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per Mb (0.48 nonsilent) and notably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, and an additional 7.1% had focal deletions), MYCN (1.7%, causing a recurrent p.Pro44Leu alteration) and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1 and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies that rely on frequently altered oncogenic drivers.

  10. The genetic landscape of high-risk neuroblastoma

    Science.gov (United States)

    Pugh, Trevor J.; Morozova, Olena; Attiyeh, Edward F.; Asgharzadeh, Shahab; Wei, Jun S.; Auclair, Daniel; Carter, Scott L.; Cibulskis, Kristian; Hanna, Megan; Kiezun, Adam; Kim, Jaegil; Lawrence, Michael S.; Lichenstein, Lee; McKenna, Aaron; Pedamallu, Chandra Sekhar; Ramos, Alex H.; Shefler, Erica; Sivachenko, Andrey; Sougnez, Carrie; Stewart, Chip; Ally, Adrian; Birol, Inanc; Chiu, Readman; Corbett, Richard D.; Hirst, Martin; Jackman, Shaun D.; Kamoh, Baljit; Khodabakshi, Alireza Hadj; Krzywinski, Martin; Lo, Allan; Moore, Richard A.; Mungall, Karen L.; Qian, Jenny; Tam, Angela; Thiessen, Nina; Zhao, Yongjun; Cole, Kristina A.; Diamond, Maura; Diskin, Sharon J.; Mosse, Yael P.; Wood, Andrew C.; Ji, Lingyun; Sposto, Richard; Badgett, Thomas; London, Wendy B.; Moyer, Yvonne; Gastier-Foster, Julie M.; Smith, Malcolm A.; Auvil, Jaime M. Guidry; Gerhard, Daniela S.; Hogarty, Michael D.; Jones, Steven J. M.; Lander, Eric S.; Gabriel, Stacey B.; Getz, Gad; Seeger, Robert C.; Khan, Javed; Marra, Marco A.; Meyerson, Matthew; Maris, John M.

    2013-01-01

    Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%1. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 cases using a combination of whole exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per megabase (0.48 non-silent), and remarkably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, an additional 7.1% had focal deletions), MYCN (1.7%, a recurrent p.Pro44Leu alteration), and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1, and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies reliant upon frequently altered oncogenic drivers. PMID:23334666

  11. ANTHOCYANIN PIGMENTATION IN TRITICUM AESTIVUM L.: GENETIC BASIS AND ROLE UNDER ABIOTIC STRESS CONDITIONS

    Directory of Open Access Journals (Sweden)

    Tereshchenko O.Yu.

    2012-08-01

    Full Text Available Anthocyanins are secondary metabolites of plants. They have a wide range of biological activity such as antioxidant, photoprotection, osmoregulation, heavy metal ions chelation, antimicrobial and antifungal activities, which help plants to survive under different stress conditions. Bread wheat (T. aestivum L. can have purple pigmentation provided by anthocyanin compounds in different organs, such as grain pericarp, coleoptile, culm, leaf blades, leaf sheaths, glumes and anthers. However, the genetic mechanisms underlying formation of these traits as well as contribution of the pigmentation to stress tolerance have not been widely studied in wheat. The aim of the current study was to investigate molecular-genetic mechanisms underlying anthocyanin pigmentation in different wheat organs and to estimate the role of the pigmentation under different abiotic stress conditions in wheat seedlings. In the current study, near-isogenic lines (NILs: cv. ‘Saratovskaya 29’ (‘S29’ and lines i:S29Pp1Pp2PF and i:S29Pp1Pp3P developed on the ‘S29’ background but having grain pericarp coloration (genes Pp and more intense coleoptile (Rc, culm (Pc, leaf blade (Plb, leaf sheath (Pls pigmentation in comparison with ‘S29’, were used. Comparative transcriptional analysis of the five structural genes Chs, Chi, F3h, Dfr, Ans, encoding enzymes participating in the anthocyanin biosynthesis, was performed in different organs of NILs. It was shown that the presence of the Rc, Pc, Plb, Pls and Pp alleles conferring strong anthocyanin pigmentation induced more intense transcription of the structural genes, suggesting the genes Rc, Pc, Plb, Pls and Pp to play a regulatory role in anthocyanin biosynthesis network. To evaluate the role of anthocyanins in stress response at the seedling stage, growth ability of the NILs and anthocyanin content in their coleoptiles were assessed after treatments with NaCl (100 and 200 mM, CdCl2 (25 and 50 μM and 15% PEG 6000

  12. Risk of genetic maladaptation due to climate change in three major European tree species.

    Science.gov (United States)

    Frank, Aline; Howe, Glenn T; Sperisen, Christoph; Brang, Peter; Clair, J Bradley St; Schmatz, Dirk R; Heiri, Caroline

    2017-12-01

    Tree populations usually show adaptations to their local environments as a result of natural selection. As climates change, populations can become locally maladapted and decline in fitness. Evaluating the expected degree of genetic maladaptation due to climate change will allow forest managers to assess forest vulnerability, and develop strategies to preserve forest health and productivity. We studied potential genetic maladaptation to future climates in three major European tree species, Norway spruce (Picea abies), silver fir (Abies alba), and European beech (Fagus sylvatica). A common garden experiment was conducted to evaluate the quantitative genetic variation in growth and phenology of seedlings from 77 to 92 native populations of each species from across Switzerland. We used multivariate genecological models to associate population variation with past seed source climates, and to estimate relative risk of maladaptation to current and future climates based on key phenotypic traits and three regional climate projections within the A1B scenario. Current risks from climate change were similar to average risks from current seed transfer practices. For all three climate models, future risks increased in spruce and beech until the end of the century, but remained low in fir. Largest average risks associated with climate projections for the period 2061-2090 were found for spruce seedling height (0.64), and for beech bud break and leaf senescence (0.52 and 0.46). Future risks for spruce were high across Switzerland. However, areas of high risk were also found in drought-prone regions for beech and in the southern Alps for fir. Genetic maladaptation to future climates is likely to become a problem for spruce and beech by the end of this century, but probably not for fir. Consequently, forest management strategies should be adjusted in the study area for spruce and beech to maintain productive and healthy forests in the future. © 2017 John Wiley & Sons Ltd.

  13. Massively Parallel Genetics.

    Science.gov (United States)

    Shendure, Jay; Fields, Stanley

    2016-06-01

    Human genetics has historically depended on the identification of individuals whose natural genetic variation underlies an observable trait or disease risk. Here we argue that new technologies now augment this historical approach by allowing the use of massively parallel assays in model systems to measure the functional effects of genetic variation in many human genes. These studies will help establish the disease risk of both observed and potential genetic variants and to overcome the problem of "variants of uncertain significance." Copyright © 2016 by the Genetics Society of America.

  14. Genetic Factors Influencing Coagulation Factor XIII B-Subunit Contribute to Risk of Ischemic Stroke.

    Science.gov (United States)

    Hanscombe, Ken B; Traylor, Matthew; Hysi, Pirro G; Bevan, Stephen; Dichgans, Martin; Rothwell, Peter M; Worrall, Bradford B; Seshadri, Sudha; Sudlow, Cathie; Williams, Frances M K; Markus, Hugh S; Lewis, Cathryn M

    2015-08-01

    Abnormal coagulation has been implicated in the pathogenesis of ischemic stroke, but how this association is mediated and whether it differs between ischemic stroke subtypes is unknown. We determined the shared genetic risk between 14 coagulation factors and ischemic stroke and its subtypes. Using genome-wide association study results for 14 coagulation factors from the population-based TwinsUK sample (N≈2000 for each factor), meta-analysis results from the METASTROKE consortium ischemic stroke genome-wide association study (12 389 cases, 62 004 controls), and genotype data for 9520 individuals from the WTCCC2 ischemic stroke study (3548 cases, 5972 controls-the largest METASTROKE subsample), we explored shared genetic risk for coagulation and stroke. We performed three analyses: (1) a test for excess concordance (or discordance) in single nucleotide polymorphism effect direction across coagulation and stroke, (2) an estimation of the joint effect of multiple coagulation-associated single nucleotide polymorphisms in stroke, and (3) an evaluation of common genetic risk between coagulation and stroke. One coagulation factor, factor XIII subunit B (FXIIIB), showed consistent effects in the concordance analysis, the estimation of polygenic risk, and the validation with genotype data, with associations specific to the cardioembolic stroke subtype. Effect directions for FXIIIB-associated single nucleotide polymorphisms were significantly discordant with cardioembolic disease (smallest P=5.7×10(-04)); the joint effect of FXIIIB-associated single nucleotide polymorphisms was significantly predictive of ischemic stroke (smallest P=1.8×10(-04)) and the cardioembolic subtype (smallest P=1.7×10(-04)). We found substantial negative genetic covariation between FXIIIB and ischemic stroke (rG=-0.71, P=0.01) and the cardioembolic subtype (rG=-0.80, P=0.03). Genetic markers associated with low FXIIIB levels increase risk of ischemic stroke cardioembolic subtype. © 2015 The

  15. Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study.

    Science.gov (United States)

    Chittoor, Geetha; Haack, Karin; Mehta, Nitesh R; Laston, Sandra; Cole, Shelley A; Comuzzie, Anthony G; Butte, Nancy F; Voruganti, V Saroja

    2017-01-17

    Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic polymorphisms with renal urate excretion measures. Therefore, we investigated the genetic factors that influence the excretion of uric acid and related indices in 768 Hispanic children of the Viva La Familia Study. We performed a genome-wide association analysis for 24-h urinary excretion measures such as urinary uric acid/urinary creatinine ratio, uric acid clearance, fractional excretion of uric acid, and glomerular load of uric acid in SOLAR, while accounting for non-independence among family members. All renal urate excretion measures were significantly heritable (p uric acid clearance with a single nucleotide polymorphism (SNP) in zinc finger protein 446 (ZNF446) (rs2033711 (A/G), MAF: 0.30). The minor allele (G) was associated with increased uric acid clearance. Also, we found suggestive associations of uric acid clearance with SNPs in ZNF324, ZNF584, and ZNF132 (in a 72 kb region of 19q13; p <1 × 10 -6 , MAFs: 0.28-0.31). For the first time, we showed the importance of 19q13 region in the regulation of renal urate excretion in Hispanic children. Our findings indicate differences in inherent genetic architecture and shared environmental risk factors between our cohort and other pediatric and adult populations.

  16. Genetic regulation of serum phytosterol levels and risk of coronary artery disease.

    Science.gov (United States)

    Teupser, Daniel; Baber, Ronny; Ceglarek, Uta; Scholz, Markus; Illig, Thomas; Gieger, Christian; Holdt, Lesca M; Leichtle, Alexander; Greiser, Karin H; Huster, Dominik; Linsel-Nitschke, Patrick; Schäfer, Arne; Braund, Peter S; Tiret, Laurence; Stark, Klaus; Raaz-Schrauder, Dorette; Fiedler, Georg M; Wilfert, Wolfgang; Beutner, Frank; Gielen, Stephan; Grosshennig, Anika; König, Inke R; Lichtner, Peter; Heid, Iris M; Kluttig, Alexander; El Mokhtari, Nour E; Rubin, Diana; Ekici, Arif B; Reis, André; Garlichs, Christoph D; Hall, Alistair S; Matthes, Gert; Wittekind, Christian; Hengstenberg, Christian; Cambien, Francois; Schreiber, Stefan; Werdan, Karl; Meitinger, Thomas; Loeffler, Markus; Samani, Nilesh J; Erdmann, Jeanette; Wichmann, H-Erich; Schunkert, Heribert; Thiery, Joachim

    2010-08-01

    Phytosterols are plant-derived sterols that are taken up from food and can serve as biomarkers of cholesterol uptake. Serum levels are under tight genetic control. We used a genomic approach to study the molecular regulation of serum phytosterol levels and potential links to coronary artery disease (CAD). A genome-wide association study for serum phytosterols (campesterol, sitosterol, brassicasterol) was conducted in a population-based sample from KORA (Cooperative Research in the Region of Augsburg) (n=1495) with subsequent replication in 2 additional samples (n=1157 and n=1760). Replicated single-nucleotide polymorphisms (SNPs) were tested for association with premature CAD in a metaanalysis of 11 different samples comprising 13 764 CAD cases and 13 630 healthy controls. Genetic variants in the ATP-binding hemitransporter ABCG8 and at the blood group ABO locus were significantly associated with serum phytosterols. Effects in ABCG8 were independently related to SNPs rs4245791 and rs41360247 (combined P=1.6 x 10(-50) and 6.2 x 10(-25), respectively; n=4412). Serum campesterol was elevated 12% for each rs4245791 T-allele. The same allele was associated with 40% decreased hepatic ABCG8 mRNA expression (P=0.009). Effects at the ABO locus were related to SNP rs657152 (combined P=9.4x10(-13)). Alleles of ABCG8 and ABO associated with elevated phytosterol levels displayed significant associations with increased CAD risk (rs4245791 odds ratio, 1.10; 95% CI, 1.06 to 1.14; P=2.2 x 10(-6); rs657152 odds ratio, 1.13; 95% CI, 1.07 to 1.19; P=9.4 x 10(-6)), whereas alleles at ABCG8 associated with reduced phytosterol levels were associated with reduced CAD risk (rs41360247 odds ratio, 0.84; 95% CI, 0.78 to 0.91; P=1.3 x 10(-5)). Common variants in ABCG8 and ABO are strongly associated with serum phytosterol levels and show concordant and previously unknown associations with CAD.

  17. GFC-Robust Risk Management Strategies under the Basel Accord

    NARCIS (Netherlands)

    M.J. McAleer (Michael); J.A. Jiménez-Martín (Juan-Ángel); T. Pérez-Amaral (Teodosio)

    2010-01-01

    textabstractA risk management strategy is proposed as being robust to the Global Financial Crisis (GFC) by selecting a Value-at-Risk (VaR) forecast that combines the forecasts of different VaR models. The robust forecast is based on the median of the point VaR forecasts of a set of conditional

  18. Community risk assessment of rainfall variability under rain-fed ...

    African Journals Online (AJOL)

    However, a nuanced understanding of the perspectives of climate related risks among local populations affected is often lacking and or seldom explored in vulnerability assessments due to the dominance of top-down approaches. This paper explores the potential of Community Risk Assessment (CRA) and local knowledge ...

  19. Energy infrastructure in India: Profile and risks under climate change

    International Nuclear Information System (INIS)

    Garg, Amit; Naswa, Prakriti; Shukla, P.R.

    2015-01-01

    India has committed large investments to energy infrastructure assets-power plants, refineries, energy ports, pipelines, roads, railways, etc. The coastal infrastructure being developed to meet the rising energy imports is vulnerable to climate extremes. This paper provides an overview of climate risks to energy infrastructures in India and details two case studies – a crude oil importing port and a western coast railway transporting coal. The climate vulnerability of the port has been mapped using an index while that of the railway has been done through a damage function for RCP 4.5.0 and 8.5 scenarios. Our analysis shows that risk management through adaptation is likely to be very expensive. The system risks can be even greater and might adversely affect energy security and access objectives. Aligning sustainable development and climate adaptation measures can deliver substantial co-benefits. The key policy recommendations include: i) mandatory vulnerability assessment to future climate risks for energy infrastructures; ii) project and systemic risks in the vulnerability index; iii) adaptation funds for unmitigated climate risks; iv) continuous monitoring of climatic parameters and implementation of adaptation measures, and iv) sustainability actions along energy infrastructures that enhance climate resilience and simultaneously deliver co-benefits to local agents. -- Highlights: •Climate risks to energy infrastructures adversely impact energy security. •Case studies of a port and a railway show their future climate change vulnerability. •Managing climate-induced risks through preventive adaptation policies

  20. Effectiveness of insurance risk management under crisis conditions

    Directory of Open Access Journals (Sweden)

    I.G. Goncharenko

    2015-06-01

    Full Text Available In the article some historical aspects of insurance, domestic trends in insurance risk management with aspects of international experience, the modern role of insurance and insurance companies in a market economy, factors of risk management system and the nature of the insurance portfolio are analyzed. Factors of risk events in insurance, the spectrum of risks, imbalance of the insurance market in crisis conditions are outlined; expert’s estimations of the insurance market in recent years are examined. Problems of insurance business perform are determined, especially insurance risk management. The ability to use the provisions of European insurance regulation on internal domestic insurance market is analyzed, and also the aspects of integration of Ukrainian insurance market are determined.

  1. The Association between Infants' Attention Control and Social Inhibition Is Moderated by Genetic and Environmental Risk for Anxiety

    Science.gov (United States)

    Brooker, Rebecca J.; Neiderhiser, Jenae M.; Kiel, Elizabeth J.; Leve, Leslie D.; Shaw, Daniel S.; Reiss, David

    2011-01-01

    Infant social inhibition is associated with increased risk for anxiety later in life. Although both genetic and environmental factors are associated with anxiety, little empirical work has addressed how developing regulatory abilities work with genetic and environmental risk to exacerbate or mitigate problem behaviors. The current study was aimed…

  2. New developments on the neurobiological and pharmaco-genetic mechanisms underlying internet and videogame addiction.

    Science.gov (United States)

    Weinstein, Aviv; Lejoyeux, Michel

    2015-03-01

    There is emerging evidence that the psychobiological mechanisms underlying behavioral addictions such as internet and videogame addiction resemble those of addiction for substances of abuse. Review of brain imaging, treatment and genetic studies on videogame and internet addiction. Literature search of published articles between 2009 and 2013 in Pubmed using "internet addiction" and "videogame addiction" as the search word. Twenty-nine studies have been selected and evaluated under the criteria of brain imaging, treatment, and genetics. Brain imaging studies of the resting state have shown that long-term internet game playing affected brain regions responsible for reward, impulse control and sensory-motor coordination. Brain activation studies have shown that videogame playing involved changes in reward and loss of control and that gaming pictures have activated regions similarly to those activated by cue-exposure to drugs. Structural studies have shown alterations in the volume of the ventral striatum possible as result of changes in reward. Furthermore, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and that there were faulty inhibitory control and reward mechanisms videogame addicted individuals. Finally, treatment studies using fMRI have shown reduction in craving for videogames and reduced associated brain activity. Videogame playing may be supported by similar neural mechanisms underlying drug abuse. Similar to drug and alcohol abuse, internet addiction results in sub-sensitivity of dopamine reward mechanisms. Given the fact that this research is in its early stage it is premature to conclude that internet addiction is equivalent to substance addictions. © American Academy of Addiction Psychiatry.

  3. Genetic risk scores and family history as predictors of schizophrenia in Nordic registers.

    Science.gov (United States)

    Lu, Y; Pouget, J G; Andreassen, O A; Djurovic, S; Esko, T; Hultman, C M; Metspalu, A; Milani, L; Werge, T; Sullivan, P F

    2017-09-25

    Family history is a long-standing and readily obtainable risk factor for schizophrenia (SCZ). Low-cost genotyping technologies have enabled large genetic studies of SCZ, and the results suggest the utility of genetic risk scores (GRS, direct assessments of inherited common variant risk). Few studies have evaluated family history and GRS simultaneously to ask whether one can explain away the other. We studied 5959 SCZ cases and 8717 controls from four Nordic countries. All subjects had family history data from national registers and genome-wide genotypes that were processed through the quality control procedures used by the Psychiatric Genomics Consortium. Using external training data, GRS were estimated for SCZ, bipolar disorder (BIP), major depression, autism, educational attainment, and body mass index. Multivariable modeling was used to estimate effect sizes. Using harmonized genomic and national register data from Denmark, Estonia, Norway, and Sweden, we confirmed that family history of SCZ and GRS for SCZ and BIP were risk factors for SCZ. In a joint model, the effects of GRS for SCZ and BIP were essentially unchanged, and the effect of family history was attenuated but remained significant. The predictive capacity of a model including GRS and family history neared the minimum for clinical utility. Combining national register data with measured genetic risk factors represents an important investigative approach for psychotic disorders. Our findings suggest the potential clinical utility of combining GRS and family history for early prediction and diagnostic improvements.

  4. C-reactive protein, genetically elevated levels and risk of ischemic heart and cerebrovascular disease

    DEFF Research Database (Denmark)

    Zacho, Jeppe; Tybjaerg-Hansen, Anne; Nordestgaard, Børge Grønne

    2009-01-01

    We tested whether genetically elevated levels of C-reactive protein (CRP) cause increased risk of ischemic heart disease and ischemic cerebrovascular disease. Levels of CRP >3mg/L, compared with levels disease and ischemic...... cerebrovascular disease. Genotype combinations of the 4 CRP polymorphisms associated with up to a 64% increase in CRP levels, resulting in a theoretically predicted increased risk of up to 32% for ischemic heart disease and up to 25% for ischemic cerebrovascular disease. However, these genotype combinations did...... not associate with increased risk of ischemic heart and cerebrovascular disease....

  5. Genetic and environmental influences on risk of death due to infections assessed in Danish twins, 1943-2001

    DEFF Research Database (Denmark)

    Obel, Niels; Christensen, Kaare; Petersen, Inge

    2010-01-01

    Genetic differences have been proposed to play a strong role in risk of death from infectious diseases. The study base of 44,005 included all same-sex twin pairs born in 1870-2001, with both twins alive on January 1, 1943, or those born thereafter. Cause of death was obtained from the Danish Cause...... from infectious diseases could be demonstrated, the absolute effect of the genetic component on mortality was small....... genetic influence on the risk of death...

  6. Genetic Parameters And Selection Response For Yield Traits In Bread Wheat Under Irrigated And Rainfed Environments

    Science.gov (United States)

    Khalil, Iftikhar Hussain; at-ur-Rahman, Hiday; Khan, Imran

    2008-01-01

    A set of 22 F5:7 experimental wheat lines along with four check cultivars (Dera-98, Fakhr-e-Sarhad, Ghaznavi-98 and Tatara) were evaluated as independent experiments under irrigated and rainfed environments using a randomized complete block design at NWFP Agricultural University, Peshawar during 2004-05. The two environments were statistically different for days to heading and spike length only. Highly significant genetic variability existed among the wheat lines (P<0.01) in the combined analysis across environments for all traits. Genotype×environment interactions were non-significant for all traits except 1000-grain weight indicating consistent performance of wheat genotypes across the two environments. Wheat lines and check cultivars were 2 to 5 days early in heading under rainfed environment compared to the irrigated. Plant height, spike length, 1000-grain weight, biological and grain yields were generally reduced under rainfed environment. Genetic variances were of greater magnitude than environmental variances for most of the traits in both environments. The heritability estimates were of higher magnitude (0.74 to 0.96) for days to heading, plant height, spike length, biological and grain yield, while medium (0.31 to 0.51) for 1000-grain weight. Selection differentials were negative for heading (-7.3 days in irrigated vs -9.4 days in rainfed) and plant height (-9.0 cm in irrigated vs -8.7 cm in rainfed) indicating possibility of selecting wheat genotypes with early heading and short plant stature. Positive selection differentials of 1.3 vs 1.6 cm for spike length, 3.8 vs 3.4 g for 1000-grain weight, 2488.2 vs 3139.7 kg ha-1 for biological yield and 691.6 vs 565.4 kg ha-1 for grain yield at 20% selection intensity were observed under irrigated and rainfed environments, respectively. Expected selection responses were 7.98 vs 8.91 days for heading, 8.20 vs 9.52 cm for plant height, 1.01 vs 1.61 cm for spike length, 2.12 vs 1.15 g for 1000-grain weight, 1655

  7. A population-based survey in Australia of men's and women's perceptions of genetic risk and predictive genetic testing and implications for primary care.

    Science.gov (United States)

    Taylor, S

    2011-01-01

    Community attitudes research regarding genetic issues is important when contemplating the potential value and utilisation of predictive testing for common diseases in mainstream health services. This article aims to report population-based attitudes and discuss their relevance to integrating genetic services in primary health contexts. Men's and women's attitudes were investigated via population-based omnibus telephone survey in Queensland, Australia. Randomly selected adults (n = 1,230) with a mean age of 48.8 years were interviewed regarding perceptions of genetic determinants of health; benefits of genetic testing that predict 'certain' versus 'probable' future illness; and concern, if any, regarding potential misuse of genetic test information. Most (75%) respondents believed genetic factors significantly influenced health status; 85% regarded genetic testing positively although attitudes varied with age. Risk-based information was less valued than certainty-based information, but women valued risk information significantly more highly than men. Respondents reported 'concern' (44%) and 'no concern' (47%) regarding potential misuse of genetic information. This study contributes important population-based data as most research has involved selected individuals closely impacted by genetic disorders. While community attitudes were positive regarding genetic testing, genetic literacy is important to establish. The nature of gender differences regarding risk perception merits further study and has policy and service implications. Community concern about potential genetic discrimination must be addressed if health benefits of testing are to be maximised. Larger questions remain in scientific, policy, service delivery, and professional practice domains before predictive testing for common disorders is efficacious in mainstream health care. Copyright © 2011 S. Karger AG, Basel.

  8. Communicating genetic risk information for common disorders in the era of genomic medicine.

    Science.gov (United States)

    Lautenbach, Denise M; Christensen, Kurt D; Sparks, Jeffrey A; Green, Robert C

    2013-01-01

    Communicating genetic risk information in ways that maximize understanding and promote health is increasingly important given the rapidly expanding availability and capabilities of genomic technologies. A well-developed literature on risk communication in general provides guidance for best practices, including presentation of information in multiple formats, attention to framing effects, use of graphics, sensitivity to the way numbers are presented, parsimony of information, attentiveness to emotions, and interactivity as part of the communication process. Challenges to communicating genetic risk information include deciding how best to tailor it, streamlining the process, deciding what information to disclose, accepting that communications may have limited influence, and understanding the impact of context. Meeting these challenges has great potential for empowering individuals to adopt healthier lifestyles and improve public health, but will require multidisciplinary approaches and collaboration.

  9. Genetic and modifying factors that determine the risk of brain tumors

    DEFF Research Database (Denmark)

    Montelli, Terezinha de Cresci Braga; Peraçoli, Maria Terezinha Serrão; Rogatto, Silvia Regina

    2011-01-01

    Some modifying factors may determine the risk of brain tumors. Until now, it could not be attempted to identify people at risk and also to improve significantly disease progression. Current therapy consists of surgical resection, followed by radiation therapy and chemotherapy. Despite...... of these treatments, the prognosis for patients is poor. In this review, we highlight general aspects concerning genetic alterations in brain tumors, namely astrocytomas, glioblastomas, oligodendrogliomas, medulloblastomas and ependymomas. The influence of these genetic alterations in patients' prognosis is discussed....... Mutagen sensitivity is associated with cancer risk. The convincing studies that linked DNA damages and DNA repair alterations with brain tumors are also described. Another important modifying factor is immunity. General immune response against cancer, tumor microenvironment and immune response, mechanisms...

  10. Woman's Pre-Conception Evaluation: Genetic and Fetal Risk Considerations for Counselling and Informed Choice.

    Science.gov (United States)

    Wilson, R Douglas

    2017-10-11

    To inform reproductive and other health care providers about genetic and fetal risk information to consider during a woman/couples' pre-conception evaluation, including considerations for genetic risk assessment, genetic screening, or testing to allow for improved counselling and informed choice. This genetic information can be used for patient education, planning, and possible pre-conception and/or prenatal testing. This information may allow improved risk assessment for pre-conception counselling for individual patients and their families. PubMed or Medline and the Cochrane Database were searched in May 2017 using appropriate key words ("pre-conception," "genetic disease," "maternal," "family history," "genetic," "health risk," "genetic health surveillance," "prenatal screening," "prenatal diagnosis," "birth defects," and "teratogen"). Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, and national and international medical specialty societies. The benefits for the patient and her family include an increased understanding of relevant genetic risk pre-conception and in early pregnancy, and better pregnancy outcomes as a result of use of the information. The harm includes potential increased anxiety or psychological stress associated with the possibility of identifying genetic risks. The evidence obtained was peer-reviewed by the Genetics Committee of The Society of Obstetricians and Gynaecologists of Canada. Consideration for Care Statements For this review article, the Consideration for Care Statements use the GRADE strength and quality as it is comparable for the clinician and the patient/public user. [GRADE from the Canadian Task Force on Preventive Health Care (www.canadiantaskforce.ca). For clinicians, Strong = The recommendation would apply to most individuals. Formal discussion aids are not likely to be

  11. Melanoma genetics

    DEFF Research Database (Denmark)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2015-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

  12. Adoption and the communication of genetic risk: experiences in Huntington disease.

    Science.gov (United States)

    Bombard, Y; Semaka, A; Hayden, M R

    2012-01-01

    Adoption agencies can use genetic information to determine the eligibility of prospective adoptive parents and to establish a child's suitability for adoption. We describe experiences and implications of communicating genetic risk for Huntington disease (HD) in the context of adoption. A secondary analysis was employed using data collected from a cross-sectional survey (n = 233) and two qualitative studies on the psychosocial effects of predictive testing for HD. We demonstrate several ethical and practical challenges in the search for and communication of genetic information for adoptees and their birth relatives. We also found that concern for adoption discrimination was reported by 13.7% of survey respondents (n = 32). Concerns were higher among tested respondents than those who had not been tested (n = 29 vs n = 3, p = 0.010). However, more respondents were concerned about being discriminated based on their family history (FHx) vs their genetic test results (GTR) (concern based on FHx: n = 18 vs based on GTR: n = 1 vs based on both: n =10). These findings contribute to the limited empirical literature by offering evidence on the experiences and implications of communicating genetic risk information in the context of adoption with reference to HD. © 2011 John Wiley & Sons A/S.

  13. Precision Oncology and Genetic Risk Information: Exploring Patients' Preferences and Responses

    Science.gov (United States)

    Dr. Jada Hamilton is an Assistant Member at Memorial Sloan Kettering Cancer Center, as well as an Assistant Attending Psychologist in the Behavioral Sciences Service, Department of Psychiatry and Behavioral Sciences and in the Clinical Genetics Service, Department of Medicine at Memorial Hospital in New York, New York.  She leads a program of research at the intersection of behavioral science, cancer prevention, and genomics, with the goal of translating advances in genetic and genomic medicine into improved cancer care that is of high quality, aligned with patient preferences, and ultimately improves public health.  Dr. Hamilton is also currently leading a study to assess how patients and their families respond to inherited risk information that is revealed as part of tumor sequencing (funded through a Mentored Research Scholar Grant from the American Cancer Society), as well as studies to evaluate alternative models for offering genetic counseling and testing to patients with cancer, and to examine the effects of novel breast cancer genetic risk feedback on patients’ decision-making, psychological, and behavioral outcomes. Prior to joining the faculty of Memorial Sloan Kettering, Dr. Hamilton received a BA in Genetics and Psychology from Ohio Wesleyan University (2004), an MA and PhD in Social and Health Psychology from Stony Brook University (2006, 2009), and an MPH from the Mailman School of Public Health at Columbia University (2010).  She also completed a postdoctoral fellowship as part of the National Cancer Institute’s Cancer Prevention Fellowship Program.

  14. Epidemiology, major risk factors and genetic predisposition for breast cancer in the Pakistani population.

    Science.gov (United States)

    Shaukat, Uzma; Ismail, Muhammad; Mehmood, Nasir

    2013-01-01

    Occurrence of breast cancer is related to genetic as well as cultural, environmental and life-style factors. Variations in diversity of these factors among different ethnic groups and geographical areas emphasize the immense need for studies in all racial-ethnic populations. The incidence of breast cancer in Pakistan is highest in Asians after Jews in Israel and 2.5 times higher than that in neighboring countries like Iran and India, accounting for 34.6% of female cancers. The Pakistani population is deficient in information regarding breast cancer etiology and epidemiology, but efforts done so far had suggested consanguinity as a major risk factor for frequent mutations leading to breast cancer and has also shed light on genetic origins in different ethnic groups within Pakistan. World-wide research efforts on different ethnicities have enhanced our understanding of genetic predisposition to breast cancer but despite these discoveries, 75% of the familial risk of breast cancer remains unexplained, highlighting the fact that the majority of breast cancer susceptibility genes remain unidentified. For this purpose Pakistani population provides a strong genetic pool to elucidate the genetic etiology of breast cancer because of cousin marriages. In this review, we describe the known breast cancer predisposition factors found in the local Pakistani population and the epidemiological research work done to emphasize the importance of exploring factors/variants contributing to breast cance, in order to prevent, cure and decrease its incidence in our country.

  15. Genes and/or jeans?: Genetic and socio-cultural contributions to risk for eating disorders.

    Science.gov (United States)

    Becker, Anne E; Keel, Pamela; Anderson-Fye, Eileen P; Thomas, Jennifer J

    2004-01-01

    Eating disorders are prevalent among young adult females and pose serious psychological and medical risks. Notwithstanding important advances, efforts to develop effective means of preventing and treating eating disorders have been limited by an incomplete understanding of their multifactorial etiology. Whereas epidemiologic data strongly suggest the influence of socio-cultural context in moderating risk, many hypotheses about how these effects are exerted have remained empirically unevaluated. Specifically, experimental and observational data suggest that social transition (e.g., transnational migration, urbanization, modernization), Western media exposure, and certain peer environments (involving social comparison and teasing) may all contribute to risk. With respect to genetic influences on etiology, family and twin studies have supported a genetic diathesis to eating disorders. Whereas, molecular genetic studies have generated interesting leads- with the most promising findings emerging for genes related to the function of serotonin-they have yet to identify well-replicated susceptibility loci. This paper reviews the data supporting both socio-cultural and genetic contributions for eating disorders and suggests productive future strategies for continuing to unravel their likely multiple and complex interactions.

  16. Exploring the cancer risk perception and interest in genetic services among Indigenous people in Queensland, Australia.

    Science.gov (United States)

    Bernardes, Christina M; Valery, Patricia C; Garvey, Gail

    2014-08-01

    The purpose of this study is to explore the levels of interest among Indigenous people with cancer in identifying cancer risk in their family and seeking genetic counselling/testing. A cross-sectional survey of Indigenous cancer patients recruited from four major treating hospitals in Queensland. Participants' family history of cancer and interest in genetic counselling/testing was sought using a structured questionnaire. Overall, 73.0% of 252 participants reported having a family history of cancer; of those, 52.8% had at least one first-degree relative with cancer. A total of 68.3% of participants indicated concern about relatives being affected by cancer and 54.4% of participants indicated they would like to assess the cancer risk in their family with a specialist. Concern was associated with willingness to discuss the risk of cancer with a specialist (pIndigenous cancer patients do have a family history of cancer and appear willing to undergo genetic counselling/investigation. It is of great concern that this population could miss the benefits of the technological advances in health care, creating a much larger disparity in health outcomes. Health service providers should not assume that Indigenous cancer patients will not follow their recommendations when referred to genetic counselling/investigation services. © 2014 Public Health Association of Australia.

  17. Genetic predisposition of IL-10 promoter polymorphisms with risk of multiple sclerosis: A meta-analysis.

    Science.gov (United States)

    Ramakrishnan, V; Akram Husain, R S; Ahmed, Shiek Ssj

    2017-05-15

    Interleukin-10 (IL-10) is a anti-inflammatory cytokine, which controls inflammation by inhibiting the synthesis of several cytokines produced by Th1 cells and macrophages. The association between Interleukin-10 promoter polymorphisms with the risk of multiple sclerosis (MS) remains inconclusive. In this study, a meta-analysis has been performed to assess the relationship between IL-10 gene polymorphisms rs1800896, rs1800871 and rs1800872 with the risk of MS. Nine case-control studies were selected involving 2755 participants. The association between the polymorphisms and MS was examined by the pooled odds ratios (ORs) with 95% confidence intervals (CIs) in allelic, homozygote, heterozygote, dominant and recessive genetic models. Of analyzed genetic models, the pooled ORs and CIs of each SNPs calculated based on random (I 2 >50) or fixed effects (I 2 0.05) of genetic predisposition with MS susceptibility across Asian and Caucasian populations. In addition, assessment based on funnel plot and Egger's linear regression test suggests no publication bias in all analyzed genetic models. Overall, our results demonstrated that rs1800896, rs1800871 and rs1800872 polymorphisms may not be the risk factor for the development of MS in both the populations. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Use of net reclassification improvement (NRI) method confirms the utility of combined genetic risk score to predict type 2 diabetes.

    Science.gov (United States)

    Tam, Claudia H T; Ho, Janice S K; Wang, Ying; Lam, Vincent K L; Lee, Heung Man; Jiang, Guozhi; Lau, Eric S H; Kong, Alice P S; Fan, Xiaodan; Woo, Jean L F; Tsui, Stephen K W; Ng, Maggie C Y; So, Wing Yee; Chan, Juliana C N; Ma, Ronald C W

    2013-01-01

    Recent genome-wide association studies (GWAS) identified more than 70 novel loci for type 2 diabetes (T2D), some of which have been widely replicated in Asian populations. In this study, we investigated their individual and combined effects on T2D in a Chinese population. We selected 14 single nucleotide polymorphisms (SNPs) in T2D genes relating to beta-cell function validated in Asian populations and genotyped them in 5882 Chinese T2D patients and 2569 healthy controls. A combined genetic score (CGS) was calculated by summing up the number of risk alleles or weighted by the effect size for each SNP under an additive genetic model. We tested for associations by either logistic or linear regression analysis for T2D and quantitative traits, respectively. The contribution of the CGS for predicting T2D risk was evaluated by receiver operating characteristic (ROC) analysis and net reclassification improvement (NRI). We observed consistent and significant associations of IGF2BP2, WFS1, CDKAL1, SLC30A8, CDKN2A/B, HHEX, TCF7L2 and KCNQ1 (8.5×10(-18)NRI approach (P<0.001). In a Chinese population, the use of a CGS of 8 SNPs modestly but significantly improved its discriminative ability to predict T2D above and beyond that attributed to clinical risk factors (sex, age and BMI).

  19. Joint effects of genetic variants and residential proximity to pesticide applications on hypospadias risk.

    Science.gov (United States)

    Carmichael, Suzan L; Yang, Wei; Ma, Chen; Roberts, Eric; Kegley, Susan; English, Paul; Lammer, Edward J; Witte, John S; Shaw, Gary M

    2016-08-01

    We examined risks associated with joint exposure of gene variants and pesticides. Analyses included 189 cases and 390 male controls born from 1991 to 2003 in California's San Joaquin Valley. We used logistic regression to examine risks associated with joint exposures of gene variants and pesticides that our previous work identified as associated with hypospadias. Genetic variables were based on variants in DGKK, genes involved in sex steroid synthesis/metabolism, and genes involved in genital tubercle development. Pesticide exposure was based on residential proximity to commercial agricultural pesticide applications. Odds ratios (ORs) were highest among babies with joint exposures, who had two- to fourfold increased risks; for example, the OR was 3.7 (95% confidence interval [CI], 0.8-16.5) among subjects with the risk-associated DGKK haplotype and pesticide exposure; OR, 1.5 (95% CI, 0.7-3.1) among subjects with the haplotype and no pesticide exposure; and OR, 0.9 (95% CI, 0.5-1.6) among subjects without the haplotype but with pesticide exposure, relative to subjects with neither. However, results did not provide statistical evidence that these risks were significantly greater than expected on an additive scale, relative to risks associated with one exposure at a time. We observed elevated risks associated with joint exposures to selected pesticides and genetic variants but no statistical evidence for interaction. Birth Defects Research (Part A) 106:653-658, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Memory Resilience to Alzheimer's Genetic Risk: Sex Effects in Predictor Profiles.

    Science.gov (United States)

    McDermott, Kirstie L; McFall, G Peggy; Andrews, Shea J; Anstey, Kaarin J; Dixon, Roger A

    2017-10-01

    Apolipoprotein E (APOE) ɛ4 and Clusterin (CLU) C alleles are risk factors for Alzheimer's disease (AD) and episodic memory (EM) decline. Memory resilience occurs when genetically at-risk adults perform at high and sustained levels. We investigated whether (a) memory resilience to AD genetic risk is predicted by biological and other risk markers and (b) the prediction profiles vary by sex and AD risk variant. Using a longitudinal sample of nondemented adults (n = 642, aged 53-95) we focused on memory resilience (over 9 years) to 2 AD risk variants (APOE, CLU). Growth mixture models classified resilience. Random forest analysis, stratified by sex, tested the predictive importance of 22 nongenetic risk factors from 5 domains (n = 24-112). For both sexes, younger age, higher education, stronger grip, and everyday novel cognitive activity predicted memory resilience. For women, 9 factors from functional, health, mobility, and lifestyle domains were also predictive. For men, only fewer depressive symptoms was an additional important predictor. The prediction profiles were similar for APOE and CLU. Although several factors predicted resilience in both sexes, a greater number applied only to women. Sex-specific mechanisms and intervention targets are implied. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Differential genetic susceptibility to child risk at birth in predicting observed maternal behavior.

    Directory of Open Access Journals (Sweden)

    Keren Fortuna

    Full Text Available This study examined parenting as a function of child medical risks at birth and parental genotype (dopamine D4 receptor; DRD4. Our hypothesis was that the relation between child risks and later maternal sensitivity would depend on the presence/absence of a genetic variant in the mothers, thus revealing a gene by environment interaction (GXE. Risk at birth was defined by combining risk indices of children's gestational age at birth, birth weight, and admission to the neonatal intensive care unit. The DRD4-III 7-repeat allele was chosen as a relevant genotype as it was recently shown to moderate the effect of environmental stress on parental sensitivity. Mothers of 104 twin pairs provided DNA samples and were observed with their children in a laboratory play session when the children were 3.5 years old. Results indicate that higher levels of risk at birth were associated with less sensitive parenting only among mothers carrying the 7-repeat allele, but not among mothers carrying shorter alleles. Moreover, mothers who are carriers of the 7-repeat allele and whose children scored low on the risk index were observed to have the highest levels of sensitivity. These findings provide evidence for the interactive effects of genes and environment (in this study, children born at higher risk on parenting, and are consistent with a genetic differential susceptibility model of parenting by demonstrating that some parents are inherently more susceptible to environmental influences, both good and bad, than are others.

  2. Invited commentary: genetic variants and individual- and societal-level risk factors.

    Science.gov (United States)

    Coughlin, Steven S

    2010-01-01

    Over the past decade, leading epidemiologists have noted the importance of social factors in studying and understanding the distribution and determinants of disease in human populations; but to what extent are epidemiologic studies integrating genetic information and other biologic variables with information about individual-level risk factors and group-level or societal factors related to the broader residential, behavioral, or cultural context? There remains a need to consider ways to integrate genetic information with social and contextual information in epidemiologic studies, partly to combat the overemphasis on the importance of genetic factors as determinants of disease in human populations. Even in genome-wide association studies of coronary heart disease and other common complex diseases, only a small proportion of heritability is explained by the genetic variants identified to date. It is possible that familial clustering due to genetic factors has been overestimated and that important environmental or social influences (acting alone or in combination with genetic variants) have been overlooked. The accompanying article by Bressler et al. (Am J Epidemiol. 2010;171(1):14-23) highlights some of these important issues.

  3. Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles

    DEFF Research Database (Denmark)

    Mero, Inger-Lise; Gustavsen, Marte W; Sæther, Hanne S

    2013-01-01

    The presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF) is a typical finding in multiple sclerosis (MS). We applied data from Norwegian, Swedish and Danish (i.e. Scandinavian) MS patients from a genome-wide association study (GWAS) to search for genetic differences in MS relating...... at onset (AAO), MS outcome measures and gender. This study confirms both shared and distinct genetic risk for MS subtypes in the Scandinavian population defined by OCB status and indicates different clinical characteristics between the groups. This suggests differences in disease mechanisms between OCB...

  4. Genetic Variants in Epigenetic Pathways and Risks of Multiple Cancers in the GAME-ON Consortium.

    Science.gov (United States)

    Toth, Reka; Scherer, Dominique; Kelemen, Linda E; Risch, Angela; Hazra, Aditi; Balavarca, Yesilda; Issa, Jean-Pierre J; Moreno, Victor; Eeles, Rosalind A; Ogino, Shuji; Wu, Xifeng; Ye, Yuanqing; Hung, Rayjean J; Goode, Ellen L; Ulrich, Cornelia M

    2017-06-01

    Background: Epigenetic disturbances are crucial in cancer initiation, potentially with pleiotropic effects, and may be influenced by the genetic background. Methods: In a subsets (ASSET) meta-analytic approach, we investigated associations of genetic variants related to epigenetic mechanisms with risks of breast, lung, colorectal, ovarian and prostate carcinomas using 51,724 cases and 52,001 controls. False discovery rate-corrected P values (q values epigenetic function, and cancer etiology. Impact: This approach provides novel insight into possible pleiotropic effects of genes involved in epigenetic processes. Cancer Epidemiol Biomarkers Prev; 26(6); 816-25. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. Communicating Health Risks under Pressure: Homeland Security Applications

    International Nuclear Information System (INIS)

    Garrahan, K.G.; Collie, S.L.

    2006-01-01

    The U.S. Environmental Protection Agency's (EPA) Office of Research and Development (ORD) Threat and Consequence Assessment Division (TCAD) within the National Homeland Security Research Center (NHSRC) has developed a tool for rapid communication of health risks and likelihood of exposure in preparation for terrorist incidents. The Emergency Consequence Assessment Tool (ECAT) is a secure web-based tool designed to make risk assessment and consequence management faster and easier for high priority terrorist threat scenarios. ECAT has been designed to function as 'defensive play-book' for health advisors, first responders, and decision-makers by presenting a series of evaluation templates for priority scenarios that can be modified for site-specific applications. Perhaps most importantly, the risk communication aspect is considered prior to an actual release event, so that management or legal advisors can concur on general risk communication content in preparation for press releases that can be anticipated in case of an actual emergency. ECAT serves as a one-stop source of information for retrieving toxicological properties for agents of concern, estimating exposure to these agents, characterizing health risks, and determining what actions need to be undertaken to mitigate the risks. ECAT has the capability to be used at a command post where inputs can be checked and communicated while the response continues in real time. This front-end planning is intended to fill the gap most commonly identified during tabletop exercises: a need for concise, timely, and informative risk communication to all parties. Training and customization of existing chemical and biological release scenarios with modeling of exposure to air and water, along with custom risk communication 'messages' intended for public, press, shareholders, and other partners enable more effective communication during times of crisis. For DOE, the ECAT could serve as a prototype that would be amenable to

  6. Genetic engineering of Trypanosoma (Dutonella vivax and in vitro differentiation under axenic conditions.

    Directory of Open Access Journals (Sweden)

    Simon D'Archivio

    2011-12-01

    Full Text Available Trypanosoma vivax is one of the most common parasites responsible for animal trypanosomosis, and although this disease is widespread in Africa and Latin America, very few studies have been conducted on the parasite's biology. This is in part due to the fact that no reproducible experimental methods had been developed to maintain the different evolutive forms of this trypanosome under laboratory conditions. Appropriate protocols were developed in the 1990s for the axenic maintenance of three major animal Trypanosoma species: T. b. brucei, T. congolense and T. vivax. These pioneer studies rapidly led to the successful genetic manipulation of T. b. brucei and T. congolense. Advances were made in the understanding of these parasites' biology and virulence, and new drug targets were identified. By contrast, challenging in vitro conditions have been developed for T. vivax in the past, and this per se has contributed to defer both its genetic manipulation and subsequent gene function studies. Here we report on the optimization of non-infective T. vivax epimastigote axenic cultures and on the process of parasite in vitro differentiation into metacyclic infective forms. We have also constructed the first T. vivax specific expression vector that drives constitutive expression of the luciferase reporter gene. This vector was then used to establish and optimize epimastigote transfection. We then developed highly reproducible conditions that can be used to obtain and select stably transfected mutants that continue metacyclogenesis and are infectious in immunocompetent rodents.

  7. Effects of trawl selectivity and genetic parameters on fish body length under long-term trawling

    Science.gov (United States)

    Yu, Yang; Sun, Peng; Cui, He; Sheng, Huaxiang; Zhao, Fenfang; Tang, Yanli; Chen, Zelin

    2015-10-01

    Long-term fishing pressure affects the biological characteristics of exploited fish stocks. The biological characteristics of hairtail ( Trichiurus lepturus) in the East China Sea are unable to recover because of long-term trawling. Fishing induces evolutionary effects on the fish's biological characteristics. Evidence of these changes includes small size at age, a shift to earlier age structure, and early maturation. Natural and artificial selection usually affect the fish's life history. Selection can induce different chances of reproduction, and individual fish can give a different genetic contribution to the next generation. In this study, analysis of time-dependent probability of significance and test of sensitivity were used to explore the effects of fish exploitation rate, mesh size, and heritability with long-term trawling. Results showed that fishing parameters were important drivers to exploited fish population. However, genetic traits altered by fishing were slow, and the changes in biological characteristics were weaker than those caused by fishing selection. Exploitation rate and mesh size exhibited similar evolutionary trend tendency under long-term fishing. The time-dependent probability of significance trend showed a gradual growth and tended to be stable. Therefore, the direction of fishing-induced evolution and successful management of fish species require considerable attention to contribute to sustainable fisheries in China.

  8. Neuropsychological Functioning in Adolescents and Young Adults at Genetic Risk for Schizophrenia and Affective Psychoses: Results from the Harvard and Hillside Adolescent High Risk Studies

    OpenAIRE

    Seidman, Larry J.; Giuliano, Anthony J.; Smith, Christopher W.; Stone, William S.; Glatt, Stephen J.; Meyer, Eric; Faraone, Stephen V.; Tsuang, Ming T.; Cornblatt, Barbara

    2006-01-01

    Siblings and offspring of persons with schizophrenia carry elevated genetic risk for the illness and manifest attentional and memory impairments. Because less is known about other neuropsychological functions and their specificity in adolescents, we conducted a genetic high-risk (HR) study of schizophrenia (HR-SCZ) and affective psychosis (HR-AFF). Participants (ages 12–25) were from the Harvard Adolescent High-Risk and Hillside Family studies, including 73 HR-SCZ, 18 HR-AFF, and 84 community...

  9. Evidence for Shared Genetic Risk between ADHD Symptoms and Reduced Mathematics Ability: A Twin Study

    Science.gov (United States)

    Greven, Corina U.; Kovas, Yulia; Willcutt, Erik G.; Petrill, Stephen A.; Plomin, Robert

    2013-01-01

    Background: Attention-deficit/hyperactivity disorder (ADHD) symptoms and mathematics ability are associated, but little is known about the genetic and environmental influences underlying this association. Methods: Data came from more than 6,000 twelve-year-old twin pairs from the UK population-representative Twins Early Development Study. Parents…

  10. Evidence for shared genetic risk between ADHD symptoms and reduced mathematics ability: a twin study

    NARCIS (Netherlands)

    Greven, C.U.; Kovas, Y.; Willcutt, E.G.; Petrill, S.A.; Plomin, R.

    2014-01-01

    BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) symptoms and mathematics ability are associated, but little is known about the genetic and environmental influences underlying this association. METHODS: Data came from more than 6,000 twelve-year-old twin pairs from the UK

  11. Non-genetic risk factors and predicting efficacy for docetaxel--drug-induced liver injury among metastatic breast cancer patients.

    Science.gov (United States)

    Wang, Zheng; Liang, Xu; Yu, Jing; Zheng, Xiaohui; Zhu, Yulin; Yan, Ying; Dong, Ningning; Di, Lijun; Song, Guohong; Zhou, Xinna; Wang, Xiaoli; Yang, Huabing; Ren, Jun; Lyerly, Herbert Kim

    2012-08-01

    Docetaxel has been chosen as one of the most popular anticancer drugs in the treatment of breast cancer for more than a decade. There is increasingly awareness for the occurrence of docetaxel and/or docetaxel-drug-induced liver injury (DILI), although the underlying mechanism of occurrence and its risk factors remain unclear. We conducted a retrospective cohort study to identify non-genetic risk factors for docetaxel-DILI among 647 metastasis breast cancer patients treated with docetaxel-containing regimens. Sixty-seven (10.36%) patients were diagnosed as docetaxel-DILI. By logistic regression analysis, premenopausal status (odds ratio [OR][95% confidence interval {CI}] = 2.24 [1.30-3.87]), past hepatitis B virus (HBV) infections (OR [95% CI] = 4.23 [1.57-11.42]), liver metastasis (OR [95% CI] = 3.70 [2.16-6.34]). The predominant occurrence of DILI was seen in groups with docetaxel combination regimens. (OR [95% CI] = 2.66 [1.59-4.55]). The potential increasing occurrence of docetaxel-DILI was associated with multiple risk factors in an exposure-response manner (P < 0.001), and patients with more than three risk factors would be exposed to a 36.61-fold risk of DILI (95% CI = 10.18-131.62). Further analysis by the risk score and area under the receiver-operator characteristic curve (AUC) showed that those four factors contributed to an AUC of 0.7536 (95% CI = 0.70-0.81), with a predictive sensitivity of 74.63% and specificity of 65.17%. Docetaxel-DILI with a relatively higher incidence should be addressed among metastatic breast cancer patients. Four predominant risk factors, including premenopausal status, past HBV infection, liver metastasis, and docetaxel combination regimens, were potential predicators for DILI. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  12. Genetic Algorithm for Multiuser Discrete Network Design Problem under Demand Uncertainty

    Directory of Open Access Journals (Sweden)

    Wu Juan

    2012-01-01

    Full Text Available Discrete network design is an important part of urban transportation planning. The purpose of this paper is to present a bilevel model for discrete network design. The upper-level model aims to minimize the total travel time under a stochastic demand to design a discrete network. In the lower-level model, demands are assigned to the network through a multiuser traffic equilibrium assignment. Generally, discrete network could affect path selections of demands, while the results of the multiuser traffic equilibrium assignment need to reconstruct a new discrete network. An iterative approach including an improved genetic algorithm and Frank-Wolfe algorithm is used to solve the bi-level model. The numerical results on Nguyen Dupuis network show that the model and the related algorithms were effective for discrete network design.

  13. Genetic architecture of factors underlying partial resistance to Alternaria leaf blight in carrot.

    Science.gov (United States)

    Le Clerc, Valérie; Pawelec, Anna; Birolleau-Touchard, Christelle; Suel, Anita; Briard, Mathilde

    2009-05-01

    In most production areas, Alternaria leaf blight (ALB) is recognized as the most common and destructive foliage disease in carrot. To assess the genetic architecture of carrot ALB resistance, two parental coupling maps were developed with similar number of dominant markers (around 70), sizes (around 650 cM), densities (around 9.5 cM), and marker composition. The F(2:3) progenies were evaluated in field and tunnel for two scoring dates. The continuous distribution of the disease severity value indicated that ALB resistance is under polygenic control. Three QTLs regions were found on three linkage groups. Two of them were tunnel or field specific and were detected only at the second screening date suggesting that the expression of these two QTLs regions involved in resistance to Alternaria dauci might depend on environment and delay after infection.

  14. Application of multi-objective optimization based on genetic algorithm for sustainable strategic supplier selection under fuzzy environment

    Directory of Open Access Journals (Sweden)

    Muhammad Hashim

    2017-05-01

    Full Text Available Purpose:  The incorporation of environmental objective into the conventional supplier selection practices is crucial for corporations seeking to promote green supply chain management (GSCM. Challenges and risks associated with green supplier selection have been broadly recognized by procurement and supplier management professionals. This paper aims to solve a Tetra “S” (SSSS problem based on a fuzzy multi-objective optimization with genetic algorithm in a holistic supply chain environment. In this empirical study, a mathematical model with fuzzy coefficients is considered for sustainable strategic supplier selection (SSSS problem and a corresponding model is developed to tackle this problem. Design/methodology/approach: Sustainable strategic supplier selection (SSSS decisions are typically multi-objectives in nature and it is an important part of green production and supply chain management for many firms. The proposed uncertain model is transferred into deterministic model by applying the expected value mesurement (EVM and genetic algorithm with weighted sum approach for solving the multi-objective problem. This research focus on a multi-objective optimization model for minimizing lean cost, maximizing sustainable service and greener product quality level. Finally, a mathematical case of textile sector is presented to exemplify the effectiveness of the proposed model with a sensitivity analysis. Findings: This study makes a certain contribution by introducing the Tetra ‘S’ concept in both the theoretical and practical research related to multi-objective optimization as well as in the study of sustainable strategic supplier selection (SSSS under uncertain environment. Our results suggest that decision makers tend to select strategic supplier first then enhance the sustainability. Research limitations/implications: Although the fuzzy expected value model (EVM with fuzzy coefficients constructed in present research should be helpful for

  15. Application of multi-objective optimization based on genetic algorithm for sustainable strategic supplier selection under fuzzy environment

    Energy Technology Data Exchange (ETDEWEB)

    Hashim, M.; Nazam, M.; Yao, L.; Baig, S.A.; Abrar, M.; Zia-ur-Rehman, M.

    2017-07-01

    The incorporation of environmental objective into the conventional supplier selection practices is crucial for corporations seeking to promote green supply chain management (GSCM). Challenges and risks associated with green supplier selection have been broadly recognized by procurement and supplier management professionals. This paper aims to solve a Tetra “S” (SSSS) problem based on a fuzzy multi-objective optimization with genetic algorithm in a holistic supply chain environment. In this empirical study, a mathematical model with fuzzy coefficients is considered for sustainable strategic supplier selection (SSSS) problem and a corresponding model is developed to tackle this problem. Design/methodology/approach: Sustainable strategic supplier selection (SSSS) decisions are typically multi-objectives in nature and it is an important part of green production and supply chain management for many firms. The proposed uncertain model is transferred into deterministic model by applying the expected value mesurement (EVM) and genetic algorithm with weighted sum approach for solving the multi-objective problem. This research focus on a multi-objective optimization model for minimizing lean cost, maximizing sustainable service and greener product quality level. Finally, a mathematical case of textile sector is presented to exemplify the effectiveness of the proposed model with a sensitivity analysis. Findings: This study makes a certain contribution by introducing the Tetra ‘S’ concept in both the theoretical and practical research related to multi-objective optimization as well as in the study of sustainable strategic supplier selection (SSSS) under uncertain environment. Our results suggest that decision makers tend to select strategic supplier first then enhance the sustainability. Research limitations/implications: Although the fuzzy expected value model (EVM) with fuzzy coefficients constructed in present research should be helpful for solving real world

  16. Application of multi-objective optimization based on genetic algorithm for sustainable strategic supplier selection under fuzzy environment

    International Nuclear Information System (INIS)

    Hashim, M.; Nazam, M.; Yao, L.; Baig, S.A.; Abrar, M.; Zia-ur-Rehman, M.

    2017-01-01

    The incorporation of environmental objective into the conventional supplier selection practices is crucial for corporations seeking to promote green supply chain management (GSCM). Challenges and risks associated with green supplier selection have been broadly recognized by procurement and supplier management professionals. This paper aims to solve a Tetra “S” (SSSS) problem based on a fuzzy multi-objective optimization with genetic algorithm in a holistic supply chain environment. In this empirical study, a mathematical model with fuzzy coefficients is considered for sustainable strategic supplier selection (SSSS) problem and a corresponding model is developed to tackle this problem. Design/methodology/approach: Sustainable strategic supplier selection (SSSS) decisions are typically multi-objectives in nature and it is an important part of green production and supply chain management for many firms. The proposed uncertain model is transferred into deterministic model by applying the expected value mesurement (EVM) and genetic algorithm with weighted sum approach for solving the multi-objective problem. This research focus on a multi-objective optimization model for minimizing lean cost, maximizing sustainable service and greener product quality level. Finally, a mathematical case of textile sector is presented to exemplify the effectiveness of the proposed model with a sensitivity analysis. Findings: This study makes a certain contribution by introducing the Tetra ‘S’ concept in both the theoretical and practical research related to multi-objective optimization as well as in the study of sustainable strategic supplier selection (SSSS) under uncertain environment. Our results suggest that decision makers tend to select strategic supplier first then enhance the sustainability. Research limitations/implications: Although the fuzzy expected value model (EVM) with fuzzy coefficients constructed in present research should be helpful for solving real world

  17. Prevalence and risk factors of asymptomatic malaria among under ...

    African Journals Online (AJOL)

    user

    Children who were not sleeping under insecticide treated nets were 15 times more likely to be infected with malaria parasites compared to those who were sleeping under nets [AOR=15.27; 95%CI=4.42-. 52.82; p<0.001]. ... environmental modification, human behaviour and insecticide resistance (MOH, 2014). Although.

  18. Population genetics inference for longitudinally-sampled mutants under strong selection.

    Science.gov (United States)

    Lacerda, Miguel; Seoighe, Cathal

    2014-11-01

    Longitudinal allele frequency data are becoming increasingly prevalent. Such samples permit statistical inference of the population genetics parameters that influence the fate of mutant variants. To infer these parameters by maximum likelihood, the mutant frequency is often assumed to evolve according to the Wright-Fisher model. For computational reasons, this discrete model is commonly approximated by a diffusion process that requires the assumption that the forces of natural selection and mutation are weak. This assumption is not always appropriate. For example, mutations that impart drug resistance in pathogens may evolve under strong selective pressure. Here, we present an alternative approximation to the mutant-frequency distribution that does not make any assumptions about the magnitude of selection or mutation and is much more computationally efficient than the standard diffusion approximation. Simulation studies are used to compare the performance of our method to that of the Wright-Fisher and Gaussian diffusion approximations. For large populations, our method is found to provide a much better approximation to the mutant-frequency distribution when selection is strong, while all three methods perform comparably when selection is weak. Importantly, maximum-likelihood estimates of the selection coefficient are severely attenuated when selection is strong under the two diffusion models, but not when our method is used. This is further demonstrated with an application to mutant-frequency data from an experimental study of bacteriophage evolution. We therefore recommend our method for estimating the selection coefficient when the effective population size is too large to utilize the discrete Wright-Fisher model. Copyright © 2014 by the Genetics Society of America.

  19. Linking genetic counseling content to short-term outcomes in individuals at elevated breast cancer risk.

    Science.gov (United States)

    Kelly, Kimberly M; Ellington, Lee; Schoenberg, Nancy; Agarwal, Parul; Jackson, Thomas; Dickinson, Stephanie; Abraham, Jame; Paskett, Electra D; Leventhal, Howard; Andrykowski, Michael

    2014-10-01

    Few studies have linked actual genetic counseling content to short-term outcomes. Using the Self-regulation Model, the impact of cognitive and affective content in genetic counseling on short-term outcomes was studied in individuals at elevated risk of familial breast-ovarian cancer. Surveys assessed dependent variables: distress, perceived risk, and 6 knowledge measures (Meaning of Positive Test; Meaning of Negative Test; Personal Behavior; Practitioner Knowledge; Mechanisms of Cancer Inheritance; Frequency of Inherited Cancer) measured at pre- and post-counseling. Proportion of participant cognitive and affective and counselor cognitive and affective content during sessions (using LIWC software) were predictors in regressions. Knowledge increased for 5 measures and decreased for Personal Behavior, Distress and Perceived Risk. Controlling for age and education, results were significant/marginally significant for three measures. More counselor content was associated with decreases in knowledge of Personal Behavior. More participant and less counselor affective content was associated with gains in Practitioner Knowledge. More counselor cognitive, and interaction of counselor cognitive and affective content, were associated with higher perceived risk. Genetic counselors dominate the content of counseling sessions. Therefore, their content is tied more closely to short term outcomes than participant content. A lack of patient communication in sessions may pose problems for understanding of complex concepts.

  20. Genetic predisposition to dyslipidemia and type 2 diabetes risk in two prospective cohorts.

    Science.gov (United States)

    Qi, Qibin; Liang, Liming; Doria, Alessandro; Hu, Frank B; Qi, Lu

    2012-03-01

    Dyslipidemia has been associated with type 2 diabetes, but it remains unclear whether dyslipidemia plays a causal role in type 2 diabetes. We aimed to examine the association between the genetic predisposition to dyslipdemia and type 2 diabetes risk. The current study included 2,447 patients with type 2 diabetes and 3,052 control participants of European ancestry from the Nurses' Health Study and the Health Professionals Follow-up Study. Genetic predisposition to dyslipidemia was estimated by three genotype scores of lipids (LDL cholesterol, HDL cholesterol, and triglycerides) on the basis of the established loci for blood lipids. Linear relation analysis indicated that the HDL cholesterol and triglyceride genotype scores, but not the LDL cholesterol genotype score, were linearly related to elevated type 2 diabetes risk. Each point of the HDL cholesterol and triglyceride genotype scores was associated with a 3% (odds ratio [OR] 1.03 [95% CI 1.01-1.04]) and a 2% (1.02 [1.00-1.04]) increased risk of developing type 2 diabetes, respectively. The ORs were 1.39 (1.17-1.65) and 1.19 (1.01-1.41) for type 2 diabetes by comparing extreme quartiles of the HDL cholesterol genotype score and triglyceride genotype score, respectively. In conclusion, genetic predisposition to low HDL cholesterol or high triglycerides is related to elevated type 2 diabetes risk.

  1. Genetic risk and longitudinal disease activity in systemic lupus erythematosus using targeted maximum likelihood estimation.

    Science.gov (United States)

    Gianfrancesco, M A; Balzer, L; Taylor, K E; Trupin, L; Nititham, J; Seldin, M F; Singer, A W; Criswell, L A; Barcellos, L F

    2016-09-01

    Systemic lupus erythematous (SLE) is a chronic autoimmune disease associated with genetic and environmental risk factors. However, the extent to which genetic risk is causally associated with disease activity is unknown. We utilized longitudinal-targeted maximum likelihood estimation to estimate the causal association between a genetic risk score (GRS) comprising 41 established SLE variants and clinically important disease activity as measured by the validated Systemic Lupus Activity Questionnaire (SLAQ) in a multiethnic cohort of 942 individuals with SLE. We did not find evidence of a clinically important SLAQ score difference (>4.0) for individuals with a high GRS compared with those with a low GRS across nine time points after controlling for sex, ancestry, renal status, dialysis, disease duration, treatment, depression, smoking and education, as well as time-dependent confounding of missing visits. Individual single-nucleotide polymorphism (SNP) analyses revealed that 12 of the 41 variants were significantly associated with clinically relevant changes in SLAQ scores across time points eight and nine after controlling for multiple testing. Results based on sophisticated causal modeling of longitudinal data in a large patient cohort suggest that individual SLE risk variants may influence disease activity over time. Our findings also emphasize a role for other biological or environmental factors.

  2. Common genetic polymorphisms within NFκB-related genes and the risk of developing invasive aspergillosis

    Directory of Open Access Journals (Sweden)

    Carmen Belén Lupiañez

    2016-08-01

    Full Text Available Invasive Aspergillosis (IA is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mould. A growing number of studies suggest a major host genetic component in disease susceptibility. Here, we evaluated whether 14 single-nucleotide polymorphisms within NFκB1, NFκB2, RelA, RelB, Rel and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non-IA recruited through a collaborative effort involving the aspBIOmics consortium and four European clinical institutions. No significant overall associations between selected SNPs and the risk of IA were found in this large cohort. Although a hematopoietic stem cell transplantation (HSCT-stratified analysis revealed that carriers of the IRF4rs12203592T/T genotype had a 6-fold increased risk of developing the infection when compared with those carrying the C allele (OR-Rec=6.24, 95%CI 1.25-31.2, P=0.026, the association of this variant with IA risk did not reach significance at experiment-wide significant threshold. In addition, we found an association of the IRF4AATC and IRF4GGTC haplotypes (not including the IRF4rs12203592T risk allele with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4rs12203592 SNP. Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found. These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA.

  3. Common Genetic Polymorphisms within NFκB-Related Genes and the Risk of Developing Invasive Aspergillosis

    Science.gov (United States)

    Lupiañez, Carmen B.; Villaescusa, María T.; Carvalho, Agostinho; Springer, Jan; Lackner, Michaela; Sánchez-Maldonado, José M.; Canet, Luz M.; Cunha, Cristina; Segura-Catena, Juana; Alcazar-Fuoli, Laura; Solano, Carlos; Fianchi, Luana; Pagano, Livio; Potenza, Leonardo; Aguado, José M.; Luppi, Mario; Cuenca-Estrella, Manuel; Lass-Flörl, Cornelia; Einsele, Hermann; Vázquez, Lourdes; Ríos-Tamayo, Rafael; Loeffler, Jurgen; Jurado, Manuel; Sainz, Juan

    2016-01-01

    Invasive Aspergillosis (IA) is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mold. A growing number of studies suggest a major host genetic component in disease susceptibility. Here, we evaluated whether 14 single-nucleotide polymorphisms within NFκB1, NFκB2, RelA, RelB, Rel, and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non-IA) recruited through a collaborative effort involving the aspBIOmics consortium and four European clinical institutions. No significant overall associations between selected SNPs and the risk of IA were found in this large cohort. Although a hematopoietic stem cell transplantation (HSCT)-stratified analysis revealed that carriers of the IRF4rs12203592T/T genotype had a six-fold increased risk of developing the infection when compared with those carrying the C allele (ORREC = 6.24, 95%CI 1.25–31.2, P = 0.026), the association of this variant with IA risk did not reach significance at experiment-wide significant threshold. In addition, we found an association of the IRF4AATC and IRF4GGTC haplotypes (not including the IRF4rs12203592T risk allele) with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4rs12203592 SNP. Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found. These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA. PMID:27570521

  4. Psychological stress and risk of incident atrial fibrillation in men and women with known atrial fibrillation genetic risk scores

    Science.gov (United States)

    Svensson, Thomas; Kitlinski, Mariusz; Engström, Gunnar; Melander, Olle

    2017-01-01

    Psychological stress has been reported as a possible trigger of atrial fibrillation (AF). No studies have investigated whether any association between stress and AF could be modified by genetic susceptibility to AF (AF-genetic risk score (AF-GRS)). 8765 men and 13,543 women from the Malmö Diet Cancer Study, a population-based cohort, were included in the analyses. A variable representing stress was constructed from questions measuring job strain, and from one question assessing non-occupational stress. Cox proportional hazards regression models were adjusted for known covariates of AF. Mean follow-up times and number of recorded incident AF were 14.2 years and 1116 events for men, and 15.1 years and 932 events for women. Among women, high stress was associated with AF in the age adjusted model (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01–1.47) but not following multivariable adjustment (HR, 1.15; 95% CI, 0.95–1.39). Stress was not associated with incident AF in men. AF-GRS was significantly associated with incident AF for both genders. Stress did not interact significantly with genetic susceptibility to AF in men or women. Chronic stress is not associated with long-term incident hospital diagnosed AF. This association does not appear to be modified by genetic susceptibility to AF. PMID:28195211

  5. Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese.

    Science.gov (United States)

    Lubitz, Steven A; Lunetta, Kathryn L; Lin, Honghuang; Arking, Dan E; Trompet, Stella; Li, Guo; Krijthe, Bouwe P; Chasman, Daniel I; Barnard, John; Kleber, Marcus E; Dörr, Marcus; Ozaki, Kouichi; Smith, Albert V; Müller-Nurasyid, Martina; Walter, Stefan; Agarwal, Sunil K; Bis, Joshua C; Brody, Jennifer A; Chen, Lin Y; Everett, Brendan M; Ford, Ian; Franco, Oscar H; Harris, Tamara B; Hofman, Albert; Kääb, Stefan; Mahida, Saagar; Kathiresan, Sekar; Kubo, Michiaki; Launer, Lenore J; MacFarlane, Peter W; Magnani, Jared W; McKnight, Barbara; McManus, David D; Peters, Annette; Psaty, Bruce M; Rose, Lynda M; Rotter, Jerome I; Silbernagel, Guenther; Smith, Jonathan D; Sotoodehnia, Nona; Stott, David J; Taylor, Kent D; Tomaschitz, Andreas; Tsunoda, Tatsuhiko; Uitterlinden, Andre G; Van Wagoner, David R; Völker, Uwe; Völzke, Henry; Murabito, Joanne M; Sinner, Moritz F; Gudnason, Vilmundur; Felix, Stephan B; März, Winfried; Chung, Mina; Albert, Christine M; Stricker, Bruno H; Tanaka, Toshihiro; Heckbert, Susan R; Jukema, J Wouter; Alonso, Alvaro; Benjamin, Emelia J; Ellinor, Patrick T

    2014-04-01

    This study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk. AF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored. We performed association testing conditioned on the most significant, independently associated genetic markers at 9 established AF loci using 2 complementary techniques in 64,683 individuals of European ancestry (3,869 incident and 3,302 prevalent AF cases). Genetic risk scores were created and tested for association with AF in Europeans and an independent sample of 11,309 individuals of Japanese ancestry (7,916 prevalent AF cases). We observed at least 4 distinct AF susceptibility signals on chromosome 4q25 upstream of PITX2, but not at the remaining 8 AF loci. A multilocus score comprised 12 genetic markers demonstrated an estimated 5-fold gradient in AF risk. We observed a similar spectrum of risk associated with these markers in Japanese. Regions containing AF signals on chromosome 4q25 displayed a greater degree of evolutionary conservation than the remainder of the locus, suggesting that they may tag regulatory elements. The chromosome 4q25 AF locus is architecturally complex and harbors at least 4 AF susceptibility signals in individuals of European ancestry. Similar polygenic AF susceptibility exists between Europeans and Japanese. Future work is necessary to identify causal variants, determine mechanisms by which associated loci predispose to AF, and explore whether AF susceptibility signals classify individuals at risk for AF and related morbidity. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  6. Genetic Factors Contribute to Risk for Neonatal Respiratory Distress Syndrome among Moderately Preterm, Late Preterm, and Term Infants

    Science.gov (United States)

    Shen, Carol L.; Zhang, Qunyuan; Meyer, Julia; Cole, F. Sessions; Wambach, Jennifer A.

    2016-01-01

    Objective To determine the genetic contribution to risk for respiratory distress syndrome (RDS) among moderately preterm, late preterm, and term infants (estimated gestational age ≥32 weeks) of African and European-descent. Study Design We reviewed clinical records for 524 consecutive twin pairs ≥32 weeks gestation. We identified pairs in which at least 1 twin had RDS (n=225) and compared the concordance of RDS between monozygotic (MZ) and dizygotic twins (DZ). Using mixed effects logistic regression, we identified covariates that increased disease risk. We performed additive genetic, common environmental, and residual effects modeling to estimate genetic variance and used the ratio of genetic variance to total variance to estimate genetic contribution to RDS disease risk. Results Monozygotic twins were more concordant for RDS than dizygotic twins (p=0.0040). Estimated gestational age, European-descent, male sex, delivery by cesarean, and five minute Apgar score each independently increased risk for RDS. After adjusting for these covariates, genetic effects accounted for 58% (p=0.0002) of the RDS d