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Sample records for candidate gene-environment interactions

  1. Candidate Gene-Environment Interaction Research: Reflections and Recommendations

    PubMed Central

    Dick, Danielle M.; Agrawal, Arpana; Keller, Matthew C.; Adkins, Amy; Aliev, Fazil; Monroe, Scott; Hewitt, John K.; Kendler, Kenneth S.; Sher, Kenneth J.

    2014-01-01

    Studying how genetic predispositions come together with environmental factors to contribute to complex behavioral outcomes has great potential for advancing our understanding of the development of psychopathology. It represents a clear theoretical advance over studying these factors in isolation. However, research at the intersection of multiple fields creates many challenges. We review several reasons why the rapidly expanding candidate gene-environment interaction (cGxE) literature should be considered with a degree of caution. We discuss lessons learned about candidate gene main effects from the evolving genetics literature and how these inform the study of cGxE. We review the importance of the measurement of the gene and environment of interest in cGxE studies. We discuss statistical concerns with modeling cGxE that are frequently overlooked. And we review other challenges that have likely contributed to the cGxE literature being difficult to interpret, including low power and publication bias. Many of these issues are similar to other concerns about research integrity (e.g., high false positive rates) that have received increasing attention in the social sciences. We provide recommendations for rigorous research practices for cGxE studies that we believe will advance its potential to contribute more robustly to the understanding of complex behavioral phenotypes. PMID:25620996

  2. Refining the Candidate Environment: Interpersonal Stress, the Serotonin Transporter Polymorphism, and Gene-Environment Interactions in Major Depression.

    PubMed

    Vrshek-Schallhorn, Suzanne; Mineka, Susan; Zinbarg, Richard E; Craske, Michelle G; Griffith, James W; Sutton, Jonathan; Redei, Eva E; Wolitzky-Taylor, Kate; Hammen, Constance; Adam, Emma K

    2014-05-01

    Meta-analytic evidence supports a gene-environment (G×E) interaction between life stress and the serotonin transporter polymorphism (5-HTTLPR) on depression, but few studies have examined factors that influence detection of this effect, despite years of inconsistent results. We propose that the "candidate environment" (akin to a candidate gene) is key. Theory and evidence implicate major stressful life events (SLEs)-particularly major interpersonal SLEs-as well as chronic family stress. Participants (N = 400) from the Youth Emotion Project (which began with 627 high school juniors oversampled for high neuroticism) completed up to five annual diagnostic and life stress interviews and provided DNA samples. A significant G×E effect for major SLEs and S-carrier genotype was accounted for significantly by major interpersonal SLEs but not significantly by major non-interpersonal SLEs. S-carrier genotype and chronic family stress also significantly interacted. Identifying such candidate environments may facilitate future G×E research in depression and psychopathology more broadly.

  3. A Candidate-Pathway Approach to Identify Gene-Environment Interactions: Analyses of Colon Cancer Risk and Survival

    PubMed Central

    Sharafeldin, Noha; Slattery, Martha L.; Liu, Qi; Franco-Villalobos, Conrado; Caan, Bette J.; Potter, John D.

    2015-01-01

    Background: Genetic association studies have traditionally focused on associations between individual single nucleotide polymorphisms (SNPs) and disease. Standard analysis ignores interactions between multiple SNPs and environmental exposures explaining a small portion of disease heritability: the often-cited issue of “missing heritability.” Methods: We present a novel three-step analytic framework for modeling gene-environment interactions (GEIs) between an angiogenesis candidate-gene pathway and three lifestyle exposures (dietary protein, smoking, and alcohol consumption) on colon cancer risk and survival. Logic regression was used to summarize the gene-pathway effects, and GEIs were modeled using logistic regression and Cox proportional hazards models. We analyzed data from 1541 colon cancer case patients and 1934 control subjects in the Diet, Activity and Lifestyle as a Risk Factor for Colon Cancer Study. Results: We identified five statistically significant GEIs for colon cancer risk. For risk interaction, odds ratios (ORINT) and 95% confidence intervals (CIs) were FLT1(rs678714) and BMP4(rs17563) and smoking (ORINT = 1.64, 95% CI = 1.11 to 2.41 and ORINT = 1.60, 95% CI = 1.10 to 2.32, respectively); FLT1(rs2387632 OR rs9513070) and protein intake (ORINT = 1.69, 95% CI = 1.03 to 2.77); KDR(rs6838752) and TLR2(rs3804099) and alcohol (ORINT = 1.53, 95% CI = 1.10 to 2.13 and ORINT = 1.59, 95% CI = 1.05 to 2.38, respectively). Three GEIs between TNF, BMP1, and BMPR2 genes and the three exposures were statistically significant at the 5% level in relation to colon cancer survival but not after multiple-testing adjustment. Conclusions: Adopting a comprehensive biologically informed candidate-pathway approach identified GEI effects on colon cancer. Findings may have important implications for public health and personalized medicine targeting prevention and therapeutic strategies. Findings from this study need to be validated in other studies. PMID:26072521

  4. Gene-environment interaction and suicidal behavior.

    PubMed

    Roy, Alec; Sarchiopone, Marco; Carli, Vladimir

    2009-07-01

    Studies have increasingly shown that gene-environment interactions are important in psychiatry. Suicidal behavior is a major public health problem. Suicide is generally considered to be a multi-determined act involving various areas of proximal and distal risk. Genetic risk factors are estimated to account for approximately 30% to 40% of the variance in suicidal behavior. In this article, the authors review relevant studies concerning the interaction between the serotonin transporter gene and environmental variables as a model of gene-environment interactions that may have an impact on suicidal behavior. The findings reviewed here suggest that there may be meaningful interactions between distal and proximal suicide risk factors that may amplify the risk of suicidal behavior. Future studies of suicidal behavior should examine both genetic and environmental variables and examine for gene-environment interactions.

  5. Why study gene-environment interactions?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    PURPOSE OF REVIEW: We examine the reasons for investigating gene-environment interactions and address recent reports evaluating interactions between genes and environmental modulators in relation to cardiovascular disease and its common risk factors. RECENT FINDINGS: Studies focusing on smoking, phy...

  6. Biological Implications of Gene-Environment Interaction

    ERIC Educational Resources Information Center

    Rutter, Michael

    2008-01-01

    Gene-environment interaction (G x E) has been treated as both a statistical phenomenon and a biological reality. It is argued that, although there are important statistical issues that need to be considered, the focus has to be on the biological implications of G x E. Four reports of G x E deriving from the Dunedin longitudinal study are used as…

  7. Gene-environment interactions in obesity.

    PubMed

    Hetherington, Marion M; Cecil, Joanne E

    2010-01-01

    Obesity is a global and growing problem. The detrimental health consequences of obesity are significant and include co-morbidities such as diabetes, cancer and coronary heart disease. The marked rise in obesity observed over the last three decades suggests that behavioural and environmental factors underpin the chronic mismatch between energy intake and energy expenditure. However, not all individuals become obese, suggesting that there is considerable variation in responsiveness to 'obesogenic' environments. Some individuals defend easily against a propensity to accumulate fat mass and become overweight whilst others are predisposed to gain weight, possibly as a function of genotype. The genetic contribution to obesity is well established. Common obesity is polygenic, involving complex gene-gene and gene-environment interactions, and it is these interactions that produce the multi-factorial obese phenotypes. Candidate gene variants for polygenic obesity appear to disrupt pathways involved in the regulation of energy intake and expenditure and include adrenergic receptors, uncoupling proteins, PPARG, POMC, MC4R and a set of single nucleotide polymorphisms in the FTO locus. Notably, the FTO gene is the most robust gene for common obesity characterised to date, and recent data shows that the FTO locus seems to confer risk of obesity through increasing energy intake and reduced satiety. Gene variants involved in pathways regulating addiction and reward behaviours may also play a role in predisposition to obesity. Understanding the routes through which the genotype is expressed will ultimately provide opportunities for developing strategies to intervene, as the interaction between genotype and environment is potentially modifiable through behaviour change.

  8. Gene-environment interactions in sarcoidosis

    PubMed Central

    Culver, Daniel A.; Newman, Lee S.; Kavuru, Mani S.

    2007-01-01

    Susceptibility to most human diseases is polygenic, with complex interactions between functional polymorphisms of single genes governing disease incidence, phenotype, or both. In this context, the contribution of any discrete gene is generally modest for a single individual, but may confer substantial attributable risk on a population level. Environmental exposure can modify the effects of a polymorphism, either by providing a necessary substrate for development of human disease or because the effects of a given exposure modulate the effects of the gene. In several diseases, genetic polymorphisms have been shown to be context-dependent, i.e. the effects of a genetic variant are realized only in the setting of a relevant exposure. Since sarcoidosis susceptibility is dependent on both genetic and environmental modifiers, the study of gene-environment interactions may yield important pathogenetic information and will likely be crucial for uncovering the range of genetic susceptibility loci. However, the complexity of these relationships implies that investigations of gene-environment interactions will require the study of large cohorts with carefully-defined exposures and similar clinical phenotypes. A general principle is that the study of gene-environment interactions requires a sample size at least several-fold greater than for either factor alone. To date, the presence of environmental modifiers has been demonstrated for one sarcoidosis susceptibility locus, HLA-DQB1, in African-American families. This article reviews general considerations obtaining for the study of gene-environment interactions in sarcoidosis. It also describes the limited current understanding of the role of environmental influences on sarcoidosis susceptibility genes. PMID:17560304

  9. Finding gene-environment interactions for phobias.

    PubMed

    Gregory, Alice M; Lau, Jennifer Y F; Eley, Thalia C

    2008-03-01

    Phobias are common disorders causing a great deal of suffering. Studies of gene-environment interaction (G x E) have revealed much about the complex processes underlying the development of various psychiatric disorders but have told us little about phobias. This article describes what is already known about genetic and environmental influences upon phobias and suggests how this information can be used to optimise the chances of discovering G x Es for phobias. In addition to the careful conceptualisation of new studies, it is suggested that data already collected should be re-analysed in light of increased understanding of processes influencing phobias.

  10. Autism risk factors: genes, environment, and gene-environment interactions

    PubMed Central

    Chaste, Pauline; Leboyer, Marion

    2012-01-01

    The aim of this review is to summarize the key findings from genetic and epidemiological research, which show that autism is a complex disorder resulting from the combination of genetic and environmental factors. Remarkable advances in the knowledge of genetic causes of autism have resulted from the great efforts made in the field of genetics. The identification of specific alleles contributing to the autism spectrum has supplied important pieces for the autism puzzle. However, many questions remain unanswered, and new questions are raised by recent results. Moreover, given the amount of evidence supporting a significant contribution of environmental factors to autism risk, it is now clear that the search for environmental factors should be reinforced. One aspect of this search that has been neglected so far is the study of interactions between genes and environmental factors. PMID:23226953

  11. Autism risk factors: genes, environment, and gene-environment interactions.

    PubMed

    Chaste, Pauline; Leboyer, Marion

    2012-09-01

    The aim of this review is to summarize the key findings from genetic and epidemiological research, which show that autism is a complex disorder resulting from the combination of genetic and environmental factors. Remarkable advances in the knowledge of genetic causes of autism have resulted from the great efforts made in the field of genetics. The identification of specific alleles contributing to the autism spectrum has supplied important pieces for the autism puzzle. However, many questions remain unanswered, and new questions are raised by recent results. Moreover, given the amount of evidence supporting a significant contribution of environmental factors to autism risk, it is now clear that the search for environmental factors should be reinforced. One aspect of this search that has been neglected so far is the study of interactions between genes and environmental factors.

  12. Gene-Environment Interactions in Asthma: Genetic and Epigenetic Effects.

    PubMed

    Lee, Jong-Uk; Kim, Jeong Dong; Park, Choon-Sik

    2015-07-01

    Over the past three decades, a large number of genetic studies have been aimed at finding genetic variants associated with the risk of asthma, applying various genetic and genomic approaches including linkage analysis, candidate gene polymorphism studies, and genome-wide association studies (GWAS). However, contrary to general expectation, even single nucleotide polymorphisms (SNPs) discovered by GWAS failed to fully explain the heritability of asthma. Thus, application of rare allele polymorphisms in well defined phenotypes and clarification of environmental factors have been suggested to overcome the problem of 'missing' heritability. Such factors include allergens, cigarette smoke, air pollutants, and infectious agents during pre- and post-natal periods. The first and simplest interaction between a gene and the environment is a candidate interaction of both a well known gene and environmental factor in a direct physical or chemical interaction such as between CD14 and endotoxin or between HLA and allergens. Several GWAS have found environmental interactions with occupational asthma, aspirin exacerbated respiratory disease, tobacco smoke-related airway dysfunction, and farm-related atopic diseases. As one of the mechanisms behind gene-environment interaction is epigenetics, a few studies on DNA CpG methylation have been reported on subphenotypes of asthma, pitching the exciting idea that it may be possible to intervene at the junction between the genome and the environment. Epigenetic studies are starting to include data from clinical samples, which will make them another powerful tool for re-search on gene-environment interactions in asthma.

  13. Gene-environment interactions in esophageal cancer.

    PubMed

    Matejcic, Marco; Iqbal Parker, M

    2015-01-01

    Esophageal cancer (EC) is one of the most common malignancies in low- and medium-income countries and represents a disease of public health importance because of its poor prognosis and high mortality rate in these regions. The striking variation in the prevalence of EC among different ethnic groups suggests a significant contribution of population-specific environmental and dietary factors to susceptibility to the disease. Although individuals within a demarcated geographical area are exposed to the same environment and share similar dietary habits, not all of them will develop the disease; thus genetic susceptibility to environmental risk factors may play a key role in the development of EC. A wide range of xenobiotic-metabolizing enzymes are responsible for the metabolism of carcinogens introduced via the diet or inhaled from the environment. Such dietary or environmental carcinogens can bind to DNA, resulting in mutations that may lead to carcinogenesis. Genes involved in the biosynthesis of these enzymes are all subject to genetic polymorphisms that can lead to altered expression or activity of the encoded proteins. Genetic polymorphisms may, therefore, act as molecular biomarkers that can provide important predictive information about carcinogenesis. The aim of this review is to discuss our current knowledge on the genetic risk factors associated with the development of EC in different populations; it addresses mainly the topics of genetic polymorphisms, gene-environment interactions, and carcinogenesis. We have reviewed the published data on genetic polymorphisms of enzymes involved in the metabolism of xenobiotics and discuss some of the potential gene-environment interactions underlying esophageal carcinogenesis. The main enzymes discussed in this review are the glutathione S-transferases (GSTs), N-acetyltransferases (NATs), cytochrome P450s (CYPs), sulfotransferases (SULTs), UDP-glucuronosyltransferases (UGTs), and epoxide hydrolases (EHs), all of which

  14. Environmental confounding in gene-environment interaction studies.

    PubMed

    Vanderweele, Tyler J; Ko, Yi-An; Mukherjee, Bhramar

    2013-07-01

    We show that, in the presence of uncontrolled environmental confounding, joint tests for the presence of a main genetic effect and gene-environment interaction will be biased if the genetic and environmental factors are correlated, even if there is no effect of either the genetic factor or the environmental factor on the disease. When environmental confounding is ignored, such tests will in fact reject the joint null of no genetic effect with a probability that tends to 1 as the sample size increases. This problem with the joint test vanishes under gene-environment independence, but it still persists if estimating the gene-environment interaction parameter itself is of interest. Uncontrolled environmental confounding will bias estimates of gene-environment interaction parameters even under gene-environment independence, but it will not do so if the unmeasured confounding variable itself does not interact with the genetic factor. Under gene-environment independence, if the interaction parameter without controlling for the environmental confounder is nonzero, then there is gene-environment interaction either between the genetic factor and the environmental factor of interest or between the genetic factor and the unmeasured environmental confounder. We evaluate several recently proposed joint tests in a simulation study and discuss the implications of these results for the conduct of gene-environment interaction studies.

  15. Gene environment interaction from international cohorts

    PubMed Central

    Gaffney, Adam; Christiani, David C.

    2016-01-01

    Environmental and occupational pulmonary diseases impose a substantial burden of morbidity and mortality on the global population. However, it has been long observed that only some of those who are exposed to pulmonary toxicants go on to develop disease; increasingly, it is being recognized that genetic differences may underlie some of this person-to-person variability. Studies performed throughout the globe are demonstrating important gene-by-environment interactions for diseases as diverse as chronic beryllium disease, coal workers’ pneumoconiosis, silicosis, asbestosis, bysinnosis, occupational asthma, and pollution-associated asthma. These findings have, in many instances, elucidated the pathogenesis of these highly complex diseases. At the same time, however, translation of this research into clinical practice has, for good reasons, proceeded slowly. No genetic test has yet emerged with sufficiently robust operating characteristics to be clearly useful or practicable in an occupational or environmental setting. Additionally, occupational genetic testing raises serious ethical and policy concerns. Therefore, the primary objective must remain ensuring that the workplace and the environment are safe for all. PMID:26024343

  16. Gene-Environment Interactions in Genome-Wide Association Studies: Current Approaches and New Directions

    ERIC Educational Resources Information Center

    Winham, Stacey J.; Biernacka, Joanna M.

    2013-01-01

    Background: Complex psychiatric traits have long been thought to be the result of a combination of genetic and environmental factors, and gene-environment interactions are thought to play a crucial role in behavioral phenotypes and the susceptibility and progression of psychiatric disorders. Candidate gene studies to investigate hypothesized…

  17. Gene-Environment Interactions in Genome-Wide Association Studies: Current Approaches and New Directions

    PubMed Central

    Winham, Stacey J; Biernacka, Joanna M.

    2013-01-01

    Background Complex psychiatric traits have long been thought to be the result of a combination of genetic and environmental factors, and gene-environment interactions are thought to play a crucial role in behavioral phenotypes and the susceptibility and progression of psychiatric disorders. Candidate gene studies to investigate hypothesized gene-environment interactions are now fairly common in human genetic research, and with the shift towards genome-wide association studies, genome-wide gene-environment interaction studies are beginning to emerge. Methods We summarize the basic ideas behind gene-environment interaction, and provide an overview of possible study designs and traditional analysis methods in the context of genome-wide analysis. We then discuss novel approaches beyond the traditional strategy of analyzing the interaction between the environmental factor and each polymorphism individually. Results Two-step filtering approaches that reduce the number of polymorphisms tested for interactions can substantially increase the power of genome-wide gene-environment studies. New analytical methods including data-mining approaches, and gene-level and pathway-level analyses, also have the capacity to improve our understanding of how complex genetic and environmental factors interact to influence psychological and psychiatric traits. Such methods, however, have not yet been utilized much in behavioral and mental health research. Conclusions Although methods to investigate gene-environment interactions are available, there is a need for further development and extension of these methods to identify gene-environment interactions in the context of genome-wide association studies. These novel approaches need to be applied in studies of psychology and psychiatry. PMID:23808649

  18. Understanding risk for psychopathology through imaging gene-environment interactions

    PubMed Central

    Hyde, Luke W.; Bogdan, Ryan; Hariri, Ahmad R.

    2011-01-01

    Examining the interplay of genes, experience, and the brain is critical to understanding psychopathology. We review the recent gene-environment interaction (GxE) and imaging genetics literature with the goal of developing models to bridge these approaches within single imaging gene-environment interaction (IGxE) studies. We explore challenges inherent in both GxE and imaging genetics and highlight studies that address these limitations. In specifying IGxE models, we examine statistical methods for combining these approaches, and explore plausible biological mechanisms (e.g., epigenetics) through which these conditional mechanisms can be understood. Finally, we discuss the potential contribution that IGxE studies can make to understanding psychopathology and developing more personalized and effective prevention and treatment. PMID:21839667

  19. Gene-Environment Interactions and the Etiology of Birth Defects.

    PubMed

    Krauss, Robert S; Hong, Mingi

    2016-01-01

    It is thought that most structural birth defects are caused by a complex combination of genetic and environmental factors that interact to interfere with morphogenetic processes. It is important not only to identify individual genetic and environmental risk factors for particular defects but also to identify which environmental factors interact specifically with which genetic variants that predispose to the same defect. Genomic and epidemiological studies are critical to this end. Development and analysis of model systems will also be essential for this goal, as well as for understanding the mechanisms that underlie specific gene-environment interactions.

  20. The importance of gene-environment interactions in human obesity.

    PubMed

    Reddon, Hudson; Guéant, Jean-Louis; Meyre, David

    2016-09-01

    The worldwide obesity epidemic has been mainly attributed to lifestyle changes. However, who becomes obese in an obesity-prone environment is largely determined by genetic factors. In the last 20 years, important progress has been made in the elucidation of the genetic architecture of obesity. In parallel with successful gene identifications, the number of gene-environment interaction (GEI) studies has grown rapidly. This paper reviews the growing body of evidence supporting gene-environment interactions in the field of obesity. Heritability, monogenic and polygenic obesity studies provide converging evidence that obesity-predisposing genes interact with a variety of environmental, lifestyle and treatment exposures. However, some skepticism remains regarding the validity of these studies based on several issues, which include statistical modelling, confounding, low replication rate, underpowered analyses, biological assumptions and measurement precision. What follows in this review includes (1) an introduction to the study of GEI, (2) the evidence of GEI in the field of obesity, (3) an outline of the biological mechanisms that may explain these interaction effects, (4) methodological challenges associated with GEI studies and potential solutions, and (5) future directions of GEI research. Thus far, this growing body of evidence has provided a deeper understanding of GEI influencing obesity and may have tremendous applications in the emerging field of personalized medicine and individualized lifestyle recommendations.

  1. Music training and speech perception: a gene-environment interaction.

    PubMed

    Schellenberg, E Glenn

    2015-03-01

    Claims of beneficial side effects of music training are made for many different abilities, including verbal and visuospatial abilities, executive functions, working memory, IQ, and speech perception in particular. Such claims assume that music training causes the associations even though children who take music lessons are likely to differ from other children in music aptitude, which is associated with many aspects of speech perception. Music training in childhood is also associated with cognitive, personality, and demographic variables, and it is well established that IQ and personality are determined largely by genetics. Recent evidence also indicates that the role of genetics in music aptitude and music achievement is much larger than previously thought. In short, music training is an ideal model for the study of gene-environment interactions but far less appropriate as a model for the study of plasticity. Children seek out environments, including those with music lessons, that are consistent with their predispositions; such environments exaggerate preexisting individual differences.

  2. Gene-environment interactions in chronic obstructive pulmonary disease.

    PubMed

    Molfino, Nestor A; Coyle, Anthony J

    2008-01-01

    Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death throughout the world and is largely associated with cigarette smoking. Despite the appreciation of the central role of smoking in the development of COPD, only a relatively small number of smokers (15%-20%) develop COPD. Recent studies depicting familial aggregation suggest that some subjects may have a genetic predisposition to developing COPD. In this respect, a number of single nucleotide polymorphisms have been reported in association with different COPD features (subphenotypes), although much of this data remains controversial. Classical genetic studies (including twin and family studies) assume an "equal-environment" scenario, but as gene-environment interactions occur in COPD, this assumption needs revision. Thus, new integrated models are needed to examine the major environmental factors associated with COPD which include smoking as well as air pollution, and respiratory infections, and not only genetic predisposition. Revisiting this area, may help answer the question of what has more bearing in the pathogenesis of COPD--the environment or the genomic sequence of the affected subjects. It is anticipated that an improved understanding of this interaction will both enable improved identification of individuals susceptible to developing this disease, as well as improved future treatments for this disease.

  3. Study of oral clefts: Indication of gene-environment interaction

    SciTech Connect

    Hwang, S.J.; Beaty, T.H.; Panny, S.

    1994-09-01

    In this study of infants with isolated birth defects, 69 cleft palate-only (CPO) cases, 114 cleft lip with or without palate (CL/P), and 284 controls with non-cleft birth defects (all born in Maryland during 1984-1992) were examined to test for associations among genetic markers and different oral clefts. Modest associations were found between transforming growth factor {alpha} (TGF{alpha}) marker and CPO, as well as that between D17S579 (Mfd188) and CL/P in this study. The association between TGF{alpha} marker and CPO reflects a statistical interaction between mother`s smoking and child`s TGF{alpha} genotype. A significantly higher risk of CPO was found among those reporting maternal smoking during pregnancy and carrying less common TGF{alpha} TaqI allele (odds ratio=7.02 with 95% confidence interval 1.8-27.6). This gene-environment interaction was also found among those who reported no family history of any type of birth defect (odds ratio=5.60 with 95% confidence interval 1.4-22.9). Similar associations were seen for CL/P, but these were not statistically significant.

  4. Subtle gene-environment interactions driving paranoia in daily life.

    PubMed

    Simons, C J P; Wichers, M; Derom, C; Thiery, E; Myin-Germeys, I; Krabbendam, L; van Os, J

    2009-02-01

    It has been suggested that genes impact on the degree to which minor daily stressors cause variation in the intensity of subtle paranoid experiences. The objective of the present study was to test the hypothesis that catechol-O-methyltransferase (COMT) Val(158)Met and brain-derived neurotrophic factor (BDNF) Val(66)Met in part mediate genetic effects on paranoid reactivity to minor stressors. In a general population sample of 579 young adult female twins, on the one hand, appraisals of (1) event-related stress and (2) social stress and, on the other hand, feelings of paranoia in the flow of daily life were assessed using momentary assessment technology for five consecutive days. Multilevel regression analyses were used to examine moderation of daily life stress-induced paranoia by COMT Val(158)Met and BDNF Val(66)Met genotypes. Catechol-O-methyltransferase Val carriers displayed more feelings of paranoia in response to event stress compared with Met carriers. Brain-derived neurotrophic factor Met carriers showed more social-stress-induced paranoia than individuals with the Val/Val genotype. Thus, paranoia in the flow of daily life may be the result of gene-environment interactions that can be traced to different types of stress being moderated by different types of genetic variation.

  5. Gene-environment Interactions in the Etiology of Dental Caries.

    PubMed

    Yildiz, G; Ermis, R B; Calapoglu, N S; Celik, E U; Türel, G Y

    2016-01-01

    Dental caries is a multifactorial disease that can be conceptualized as an interaction between genetic and environmental risk factors. The aim of this study is to examine the effects of AMELX, CA6, DEFB1, and TAS2R38 gene polymorphism and gene-environment interactions on caries etiology and susceptibility in adults. Genomic DNA was extracted from the buccal mucosa, and adults aged 20 to 60 y were placed into 1 of 2 groups: low caries risk (DMFT ≤ 5; n = 77) and high caries risk (DMFT ≥ 14; n = 77). The frequency of AMELX (+522), CA6 (T55M), DEFB1 (G-20A), and TAS2R38 (A49P) single-nucleotide polymorphisms was genotyped with the polymerase chain reaction-restriction fragment length polymorphism method. Environmental risk factors examined in the study included plaque amount, toothbrushing frequency, dietary intake between meals, saliva secretion rate, saliva buffer capacity, mutans streptococci counts, and lactobacilli counts. There was no difference between the caries risk groups in relation to AMELX (+522) polymorphism (χ(2) test, P > 0.05). The distribution of CA6 genotype and allele frequencies in the low caries risk group did not differ from the high caries risk group (χ(2) test, P > 0.05). Polymorphism of DEFB1 (G-20A) was positively associated, and TAS2R38 (A49P) negatively associated, with caries risk (χ(2) test, P = 0.000). There were significant differences between caries susceptibility and each environmental risk factor, except for the saliva secretion rate (Mann-Whitney U test, P = 0.000). Based on stepwise multiple linear regression analyses, dental plaque amount, lactobacilli count, age, and saliva buffer capacity, as well as DEFB1 (G-20A), TAS2R38 (A49P), and CA6 (T55M) gene polymorphism, explained a total of 87.8% of the variations in DMFT scores. It can be concluded that variation in CA6 (T55M), DEFB1 (G-20A), and TAS2R38 (A49P) may be associated with caries experience in Turkish adults with a high level of dental plaque, lactobacilli count

  6. Efficient Designs of Gene-Environment Interaction Studies: Implications of Hardy-Weinberg Equilibrium and Gene-Environment Independence

    PubMed Central

    Chen, Jinbo; Kang, Guolian; VanderWeele, Tyler; Zhang, Cuilin; Mukherjee, Bhramar

    2012-01-01

    SUMMARY It is important to investigate whether genetic susceptible variants exercise the same effects in populations that are differentially exposed to environmental risk factors. Here, we assess the power of four two-phase case-control design strategies for assessing multiplicative gene-environment (G-E) interactions or for assessing genetic or environmental effects in the presence of G-E interactions. With a di-allelic SNP and a binary E, we obtained closed-form maximum likelihood estimates of both main effect and interaction odds ratio parameters under the constraints of G-E independence and Hardy-Weinberg Equilibrium, and used the Wald statistic for all tests. We concluded that i) for testing G-E interactions or genetic effects in the presence of G-E interactions when data for E is fully available, it is preferable to ascertain data for G in a subsample of cases with similar numbers of exposed and unexposed and a random subsample of controls; and ii) for testing G-E interactions or environmental effects in the presence of G-E interactions when data for G is fully available, it is preferable to ascertain data for E in a subsample of cases that has similar numbers for each genotype and a random subsample of controls. In addition, supplementing external control data to an existing casecontrol sample leads to improved power for assessing effects of G or E in the presence of G-E interactions. PMID:22362617

  7. Disentangling Gene-Environment Correlations and Interactions on Adolescent Depressive Symptoms

    ERIC Educational Resources Information Center

    Lau, Jennifer Y. F.; Eley, Thalia C.

    2008-01-01

    Background: Genetic risks for depression may be expressed through greater exposure towards environmental stressors (gene-environment correlation, rGE) and increased susceptibility to these stressors (gene-environment interaction, G x E). While these effects are often studied independently, evidence supports their co-occurrence on depression.…

  8. Genetics and gene-environment interactions on longevity and lifespan

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Longevity is a complex trait and highly associated with healthspan – lifespan without major diseases. In human populations there is a large amount of variation in longevity, which can be attributed to genetics, environment, and interactions between them. The genetic contribution to longevity is abou...

  9. Celiac disease: a model disease for gene-environment interaction.

    PubMed

    Uibo, Raivo; Tian, Zhigang; Gershwin, M Eric

    2011-03-01

    Celiac sprue remains a model autoimmune disease for dissection of genetic and environmental influences on disease progression. The 2010 Congress of Autoimmunity included several key sessions devoted to genetics and environment. Several papers from these symposia were selected for in-depth discussion and publication. This issue is devoted to this theme. The goal is not to discuss genetic and environmental interactions, but rather to focus on key elements of diagnosis, the inflammatory response and the mechanisms of autoimmunity.

  10. Modeling Gene-Environment Interactions With Quasi-Natural Experiments.

    PubMed

    Schmitz, Lauren; Conley, Dalton

    2017-02-01

    This overview develops new empirical models that can effectively document Gene × Environment (G×E) interactions in observational data. Current G×E studies are often unable to support causal inference because they use endogenous measures of the environment or fail to adequately address the nonrandom distribution of genes across environments, confounding estimates. Comprehensive measures of genetic variation are incorporated into quasi-natural experimental designs to exploit exogenous environmental shocks or isolate variation in environmental exposure to avoid potential confounders. In addition, we offer insights from population genetics that improve upon extant approaches to address problems from population stratification. Together, these tools offer a powerful way forward for G×E research on the origin and development of social inequality across the life course.

  11. Gene-environment interactions and obesity: recent developments and future directions

    PubMed Central

    2015-01-01

    Obesity, a major public health concern, is a multifactorial disease caused by both environmental and genetic factors. Although recent genome-wide association studies have identified many loci related to obesity or body mass index, the identified variants explain only a small proportion of the heritability of obesity. Better understanding of the interplay between genetic and environmental factors is the basis for developing effective personalized obesity prevention and management strategies. This article reviews recent advances in identifying gene-environment interactions related to obesity and describes epidemiological designs and newly developed statistical approaches to characterizing and discovering gene-environment interactions on obesity risk. PMID:25951849

  12. Variance components models for gene-environment interaction in twin analysis.

    PubMed

    Purcell, Shaun

    2002-12-01

    Gene-environment interaction is likely to be a common and important source of variation for complex behavioral traits. Often conceptualized as the genetic control of sensitivity to the environment, it can be incorporated in variance components twin analyses by partitioning genetic effects into a mean part, which is independent of the environment, and a part that is a linear function of the environment. The model allows for one or more environmental moderator variables (that possibly interact with each other) that may i). be continuous or binary ii). differ between twins within a pair iii). interact with residual environmental as well as genetic effects iv) have nonlinear moderating properties v). show scalar (different magnitudes) or qualitative (different genes) interactions vi). be correlated with genetic effects acting upon the trait, to allow for a test of gene-environment interaction in the presence of gene-environment correlation. Aspects and applications of a class of models are explored by simulation, in the context of both individual differences twin analysis and, in a companion paper (Purcell & Sham, 2002) sibpair quantitative trait locus linkage analysis. As well as elucidating environmental pathways, consideration of gene-environment interaction in quantitative and molecular studies will potentially direct and enhance gene-mapping efforts.

  13. Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations.

    PubMed

    van Os, Jim; Rutten, Bart P; Myin-Germeys, Inez; Delespaul, Philippe; Viechtbauer, Wolfgang; van Zelst, Catherine; Bruggeman, Richard; Reininghaus, Ulrich; Morgan, Craig; Murray, Robin M; Di Forti, Marta; McGuire, Philip; Valmaggia, Lucia R; Kempton, Matthew J; Gayer-Anderson, Charlotte; Hubbard, Kathryn; Beards, Stephanie; Stilo, Simona A; Onyejiaka, Adanna; Bourque, Francois; Modinos, Gemma; Tognin, Stefania; Calem, Maria; O'Donovan, Michael C; Owen, Michael J; Holmans, Peter; Williams, Nigel; Craddock, Nicholas; Richards, Alexander; Humphreys, Isla; Meyer-Lindenberg, Andreas; Leweke, F Markus; Tost, Heike; Akdeniz, Ceren; Rohleder, Cathrin; Bumb, J Malte; Schwarz, Emanuel; Alptekin, Köksal; Üçok, Alp; Saka, Meram Can; Atbaşoğlu, E Cem; Gülöksüz, Sinan; Gumus-Akay, Guvem; Cihan, Burçin; Karadağ, Hasan; Soygür, Haldan; Cankurtaran, Eylem Şahin; Ulusoy, Semra; Akdede, Berna; Binbay, Tolga; Ayer, Ahmet; Noyan, Handan; Karadayı, Gülşah; Akturan, Elçin; Ulaş, Halis; Arango, Celso; Parellada, Mara; Bernardo, Miguel; Sanjuán, Julio; Bobes, Julio; Arrojo, Manuel; Santos, Jose Luis; Cuadrado, Pedro; Rodríguez Solano, José Juan; Carracedo, Angel; García Bernardo, Enrique; Roldán, Laura; López, Gonzalo; Cabrera, Bibiana; Cruz, Sabrina; Díaz Mesa, Eva Ma; Pouso, María; Jiménez, Estela; Sánchez, Teresa; Rapado, Marta; González, Emiliano; Martínez, Covadonga; Sánchez, Emilio; Olmeda, Ma Soledad; de Haan, Lieuwe; Velthorst, Eva; van der Gaag, Mark; Selten, Jean-Paul; van Dam, Daniella; van der Ven, Elsje; van der Meer, Floor; Messchaert, Elles; Kraan, Tamar; Burger, Nadine; Leboyer, Marion; Szoke, Andrei; Schürhoff, Franck; Llorca, Pierre-Michel; Jamain, Stéphane; Tortelli, Andrea; Frijda, Flora; Vilain, Jeanne; Galliot, Anne-Marie; Baudin, Grégoire; Ferchiou, Aziz; Richard, Jean-Romain; Bulzacka, Ewa; Charpeaud, Thomas; Tronche, Anne-Marie; De Hert, Marc; van Winkel, Ruud; Decoster, Jeroen; Derom, Catherine; Thiery, Evert; Stefanis, Nikos C; Sachs, Gabriele; Aschauer, Harald; Lasser, Iris; Winklbaur, Bernadette; Schlögelhofer, Monika; Riecher-Rössler, Anita; Borgwardt, Stefan; Walter, Anna; Harrisberger, Fabienne; Smieskova, Renata; Rapp, Charlotte; Ittig, Sarah; Soguel-dit-Piquard, Fabienne; Studerus, Erich; Klosterkötter, Joachim; Ruhrmann, Stephan; Paruch, Julia; Julkowski, Dominika; Hilboll, Desiree; Sham, Pak C; Cherny, Stacey S; Chen, Eric Y H; Campbell, Desmond D; Li, Miaoxin; Romeo-Casabona, Carlos María; Emaldi Cirión, Aitziber; Urruela Mora, Asier; Jones, Peter; Kirkbride, James; Cannon, Mary; Rujescu, Dan; Tarricone, Ilaria; Berardi, Domenico; Bonora, Elena; Seri, Marco; Marcacci, Thomas; Chiri, Luigi; Chierzi, Federico; Storbini, Viviana; Braca, Mauro; Minenna, Maria Gabriella; Donegani, Ivonne; Fioritti, Angelo; La Barbera, Daniele; La Cascia, Caterina Erika; Mulè, Alice; Sideli, Lucia; Sartorio, Rachele; Ferraro, Laura; Tripoli, Giada; Seminerio, Fabio; Marinaro, Anna Maria; McGorry, Patrick; Nelson, Barnaby; Amminger, G Paul; Pantelis, Christos; Menezes, Paulo R; Del-Ben, Cristina M; Gallo Tenan, Silvia H; Shuhama, Rosana; Ruggeri, Mirella; Tosato, Sarah; Lasalvia, Antonio; Bonetto, Chiara; Ira, Elisa; Nordentoft, Merete; Krebs, Marie-Odile; Barrantes-Vidal, Neus; Cristóbal, Paula; Kwapil, Thomas R; Brietzke, Elisa; Bressan, Rodrigo A; Gadelha, Ary; Maric, Nadja P; Andric, Sanja; Mihaljevic, Marina; Mirjanic, Tijana

    2014-07-01

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.

  14. Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations

    PubMed Central

    2014-01-01

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi–center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. PMID:24860087

  15. How Gene-Environment Interaction Affects Children's Anxious and Fearful Behavior. Science Briefs

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This brief reports on the study "Evidence for a Gene-Environment Interaction in Predicting Behavioral Inhibition in Middle Childhood" (N. A. Fox, K E. Nichols, H. A. Henderson, K. Rubin, L. Schmidt, D. Hamer, M. Ernst, and D. S.…

  16. Confirmatory and Competitive Evaluation of Alternative Gene-Environment Interaction Hypotheses

    ERIC Educational Resources Information Center

    Belsky, Jay; Pluess, Michael; Widaman, Keith F.

    2013-01-01

    Background: Most gene-environment interaction (GXE) research, though based on clear, vulnerability-oriented hypotheses, is carried out using exploratory rather than hypothesis-informed statistical tests, limiting power and making formal evaluation of competing GXE propositions difficult. Method: We present and illustrate a new regression technique…

  17. Gene-Environment Interaction and Breast Cancer on Long Island, NY

    DTIC Science & Technology

    2006-05-01

    exposures, endocrine disruptors , estrogen receptor genes, gene-environment interaction, methodologic approaches to examining multiple exposures 16...phthalates and pyrethroid pesticides . o The collection of serial urine samples was completed. o The CDC has competed sample analysis and has...Environmental Epidemiology 2005). Teitelbaum SL, Gammon MD, Britton JA, Neugut AI, Levin B, Stellman SD. Reported residential pesticide use and breast

  18. Meta-regression of gene-environment interaction in genome-wide association studies.

    PubMed

    Xu, Xiaoxiao; Shi, Gang; Nehorai, Arye

    2013-12-01

    Genome-wide association studies (GWAS) have created heightened interest in understanding the effects of gene-environment interaction on complex human diseases or traits. Applying methods for analyzing such interaction can help uncover novel genes and identify environmental hazards that influence only certain genetically susceptible groups. However, the number of interaction analysis methods is still limited, so there is a need to develop more efficient and powerful methods. In this paper, we propose two novel meta-analysis methods of studying gene-environment interaction, based on meta-regression of estimated genetic effects on the environmental factor. The two methods can perform joint analysis of a single nucleotide polymorphism's (SNP) main and interaction effects, or analyze only the effect of the interaction. They can readily estimate any linear or non-linear interactions by simply modifying the gene-environment regression function. Thus, they are efficient methods to be applied to different scenarios. We use numerical examples to demonstrate the performance of our methods. We also compare them with two other methods commonly used in current GWAS, i.e., meta-analysis of SNP main effects (MAIN) and joint meta-analysis of SNP main and interaction effects (JMA). The results show that our methods are more powerful than MAIN when the interaction effect exists, and are comparable to JMAin the linear or quadratic interaction cases. In the numerical examples, we also investigate how the number of the divided groups and the sample size of the studies affect the performance of our methods.

  19. Identifying gene-environment and gene-gene interactions using a progressive penalization approach.

    PubMed

    Zhu, Ruoqing; Zhao, Hongyu; Ma, Shuangge

    2014-05-01

    In genomic studies, identifying important gene-environment and gene-gene interactions is a challenging problem. In this study, we adopt the statistical modeling approach, where interactions are represented by product terms in regression models. For the identification of important interactions, we adopt penalization, which has been used in many genomic studies. Straightforward application of penalization does not respect the "main effect, interaction" hierarchical structure. A few recently proposed methods respect this structure by applying constrained penalization. However, they demand very complicated computational algorithms and can only accommodate a small number of genomic measurements. We propose a computationally fast penalization method that can identify important gene-environment and gene-gene interactions and respect a strong hierarchical structure. The method takes a stagewise approach and progressively expands its optimization domain to account for possible hierarchical interactions. It is applicable to multiple data types and models. A coordinate descent method is utilized to produce the entire regularized solution path. Simulation study demonstrates the superior performance of the proposed method. We analyze a lung cancer prognosis study with gene expression measurements and identify important gene-environment interactions.

  20. Tests for Gene-Environment Interactions and Joint Effects With Exposure Misclassification

    PubMed Central

    Boonstra, Philip S.; Mukherjee, Bhramar; Gruber, Stephen B.; Ahn, Jaeil; Schmit, Stephanie L.; Chatterjee, Nilanjan

    2016-01-01

    The number of methods for genome-wide testing of gene-environment (G-E) interactions continues to increase, with the aim of discovering new genetic risk factors and obtaining insight into the disease-gene-environment relationship. The relative performance of these methods, assessed on the basis of family-wise type I error rate and power, depends on underlying disease-gene-environment associations, estimates of which may be biased in the presence of exposure misclassification. This simulation study expands on a previously published simulation study of methods for detecting G-E interactions by evaluating the impact of exposure misclassification. We consider 7 single-step and modular screening methods for identifying G-E interaction at a genome-wide level and 7 joint tests for genetic association and G-E interaction, for which the goal is to discover new genetic susceptibility loci by leveraging G-E interaction when present. In terms of statistical power, modular methods that screen on the basis of the marginal disease-gene relationship are more robust to exposure misclassification. Joint tests that include main/marginal effects of a gene display a similar robustness, which confirms results from earlier studies. Our results offer an increased understanding of the strengths and limitations of methods for genome-wide searches for G-E interaction and joint tests in the presence of exposure misclassification. PMID:26755675

  1. Gene-Environment Interaction and Breast Cancer on Long Island, NY

    DTIC Science & Technology

    2007-05-01

    TERMS epidemiology, environmental exposures, endocrine disruptors , estrogen receptor genes, gene-environment interaction, methodologic approaches...phthalates and pyrethroid pesticides . o The collection of serial urine samples was completed. W81XWH-04-1-0507 6 o The CDC has competed sample...manuscripts are in preparation. • Published manuscript examining combined effect of multiple exposures “Reported residential pesticide use and breast

  2. The genetics of music accomplishment: evidence for gene-environment correlation and interaction.

    PubMed

    Hambrick, David Z; Tucker-Drob, Elliot M

    2015-02-01

    Theories of skilled performance that emphasize training history, such as K. Anders Ericsson and colleagues' deliberate-practice theory, have received a great deal of recent attention in both the scientific literature and the popular press. Twin studies, however, have demonstrated evidence for moderate-to-strong genetic influences on skilled performance. Focusing on musical accomplishment in a sample of over 800 pairs of twins, we found evidence for gene-environment correlation, in the form of a genetic effect on music practice. However, only about one quarter of the genetic effect on music accomplishment was explained by this genetic effect on music practice, suggesting that genetically influenced factors other than practice contribute to individual differences in music accomplishment. We also found evidence for gene-environment interaction, such that genetic effects on music accomplishment were most pronounced among those engaging in music practice, suggesting that genetic potentials for skilled performance are most fully expressed and fostered by practice.

  3. Genome-wide gene-environment interactions on quantitative traits using family data.

    PubMed

    Sitlani, Colleen M; Dupuis, Josée; Rice, Kenneth M; Sun, Fangui; Pitsillides, Achilleas N; Cupples, L Adrienne; Psaty, Bruce M

    2016-07-01

    Gene-environment interactions may provide a mechanism for targeting interventions to those individuals who would gain the most benefit from them. Searching for interactions agnostically on a genome-wide scale requires large sample sizes, often achieved through collaboration among multiple studies in a consortium. Family studies can contribute to consortia, but to do so they must account for correlation within families by using specialized analytic methods. In this paper, we investigate the performance of methods that account for within-family correlation, in the context of gene-environment interactions with binary exposures and quantitative outcomes. We simulate both cross-sectional and longitudinal measurements, and analyze the simulated data taking family structure into account, via generalized estimating equations (GEE) and linear mixed-effects models. With sufficient exposure prevalence and correct model specification, all methods perform well. However, when models are misspecified, mixed modeling approaches have seriously inflated type I error rates. GEE methods with robust variance estimates are less sensitive to model misspecification; however, when exposures are infrequent, GEE methods require modifications to preserve type I error rate. We illustrate the practical use of these methods by evaluating gene-drug interactions on fasting glucose levels in data from the Framingham Heart Study, a cohort that includes related individuals.

  4. A mechanism for gene-environment interaction in the etiology of congenital scoliosis.

    PubMed

    Sparrow, Duncan B; Chapman, Gavin; Smith, Allanceson J; Mattar, Muhammad Z; Major, Joelene A; O'Reilly, Victoria C; Saga, Yumiko; Zackai, Elaine H; Dormans, John P; Alman, Benjamin A; McGregor, Lesley; Kageyama, Ryoichiro; Kusumi, Kenro; Dunwoodie, Sally L

    2012-04-13

    Congenital scoliosis, a lateral curvature of the spine caused by vertebral defects, occurs in approximately 1 in 1,000 live births. Here we demonstrate that haploinsufficiency of Notch signaling pathway genes in humans can cause this congenital abnormality. We also show that in a mouse model, the combination of this genetic risk factor with an environmental condition (short-term gestational hypoxia) significantly increases the penetrance and severity of vertebral defects. We demonstrate that hypoxia disrupts FGF signaling, leading to a temporary failure of embryonic somitogenesis. Our results potentially provide a mechanism for the genesis of a host of common sporadic congenital abnormalities through gene-environment interaction.

  5. Gene-Gene and Gene-Environment Interactions in Ulcerative Colitis

    PubMed Central

    Wang, Ming-Hsi; Fiocchi, Claudio; Zhu, Xiaofeng; Ripke, Stephan; Kamboh, M. Ilyas; Rebert, Nancy; Duerr, Richard H.; Achkar, Jean-Paul

    2014-01-01

    Genome-wide association studies (GWAS) have identified at least 133 ulcerative colitis (UC) associated loci. The role of genetic factors in clinical practice is not clearly defined. The relevance of genetic variants to disease pathogenesis is still uncertain because of not characterized gene-gene and gene-environment interactions. We examined the predictive value of combining the 133 UC risk loci with genetic interactions in an ongoing inflammatory bowel disease (IBD) GWAS. The Wellcome Trust Case-Control Consortium (WTCCC) IBD GWAS was used as a replication cohort. We applied logic regression (LR), a novel adaptive regression methodology, to search for high order interactions. Exploratory genotype correlations with UC sub-phenotypes (extent of disease, need of surgery, age of onset, extra-intestinal manifestations and primary sclerosing cholangitis (PSC)) were conducted. The combination of 133 UC loci yielded good UC risk predictability (area under the curve [AUC] of 0.86). A higher cumulative allele score predicted higher UC risk. Through LR, several lines of evidence for genetic interactions were identified and successfully replicated in the WTCCC cohort. The genetic interactions combined with the gene-smoking interaction significantly improved predictability in the model (AUC, from 0.86 to 0.89, P=3.26E-05). Explained UC variance increased from 37% to 42% after adding the interaction terms. A within case analysis found suggested genetic association with PSC. Our study demonstrates that the LR methodology allows the identification and replication of high order genetic interactions in UC GWAS datasets. UC risk can be predicted by a 133 loci and improved by adding gene-gene and gene-environment interactions. PMID:24241240

  6. Importance of gene-environment interactions in the etiology of selected birth defects.

    PubMed

    Zhu, H; Kartiko, S; Finnell, R H

    2009-05-01

    It is generally understood that both genetic and environmental factors contribute to the highly complex etiology of structural birth defects, including neural tube defects, oral clefts and congenital heart defects, by disrupting highly regulated embryonic developmental processes. The intrauterine environment of the developing embryo/fetus is determined by maternal factors such as health/disease status, lifestyle, medication, exposure to environmental teratogens, as well as the maternal genotype. Certain genetic characteristics of the embryo/fetus also predispose it to developmental abnormalities. Epidemiologic and animal studies conducted over the last few decades have suggested that the interplay between genes and environmental factors underlies the etiological heterogeneity of these defects. It is now widely believed that the study of gene-environment interactions will lead to better understanding of the biological mechanisms and pathological processes that contribute to the development of complex birth defects. It is only through such an understanding that more efficient measures will be developed to prevent these severe, costly and often deadly defects. In this review, we attempt to summarize the complex clinical and experimental literature on current hypotheses of interactions between several select environmental factors and those genetic pathways in which they are most likely to have significant modifying effects. These include maternal folate nutritional status, maternal diabetes/obesity-related conditions, and maternal exposure to selected medications and environmental contaminants. Our goal is to highlight the potential gene-environment interactions affecting early embryogenesis that deserve comprehensive study.

  7. Gene-Environment Interaction in the Etiology of Mathematical Ability Using SNP Sets

    PubMed Central

    Kovas, Yulia; Plomin, Robert

    2010-01-01

    Mathematics ability and disability is as heritable as other cognitive abilities and disabilities, however its genetic etiology has received relatively little attention. In our recent genome-wide association study of mathematical ability in 10-year-old children, 10 SNP associations were nominated from scans of pooled DNA and validated in an individually genotyped sample. In this paper, we use a ‘SNP set’ composite of these 10 SNPs to investigate gene-environment (GE) interaction, examining whether the association between the 10-SNP set and mathematical ability differs as a function of ten environmental measures in the home and school in a sample of 1888 children with complete data. We found two significant GE interactions for environmental measures in the home and the school both in the direction of the diathesis-stress type of GE interaction: The 10-SNP set was more strongly associated with mathematical ability in chaotic homes and when parents are negative. PMID:20978832

  8. [Detecting gene-gene/environment interactions by model-based multifactor dimensionality reduction].

    PubMed

    Fan, Wei; Shen, Chao; Guo, Zhirong

    2015-11-01

    This paper introduces a method called model-based multifactor dimensionality reduction (MB-MDR), which was firstly proposed by Calle et al., and can be applied for detecting gene-gene or gene-environment interactions in genetic studies. The basic principle and characteristics of MB-MDR as well as the operation in R program are briefly summarized. Besides, the detailed procedure of MB-MDR is illustrated by using example. Compared with classical MDR, MB-MDR has similar principle, which merges multi-locus genotypes into a one-dimensional construct and can be used in the study with small sample size. However, there is some difference between MB-MDR and classical MDR. First, it has higher statistical power than MDR and other MDR in the presence of different noises due to the different way the genotype cells merged. Second, compared with MDR, it can deal with all binary and quantitative traits, adjust marginal effects of factors and confounders. MBMDR could be a useful method in the analyses of gene-gene/environment interactions.

  9. Gene-Environment Interaction and Children’s Health and Development

    PubMed Central

    Wright, Robert O.; Christiani, David

    2010-01-01

    Purpose of Review A systematic approach to studying gene-environment interaction can have immediate impact on our understanding of how environmental factors induce developmental disease and toxicity and provide biological insight for potential treatment and prevention measures. Recent Findings Because DNA sequence is static, genetic studies typically are not conducted prospectively. This limits the ability to incorporate environmental data into an analysis, as such data is usually collected cross-sectionally. Prospective environmental data collection could account for the role of critical windows of susceptibility that likely corresponds to the expression of specific genes and gene pathways. The use of large scale genomic platforms to discover genetic variants that modify environmental exposure in conjunction with a priori planned replication studies would reduce the number of false positive results. Summary Using a genome-wide approach, combined with a prospective longitudinal of environmental exposure at critical developmental windows is the optimal design for gene-environment interaction research. This approach would discover susceptibility variants, then validate the findings in an independent sample of children. Designs which combine the strengths and methodologies of each field will yield data which can account for both genetic variability and the role of critical developmental windows in the etiology of childhood disease and development. PMID:20090521

  10. Bisphenol-A and Female Infertility: A Possible Role of Gene-Environment Interactions

    PubMed Central

    Huo, Xiaona; Chen, Dan; He, Yonghua; Zhu, Wenting; Zhou, Wei; Zhang, Jun

    2015-01-01

    Background: Bisphenol-A (BPA) is widely used and ubiquitous in the environment. Animal studies indicate that BPA affects reproduction, however, the gene-environment interaction mechanism(s) involved in this association remains unclear. We performed a literature review to summarize the evidence on this topic. Methods: A comprehensive search was conducted in PubMed using as keywords BPA, gene, infertility and female reproduction. Full-text articles in both human and animals published in English prior to December 2014 were selected. Results: Evidence shows that BPA can interfere with endocrine function of hypothalamic-pituitary axis, such as by changing gonadotropin-releasing hormones (GnRH) secretion in hypothalamus and promoting pituitary proliferation. Such actions affect puberty, ovulation and may even result in infertility. Ovary, uterus and other reproductive organs are also targets of BPA. BPA exposure impairs the structure and functions of female reproductive system in different times of life cycle and may contribute to infertility. Both epidemiological and experimental evidences demonstrate that BPA affects reproduction-related gene expression and epigenetic modification that are closely associated with infertility. The detrimental effects on reproduction may be lifelong and transgenerational. Conclusions: Evidence on gene-environment interactions, especially from human studies, is still limited. Further research on this topic is warranted. PMID:26371021

  11. The role of gene-environment correlations and interactions in middle childhood depressive symptoms.

    PubMed

    Wilkinson, Paul O; Trzaskowski, Maciej; Haworth, Claire M A; Eley, Thalia C

    2013-02-01

    Depression is known to be associated with a wide array of environmental factors. Such associations are due at least in part to genetic influences on both. This issue has been little explored with preadolescent children. Measures of family chaos and parenting style at age 9 and child depressive symptoms at age 12 were completed by 3,258 twin pairs from the Twins Early Development Study and their parents. Quantitative genetic modeling was used to explore common and unique genetic and environmental influences on both family environment and later depressive symptoms. Depressive symptoms at age 12 were significantly heritable. Moderate genetic effects influenced parenting style and family chaos at the age of 9, indicating gene-environment correlation. There were significant genetic correlations between family environment and depressive symptoms. There was some evidence of a Gene × Environment interaction, with stronger genetic effects on depressive symptoms for children with more suboptimal family environment. There was an Environment × Environment interaction, with effects of nonshared environment on depressive symptoms stronger for twins with more adverse parenting experiences. There is some evidence for gene-environment correlation between aspects of family environment in middle childhood and subsequent depressive symptoms. This suggests that one of the mechanisms by which genes lead to depressive symptoms may be by themselves influencing depressogenic environments.

  12. Genome-wide gene-environment interaction analysis for asbestos exposure in lung cancer susceptibility.

    PubMed

    Wei, Sheng; Wang, Li-E; McHugh, Michelle K; Han, Younghun; Xiong, Momiao; Amos, Christopher I; Spitz, Margaret R; Wei, Qingyi Wei

    2012-08-01

    Asbestos exposure is a known risk factor for lung cancer. Although recent genome-wide association studies (GWASs) have identified some novel loci for lung cancer risk, few addressed genome-wide gene-environment interactions. To determine gene-asbestos interactions in lung cancer risk, we conducted genome-wide gene-environment interaction analyses at levels of single nucleotide polymorphisms (SNPs), genes and pathways, using our published Texas lung cancer GWAS dataset. This dataset included 317 498 SNPs from 1154 lung cancer cases and 1137 cancer-free controls. The initial SNP-level P-values for interactions between genetic variants and self-reported asbestos exposure were estimated by unconditional logistic regression models with adjustment for age, sex, smoking status and pack-years. The P-value for the most significant SNP rs13383928 was 2.17×10(-6), which did not reach the genome-wide statistical significance. Using a versatile gene-based test approach, we found that the top significant gene was C7orf54, located on 7q32.1 (P = 8.90×10(-5)). Interestingly, most of the other significant genes were located on 11q13. When we used an improved gene-set-enrichment analysis approach, we found that the Fas signaling pathway and the antigen processing and presentation pathway were most significant (nominal P < 0.001; false discovery rate < 0.05) among 250 pathways containing 17 572 genes. We believe that our analysis is a pilot study that first describes the gene-asbestos interaction in lung cancer risk at levels of SNPs, genes and pathways. Our findings suggest that immune function regulation-related pathways may be mechanistically involved in asbestos-associated lung cancer risk.

  13. The role of gene-environment interactions in the development of food allergy.

    PubMed

    Neeland, Melanie R; Martino, David J; Allen, Katrina J

    2015-01-01

    The rates of IgE-mediated food allergy have increased globally, particularly in developed countries. The rising incidence is occurring more rapidly than changes to the genome sequence would allow, suggesting that environmental exposures that alter the immune response play an important role. Genetic factors may also be used to predict an increased predisposition to these environmental risk factors, giving rise to the concept of gene-environment interactions, whereby differential risk of environmental exposures is mediated through the genome. Increasing evidence also suggests a role for epigenetic mechanisms, which are sensitive to environmental exposures, in the development of food allergy. This paper discusses the current state of knowledge regarding the environmental and genetic risk factors for food allergy and how environmental exposures may interact with immune genes to modify disease risk or outcome.

  14. Gene-environment interactions in cancer epidemiology: a National Cancer Institute Think Tank report.

    PubMed

    Hutter, Carolyn M; Mechanic, Leah E; Chatterjee, Nilanjan; Kraft, Peter; Gillanders, Elizabeth M

    2013-11-01

    Cancer risk is determined by a complex interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified hundreds of common (minor allele frequency [MAF] > 0.05) and less common (0.01 < MAF < 0.05) genetic variants associated with cancer. The marginal effects of most of these variants have been small (odds ratios: 1.1-1.4). There remain unanswered questions on how best to incorporate the joint effects of genes and environment, including gene-environment (G × E) interactions, into epidemiologic studies of cancer. To help address these questions, and to better inform research priorities and allocation of resources, the National Cancer Institute sponsored a "Gene-Environment Think Tank" on January 10-11, 2012. The objective of the Think Tank was to facilitate discussions on (1) the state of the science, (2) the goals of G × E interaction studies in cancer epidemiology, and (3) opportunities for developing novel study designs and analysis tools. This report summarizes the Think Tank discussion, with a focus on contemporary approaches to the analysis of G × E interactions. Selecting the appropriate methods requires first identifying the relevant scientific question and rationale, with an important distinction made between analyses aiming to characterize the joint effects of putative or established genetic and environmental factors and analyses aiming to discover novel risk factors or novel interaction effects. Other discussion items include measurement error, statistical power, significance, and replication. Additional designs, exposure assessments, and analytical approaches need to be considered as we move from the current small number of success stories to a fuller understanding of the interplay of genetic and environmental factors.

  15. Gene-environment interactions in psychopathology throughout early childhood: a systematic review.

    PubMed

    Pinto, Raquel Q; Soares, Isabel; Carvalho-Correia, Eduarda; Mesquita, Ana R

    2015-12-01

    Up to 20% of children and adolescents worldwide suffer from mental health problems. Epidemiological studies have shown that some of these problems are already present at an early age. The recognition that psychopathology is a result of an interaction between individual experiences and genetic characteristics has led to an increase in the number of studies using a gene-environment approach (G×E). However, to date, there has been no systematic review of G×E studies on psychopathology in the first 6 years of life. Following a literature search and a selection process, 14 studies were identified and most (n=12) of the studies found at least one significant G×E effect. This review provides a systematic characterization of the published G×E studies, providing insights into the neurobiological and environmental determinants involved in the etiology of children's psychopathology.

  16. Animal models of gene-environment interaction in schizophrenia: a dimensional perspective

    PubMed Central

    Ayhan, Yavuz; McFarland, Ross; Pletnikov, Mikhail V.

    2015-01-01

    Schizophrenia has long been considered as a disorder with multifactorial origins. Recent discoveries have advanced our understanding of the genetic architecture of the disease. However, even with the increase of identified risk variants, heritability estimates suggest an important contribution of non-genetic factors. Various environmental risk factors have been proposed to play a role in the etiopathogenesis of schizophrenia. These include season of birth, maternal infections, obstetric complications, adverse events at early childhood, and drug abuse. Despite the progress in identification of genetic and environmental risk factors, we still have a limited understanding of the mechanisms whereby gene-environment interactions (GxE) operate in schizophrenia and psychoses at large. In this review we provide a critical analysis of current animal models of GxE relevant to psychotic disorders and propose that dimensional perspective will advance our understanding of the complex mechanisms of these disorders. PMID:26510407

  17. A Fast Multiple-Kernel Method With Applications to Detect Gene-Environment Interaction.

    PubMed

    Marceau, Rachel; Lu, Wenbin; Holloway, Shannon; Sale, Michèle M; Worrall, Bradford B; Williams, Stephen R; Hsu, Fang-Chi; Tzeng, Jung-Ying

    2015-09-01

    Kernel machine (KM) models are a powerful tool for exploring associations between sets of genetic variants and complex traits. Although most KM methods use a single kernel function to assess the marginal effect of a variable set, KM analyses involving multiple kernels have become increasingly popular. Multikernel analysis allows researchers to study more complex problems, such as assessing gene-gene or gene-environment interactions, incorporating variance-component based methods for population substructure into rare-variant association testing, and assessing the conditional effects of a variable set adjusting for other variable sets. The KM framework is robust, powerful, and provides efficient dimension reduction for multifactor analyses, but requires the estimation of high dimensional nuisance parameters. Traditional estimation techniques, including regularization and the "expectation-maximization (EM)" algorithm, have a large computational cost and are not scalable to large sample sizes needed for rare variant analysis. Therefore, under the context of gene-environment interaction, we propose a computationally efficient and statistically rigorous "fastKM" algorithm for multikernel analysis that is based on a low-rank approximation to the nuisance effect kernel matrices. Our algorithm is applicable to various trait types (e.g., continuous, binary, and survival traits) and can be implemented using any existing single-kernel analysis software. Through extensive simulation studies, we show that our algorithm has similar performance to an EM-based KM approach for quantitative traits while running much faster. We also apply our method to the Vitamin Intervention for Stroke Prevention (VISP) clinical trial, examining gene-by-vitamin effects on recurrent stroke risk and gene-by-age effects on change in homocysteine level.

  18. Gene-environment interaction signatures by quantitative mRNA profiling in exfoliated buccal mucosal cells.

    PubMed

    Spivack, Simon D; Hurteau, Gregory J; Jain, Ritu; Kumar, Shalini V; Aldous, Kenneth M; Gierthy, John F; Kaminsky, Laurence S

    2004-09-15

    Exfoliated cytologic specimens from mouth (buccal) epithelium may contain viable cells, permitting assay of gene expression for direct and noninvasive measurement of gene-environment interactions, such as for inhalation (e.g., tobacco smoke) exposures. We determined specific mRNA levels in exfoliated buccal cells collected by cytologic brush, using a recently developed RNA-specific real-time quantitative reverse transcription-PCR strategy. In a pilot study, metabolic activity of exfoliated buccal cells was verified by 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium assay in vitro. Transcriptional activity was observed, after timed in vivo exposure to mainstream tobacco smoke resulted in induction of CYP1B1 in serially collected buccal samples from the one subject examined. For a set of 11 subjects, mRNA expression of nine genes encoding carcinogen- and oxidant-metabolizing enzymes qualitatively detected in buccal cells was then shown to correlate with that in laser-microdissected lung from the same individuals (Chi2 = 52.91, P < 0.001). Finally, quantitative real-time reverse transcription-PCR assays for seven target gene (AhR, CYP1A1, CYP1B1, GSTM1, GSTM3, GSTP1, and GSTT1) and three reference gene [glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta-actin, and 36B4] transcripts were performed on buccal specimens from 42 subjects. In multivariate analyses, gender, tobacco smoke exposure, and other factors were associated with the level of expression of CYP1B1, GSTP1, and other transcripts on a gene-specific basis, but substantial interindividual variability in mRNA expression remained unexplained. Within the power limits of this pilot study, gene expression signature was not clearly predictive of lung cancer case or control status. This noninvasive and quantitative method may be incorporated into high-throughput human applications for probing gene-environment interactions associated with cancer.

  19. A Fast Multiple-Kernel Method with Applications to Detect Gene-Environment Interaction

    PubMed Central

    Marceau, Rachel; Lu, Wenbin; Holloway, Shannon; Sale, Michèle M.; Worrall, Bradford B.; Williams, Stephen R.; Hsu, Fang-Chi; Tzeng, Jung-Ying

    2015-01-01

    Kernel machine (KM) models are a powerful tool for exploring associations between sets of genetic variants and complex traits. While most KM methods use a single kernel function to assess the marginal effect of a variable set, KM analyses involving multiple kernels have become increasingly popular. Multi-kernel analysis allows researchers to study more complex problems, such as assessing gene-gene or gene-environment interactions, incorporating variance-component based methods for population substructure into rare-variant association testing, and assessing the conditional effects of a variable set adjusting for other variable sets. The KM framework is robust, powerful, and provides efficient dimension reduction for multi-factor analyses, but requires the estimation of high dimensional nuisance parameters. Traditional estimation techniques, including regularization and the EM algorithm, have a large computational cost and are not scalable to large sample sizes needed for rare variant analysis. Therefore, under the context of gene-environment interaction, we propose a computationally efficient and statistically rigorous “fastKM” algorithm for multi-kernel analysis that is based on a low-rank approximation to the nuisance-effect kernel matrices. Our algorithm is applicable to various trait types (e.g., continuous, binary, and survival traits) and can be implemented using any existing single-kernel analysis software. Through extensive simulation studies, we show that our algorithm has similar performance to an EM-based KM approach for quantitative traits while running much faster. We also apply our method to the Vitamin Intervention for Stroke Prevention (VISP) clinical trial, examining gene-by-vitamin effects on recurrent stroke risk and gene-by-age effects on change in homocysteine level. PMID:26139508

  20. Local Area Disadvantage and Gambling Involvement and Disorder: Evidence for Gene-Environment Correlation and Interaction

    PubMed Central

    Slutske, Wendy S.; Deutsch, Arielle R.; Statham, Dixie B.; Martin, Nicholas G.

    2015-01-01

    Previous research has demonstrated that local area characteristics (such as disadvantage and gambling outlet density) and genetic risk factors are associated with gambling involvement and disordered gambling. These two lines of research were brought together in the present study by examining the extent to which genetic contributions to individual differences in gambling involvement and disorder contributed to being exposed to, and were also accentuated by, local area disadvantage. Participants were members of the national community-based Australian Twin Registry who completed a telephone interview in which the past-year frequency of gambling and symptoms of disordered gambling were assessed. Indicators of local area disadvantage were based on census data matched to the participants' postal codes. Univariate biometric model-fitting revealed that exposure to area disadvantage was partially explained by genetic factors. Bivariate biometric model-fitting was conducted to examine the evidence for gene-environment interaction while accounting for gene-environment correlation. These analyses demonstrated that: (a) a small portion of the genetic propensity to gamble was explained by moving to or remaining in a disadvantaged area, and (b) the remaining genetic and unique environmental variation in the frequency of participating in electronic machine gambling (among men and women) and symptoms of disordered gambling (among women) was greater in more disadvantaged localities. As the gambling industry continues to grow, it will be important to take into account the multiple contexts in which problematic gambling behavior can emerge -- from genes to geography -- as well as the ways in which such contexts may interact with each other. PMID:26147321

  1. A Combinatorial Approach to Detecting Gene-Gene and Gene-Environment Interactions in Family Studies

    PubMed Central

    Lou, Xiang-Yang; Chen, Guo-Bo; Yan, Lei; Ma, Jennie Z.; Mangold, Jamie E.; Zhu, Jun; Elston, Robert C.; Li, Ming D.

    2008-01-01

    Widespread multifactor interactions present a significant challenge in determining risk factors of complex diseases. Several combinatorial approaches, such as the multifactor dimensionality reduction (MDR) method, have emerged as a promising tool for better detecting gene-gene (G × G) and gene-environment (G × E) interactions. We recently developed a general combinatorial approach, namely the generalized multifactor dimensionality reduction (GMDR) method, which can entertain both qualitative and quantitative phenotypes and allows for both discrete and continuous covariates to detect G × G and G × E interactions in a sample of unrelated individuals. In this article, we report the development of an algorithm that can be used to study G × G and G × E interactions for family-based designs, called pedigree-based GMDR (PGMDR). Compared to the available method, our proposed method has several major improvements, including allowing for covariate adjustments and being applicable to arbitrary phenotypes, arbitrary pedigree structures, and arbitrary patterns of missing marker genotypes. Our Monte Carlo simulations provide evidence that the PGMDR method is superior in performance to identify epistatic loci compared to the MDR-pedigree disequilibrium test (PDT). Finally, we applied our proposed approach to a genetic data set on tobacco dependence and found a significant interaction between two taste receptor genes (i.e., TAS2R16 and TAS2R38) in affecting nicotine dependence. PMID:18834969

  2. CardioGxE, a catalog of gene-environment interactions for cardiometabolic traits

    PubMed Central

    2014-01-01

    Background Genetic understanding of complex traits has developed immensely over the past decade but remains hampered by incomplete descriptions of contribution to phenotypic variance. Gene-environment (GxE) interactions are one of these contributors and in the guise of diet and physical activity are important modulators of cardiometabolic phenotypes and ensuing diseases. Results We mined the scientific literature to collect GxE interactions from 386 publications for blood lipids, glycemic traits, obesity anthropometrics, vascular measures, inflammation and metabolic syndrome, and introduce CardioGxE, a gene-environment interaction resource. We then analyzed the genes and SNPs supporting cardiometabolic GxEs in order to demonstrate utility of GxE SNPs and to discern characteristics of these important genetic variants. We were able to draw many observations from our extensive analysis of GxEs. 1) The CardioGxE SNPs showed little overlap with variants identified by main effect GWAS, indicating the importance of environmental interactions with genetic factors on cardiometabolic traits. 2) These GxE SNPs were enriched in adaptation to climatic and geographical features, with implications on energy homeostasis and response to physical activity. 3) Comparison to gene networks responding to plasma cholesterol-lowering or regression of atherosclerotic plaques showed that GxE genes have a greater role in those responses, particularly through high-energy diets and fat intake, than do GWAS-identified genes for the same traits. Other aspects of the CardioGxE dataset were explored. Conclusions Overall, we demonstrate that SNPs supporting cardiometabolic GxE interactions often exhibit transcriptional effects or are under positive selection. Still, not all such SNPs can be assigned potential functional or regulatory roles often because data are lacking in specific cell types or from treatments that approximate the environmental factor of the GxE. With research on metabolic related

  3. BAYESIAN SEMIPARAMETRIC ANALYSIS FOR TWO-PHASE STUDIES OF GENE-ENVIRONMENT INTERACTION

    PubMed Central

    Ahn, Jaeil; Mukherjee, Bhramar; Gruber, Stephen B.; Ghosh, Malay

    2013-01-01

    The two-phase sampling design is a cost-efficient way of collecting expensive covariate information on a judiciously selected sub-sample. It is natural to apply such a strategy for collecting genetic data in a sub-sample enriched for exposure to environmental factors for gene-environment interaction (G × E) analysis. In this paper, we consider two-phase studies of G × E interaction where phase I data are available on exposure, covariates and disease status. Stratified sampling is done to prioritize individuals for genotyping at phase II conditional on disease and exposure. We consider a Bayesian analysis based on the joint retrospective likelihood of phase I and phase II data. We address several important statistical issues: (i) we consider a model with multiple genes, environmental factors and their pairwise interactions. We employ a Bayesian variable selection algorithm to reduce the dimensionality of this potentially high-dimensional model; (ii) we use the assumption of gene-gene and gene-environment independence to trade-off between bias and efficiency for estimating the interaction parameters through use of hierarchical priors reflecting this assumption; (iii) we posit a flexible model for the joint distribution of the phase I categorical variables using the non-parametric Bayes construction of Dunson and Xing (2009). We carry out a small-scale simulation study to compare the proposed Bayesian method with weighted likelihood and pseudo likelihood methods that are standard choices for analyzing two-phase data. The motivating example originates from an ongoing case-control study of colorectal cancer, where the goal is to explore the interaction between the use of statins (a drug used for lowering lipid levels) and 294 genetic markers in the lipid metabolism/cholesterol synthesis pathway. The sub-sample of cases and controls on which these genetic markers were measured is enriched in terms of statin users. The example and simulation results illustrate that the

  4. Gene-Environment Interactions across Development: Exploring DRD2 Genotype and Prenatal Smoking Effects on Self-Regulation

    ERIC Educational Resources Information Center

    Wiebe, Sandra A.; Espy, Kimberly Andrews; Stopp, Christian; Respass, Jennifer; Stewart, Peter; Jameson, Travis R.; Gilbert, David G.; Huggenvik, Jodi I.

    2009-01-01

    Genetic factors dynamically interact with both pre- and postnatal environmental influences to shape development. Considerable attention has been devoted to gene-environment interactions (G x E) on important outcomes (A. Caspi & T. E. Moffitt, 2006). It is also important to consider the possibility that these G x E effects may vary across…

  5. Identification of New Genetic Susceptibility Loci for Breast Cancer Through Consideration of Gene-Environment Interactions

    PubMed Central

    Schoeps, Anja; Rudolph, Anja; Seibold, Petra; Dunning, Alison M.; Milne, Roger L.; Bojesen, Stig E.; Swerdlow, Anthony; Andrulis, Irene; Brenner, Hermann; Behrens, Sabine; Orr, Nicholas; Jones, Michael; Ashworth, Alan; Li, Jingmei; Cramp, Helen; Connley, Dan; Czene, Kamila; Darabi, Hatef; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Knight, Julia; Glendon, Gord; Mulligan, Anna M.; Dumont, Martine; Severi, Gianluca; Baglietto, Laura; Olson, Janet; Vachon, Celine; Purrington, Kristen; Moisse, Matthieu; Neven, Patrick; Wildiers, Hans; Spurdle, Amanda; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M.; Hamann, Ute; Ko, Yon-Dschun; Dieffenbach, Aida K.; Arndt, Volker; Stegmaier, Christa; Malats, Núria; Arias Perez, JoséI.; Benítez, Javier; Flyger, Henrik; Nordestgaard, Børge G.; Truong, Théresè; Cordina-Duverger, Emilie; Menegaux, Florence; Silva, Isabel dos Santos; Fletcher, Olivia; Johnson, Nichola; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Braaf, Linde; Atsma, Femke; van den Broek, Alexandra J.; Makalic, Enes; Schmidt, Daniel F.; Southey, Melissa C.; Cox, Angela; Simard, Jacques; Giles, Graham G.; Lambrechts, Diether; Mannermaa, Arto; Brauch, Hiltrud; Guénel, Pascal; Peto, Julian; Fasching, Peter A.; Hopper, John; Flesch-Janys, Dieter; Couch, Fergus; Chenevix-Trench, Georgia; Pharoah, Paul D. P.; Garcia-Closas, Montserrat; Schmidt, Marjanka K.; Hall, Per; Easton, Douglas F.; Chang-Claude, Jenny

    2014-01-01

    Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10−07), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m2 (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m2 or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10−05). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci. PMID:24248812

  6. Leveraging gene-environment interactions and endotypes for asthma gene discovery.

    PubMed

    Bønnelykke, Klaus; Ober, Carole

    2016-03-01

    Asthma is a heterogeneous clinical syndrome that includes subtypes of disease with different underlying causes and disease mechanisms. Asthma is caused by a complex interaction between genes and environmental exposures; early-life exposures in particular play an important role. Asthma is also heritable, and a number of susceptibility variants have been discovered in genome-wide association studies, although the known risk alleles explain only a small proportion of the heritability. In this review, we present evidence supporting the hypothesis that focusing on more specific asthma phenotypes, such as childhood asthma with severe exacerbations, and on relevant exposures that are involved in gene-environment interactions (GEIs), such as rhinovirus infections, will improve detection of asthma genes and our understanding of the underlying mechanisms. We will discuss the challenges of considering GEIs and the advantages of studying responses to asthma-associated exposures in clinical birth cohorts, as well as in cell models of GEIs, to dissect the context-specific nature of genotypic risks, to prioritize variants in genome-wide association studies, and to identify pathways involved in pathogenesis in subgroups of patients. We propose that such approaches, in spite of their many challenges, present great opportunities for better understanding of asthma pathogenesis and heterogeneity and, ultimately, for improving prevention and treatment of disease.

  7. Gene-environment interactions in the development of complex disease phenotypes.

    PubMed

    Ramos, Rosemarie G; Olden, Kenneth

    2008-03-01

    The lack of knowledge about the earliest events in disease development is due to the multi-factorial nature of disease risk. This information gap is the consequence of the lack of appreciation for the fact that most diseases arise from the complex interactions between genes and the environment as a function of the age or stage of development of the individual. Whether an environmental exposure causes illness or not is dependent on the efficiency of the so-called "environmental response machinery" (i.e., the complex of metabolic pathways that can modulate response to environmental perturbations) that one has inherited. Thus, elucidating the causes of most chronic diseases will require an understanding of both the genetic and environmental contribution to their etiology. Unfortunately, the exploration of the relationship between genes and the environment has been hampered in the past by the limited knowledge of the human genome, and by the inclination of scientists to study disease development using experimental models that consider exposure to a single environmental agent. Rarely in the past were interactions between multiple genes or between genes and environmental agents considered in studies of human disease etiology. The most critical issue is how to relate exposure-disease association studies to pathways and mechanisms. To understand how genes and environmental factors interact to perturb biological pathways to cause injury or disease, scientists will need tools with the capacity to monitor the global expression of thousands of genes, proteins and metabolites simultaneously. The generation of such data in multiple species can be used to identify conserved and functionally significant genes and pathways involved in gene-environment interactions. Ultimately, it is this knowledge that will be used to guide agencies such as the U.S. Department of Health and Human Services in decisions regarding biomedical research funding and policy.

  8. Cognitive endophenotypes, gene-environment interactions and experience-dependent plasticity in animal models of schizophrenia.

    PubMed

    Burrows, Emma L; Hannan, Anthony J

    2016-04-01

    Schizophrenia is a devastating brain disorder caused by a complex and heterogeneous combination of genetic and environmental factors. In order to develop effective new strategies to prevent and treat schizophrenia, valid animal models are required which accurately model the disorder, and ideally provide construct, face and predictive validity. The cognitive deficits in schizophrenia represent some of the most debilitating symptoms and are also currently the most poorly treated. Therefore it is crucial that animal models are able to capture the cognitive dysfunction that characterizes schizophrenia, as well as the negative and psychotic symptoms. The genomes of mice have, prior to the recent gene-editing revolution, proven the most easily manipulable of mammalian laboratory species, and hence most genetic targeting has been performed using mouse models. Importantly, when key environmental factors of relevance to schizophrenia are experimentally manipulated, dramatic changes in the phenotypes of these animal models are often observed. We will review recent studies in rodent models which provide insight into gene-environment interactions in schizophrenia. We will focus specifically on environmental factors which modulate levels of experience-dependent plasticity, including environmental enrichment, cognitive stimulation, physical activity and stress. The insights provided by this research will not only help refine the establishment of optimally valid animal models which facilitate development of novel therapeutics, but will also provide insight into the pathogenesis of schizophrenia, thus identifying molecular and cellular targets for future preclinical and clinical investigations.

  9. Rethinking expertise: A multifactorial gene-environment interaction model of expert performance.

    PubMed

    Ullén, Fredrik; Hambrick, David Zachary; Mosing, Miriam Anna

    2016-04-01

    Scientific interest in expertise-superior performance within a specific domain-has a long history in psychology. Although there is a broad consensus that a long period of practice is essential for expertise, a long-standing controversy in the field concerns the importance of other variables such as cognitive abilities and genetic factors. According to the influential deliberate practice theory, expert performance is essentially limited by a single variable: the amount of deliberate practice an individual has accumulated. Here, we provide a review of the literature on deliberate practice, expert performance, and its neural correlates. A particular emphasis is on recent studies indicating that expertise is related to numerous traits other than practice as well as genetic factors. We argue that deliberate practice theory is unable to account for major recent findings relating to expertise and expert performance, and propose an alternative multifactorial gene-environment interaction model of expertise, which provides an adequate explanation for the available empirical data and may serve as a useful framework for future empirical and theoretical work on expert performance.

  10. Drug metabolism and liver disease: a drug-gene-environment interaction.

    PubMed

    Zgheib, Nathalie K; Branch, Robert A

    2017-02-01

    Despite the central role of the liver in drug metabolism, surprisingly there is lack of certainty in anticipating the extent of modification of the clearance of a given drug in a given patient. The intent of this review is to provide a conceptual framework in considering the impact of liver disease on drug disposition and reciprocally the impact of drug disposition on liver disease. It is proposed that improved understanding of the situation is gained by considering the issue as a special example of a drug-gene-environment interaction. This requires an integration of knowledge of the drug's properties, knowledge of the gene products involved in its metabolism, and knowledge of the pathophysiology of its disposition. This will enhance the level of predictability of drug disposition and toxicity for a drug of interest in an individual patient. It is our contention that advances in pharmacology, pharmacogenomics, and hepatology, together with concerted interests in the academic, regulatory, and pharmaceutical industry communities provide an ideal immediate environment to move from a qualitative reactive approach to quantitative proactive approach in individualizing patient therapy in liver disease.

  11. Shame and Guilt-Proneness in Adolescents: Gene-Environment Interactions

    PubMed Central

    Szentágotai-Tătar, Aurora; Chiș, Adina; Vulturar, Romana; Dobrean, Anca; Cândea, Diana Mirela; Miu, Andrei C.

    2015-01-01

    Rooted in people’s preoccupation with how they are perceived and evaluated, shame and guilt are self-conscious emotions that play adaptive roles in social behavior, but can also contribute to psychopathology when dysregulated. Shame and guilt-proneness develop during childhood and adolescence, and are influenced by genetic and environmental factors that are little known to date. This study investigated the effects of early traumatic events and functional polymorphisms in the brain-derived neurotrophic factor (BDNF) gene and the serotonin transporter gene promoter (5-HTTLPR) on shame and guilt in adolescents. A sample of N = 271 healthy adolescents between 14 and 17 years of age filled in measures of early traumatic events and proneness to shame and guilt, and were genotyped for the BDNF Val66Met and 5-HTTLPR polymorphisms. Results of moderator analyses indicated that trauma intensity was positively associated with guilt-proneness only in carriers of the low-expressing Met allele of BDNF Val66Met. This is the first study that identifies a gene-environment interaction that significantly contributes to guilt proneness in adolescents, with potential implications for developmental psychopathology. PMID:26230319

  12. Gene-Environment Interaction in Adults’ IQ Scores: Measures of Past and Present Environment

    PubMed Central

    Willemsen, Gonneke; de Geus, Eco J. C.; Boomsma, Dorret I.; Posthuma, Danielle

    2008-01-01

    Gene-environment interaction was studied in a sample of young (mean age 26 years, N = 385) and older (mean age 49 years, N = 370) adult males and females. Full scale IQ scores (FSIQ) were analyzed using biometric models in which additive genetic (A), common environmental (C), and unique environmental (E) effects were allowed to depend on environmental measures. Moderators under study were parental and partner educational level, as well as urbanization level and mean real estate price of the participants’ residential area. Mean effects were observed for parental education, partner education and urbanization level. On average, FSIQ scores were roughly 5 points higher in participants with highly educated parents, compared to participants whose parents were less well educated. In older participants, IQ scores were about 2 points higher when their partners were highly educated. In younger males, higher urbanization levels were associated with slightly higher FSIQ scores. Our analyses also showed increased common environmental variation in older males whose parents were more highly educated, and increased unique environmental effects in older males living in more affluent areas. Contrary to studies in children, however, the variance attributable to additive genetic effects was stable across all levels of the moderators under study. Most results were replicated for VIQ and PIQ. PMID:18535898

  13. Environmental factors as modulators of neurodegeneration: insights from gene-environment interactions in Huntington's disease.

    PubMed

    Mo, Christina; Hannan, Anthony J; Renoir, Thibault

    2015-05-01

    Unlike many other neurodegenerative diseases with established gene-environment interactions, Huntington's disease (HD) is viewed as a disorder governed by genetics. The cause of the disease is a highly penetrant tandem repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. In the year 2000, a pioneering study showed that the disease could be delayed in transgenic mice by enriched housing conditions. This review describes subsequent human and preclinical studies identifying environmental modulation of motor, cognitive, affective and other symptoms found in HD. Alongside the behavioral observations we also discuss potential mechanisms and the relevance to other neurodegenerative disorders, including Alzheimer's and Parkinson's disease. In mouse models of HD, increased sensorimotor and cognitive stimulation can delay or ameliorate various endophenotypes. Potential mechanisms include increased trophic support, synaptic plasticity, adult neurogenesis, and other forms of experience-dependent cellular plasticity. Subsequent clinical investigations support a role for lifetime activity levels in modulating the onset and progression of HD. Stress can accelerate memory and olfactory deficits and exacerbate cellular dysfunctions in HD mice. In the absence of effective treatments to slow the course of HD, environmental interventions offer feasible approaches to delay the disease, however further preclinical and human studies are needed in order to generate clinical recommendations. Environmental interventions could be combined with future pharmacological therapies and stimulate the identification of enviromimetics, drugs which mimic or enhance the beneficial effects of cognitive stimulation and physical activity.

  14. Education and alcohol use: A study of gene-environment interaction in young adulthood.

    PubMed

    Barr, Peter B; Salvatore, Jessica E; Maes, Hermine; Aliev, Fazil; Latvala, Antti; Viken, Richard; Rose, Richard J; Kaprio, Jaakko; Dick, Danielle M

    2016-08-01

    The consequences of heavy alcohol use remain a serious public health problem. Consistent evidence has demonstrated that both genetic and social influences contribute to alcohol use. Research on gene-environment interaction (GxE) has also demonstrated that these social and genetic influences do not act independently. Instead, certain environmental contexts may limit or exacerbate an underlying genetic predisposition. However, much of the work on GxE and alcohol use has focused on adolescence and less is known about the important environmental contexts in young adulthood. Using data from the young adult wave of the Finnish Twin Study, FinnTwin12 (N = 3402), we used biometric twin modeling to test whether education moderated genetic risk for alcohol use as assessed by drinking frequency and intoxication frequency. Education is important because it offers greater access to personal resources and helps determine one's position in the broader stratification system. Results from the twin models show that education did not moderate genetic variance components and that genetic risk was constant across levels of education. Instead, education moderated environmental variance so that under conditions of low education, environmental influences explained more of the variation in alcohol use outcomes. The implications and limitations of these results are discussed.

  15. A database of gene-environment interactions pertaining to blood lipid traits, cardiovascular disease and type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As the role of the environment – diet, exercise, alcohol and tobacco use and sleep among others – is accorded a more prominent role in modifying the relationship between genetic variants and clinical measures of disease, consideration of gene-environment (GxE) interactions is a must. To facilitate i...

  16. Gene-Environment Interaction in Externalizing Problems among Adolescents: Evidence from the Pelotas 1993 Birth Cohort Study

    ERIC Educational Resources Information Center

    Kieling, Christian; Hutz, Mara H.; Genro, Julia P.; Polanczyk, Guilherme V.; Anselmi, Luciana; Camey, Suzi; Hallal, Pedro C.; Barros, Fernando C.; Victora, Cesar G.; Menezes, Ana M. B.; Rohde, Luis Augusto

    2013-01-01

    Background: The study of gene-environment interactions (G by E) is one of the most promising strategies to uncover the origins of mental disorders. Replication of initial findings, however, is essential because there is a strong possibility of publication bias in the literature. In addition, there is a scarcity of research on the topic originated…

  17. Testing gene-environment interactions in family-based association studies using trait-based ascertained samples

    PubMed Central

    Zhang, Weiming; Langefeld, Carl D.; Grunwald, Gary K.; Fingerlin, Tasha E.

    2014-01-01

    The study of gene-environment interactions is an increasingly important aspect of genetic epidemiological investigation. Historically, it has been difficult to study gene-environment interactions using a family-based design for quantitative traits or when parent-offspring trios were incomplete. The QBAT-I[1] provides researchers a tool to estimate and test for a gene-environment interaction in families of arbitrary structure that are sampled without regard to the phenotype of interest, but is vulnerable to inflated type I error if families are ascertained based on the phenotype. In this study, we verified the potential for type I error of the QBAT-I when applied to samples ascertained on a trait of interest. The magnitude of the inflation increases as the main genetic effect increases and as the ascertainment becomes more extreme. We propose an ascertainment-corrected score test that allows use of the QBAT-I to test for gene-environment interactions in ascertained samples. Our results indicate that the score test and an ad-hoc method we propose can often restore the nominal type I error rate, and in cases where complete restoration is not possible, dramatically reduce the inflation of the type I error rate in ascertained samples. PMID:23922213

  18. Toward a 3D model of human brain development for studying gene/environment interactions.

    PubMed

    Hogberg, Helena T; Bressler, Joseph; Christian, Kimberly M; Harris, Georgina; Makri, Georgia; O'Driscoll, Cliona; Pamies, David; Smirnova, Lena; Wen, Zhexing; Hartung, Thomas

    2013-01-01

    This project aims to establish and characterize an in vitro model of the developing human brain for the purpose of testing drugs and chemicals. To accurately assess risk, a model needs to recapitulate the complex interactions between different types of glial cells and neurons in a three-dimensional platform. Moreover, human cells are preferred over cells from rodents to eliminate cross-species differences in sensitivity to chemicals. Previously, we established conditions to culture rat primary cells as three-dimensional aggregates, which will be humanized and evaluated here with induced pluripotent stem cells (iPSCs). The use of iPSCs allows us to address gene/environment interactions as well as the potential of chemicals to interfere with epigenetic mechanisms. Additionally, iPSCs afford us the opportunity to study the effect of chemicals during very early stages of brain development. It is well recognized that assays for testing toxicity in the developing brain must consider differences in sensitivity and susceptibility that arise depending on the time of exposure. This model will reflect critical developmental processes such as proliferation, differentiation, lineage specification, migration, axonal growth, dendritic arborization and synaptogenesis, which will probably display differences in sensitivity to different types of chemicals. Functional endpoints will evaluate the complex cell-to-cell interactions that are affected in neurodevelopment through chemical perturbation, and the efficacy of drug intervention to prevent or reverse phenotypes. The model described is designed to assess developmental neurotoxicity effects on unique processes occurring during human brain development by leveraging human iPSCs from diverse genetic backgrounds, which can be differentiated into different cell types of the central nervous system. Our goal is to demonstrate the feasibility of the personalized model using iPSCs derived from individuals with neurodevelopmental disorders

  19. Preliminary Evidence for a Gene-Environment Interaction in Predicting Alcohol Use Disorders in Adolescents

    PubMed Central

    Miranda, Robert; Reynolds, Elizabeth; Ray, Lara; Justus, Alicia; Knopik, Valerie S.; McGeary, John; Meyerson, Lori A.

    2013-01-01

    Background Emerging research suggests that genetic influences on adolescent drinking are moderated by environmental factors. The present study builds on molecular-genetic findings by conducting the first analysis of gene-environment interactions in the association between a functional single nucleotide polymorphism (SNP) of the µ-opioid receptor (OPRM1) gene (A118G) and risk for developing an alcohol use disorder (AUD) during adolescence. Specifically, we tested whether variation in parenting practices or affiliation with deviant peers moderated the link between the OPRM1 gene and risk for an AUD. Methods Adolescents reporting European ancestry (N = 104), ages 12–19 years (M = 15.60, SD = 1.77), were interviewed to ascertain AUD diagnoses, provided a DNA sample for genetic analyses, and completed measures of parental monitoring and deviant peer affiliation. Logistic regression was used to test the effects of environmental variable sand their interactions with OPRM1genotype as predictors of AUD diagnosis while controlling for age and sex. Results Case-control comparisons showed that the proportion of youth with an AUD (n = 18) significantly differed by genotype such that 33.3% of G allele carriers met criteria for an AUD compared to 10.8% of youth who were homozygous for the A allele (p = .006). The OPRM1 × parental monitoring (odds ratio = 0.16) and OPRM1 × deviant peer affiliation (odds ratio = 7.64) interactions were significant predictors of AUD risk, such that G allele carriers with high levels of deviant peer affiliation or lower levels of parental monitoring had the greatest likelihood of developing an AUD (p values < .01). Conclusions This study provides initial evidence that the association between the A118G SNP of the OPRM1 gene and risk for AUDs is moderated by modifiable factors. These results are limited, however, by the small sample size and require replication. PMID:23136901

  20. Gene-environment interactions linking air pollution and inflammation in Parkinson's disease.

    PubMed

    Lee, Pei-Chen; Raaschou-Nielsen, Ole; Lill, Christina M; Bertram, Lars; Sinsheimer, Janet S; Hansen, Johnni; Ritz, Beate

    2016-11-01

    Both air pollution exposure and systemic inflammation have been linked to Parkinson's disease (PD). In the PASIDA study, 408 incident cases of PD diagnosed in 2006-2009 and their 495 population controls were interviewed and provided DNA samples. Markers of long term traffic related air pollution measures were derived from geographic information systems (GIS)-based modeling. Furthermore, we genotyped functional polymorphisms in genes encoding proinflammatory cytokines, namely rs1800629 in TNFα (tumor necrosis factor alpha) and rs16944 in IL1B (interleukin-1β). In logistic regression models, long-term exposure to NO2 increased PD risk overall (odds ratio (OR)=1.06 per 2.94μg/m(3) increase, 95% CI=1.00-1.13). The OR for PD in individuals with high NO2 exposure (≧75th percentile) and the AA genotype of IL1B rs16944 was 3.10 (95% CI=1.14-8.38) compared with individuals with lower NO2 exposure (<75th percentile) and the GG genotype. The interaction term was nominally significant on the multiplicative scale (p=0.01). We did not find significant gene-environment interactions with TNF rs1800629. Our finds may provide suggestive evidence that a combination of traffic-related air pollution and genetic variation in the proinflammatory cytokine gene IL1B contribute to risk of developing PD. However, as statistical evidence was only modest in this large sample we cannot rule out that these results represent a chance finding, and additional replication efforts are warranted.

  1. Characterization of gene-environment interactions for colorectal cancer susceptibility loci

    PubMed Central

    Hutter, Carolyn M.; Chang-Claude, Jenny; Slattery, Martha L.; Pflugeisen, Bethann M.; Lin, Yi; Duggan, David; Nan, Hongmei; Lemire, Mathieu; Rangrej, Jagadish; Figueiredo, Jane C.; Jiao, Shuo; Harrison, Tabitha A.; Liu, Yan; Chen, Lin S.; Stelling, Deanna L.; Warnick, Greg S.; Hoffmeister, Michael; Küry, Sébastien; Fuchs, Charles S.; Giovannucci, Edward; Hazra, Aditi; Kraft, Peter; Hunter, David J.; Gallinger, Steven; Zanke, Brent W.; Brenner, Hermann; Frank, Bernd; Ma, Jing; Ulrich, Cornelia M.; White, Emily; Newcomb, Polly A.; Kooperberg, Charles; LaCroix, Andrea Z.; Prentice, Ross L.; Jackson, Rebecca D.; Schoen, Robert E.; Chanock, Stephen J.; Berndt, Sonja I.; Hayes, Richard B.; Caan, Bette J.; Potter, John D.; Hsu, Li; Bézieau, Stéphane; Chan, Andrew T.; Hudson, Thomas J.; Peters, Ulrike

    2012-01-01

    Genome-wide association studies (GWAS) have identified over a dozen loci associated with colorectal cancer (CRC) risk. Here we examined potential effect-modification between single nucleotide polymorphisms (SNPs) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case-control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at 8q23.3 (EIF3H/UTP23); rs6983267 at 8q24 (MYC); rs10795668 at 10p14 (FLJ3802842); rs3802842 at11q23 (LOC120376); rs4444235 at 14q22.2 (BMP4); rs4779584 at15q13 (GREM1); rs9929218 at16q22.1 (CDH1); rs4939827 at18q21 (SMAD7); rs10411210 at19q13.1 (RHPN2); and rs961253 at 20p12.3 (BMP2)] and select major CRC risk factors (sex, body mass index, height, smoking status, aspirin/non-steroidal anti-inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red meat, processed meat, vegetables, fruit, and fiber). The strongest statistical evidence for a gene-environment interaction across studies was for vegetable consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and UTP23 genes (nominal p-interaction =1.3×10–4; adjusted p-value 0.02). The magnitude of the main effect of the SNP increased with increasing levels of vegetable consumption. No other interactions were statistically significant after adjusting for multiple comparisons. Overall, the association of most CRC susceptibility loci identified in initial GWAS appears to be invariant to the other risk factors considered; however, our results suggest potential modification of the rs16892766 effect by vegetable consumption. PMID:22367214

  2. G x E: a NIAAA workshop on gene-environment interactions.

    PubMed

    Gunzerath, Lorraine; Goldman, David

    2003-03-01

    The National Institute on Alcohol Abuse and Alcoholism (NIAAA) sponsored a May 2002 workshop on gene-environment interaction (G x E) research to identify potential roadblocks to further research and to propose solutions to those roadblocks, to optimize investigative opportunities and multidisciplinary or multi-institution collaborations, and to explore ways that NIAAA can facilitate G x E studies. Sessions included panels on animal models; phenotypes; genetic findings in humans; study designs and analytical methods; and assessment of environmental risk. Key among the identified challenges to progress in G x E research were issues of study design and sampling strategies; logistic and methodological costs and constraints; availability and understanding of data analysis techniques; potential stigmatization of study populations; and organizational/bureaucratic structures that are inadequate to address the unique needs of large-scale, multicenter, longitudinal projects. Participants proposed a series of recommendations to address these issues. Session coordinators included: Gayle Boyd, Kendall Bryant, Page Chiapella, Vivian Faden, David Goldman, and Antonio Noronha. Session participants included: Laura Almasy, Henri Begleiter, Raul Caetano, Bruce Dudek, Mary Dufour, Cindy Ehlers, Mary-Anne Enoch, Joel Gelernter, David Goldman, Bridget Grant, Lorraine Gunzerath, Deborah Hasin, Andrew Heath, Victor Hesselbrock, J. Dee Higley, Shirley Hill, Kerry Jang, Raynard S. Kington, Rick Kittles, George Koob, Kenneth Leonard, Ting-Kai Li, Jeffrey Long, William McBride, Matthew McGue, Kathleen Merikangas, Tamara Phillips, Bernice Porjesz, Carol Prescott, Theodore Reich, John Rice, Richard Rose, Charmaine Royal, Arnold Sameroff, Marc Schuckit, Kenneth Sher, Renee Sieving, Robert Taylor, Michael Windle, and Robert Zucker.

  3. Gene-environment interaction in problematic substance use: interaction between DRD4 and insecure attachments.

    PubMed

    Olsson, Craig A; Moyzis, Robert K; Williamson, Elizabeth; Ellis, Justine A; Parkinson-Bates, Mandy; Patton, George C; Dwyer, Terry; Romaniuk, Helena; Moore, Elya E

    2013-07-01

    To investigate the combined effect of an exon III variable number tandem repeat in the dopamine receptor gene (DRD4) and insecure attachment style on risk for tobacco, cannabis and alcohol use problems in young adulthood. It was hypothesized that (1) individuals with 5, 6, 7 or 8 repeats (labelled 7R+) would be at increased risk for problematic drug use, and (2) risk for drug use would be further increased in individuals with 7R+ repeats who also have a history of insecure parent-child attachment relations. Data were drawn from the Victorian Adolescent Health Cohort Study, an eight-wave longitudinal study of adolescent and young adult development. DRD4 genotypes were available for 839 participants. Risk attributable to the combined effects of 7R+ genotype and insecure attachments was evaluated within a sufficient causes framework under the assumptions of additive interaction using a two-by-four table format with a common reference group. 7R+ alleles were associated with higher tobacco, cannabis and alcohol use (binging). Insecure attachments were associated with higher tobacco and cannabis use but lower alcohol use. For tobacco, there was evidence of interaction for anxious but not avoidant attachments. For cannabis, there was evidence of interaction for both anxious and avoidant attachments, although the interaction for anxious attachments was more substantial. There is no evidence of interaction for binge drinking. Results are consistent with a generic reward deficit hypothesis of drug addiction for which the 7R+ disposition may play a role. Interaction between 7R+ alleles and attachment insecurity may intensify risk for problematic tobacco and cannabis use.

  4. The challenge of causal inference in gene-environment interaction research: leveraging research designs from the social sciences.

    PubMed

    Fletcher, Jason M; Conley, Dalton

    2013-10-01

    The integration of genetics and the social sciences will lead to a more complex understanding of the articulation between social and biological processes, although the empirical difficulties inherent in this integration are large. One key challenge is the implications of moving "outside the lab" and away from the experimental tools available for research with model organisms. Social science research methods used to examine human behavior in nonexperimental, real-world settings to date have not been fully taken advantage of during this disciplinary integration, especially in the form of gene-environment interaction research. This article outlines and provides examples of several prominent research designs that should be used in gene-environment research and highlights a key benefit to geneticists of working with social scientists.

  5. Toll-like receptors and microbial exposure: gene-gene and gene-environment interaction in the development of atopy.

    PubMed

    Reijmerink, N E; Kerkhof, M; Bottema, R W B; Gerritsen, J; Stelma, F F; Thijs, C; van Schayck, C P; Smit, H A; Brunekreef, B; Postma, D S; Koppelman, G H

    2011-10-01

    Environmental and genetic factors contribute to atopy development. High microbial exposure may confer a protective effect on atopy. Toll-like receptors (TLRs) bind microbial products and are important in activating the immune system. To assess whether interactions between microbial exposures and genes encoding TLRs (and related genes) result in atopy, genes, environmental factors and gene-environment interactions of 66 single-nucleotide polymorphisms (SNPs) of 12 genes (TLR 1-6, 9 and 10, CD14, MD2, lipopolysaccharide-binding protein (LBP) and Dectin-1), and six proxy parameters of microbial exposure (sibship size, pets (three different parameters), day-care and intrauterine and childhood tobacco smoke exposure) were analysed for association with atopic phenotypes in 3,062 Dutch children (the Allergenic study). The presence of two or more older siblings increased the risk of developing high total immunoglobulin (Ig)E levels at different ages. This risk increased further in children aged 1-2 yrs carrying the minor allele of TLR6 SNP rs1039559. Furthermore, novel two- and three-factor gene-gene and gene-environment interactions were found (e.g. between sibship size, day-care and LBP SNP rs2232596). Larger sibship size is associated with increased total IgE levels. Furthermore, complex two- and three-factor interactions exist between genes and the environment. The TLRs and related genes interact with proxy parameters of high microbial exposure in atopy development.

  6. Gene-Gene-Environment Interactions of Serotonin Transporter, Monoamine Oxidase A and Childhood Maltreatment Predict Aggressive Behavior in Chinese Adolescents

    PubMed Central

    Zhang, Yun; Ming, Qing-sen; Yi, Jin-yao; Wang, Xiang; Chai, Qiao-lian; Yao, Shu-qiao

    2017-01-01

    Gene-environment interactions that moderate aggressive behavior have been identified independently in the serotonin transporter (5-HTT) gene and monoamine oxidase A gene (MAOA). The aim of the present study was to investigate epistasis interactions between MAOA-variable number tandem repeat (VNTR), 5-HTTlinked polymorphism (LPR) and child abuse and the effects of these on aggressive tendencies in a group of otherwise healthy adolescents. A group of 546 Chinese male adolescents completed the Child Trauma Questionnaire and Youth self-report of the Child Behavior Checklist. Buccal cells were collected for DNA analysis. The effects of childhood abuse, MAOA-VNTR, 5-HTTLPR genotypes and their interactive gene-gene-environmental effects on aggressive behavior were analyzed using a linear regression model. The effect of child maltreatment was significant, and a three-way interaction among MAOA-VNTR, 5-HTTLPR and sexual abuse (SA) relating to aggressive behaviors was identified. Chinese male adolescents with high expression of the MAOA-VNTR allele and 5-HTTLPR “SS” genotype exhibited the highest aggression tendencies with an increase in SA during childhood. The findings reported support aggression being a complex behavior involving the synergistic effects of gene-gene-environment interactions. PMID:28203149

  7. Gene-Gene-Environment Interactions of Serotonin Transporter, Monoamine Oxidase A and Childhood Maltreatment Predict Aggressive Behavior in Chinese Adolescents.

    PubMed

    Zhang, Yun; Ming, Qing-Sen; Yi, Jin-Yao; Wang, Xiang; Chai, Qiao-Lian; Yao, Shu-Qiao

    2017-01-01

    Gene-environment interactions that moderate aggressive behavior have been identified independently in the serotonin transporter (5-HTT) gene and monoamine oxidase A gene (MAOA). The aim of the present study was to investigate epistasis interactions between MAOA-variable number tandem repeat (VNTR), 5-HTTlinked polymorphism (LPR) and child abuse and the effects of these on aggressive tendencies in a group of otherwise healthy adolescents. A group of 546 Chinese male adolescents completed the Child Trauma Questionnaire and Youth self-report of the Child Behavior Checklist. Buccal cells were collected for DNA analysis. The effects of childhood abuse, MAOA-VNTR, 5-HTTLPR genotypes and their interactive gene-gene-environmental effects on aggressive behavior were analyzed using a linear regression model. The effect of child maltreatment was significant, and a three-way interaction among MAOA-VNTR, 5-HTTLPR and sexual abuse (SA) relating to aggressive behaviors was identified. Chinese male adolescents with high expression of the MAOA-VNTR allele and 5-HTTLPR "SS" genotype exhibited the highest aggression tendencies with an increase in SA during childhood. The findings reported support aggression being a complex behavior involving the synergistic effects of gene-gene-environment interactions.

  8. Unraveling inflammatory responses using systems genetics and gene-environment interactions in macrophages

    PubMed Central

    Orozco, Luz D.; Bennett, Brian J.; Farber, Charles R.; Ghazalpour, Anatole; Pan, Calvin; Che, Nam; Wen, Pingzi; Qi, Hong Xiu; Mutukulu, Adonisa; Siemers, Nathan; Neuhaus, Isaac; Yordanova, Roumyana; Gargalovic, Peter; Pellegrini, Matteo; Kirchgessner, Todd; Lusis, Aldons J.

    2012-01-01

    SUMMARY Many common diseases have an important inflammatory component mediated in part by macrophages. Here we used a systems genetics strategy to examine the role of common genetic variation in macrophage responses to inflammatory stimuli. We examined genome-wide transcript levels in macrophages from 92 strains of the Hybrid Mouse Diversity Panel. We exposed macrophages to control media, bacterial lipopolysaccharide, or oxidized phospholipids. We performed association mapping under each condition and identified several thousand expression quantitative trait loci (eQTL), gene-by-environment interactions and several eQTL “hotspots” that specifically control LPS responses. We validated an eQTL hotspot in chromosome 8 using siRNA knock-down of candidate genes and identified the gene 2310061C15Rik, as a novel regulator of inflammatory responses in macrophages. We have created a public database where the data presented here can be used as a resource for understanding many common inflammatory traits which are modeled in the mouse, and for the dissection of regulatory relationships between genes. PMID:23101632

  9. Unraveling inflammatory responses using systems genetics and gene-environment interactions in macrophages.

    PubMed

    Orozco, Luz D; Bennett, Brian J; Farber, Charles R; Ghazalpour, Anatole; Pan, Calvin; Che, Nam; Wen, Pingzi; Qi, Hong Xiu; Mutukulu, Adonisa; Siemers, Nathan; Neuhaus, Isaac; Yordanova, Roumyana; Gargalovic, Peter; Pellegrini, Matteo; Kirchgessner, Todd; Lusis, Aldons J

    2012-10-26

    Many common diseases have an important inflammatory component mediated in part by macrophages. Here we used a systems genetics strategy to examine the role of common genetic variation in macrophage responses to inflammatory stimuli. We examined genome-wide transcript levels in macrophages from 92 strains of the Hybrid Mouse Diversity Panel. We exposed macrophages to control media, bacterial lipopolysaccharide (LPS), or oxidized phospholipids. We performed association mapping under each condition and identified several thousand expression quantitative trait loci (eQTL), gene-by-environment interactions, and eQTL "hot spots" that specifically control LPS responses. We used siRNA knockdown of candidate genes to validate an eQTL hot spot in chromosome 8 and identified the gene 2310061C15Rik as a regulator of inflammatory responses in macrophages. We have created a public database where the data presented here can be used as a resource for understanding many common inflammatory traits that are modeled in the mouse and for the dissection of regulatory relationships between genes.

  10. Progress in the epidemiological understanding of gene-environment interactions in major diseases: cancer.

    PubMed

    Clavel, Jacqueline

    2007-04-01

    Cancer epidemiology has undergone marked development since the 1950s. One of the most spectacular and specific contributions was the demonstration of the massive effect of smoking on the occurrence of lung, larynx, and bladder cancer. Major chemical, physical, and biological carcinogenic agents have been identified in the working environment and in the overall environment. The chain of events from environmental exposures to cancer requires hundreds of polymorphic genes coding for proteins involved in the transport and metabolism of xenobiotics, or in repair, or in an immune or inflammatory response. The multifactorial and multistage characteristics of cancer create the theoretical conditions for statistical interactions that have been exceptionally detected. Over the last two decades, a considerable mass of data has been generated, mostly addressing the interactions between smoking and xenobiotic-metabolizing enzymes in smoking-related cancers. They were sometimes considered disappointing, but they actually brought a lot of information and raised many methodological issues. In parallel, the number of polymorphisms that can be considered candidate per function increased so much that multiple testing has become a major issue, and genome wide-screening approaches have more and more gained in interest. Facing the resulting complexity, some instruments are being set up: our studies are now equipped with carefully sampled biological collections, high-throughput genotyping systems are becoming available, work on statistical methodologies is ongoing, bioinformatics databases are growing larger and access to them is becoming simpler; international consortiums are being organized. The roles of environmental and genetic factors are being jointly elucidated. The basic rules of epidemiology, which are demanding with respect to sampling, with respect to the histological and molecular criteria for cancer classification, with respect to the evaluation of environmental exposures

  11. Progress in the epidemiological understanding of gene-environment interactions in major diseases: cancer

    PubMed Central

    Clavel, Jacqueline

    2007-01-01

    Cancer epidemiology has undergone marked development since the nineteen-fifties. One of the most spectacular and specific contributions was the demonstration of the massive effect of smoking on the occurrence of lung, larynx and bladder cancer. Major chemical, physical and biological carcinogenic agents have been identified in the working environment and in the overall environment. The chain of events from environmental exposures to cancer requires hundreds of polymorphic genes coding for proteins involved in the transport and metabolism of xenobiotics, or in repair, or in an immune or inflammatory response. The multifactorial and multistage characteristics of cancer create the theoretical conditions for statistical interactions which have been exceptionnally detected. Over the last two decades, a considerable mass of data has been generated, mostly addressing the interactions between smoking and xenobiotic-metabolizing enzymes in smoking-related cancers. They are sometimes considered disappointing but they actually brought a lot of information and raised many methodological issues. In parallel, the number of polymorphisms which can be considered candidate per function increased so much that multiple testing has become a major issue, and genome wide screening approaches have more and more gained in interest. Facing the resulting complexity, some instruments are being set up: our studies are now equipped with carefully sampled biological collections, high-throughput genotyping systems are becoming available, work on statistical methodologies is ongoing, bioinformatics databases are growing larger and access to them is becoming simpler; international consortiums are being organized. The roles of environmental and genetic factors are being jointly elucidated. The basic rules of epidemiology, which are demanding with respect to sampling, with respect to the histological and molecular criteria for cancer classification, with respect to the evaluation of environmental

  12. Genotype-Based Bayesian Analysis of Gene-Environment Interactions with Multiple Genetic Markers and Misclassification in Environmental Factors

    PubMed Central

    Lobach, Iryna; Fan, Ruzong

    2015-01-01

    A key component to understanding etiology of complex diseases, such as cancer, diabetes, alcohol dependence, is to investigate gene-environment interactions. This work is motivated by the following two concerns in the analysis of gene-environment interactions. First, multiple genetic markers in moderate linkage disequilibrium may be involved in susceptibility to a complex disease. Second, environmental factors may be subject to misclassification. We develop a genotype based Bayesian pseudolikelihood approach that accommodates linkage disequilibrium in genetic markers and misclassification in environmental factors. Since our approach is genotype based, it allows the observed genetic information to enter the model directly thus eliminating the need to infer haplotype phase and simplifying computations. Bayesian approach allows shrinking parameter estimates towards prior distribution to improve estimation and inference when environmental factors are subject to misclassification. Simulation experiments demonstrated that our method produced parameter estimates that are nearly unbiased even for small sample sizes. An application of our method is illustrated using a case-control study of interaction between early onset of drinking and genes involved in dopamine pathway. PMID:26180529

  13. Genotype-Based Bayesian Analysis of Gene-Environment Interactions with Multiple Genetic Markers and Misclassification in Environmental Factors.

    PubMed

    Lobach, Iryna; Fan, Ruzong

    A key component to understanding etiology of complex diseases, such as cancer, diabetes, alcohol dependence, is to investigate gene-environment interactions. This work is motivated by the following two concerns in the analysis of gene-environment interactions. First, multiple genetic markers in moderate linkage disequilibrium may be involved in susceptibility to a complex disease. Second, environmental factors may be subject to misclassification. We develop a genotype based Bayesian pseudolikelihood approach that accommodates linkage disequilibrium in genetic markers and misclassification in environmental factors. Since our approach is genotype based, it allows the observed genetic information to enter the model directly thus eliminating the need to infer haplotype phase and simplifying computations. Bayesian approach allows shrinking parameter estimates towards prior distribution to improve estimation and inference when environmental factors are subject to misclassification. Simulation experiments demonstrated that our method produced parameter estimates that are nearly unbiased even for small sample sizes. An application of our method is illustrated using a case-control study of interaction between early onset of drinking and genes involved in dopamine pathway.

  14. Gene-Environment Interdependence

    ERIC Educational Resources Information Center

    Rutter, Michael

    2007-01-01

    Behavioural genetics was initially concerned with partitioning population variance into that due to genetics and that due to environmental influences. The implication was that the two were separate and it was assumed that gene-environment interactions were usually of so little importance that they could safely be ignored. Theoretical…

  15. Gene-environment interactions: key to unraveling the mystery of Parkinson's disease.

    PubMed

    Gao, Hui-Ming; Hong, Jau-Shyong

    2011-06-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease. The gradual, irreversible loss of dopamine neurons in the substantia nigra is the signature lesion of PD. Clinical symptoms of PD become apparent when 50-60% of nigral dopamine neurons are lost. PD progresses insidiously for 5-7 years (preclinical period) and then continues to worsen even under the symptomatic treatment. To determine what triggers the disease onset and what drives the chronic, self-propelling neurodegenerative process becomes critical and urgent, since lack of such knowledge impedes the discovery of effective treatments to retard PD progression. At present, available therapeutics only temporarily relieve PD symptoms. While the identification of causative gene defects in familial PD uncovers important genetic influences in this disease, the majority of PD cases are sporadic and idiopathic. The current consensus suggests that PD develops from multiple risk factors including aging, genetic predisposition, and environmental exposure. Here, we briefly review research on the genetic and environmental causes of PD. We also summarize very recent genome-wide association studies on risk gene polymorphisms in the emergence of PD. We highlight the new converging evidence on gene-environment interplay in the development of PD with an emphasis on newly developed multiple-hit PD models involving both genetic lesions and environmental triggers.

  16. Gene-Environment Interactions Target Mitogen-activated Protein 3 Kinase 1 (MAP3K1) Signaling in Eyelid Morphogenesis*

    PubMed Central

    Mongan, Maureen; Meng, Qinghang; Wang, Jingjing; Kao, Winston W.-Y.; Puga, Alvaro; Xia, Ying

    2015-01-01

    Gene-environment interactions determine the biological outcomes through mechanisms that are poorly understood. Mouse embryonic eyelid closure is a well defined model to study the genetic control of developmental programs. Using this model, we investigated how exposure to dioxin-like environmental pollutants modifies the genetic risk of developmental abnormalities. Our studies reveal that mitogen-activated protein 3 kinase 1 (MAP3K1) signaling is a focal point of gene-environment cross-talk. Dioxin exposure, acting through the aryl hydrocarbon receptor (AHR), blocked eyelid closure in genetic mutants in which MAP3K1 signaling was attenuated but did not disturb this developmental program in either wild type or mutant mice with attenuated epidermal growth factor receptor or WNT signaling. Exposure also markedly inhibited c-Jun phosphorylation in Map3k1+/− embryonic eyelid epithelium, suggesting that dioxin-induced AHR pathways can synergize with gene mutations to inhibit MAP3K1 signaling. Our studies uncover a novel mechanism through which the dioxin-AHR axis interacts with the MAP3K1 signaling pathways during fetal development and provide strong empirical evidence that specific gene alterations can increase the risk of developmental abnormalities driven by environmental pollutant exposure. PMID:26109068

  17. The Heritability of Personality is not Always 50%: Gene-Environment Interactions and Correlations between Personality and Parenting

    PubMed Central

    Krueger, Robert F.; South, Susan; Johnson, Wendy; Iacono, William

    2008-01-01

    Twin studies of personality are consistent in attributing approximately half of the variance in personality to genetic effects, with the remaining variance attributed to environments that make people within the same families different. Such conclusions, however, are based on quantitative models of human individual differences that estimate genetic and environmental contributions as constants for entire populations. Recent advances in statistical modeling allow for the possibility of estimating genetic and environmental contributions contingent on other variables, allowing the quantification of phenomena that have traditionally been characterized as gene-environment interaction and correlation. We applied these newer models to understand how adolescents’ descriptions of their relationships with their parents might change or moderate the impact of genetic and environmental factors on personality. We documented notable moderation in the domains of positive and negative emotionality, with parental relationships acting to both enhance and diminish both genetic and environmental effects. We discuss how genetic and environmental contributions to personality might be more richly conceptualized as dynamic systems of gene-environment interplay – systems that are not captured by classical concepts, such as the overall heritability of personality. PMID:19012656

  18. Gene-environment interaction effects on lung function- a genome-wide association study within the Framingham heart study

    PubMed Central

    2013-01-01

    Background Previous studies in occupational exposure and lung function have focused only on the main effect of occupational exposure or genetics on lung function. Some disease-susceptible genes may be missed due to their low marginal effects, despite potential involvement in the disease process through interactions with the environment. Through comprehensive genome-wide gene-environment interaction studies, we can uncover these susceptibility genes. Our objective in this study was to explore gene by occupational exposure interaction effects on lung function using both the individual SNPs approach and the genetic network approach. Methods The study population comprised the Offspring Cohort and the Third Generation from the Framingham Heart Study. We used forced expiratory volume in one second (FEV1) and ratio of FEV1 to forced vital capacity (FVC) as outcomes. Occupational exposures were classified using a population-specific job exposure matrix. We performed genome-wide gene-environment interaction analysis, using the Affymetrix 550 K mapping array for genotyping. A linear regression-based generalized estimating equation was applied to account for within-family relatedness. Network analysis was conducted using results from single-nucleotide polymorphism (SNP)-level analyses and from gene expression study results. Results There were 4,785 participants in total. SNP-level analysis and network analysis identified SNP rs9931086 (Pinteraction =1.16 × 10-7) in gene SLC38A8, which may significantly modify the effects of occupational exposure on FEV1. Genes identified from the network analysis included CTLA-4, HDAC, and PPAR-alpha. Conclusions Our study implies that SNP rs9931086 in SLC38A8 and genes CTLA-4, HDAC, and PPAR-alpha, which are related to inflammatory processes, may modify the effect of occupational exposure on lung function. PMID:24289273

  19. Tests for gene-environment interaction from case-control data: a novel study of type I error, power and designs.

    PubMed

    Mukherjee, Bhramar; Ahn, Jaeil; Gruber, Stephen B; Rennert, Gad; Moreno, Victor; Chatterjee, Nilanjan

    2008-11-01

    To evaluate the risk of a disease associated with the joint effects of genetic susceptibility and environmental exposures, epidemiologic researchers often test for non-multiplicative gene-environment effects from case-control studies. In this article, we present a comparative study of four alternative tests for interactions: (i) the standard case-control method; (ii) the case-only method, which requires an assumption of gene-environment independence for the underlying population; (iii) a two-step method that decides between the case-only and case-control estimators depending on a statistical test for the gene-environment independence assumption and (iv) a novel empirical-Bayes (EB) method that combines the case-control and case-only estimators depending on the sample size and strength of the gene-environment association in the data. We evaluate the methods in terms of integrated Type I error and power, averaged with respect to varying scenarios for gene-environment association that are likely to appear in practice. These unique studies suggest that the novel EB procedure overall is a promising approach for detection of gene-environment interactions from case-control studies. In particular, the EB procedure, unlike the case-only or two-step methods, can closely maintain a desired Type I error under realistic scenarios of gene-environment dependence and yet can be substantially more powerful than the traditional case-control analysis when the gene-environment independence assumption is satisfied, exactly or approximately. Our studies also reveal potential utility of some non-traditional case-control designs that samples controls at a smaller rate than the cases. Apart from the simulation studies, we also illustrate the different methods by analyzing interactions of two commonly studied genes, N-acetyl transferase type 2 and glutathione s-transferase M1, with smoking and dietary exposures, in a large case-control study of colorectal cancer.

  20. The association of interacting neighborhood gene-environment risk with cortisol and blood pressure in African-American adults

    PubMed Central

    Coulon, Sandra M.; Wilson, Dawn K.; Van Horn, M. L.; Hand, Gregory A.; Kresovich, Stephen

    2016-01-01

    Background African-American adults are disproportionately affected by stress-related chronic conditions like high blood pressure (BP), and both environmental stress and genetic risk may play a role in its development. Purpose This study tested whether the dual risk of low neighborhood socioeconomic status (SES) and glucocorticoid genetic sensitivity interacted to predict waking cortisol and BP. Methods Cross-sectional waking cortisol and BP were collected from 208 African-American adults who were participating in a follow-up visit as part of the Positive Action for Today’s Health trial. Three single nucleotide polymorphisms were genotyped, salivary cortisol samples were collected, and neighborhood SES was calculated using 2010 Census data. Results The sample was mostly female (65%), with weight classified as overweight or obese (MBMI=32.74, SD=8.88), and a mean age of 55.64 (SD=15.21). The gene-by-neighborhood SES interaction predicted cortisol (B=0.235, p=.001, r2=.036), but not BP. For adults with high genetic risk, waking cortisol was lower with lower SES but higher with higher SES (B=0.87). Lower neighborhood SES was also related to higher systolic BP (B=−0.794, p=.028). Conclusions Findings demonstrated an interaction whereby African-American adults with high genetic sensitivity had high levels of waking cortisol with higher neighborhood SES, and low levels with lower neighborhood SES. This moderation effect is consistent with a differential susceptibility gene-environment pattern, rather than a dual-risk pattern. These findings contribute to a growing body of evidence that demonstrates the importance of investigating complex gene-environment relations in order to better understand stress-related health disparities. PMID:26685668

  1. Nature versus nurture: A systematic approach to elucidate gene-environment interactions in the development of myopic refractive errors.

    PubMed

    Miraldi Utz, Virginia

    2017-01-01

    Myopia is the most common eye disorder and major cause of visual impairment worldwide. As the incidence of myopia continues to rise, the need to further understand the complex roles of molecular and environmental factors controlling variation in refractive error is of increasing importance. Tkatchenko and colleagues applied a systematic approach using a combination of gene set enrichment analysis, genome-wide association studies, and functional analysis of a murine model to identify a myopia susceptibility gene, APLP2. Differential expression of refractive error was associated with time spent reading for those with low frequency variants in this gene. This provides support for the longstanding hypothesis of gene-environment interactions in refractive error development.

  2. Conceptual shifts needed to understand the dynamic interactions of genes, environment, epigenetics, social processes, and behavioral choices.

    PubMed

    Jackson, Fatimah L C; Niculescu, Mihai D; Jackson, Robert T

    2013-10-01

    Social and behavioral research in public health is often intimately tied to profound, but frequently neglected, biological influences from underlying genetic, environmental, and epigenetic events. The dynamic interplay between the life, social, and behavioral sciences often remains underappreciated and underutilized in addressing complex diseases and disorders and in developing effective remediation strategies. Using a case-study format, we present examples as to how the inclusion of genetic, environmental, and epigenetic data can augment social and behavioral health research by expanding the parameters of such studies, adding specificity to phenotypic assessments, and providing additional internal control in comparative studies. We highlight the important roles of gene-environment interactions and epigenetics as sources of phenotypic change and as a bridge between the life and social and behavioral sciences in the development of robust interdisciplinary analyses.

  3. Sequential tests for gene-environment interactions in matched case-control studies.

    PubMed

    Tweel, Ingeborg van der; Schipper, Maria

    2004-12-30

    The sample size necessary to detect a significant gene x environment interaction in an observational study can be large. For reasons of cost-effectiveness and efficient use of available biological samples we investigated the properties of sequential designs in matched case-control studies to test for both non-hierarchical and hierarchical interactions. We derived the test statistics Z and V and their characteristics when applied in a two-sided triangular test. Results of simulations show good agreement with theoretical values for V and the type I error. Power values were larger than their theoretical values for very large sample sizes. Median gain in efficiency was about 27 per cent. For a 'rare' phenotype gain in efficiency was larger when the alternative hypothesis was true than under the null hypothesis. Sequential designs lead to substantial efficiency gains in tests for interaction in matched case-control studies.

  4. Gene-Environment Interactions Controlling Energy and Glucose Homeostasis and the Developmental Origins of Obesity

    PubMed Central

    Bouret, Sebastien; Levin, Barry E.; Ozanne, Susan E.

    2015-01-01

    Obesity and type 2 diabetes mellitus (T2DM) often occur together and affect a growing number of individuals in both the developed and developing worlds. Both are associated with a number of other serious illnesses that lead to increased rates of mortality. There is likely a polygenic mode of inheritance underlying both disorders, but it has become increasingly clear that the pre- and postnatal environments play critical roles in pushing predisposed individuals over the edge into a disease state. This review focuses on the many genetic and environmental variables that interact to cause predisposed individuals to become obese and diabetic. The brain and its interactions with the external and internal environment are a major focus given the prominent role these interactions play in the regulation of energy and glucose homeostasis in health and disease. PMID:25540138

  5. Gene-gene and gene-environment interactions defining lipid-related traits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Steps towards reducing chronic disease progression are continuously being taken through the form of genomic research. Studies over the last year have highlighted more and more polymorphisms, pathways and interactions responsible for metabolic disorders such as cardiovascular disease, obesity and dys...

  6. Gene-gene and gene-environment interactions defining lipid-related traits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose of review Steps towards reducing chronic disease progression are continuously being taken through the form of genomic research. Studies over the last year have highlighted more and more polymorphisms, pathways and interactions responsible for metabolic disorders such as cardiovascular diseas...

  7. The Behavioural Phenotype of Smith-Magenis Syndrome: Evidence for a Gene-Environment Interaction

    ERIC Educational Resources Information Center

    Taylor, L.; Oliver, C.

    2008-01-01

    Background: Behaviour problems and a preference for adult contact are reported to be prominent in the phenotype of Smith-Magenis syndrome. In this study we examined the relationship between social interactions and self-injurious and aggressive/disruptive behaviour in Smith-Magenis syndrome to explore potential operant reinforcement of problem…

  8. Gene Environment Interactions in Women With Breast and Secondary Lung Cancer

    DTIC Science & Technology

    2006-07-01

    or due to alterations in genes whose products interact or communicate with p53. Most mutations result in the inability of the protein to activate...p53 and smoking in breast cancer can be made. The p53 gene is mutated in about 50% of lung cancers. Among the 2,372 mutations recorded for lung...carcinogenesis by affecting expression of mutated genes [44]. Methylation profiles associated with certain types of cancer could be used to identify cancer

  9. Detecting Pathway-Based Gene-Gene and Gene-Environment Interactions in Pancreatic Cancer

    PubMed Central

    Duell, Eric J.; Bracci, Paige M.; Moore, Jason H.; Burk, Robert D.; Kelsey, Karl T.; Holly, Elizabeth A.

    2015-01-01

    Data mining and data reduction methods to detect interactions in epidemiologic data are being developed and tested. In these analyses, multifactor dimensionality reduction, focused interaction testing framework, and traditional logistic regression models were used to identify potential interactions with up to three factors. These techniques were used in a population-based case-control study of pancreatic cancer from the San Francisco Bay Area (308 cases, 964 controls). From 7 biochemical pathways, along with tobacco smoking, 26 polymorphisms in 20 genes were included in these analyses. Combinations of genetic markers and cigarette smoking were identified as potential risk factors for pancreatic cancer, including genes in base excision repair (OGG1), nucleotide excision repair (XPD, XPA, XPC), and double-strand break repair (XRCC3). XPD.751, XPD.312, and cigarette smoking were the best single-factor predictors of pancreatic cancer risk, whereas XRCC3.241*smoking and OGG1.326*XPC.PAT were the best two-factor predictors. There was some evidence for a three-factor combination of OGG1.326*XPD.751*smoking, but the covariate-adjusted relative-risk estimates lacked precision. Multifactor dimensionality reduction and focused interaction testing framework showed little concordance, whereas logistic regression allowed for covariate adjustment and model confirmation. Our data suggest that multiple common alleles from DNA repair pathways in combination with cigarette smoking may increase the risk for pancreatic cancer, and that multiple approaches to data screening and analysis are necessary to identify potentially new risk factor combinations. PMID:18559563

  10. Linking Genes to Cardiovascular Diseases: Gene Action and Gene-Environment Interactions.

    PubMed

    Pasipoularides, Ares

    2015-12-01

    A unique myocardial characteristic is its ability to grow/remodel in order to adapt; this is determined partly by genes and partly by the environment and the milieu intérieur. In the "post-genomic" era, a need is emerging to elucidate the physiologic functions of myocardial genes, as well as potential adaptive and maladaptive modulations induced by environmental/epigenetic factors. Genome sequencing and analysis advances have become exponential lately, with escalation of our knowledge concerning sometimes controversial genetic underpinnings of cardiovascular diseases. Current technologies can identify candidate genes variously involved in diverse normal/abnormal morphomechanical phenotypes, and offer insights into multiple genetic factors implicated in complex cardiovascular syndromes. The expression profiles of thousands of genes are regularly ascertained under diverse conditions. Global analyses of gene expression levels are useful for cataloging genes and correlated phenotypes, and for elucidating the role of genes in maladies. Comparative expression of gene networks coupled to complex disorders can contribute insights as to how "modifier genes" influence the expressed phenotypes. Increasingly, a more comprehensive and detailed systematic understanding of genetic abnormalities underlying, for example, various genetic cardiomyopathies is emerging. Implementing genomic findings in cardiology practice may well lead directly to better diagnosing and therapeutics. There is currently evolving a strong appreciation for the value of studying gene anomalies, and doing so in a non-disjointed, cohesive manner. However, it is challenging for many-practitioners and investigators-to comprehend, interpret, and utilize the clinically increasingly accessible and affordable cardiovascular genomics studies. This survey addresses the need for fundamental understanding in this vital area.

  11. Using mouse models of autism spectrum disorders to study the neurotoxicology of gene-environment interactions

    PubMed Central

    Schwartzer, Jared J.; Koenig, Claire M.; Berman, Robert F

    2012-01-01

    To better study the role of genetics in autism, mouse models have been developed which mimic the genetics of specific autism spectrum and related disorders. These models have facilitated research on the role genetic susceptibility factors in the pathogenesis of autism in the absence of environmental factors. Inbred mouse strains have been similarly studied to assess the role of environmental agents on neurodevelopment, typically without the complications of genetic heterogeneity of the human population. What has not been as actively pursued, however, is the methodical study of the interaction between these factors (e.g., gene and environmental interactions in neurodevelopment). This review suggests that a genetic predisposition paired with exposure to environmental toxicants play an important role in the etiology of neurodevelopmental disorders including autism, and may contribute to the largely unexplained rise in the number of children diagnosed with autism worldwide. Specifically, descriptions of the major mouse models of autism and toxic mechanisms of prevalent environmental chemicals are provided followed by a discussion of current and future research strategies to evaluate the role of gene and environment interactions in neurodevelopmental disorders. PMID:23010509

  12. Gene-environment interactions on mental development in African American, Dominican, and Caucasian Mothers and Newborns

    PubMed Central

    Wang, Shuang; Chanock, Stephen; Tang, Deliang; Li, Zhigang; Edwards, Susan; Jedrychowski, Wieslaw; Perera, Frederica P.

    2009-01-01

    The health impact of environmental toxins has gained increasing recognition over the years. Polycyclic aromatic hydrocarbons (PAHs) and environmental tobacco smoke (ETS) are known to affect nervous system development in children, but no studies have investigated how polymorphisms in PAH metabolic or detoxification genes affect child cognitive development following PAH exposure during pregnancy. In two parallel prospective cohort studies of nonsmoking African American and Dominican mothers and children in New York City and of Caucasian mothers and children in Krakow, Poland, we explored the effect of gene-PAH interaction on child mental development index (MDI), as measured by the Bayley Scales of Infant Development-Revised (BSID-II). Genes known to play important roles in the metabolic activation or detoxification of PAHs were selected. Genetic variations in these genes could influence susceptibility to adverse effects of PAHs in polluted air. We explored the effects of interactions between prenatal PAH exposure and 21 polymorphisms or haplotypes in these genes on MDI at 12, 24, and 36 months among 547 newborns and 806 mothers from three different ethnic groups: African Americans, Dominicans, and Caucasians. PAHs were measured by personal air monitoring of mothers during pregnancy. Significant interaction effects between haplotypes and PAHs were observed in mothers and their newborns in all three ethnic groups after Bonferroni correction for multiple comparisons. The strongest and most consistent effect observed was between PAH and haplotype ACCGGC of the CYP1B1 gene. PMID:19860743

  13. Gene-environment interaction on neural mechanisms of orthographic processing in Chinese children

    PubMed Central

    Su, Mengmeng; Wang, Jiuju; Maurer, Urs; Zhang, Yuping; Li, Jun; McBride-Chang, Catherine; Tardif, Twila; Liu, Youyi; Shu, Hua

    2015-01-01

    The ability to process and identify visual words requires efficient orthographic processing of print, consisting of letters in alphabetic languages or characters in Chinese. The N170 is a robust neural marker for orthographic processes. Both genetic and environmental factors, such as home literacy, have been shown to influence orthographic processing at the behavioral level, but their relative contributions and interactions are not well understood. The present study aimed to reveal possible gene-by-environment interactions on orthographic processing at the behavioral and neural level in a normal children sample. Sixty 12 year old Chinese children from a 10-year longitudinal sample underwent an implicit visual-word color decision task on real words and stroke combinations. The ERP analysis focused on the increase of the occipito-temporal N170 to words compared to stroke combinations. The genetic analysis focused on two SNPs (rs1419228, rs1091047) in the gene DCDC2 based on previous findings linking these 2 SNPs to orthographic coding. Home literacy was measured previously as the number of children's books at home, when the children were at the age of 3. Relative to stroke combinations, real words evoked greater N170 in bilateral posterior brain regions. A significant interaction between rs1091047 and home literacy was observed on the changes of N170 comparing real words to stroke combinations in the left hemisphere. Particularly, children carrying the major allele “G” showed a similar N170 effect irrespective of their environment, while children carrying the minor allele “C” showed a smaller N170 effect in low home-literacy environment than those in good environment. PMID:26294811

  14. Gene-Environment Interactions of Circadian-Related Genes for Cardiometabolic Traits

    PubMed Central

    Follis, Jack L.; Smith, Caren E.; Tanaka, Toshiko; Garaulet, Marta; Gottlieb, Daniel J.; Hruby, Adela; Jacques, Paul F.; Kiefte-de Jong, Jessica C.; Lamon-Fava, Stefania; Scheer, Frank A.J.L.; Bartz, Traci M.; Kovanen, Leena; Wojczynski, Mary K.; Frazier-Wood, Alexis C.; Ahluwalia, Tarunveer S.; Perälä, Mia-Maria; Jonsson, Anna; Muka, Taulant; Kalafati, Ioanna P.; Mikkilä, Vera; Ordovás, José M.

    2015-01-01

    OBJECTIVE Common circadian-related gene variants associate with increased risk for metabolic alterations including type 2 diabetes. However, little is known about whether diet and sleep could modify associations between circadian-related variants (CLOCK-rs1801260, CRY2-rs11605924, MTNR1B-rs1387153, MTNR1B-rs10830963, NR1D1-rs2314339) and cardiometabolic traits (fasting glucose [FG], HOMA-insulin resistance, BMI, waist circumference, and HDL-cholesterol) to facilitate personalized recommendations. RESEARCH DESIGN AND METHODS We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations and interactions between dietary intake/sleep duration and selected variants on cardiometabolic traits from 15 cohort studies including up to 28,190 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. RESULTS We observed significant associations between relative macronutrient intakes and glycemic traits and short sleep duration (<7 h) and higher FG and replicated known MTNR1B associations with glycemic traits. No interactions were evident after accounting for multiple comparisons. However, we observed nominally significant interactions (all P < 0.01) between carbohydrate intake and MTNR1B-rs1387153 for FG with a 0.003 mmol/L higher FG with each additional 1% carbohydrate intake in the presence of the T allele, between sleep duration and CRY2-rs11605924 for HDL-cholesterol with a 0.010 mmol/L higher HDL-cholesterol with each additional hour of sleep in the presence of the A allele, and between long sleep duration (≥9 h) and MTNR1B-rs1387153 for BMI with a 0.60 kg/m2 higher BMI with long sleep duration in the presence of the T allele relative to normal sleep duration (≥7 to <9 h). CONCLUSIONS Our results suggest that lower carbohydrate intake and normal sleep duration may ameliorate cardiometabolic abnormalities conferred by common circadian-related genetic variants

  15. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors.

    PubMed

    Nickels, Stefan; Truong, Thérèse; Hein, Rebecca; Stevens, Kristen; Buck, Katharina; Behrens, Sabine; Eilber, Ursula; Schmidt, Martina; Häberle, Lothar; Vrieling, Alina; Gaudet, Mia; Figueroa, Jonine; Schoof, Nils; Spurdle, Amanda B; Rudolph, Anja; Fasching, Peter A; Hopper, John L; Makalic, Enes; Schmidt, Daniel F; Southey, Melissa C; Beckmann, Matthias W; Ekici, Arif B; Fletcher, Olivia; Gibson, Lorna; Silva, Isabel dos Santos; Peto, Julian; Humphreys, Manjeet K; Wang, Jean; Cordina-Duverger, Emilie; Menegaux, Florence; Nordestgaard, Børge G; Bojesen, Stig E; Lanng, Charlotte; Anton-Culver, Hoda; Ziogas, Argyrios; Bernstein, Leslie; Clarke, Christina A; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Brauch, Hiltrud; Brüning, Thomas; Harth, Volker; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Lambrechts, Diether; Smeets, Dominiek; Neven, Patrick; Paridaens, Robert; Flesch-Janys, Dieter; Obi, Nadia; Wang-Gohrke, Shan; Couch, Fergus J; Olson, Janet E; Vachon, Celine M; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Offit, Kenneth; John, Esther M; Miron, Alexander; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Chanock, Stephen J; Lissowska, Jolanta; Liu, Jianjun; Cox, Angela; Cramp, Helen; Connley, Dan; Balasubramanian, Sabapathy; Dunning, Alison M; Shah, Mitul; Trentham-Dietz, Amy; Newcomb, Polly; Titus, Linda; Egan, Kathleen; Cahoon, Elizabeth K; Rajaraman, Preetha; Sigurdson, Alice J; Doody, Michele M; Guénel, Pascal; Pharoah, Paul D P; Schmidt, Marjanka K; Hall, Per; Easton, Doug F; Garcia-Closas, Montserrat; Milne, Roger L; Chang-Claude, Jenny

    2013-01-01

    Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4)). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85) in those who drank ≥ 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 × 10(-5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92-1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.

  16. Gene-Environment Interaction of ApoE Genotype and Combat Exposure on PTSD

    PubMed Central

    Lyons, Michael J.; Genderson, Margo; Grant, Michael D.; Logue, Mark; Zink, Tyler; McKenzie, Ruth; Franz, Carol E.; Panizzon, Matthew; Lohr, James B.; Jerskey, Beth; Kremen, William S.

    2015-01-01

    Factors determining who develops PTSD following trauma are not well understood. The €4 allele of the apolipoprotein E (apoE) gene is associated with dementia and unfavorable outcome following brain insult. PTSD is also associated with dementia. Given evidence that psychological trauma adversely affects the brain, we hypothesized that the apoE genotype moderates effects of psychological trauma on PTSD pathogenesis. To investigate the moderation of the relationship between PTSD symptoms and combat exposure, we used 172 participants with combat trauma sustained during the Vietnam War. PTSD symptoms were the dependent variable and number of combat experiences, apoE genotype, and the combat experiences × apoE genotype interaction were predictors. We also examined the outcome of a diagnosis of PTSD (n = 39) versus no PTSD diagnosis (n = 131). The combat × apoE genotype interaction was significant for both PTSD symptoms (P = .014) and PTSD diagnosis (P = .009). ApoE genotype moderates the relationship between combat exposure and PTSD symptoms. Although the pathophysiology of PTSD is not well understood, the €4 allele is related to reduced resilience of the brain to insult. Our results are consistent with the €4 allele influencing the effects of psychological trauma on the brain, thereby affecting the risk of PTSD. PMID:24132908

  17. Gene-environment interaction of reelin and stress in cognitive behaviours in mice: Implications for schizophrenia.

    PubMed

    Schroeder, Anna; Buret, Laetitia; Hill, Rachel A; van den Buuse, Maarten

    2015-01-01

    Cognitive deficits are a particularly debilitating symptom group in schizophrenia. We investigated the effect of a 'two hit' combination of two factors implicated in schizophrenia development, reelin deficiency and stress, on cognitive behaviours in mice. Male and female heterozygous reelin mice (HRM) and wild-type (WT) controls received the stress hormone, corticosterone (CORT), during early adulthood to simulate chronic stress. The Y-maze, novel object recognition task (NORT), social interaction task and prepulse inhibition (PPI) were used to assess short-term spatial memory, visual non-spatial memory, social recognition memory and sensory gating, respectively. Reelin protein expression was measured in the prefrontal cortex (PFC) and hippocampus. CORT induced spatial memory deficits in male and female HRM but not in WT controls suggesting increased vulnerability of HRM to the effects of stress on cognition. By contrast, CORT disrupted PPI only in male WT mice, but not in male HRM, suggesting a protective role of reelin deficiency against effects of stress on PPI. Male HRM performed worse in the social recognition memory task compared to wild-type controls, irrespective of CORT treatment. No differences were detected in the NORT. Reelin protein expression was increased in the PFC of female CORT-treated HRM but there were no group differences in the hippocampus. Overall, these findings extend our understanding of the role of reelin-stress interactions in schizophrenia.

  18. Genotype-based association models of complex diseases to detect gene-gene and gene-environment interactions.

    PubMed

    Lobach, Iryna; Fan, Ruzong; Manga, Prashiela

    A central problem in genetic epidemiology is to identify and rank genetic markers involved in a disease. Complex diseases, such as cancer, hypertension, diabetes, are thought to be caused by an interaction of a panel of genetic factors, that can be identified by markers, which modulate environmental factors. Moreover, the effect of each genetic marker may be small. Hence, the association signal may be missed unless a large sample is considered, or a priori biomedical data are used. Recent advances generated a vast variety of a priori information, including linkage maps and information about gene regulatory dependence assembled into curated pathway databases. We propose a genotype-based approach that takes into account linkage disequilibrium (LD) information between genetic markers that are in moderate LD while modeling gene-gene and gene-environment interactions. A major advantage of our method is that the observed genetic information enters a model directly thus eliminating the need to estimate haplotype-phase. Our approach results in an algorithm that is inexpensive computationally and does not suffer from bias induced by haplotype-phase ambiguity. We investigated our model in a series of simulation experiments and demonstrated that the proposed approach results in estimates that are nearly unbiased and have small variability. We applied our method to the analysis of data from a melanoma case-control study and investigated interaction between a set of pigmentation genes and environmental factors defined by age and gender. Furthermore, an application of our method is demonstrated using a study of Alcohol Dependence.

  19. Gene-environment interactions across development: Exploring DRD2 genotype and prenatal smoking effects on self-regulation.

    PubMed

    Wiebe, Sandra A; Espy, Kimberly Andrews; Stopp, Christian; Respass, Jennifer; Stewart, Peter; Jameson, Travis R; Gilbert, David G; Huggenvik, Jodi I

    2009-01-01

    Genetic factors dynamically interact with both pre- and postnatal environmental influences to shape development. Considerable attention has been devoted to gene-environment interactions (G x E) on important outcomes (A. Caspi & T. E. Moffitt, 2006). It is also important to consider the possibility that these G x E effects may vary across development, particularly for constructs like self-regulation that emerge slowly, depend on brain regions that change qualitatively in different developmental periods, and thus may be manifested differently. To illustrate one approach to exploring such developmental patterns, the relation between variation in the TaqIA polymorphism, related to D2 dopamine receptor expression and availability, and prenatal exposure to tobacco was examined in two exploratory studies. First, in 4-week-old neonates, genotype-exposure interactions were observed for attention and irritable reactivity, but not for stress dysregulation. Second, in preschool children, genotype was related to Preschool Trail Making Test (K. A. Espy and M. F. Cwik, 2004) task performance on conditions requiring executive control; children with both the A1+ genotype and a history of prenatal tobacco exposure displayed disproportionately poor performance. Despite study limitations, these results illustrate the importance of examining the interplay between genetic and prenatal environmental factors across development.

  20. Gli2 gene-environment interactions contribute to the etiological complexity of holoprosencephaly: evidence from a mouse model.

    PubMed

    Heyne, Galen W; Everson, Joshua L; Ansen-Wilson, Lydia J; Melberg, Cal G; Fink, Dustin M; Parins, Kia F; Doroodchi, Padydeh; Ulschmid, Caden M; Lipinski, Robert J

    2016-11-01

    Holoprosencephaly (HPE) is a common and severe human developmental abnormality marked by malformations of the forebrain and face. Although several genetic mutations have been linked to HPE, phenotypic outcomes range dramatically, and most cases cannot be attributed to a specific cause. Gene-environment interaction has been invoked as a premise to explain the etiological complexity of HPE, but identification of interacting factors has been extremely limited. Here, we demonstrate that mutations in Gli2, which encodes a Hedgehog pathway transcription factor, can cause or predispose to HPE depending upon gene dosage. On the C57BL/6J background, homozygous GLI2 loss of function results in the characteristic brain and facial features seen in severe human HPE, including midfacial hypoplasia, hypotelorism and medial forebrain deficiency with loss of ventral neurospecification. Although normally indistinguishable from wild-type littermates, we demonstrate that mice with single-allele Gli2 mutations exhibit increased penetrance and severity of HPE in response to low-dose teratogen exposure. This genetic predisposition is associated with a Gli2 dosage-dependent attenuation of Hedgehog ligand responsiveness at the cellular level. In addition to revealing a causative role for GLI2 in HPE genesis, these studies demonstrate a mechanism by which normally silent genetic and environmental factors can interact to produce severe outcomes. Taken together, these findings provide a framework for the understanding of the extreme phenotypic variability observed in humans carrying GLI2 mutations and a paradigm for reducing the incidence of this morbid birth defect.

  1. Does Parental Divorce Moderate the Heritability of Body Dissatisfaction? An Extension of Previous Gene-Environment Interaction Effects

    PubMed Central

    O’Connor, Shannon M.; Klump, Kelly L.; VanHuysse, Jessica L.; McGue, Matt; Iacono, William

    2015-01-01

    Objective Previous research suggests that parental divorce moderates genetic influences on body dissatisfaction. Specifically, the heritability of body dissatisfaction is higher in children of divorced versus intact families, suggesting possible gene-environment interaction effects. However, prior research is limited to a single, self-report measure of body dissatisfaction. The primary aim of the present study was to examine whether these findings extend to a different dimension of body dissatisfaction, body image perceptions. Method Participants were 1,534 female twins from the Minnesota Twin Family Study, ages 16–20 years. The Body Rating Scale (BRS) was used to assess body image perceptions. Results Although BRS scores were heritable in twins from divorced and intact families, the heritability estimates in the divorced group were not significantly greater than estimates in the intact group. However, there were differences in nonshared environmental effects, where the magnitude of these environmental influences was larger in the divorced as compared to the intact families. Discussion Different dimensions of body dissatisfaction (i.e., negative self-evaluation versus body image perceptions) may interact with environmental risk, such as parental divorce, in discrete ways. Future research should examine this possibility and explore differential gene x environment interactions using diverse measures. PMID:26314278

  2. Gli2 gene-environment interactions contribute to the etiological complexity of holoprosencephaly: evidence from a mouse model

    PubMed Central

    Heyne, Galen W.; Everson, Joshua L.; Ansen-Wilson, Lydia J.; Melberg, Cal G.; Fink, Dustin M.; Parins, Kia F.; Doroodchi, Padydeh; Ulschmid, Caden M.

    2016-01-01

    ABSTRACT Holoprosencephaly (HPE) is a common and severe human developmental abnormality marked by malformations of the forebrain and face. Although several genetic mutations have been linked to HPE, phenotypic outcomes range dramatically, and most cases cannot be attributed to a specific cause. Gene-environment interaction has been invoked as a premise to explain the etiological complexity of HPE, but identification of interacting factors has been extremely limited. Here, we demonstrate that mutations in Gli2, which encodes a Hedgehog pathway transcription factor, can cause or predispose to HPE depending upon gene dosage. On the C57BL/6J background, homozygous GLI2 loss of function results in the characteristic brain and facial features seen in severe human HPE, including midfacial hypoplasia, hypotelorism and medial forebrain deficiency with loss of ventral neurospecification. Although normally indistinguishable from wild-type littermates, we demonstrate that mice with single-allele Gli2 mutations exhibit increased penetrance and severity of HPE in response to low-dose teratogen exposure. This genetic predisposition is associated with a Gli2 dosage-dependent attenuation of Hedgehog ligand responsiveness at the cellular level. In addition to revealing a causative role for GLI2 in HPE genesis, these studies demonstrate a mechanism by which normally silent genetic and environmental factors can interact to produce severe outcomes. Taken together, these findings provide a framework for the understanding of the extreme phenotypic variability observed in humans carrying GLI2 mutations and a paradigm for reducing the incidence of this morbid birth defect. PMID:27585885

  3. Gene-environment interaction in programming hippocampal plasticity: focus on adult neurogenesis

    PubMed Central

    Koehl, Muriel

    2015-01-01

    Interactions between genes and environment are a critical feature of development and both contribute to shape individuality. They are at the core of vulnerability resiliency for mental illnesses. During the early postnatal period, several brain structures involved in cognitive and emotional processing, such as the hippocampus, still develop and it is likely that interferences with this neuronal development, which is genetically determined, might lead to long-lasting structural and functional consequences and increase the risk of developing psychopathology. One particular target is adult neurogenesis, which is involved in the regulation of cognitive and emotional processes. Insights into the dynamic interplay between genes and environmental factors in setting up individual rates of neurogenesis have come from laboratory studies exploring experience-dependent changes in adult neurogenesis as a function of individual’s genetic makeup. These studies have implications for our understanding of the mechanisms regulating adult neurogenesis, which could constitute a link between environmental challenges and psychopathology. PMID:26300723

  4. Gene-Environment Interactions in Preventive Medicine: Current Status and Expectations for the Future.

    PubMed

    Narimatsu, Hiroto

    2017-01-30

    The progression of many common disorders involves a complex interplay of multiple factors, including numerous different genes and environmental factors. Gene-environmental cohort studies focus on the identification of risk factors that cannot be discovered by conventional epidemiological methodologies. Such epidemiological methodologies preclude precise predictions, because the exact risk factors can be revealed only after detailed analyses of the interactions among multiple factors, that is, between genes and environmental factors. To date, these cohort studies have reported some promising results. However, the findings do not yet have sufficient clinical significance for the development of precise, personalized preventive medicine. Especially, some promising preliminary studies have been conducted in terms of the prevention of obesity. Large-scale validation studies of those preliminary studies, using a prospective cohort design and long follow-ups, will produce useful and practical evidence for the development of preventive medicine in the future.

  5. A new clinical evidence-based gene-environment interaction model of depression.

    PubMed

    Bagdy, Gyorgy; Juhasz, Gabriella; Gonda, Xenia

    2012-12-01

    In our current understanding of mood disorders, the role of genes is diverse including the mediation of the effects of provoking and protective factors. Different or partially overlapping gene sets play a major role in the development of personality traits including also affective temperaments, in the mediation of the effects of environmental factors, and in the interaction of these elements in the development of depression. Certain genes are associated with personality traits and temperaments including e.g., neuroticism, impulsivity, openness, rumination and extroversion. Environmental factors consist of external (early and provoking life events, seasonal changes, social support etc.) and internal factors (hormones, biological rhythm generators, comorbid disorders etc). Some of these environmental factors, such as early life events and some prenatal events directly influence the development of personality traits and temperaments. In the NEWMOOD cohort polymorphisms of the genes of the serotonin transporter, 5-HT1A, 5-HT1B and 5-HT2A and endocannabinoid CB1 receptors, tryptophan hydroxylase, CREB1, BDNF and GIRK provide evidence for the involvement of these genes in the development of depression. Based on their role in this process they could be assigned to different gene sets. The role of certain genes, such as promoter polymorphisms of the serotonin transporter (5-HTTLPR) and CB1 receptor has been shown in more than one of the above factors. Furthermore, gene-gene interactions of these promoters associated with anxiety suggest the application of these polymorphisms in personalized medicine. In this review we introduce a new model including environmental factors, genes, trait and temperament markers based on human genetic studies.

  6. Exposure enriched case-control (EECC) design for the assessment of gene-environment interaction

    PubMed Central

    Carroll, Raymond J.; Diao, Nancy; Christiani, David C.; Ryan, Louise M.

    2016-01-01

    Genetic susceptibility and environmental exposure both play an important role in the aetiology of many diseases. Case-control studies are often the first choice to explore the joint influence of genetic and environmental factors on the risk of developing a rare disease. In practice, however, such studies may have limited power, especially when susceptibility genes are rare and exposure distributions are highly skewed. We propose a variant of the classical case-control study, the exposure enriched case-control (EECC) design, where not only cases, but also high (or low) exposed individuals are oversampled, depending on the skewness of the exposure distribution. Of course, a traditional logistic regression model is no longer valid and results in biased parameter estimation. We show that addition of a simple covariate to the regression model removes this bias and yields reliable estimates of main and interaction effects of interest. We also discuss optimal design, showing that judicious over-sampling of high/low exposed individuals can boost study power considerably. We illustrate our results using data from a study involving arsenic exposure and detoxification genes in Bangladesh. PMID:27313007

  7. New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions.

    PubMed

    Cork, Michael J; Robinson, Darren A; Vasilopoulos, Yiannis; Ferguson, Adam; Moustafa, Manar; MacGowan, Alice; Duff, Gordon W; Ward, Simon J; Tazi-Ahnini, Rachid

    2006-07-01

    Atopic dermatitis (AD) is a multifactorial, chronic inflammatory skin disorder in which genetic mutations and cutaneous hyperreactivity to environmental stimuli play a causative role. Genetic mutations alone might not be enough to cause clinical manifestations of AD, and this review will propose a new perspective on the importance of epidermal barrier dysfunction in genetically predisposed individuals, predisposing them to the harmful effects of environmental agents. The skin barrier is known to be damaged in patients with AD, both in acute eczematous lesions and also in clinically unaffected skin. Skin barrier function can be impaired first by a genetic predisposition to produce increased levels of stratum corneum chymotryptic enzyme. This protease enzyme causes premature breakdown of corneodesmosomes, leading to impairment of the epidermal barrier. The addition of environmental interactions, such as washing with soap and detergents, or long-term application of topical corticosteroids can further increase production of stratum corneum chymotryptic enzyme and impair epidermal barrier function. The epidermal barrier can also be damaged by exogenous proteases from house dust mites and Staphylococcus aureus. One or more of these factors in combination might lead to a defective barrier, thereby increasing the risk of allergen penetration and succeeding inflammatory reaction, thus contributing to exacerbations of this disease.

  8. Gene-environment interactions in severe intraventricular hemorrhage of preterm neonates.

    PubMed

    Ment, Laura R; Adén, Ulrika; Lin, Aiping; Kwon, Soo Hyun; Choi, Murim; Hallman, Mikko; Lifton, Richard P; Zhang, Heping; Bauer, Charles R

    2014-01-01

    Intraventricular hemorrhage (IVH) of the preterm neonate is a complex developmental disorder, with contributions from both the environment and the genome. IVH, or hemorrhage into the germinal matrix of the developing brain with secondary periventricular infarction, occurs in that critical period of time before the 32nd to 33rd wk postconception and has been attributed to changes in cerebral blood flow to the immature germinal matrix microvasculature. Emerging data suggest that genes subserving coagulation, inflammatory, and vascular pathways and their interactions with environmental triggers may influence both the incidence and severity of cerebral injury and are the subject of this review. Polymorphisms in the Factor V Leiden gene are associated with the atypical timing of IVH, suggesting an as yet unknown environmental trigger. The methylenetetrahydrofolate reductase (MTHFR) variants render neonates more vulnerable to cerebral injury in the presence of perinatal hypoxia. The present study demonstrates that the MTHFR 677C>T polymorphism and low 5-min Apgar score additively increase the risk of IVH. Finally, review of published preclinical data suggests the stressors of delivery result in hemorrhage in the presence of mutations in collagen 4A1, a major structural protein of the developing cerebral vasculature. Maternal genetics and fetal environment may also play a role.

  9. Gene-Environment Interactions in ADHD: The Roles of SES and Chaos.

    PubMed

    Gould, Karen L; Coventry, William L; Olson, Richard K; Byrne, Brian

    2017-03-10

    Although attention-deficit/hyperactivity disorder (ADHD) is highly heritable, emerging evidence suggests symptoms are associated with interactions between genes and the environment (GxE) during development. This study tested whether heritability of ADHD symptoms is moderated by two environmental factors: socioeconomic status (SES) and chaos (household disorganisation). A population sample of 520 twin pairs (N = 1040, 52.3% female) from 6 to 15 years completed measures of behavior and home environment. Structural equation modelling was then used to test whether environmental factors were associated with a change in the extent to which genes explain variability in ADHD symptoms. Neither chaos nor SES moderated heritability, with consistent contributions from both genes and environment indicated across socioeconomic strata and levels of chaos. This finding contrasts with those of previous research, underlining the need to replicate results in the emerging field of GxE research across different populations and statistical methods. Robust findings may assist in developing targeted interventions for genetically vulnerable individuals.

  10. Gene-environment interactions in severe intraventricular hemorrhage of preterm neonates

    PubMed Central

    Ment, Laura R.; Ådén, Ulrika; Lin, Aiping; Kwon, Soo Hyun; Choi, Murim; Hallman, Mikko; Lifton, Richard P.; Zhang, Heping; Bauer, Charles R.

    2014-01-01

    Intraventricular hemorrhage (IVH) of the preterm neonate is a complex developmental disorder, with contributions from both the environment and the genome. IVH, or hemorrhage into the germinal matrix of the developing brain with secondary periventricular infarction, occurs in that critical period of time before the 32nd – 33rd week post-conception and has been attributed to changes in cerebral blood flow to the immature germinal matrix microvasculature. Emerging data suggest that genes subserving coagulation, inflammatory and vascular pathways, and their interactions with environmental triggers may influence both the incidence and severity of cerebral injury and are the subject of this review. Polymorphisms in the Factor V Leiden gene are associated with the atypical timing of IVH suggesting an as yet unknown environmental trigger. The methylenetetra-hydrofolate reeducates (MTHFR) variants render neonates more vulnerable to cerebral injury in the presence of perinatal hypoxia. The present study demonstrates that the MTHFR 677C>T polymorphism and low 5 minute Apgar score additively increase the risk of IVH. Finally, review of published preclinical data suggests the stressors of delivery result in hemorrhage in the presence of mutations in collagen 4A1 (COL4A1), a major structural protein of the developing cerebral vasculature. Maternal genetics and fetal environment may also play a role. PMID:24192699

  11. Gene-environment interactions in a mutant mouse kindred with native airway constrictor hyperresponsiveness.

    PubMed

    Pinto, Lawrence H; Eaton, Emily; Chen, Bohao; Fleisher, Jonah; Shuster, Dmitry; McCauley, Joel; Kedainis, Dalius; Siepka, Sandra M; Shimomura, Kazuhiro; Song, Eun-Joo; Husain, Aliya; Lakser, Oren J; Mitchell, Richard W; Dowell, Maria L; Brown, Melanie; Camoretti-Mercado, Blanca; Naclerio, Robert; Sperling, Anne I; Levin, Stephen I; Turek, Fred W; Solway, Julian

    2008-01-01

    We mutagenized male BTBR mice with N-ethyl-N-nitrosourea and screened 1315 of their G3 offspring for airway hyperresponsiveness. A phenovariant G3 mouse with exaggerated methacholine bronchoconstrictor response was identified and his progeny bred in a nonspecific-pathogen-free (SPF) facility where sentinels tested positive for minute virus of mice and mouse parvovirus and where softwood bedding was used. The mutant phenotype was inherited through G11 as a single autosomal semidominant mutation with marked gender restriction, with males exhibiting almost full penetrance and very few females phenotypically abnormal. Between G11 and G12, facility infection eradication was undertaken and bedding was changed to hardwood. We could no longer detect airway hyperresponsiveness in more than 37 G12 offspring of 26 hyperresponsive G11 males. Also, we could not identify the mutant phenotype among offspring of hyperresponsive G8-G10 sires rederived into an SPF facility despite 21 attempts. These two observations suggest that both genetic and environmental factors were needed for phenotype expression. We suspect that rederivation into an SPF facility or altered exposure to pathogens or other unidentified substances modified environmental interactions with the mutant allele, and so resulted in disappearance of the hyperresponsive phenotype. Our experience suggests that future searches for genes that confer susceptibility for airway hyperresponsiveness might not be able to identify some genes that confer susceptibility if the searches are performed in SPF facilities. Experimenters are advised to arrange for multigeneration constancy of mouse care in order to clone mutant genes. Indeed, we were not able to map the mutation before losing the phenotype.

  12. Gene-environment interactions and construct validity in preclinical models of psychiatric disorders.

    PubMed

    Burrows, Emma L; McOmish, Caitlin E; Hannan, Anthony J

    2011-08-01

    The contributions of genetic risk factors to susceptibility for brain disorders are often so closely intertwined with environmental factors that studying genes in isolation cannot provide the full picture of pathogenesis. With recent advances in our understanding of psychiatric genetics and environmental modifiers we are now in a position to develop more accurate animal models of psychiatric disorders which exemplify the complex interaction of genes and environment. Here, we consider some of the insights that have emerged from studying the relationship between defined genetic alterations and environmental factors in rodent models. A key issue in such animal models is the optimization of construct validity, at both genetic and environmental levels. Standard housing of laboratory mice and rats generally includes ad libitum food access and limited opportunity for physical exercise, leading to metabolic dysfunction under control conditions, and thus reducing validity of animal models with respect to clinical populations. A related issue, of specific relevance to neuroscientists, is that most standard-housed rodents have limited opportunity for sensory and cognitive stimulation, which in turn provides reduced incentive for complex motor activity. Decades of research using environmental enrichment has demonstrated beneficial effects on brain and behavior in both wild-type and genetically modified rodent models, relative to standard-housed littermate controls. One interpretation of such studies is that environmentally enriched animals more closely approximate average human levels of cognitive and sensorimotor stimulation, whereas the standard housing currently used in most laboratories models a more sedentary state of reduced mental and physical activity and abnormal stress levels. The use of such standard housing as a single environmental variable may limit the capacity for preclinical models to translate into successful clinical trials. Therefore, there is a need to

  13. The Association between Gene-Environment Interactions and Diseases Involving the Human GST Superfamily with SNP Variants

    PubMed Central

    Hollman, Antoinesha L.; Tchounwou, Paul B.; Huang, Hung-Chung

    2016-01-01

    Exposure to environmental hazards has been associated with diseases in humans. The identification of single nucleotide polymorphisms (SNPs) in human populations exposed to different environmental hazards, is vital for detecting the genetic risks of some important human diseases. Several studies in this field have been conducted on glutathione S-transferases (GSTs), a phase II detoxification superfamily, to investigate its role in the occurrence of diseases. Human GSTs consist of cytosolic and microsomal superfamilies that are further divided into subfamilies. Based on scientific search engines and a review of the literature, we have found a large amount of published articles on human GST super- and subfamilies that have greatly assisted in our efforts to examine their role in health and disease. Because of its polymorphic variations in relation to environmental hazards such as air pollutants, cigarette smoke, pesticides, heavy metals, carcinogens, pharmaceutical drugs, and xenobiotics, GST is considered as a significant biomarker. This review examines the studies on gene-environment interactions related to various diseases with respect to single nucleotide polymorphisms (SNPs) found in the GST superfamily. Overall, it can be concluded that interactions between GST genes and environmental factors play an important role in human diseases. PMID:27043589

  14. Genetic risk for violent behavior and environmental exposure to disadvantage and violent crime: the case for gene-environment interaction.

    PubMed

    Barnes, J C; Jacobs, Bruce A

    2013-01-01

    Despite mounds of evidence to suggest that neighborhood structural factors predict violent behavior, almost no attention has been given to how these influences work synergistically (i.e., interact) with an individual's genetic propensity toward violent behavior. Indeed, two streams of research have, heretofore, flowed independently of one another. On one hand, criminologists have underscored the importance of neighborhood context in the etiology of violence. On the other hand, behavioral geneticists have argued that individual-level genetic propensities are important for understanding violence. The current study seeks to integrate these two compatible frameworks by exploring gene-environment interactions (GxE). Two GxEs were examined and supported by the data (i.e., the National Longitudinal Study of Adolescent Health). Using a scale of genetic risk based on three dopamine genes, the analysis revealed that genetic risk had a greater influence on violent behavior when the individual was also exposed to neighborhood disadvantage or when the individual was exposed to higher violent crime rates. The relevance of these findings for criminological theorizing was considered.

  15. Nrf2 regulates gene-environment interactions in an animal model of intrauterine inflammation: Implications for preterm birth and prematurity

    PubMed Central

    Sussan, Thomas E.; Sudini, Kuladeep; Talbot, C. Conover; Wang, Xiaobin; Wills-Karp, Marsha; Burd, Irina; Biswal, Shyam

    2017-01-01

    Preterm birth (PTB) is the leading cause of neonatal mortality, and surviving infants are at increased risk for lifelong disabilities. Intrauterine inflammation is an etiological factor that drives PTB, and oxidative stress is associated with PTB. Nuclear erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that is the key regulator of the response to oxidative and inflammatory stress. Here, we used the established mouse model of intrauterine inflammation-induced PTB to determine whether Nrf2 is a modifier of susceptibility to PTB and prematurity-related morbidity and mortality in the offspring. We determined that Nr2-deficient (Nrf2−/−) mice exhibited a greater sensitivity to intrauterine inflammation, as indicated by decreased time to delivery, reduced birthweight, and 100% mortality. Placentas from preterm Nrf2−/− mice showed elevated levels of markers of inflammation, oxidative stress, and cell death, and transcriptomic analysis identified numerous key signaling pathways that were differentially expressed between wild-type (WT) and Nrf2−/− mice in both preterm and control samples. Thus, Nrf2 could be a critical factor for gene-environment interactions that may determine susceptibility to PTB. Further studies are needed to determine if Nrf2 is a viable therapeutic target in women who are at risk for PTB and associated complications in the affected offspring. PMID:28071748

  16. Estimating genetic effect sizes under joint disease-endophenotype models in presence of gene-environment interactions

    PubMed Central

    Bureau, Alexandre; Croteau, Jordie; Couture, Christian; Vohl, Marie-Claude; Bouchard, Claude; Pérusse, Louis

    2015-01-01

    Effects of genetic variants on the risk of complex diseases estimated from association studies are typically small. Nonetheless, variants may have important effects in presence of specific levels of environmental exposures, and when a trait related to the disease (endophenotype) is either normal or impaired. We propose polytomous and transition models to represent the relationship between disease, endophenotype, genotype and environmental exposure in family studies. Model coefficients were estimated using generalized estimating equations and were used to derive gene-environment interaction effects and genotype effects at specific levels of exposure. In a simulation study, estimates of the effect of a genetic variant were substantially higher when both an endophenotype and an environmental exposure modifying the variant effect were taken into account, particularly under transition models, compared to the alternative of ignoring the endophenotype. Illustration of the proposed modeling with the metabolic syndrome, abdominal obesity, physical activity and polymorphisms in the NOX3 gene in the Quebec Family Study revealed that the positive association of the A allele of rs1375713 with the metabolic syndrome at high levels of physical activity was only detectable in subjects without abdominal obesity, illustrating the importance of taking into account the abdominal obesity endophenotype in this analysis. PMID:26284107

  17. Gene-environment interaction from international cohorts: impact on development and evolution of occupational and environmental lung and airway disease.

    PubMed

    Gaffney, Adam; Christiani, David C

    2015-06-01

    Environmental and occupational pulmonary diseases impose a substantial burden of morbidity and mortality on the global population. However, it has been long observed that only some of those who are exposed to pulmonary toxicants go on to develop disease; increasingly, it is being recognized that genetic differences may underlie some of this person-to-person variability. Studies performed throughout the globe are demonstrating important gene-environment interactions for diseases as diverse as chronic beryllium disease, coal workers' pneumoconiosis, silicosis, asbestosis, byssinosis, occupational asthma, and pollution-associated asthma. These findings have, in many instances, elucidated the pathogenesis of these highly complex diseases. At the same time, however, translation of this research into clinical practice has, for good reasons, proceeded slowly. No genetic test has yet emerged with sufficiently robust operating characteristics to be clearly useful or practicable in an occupational or environmental setting. In addition, occupational genetic testing raises serious ethical and policy concerns. Therefore, the primary objective must remain ensuring that the workplace and the environment are safe for all.

  18. Genotype-based association models of complex diseases to detect gene-gene and gene-environment interactions

    PubMed Central

    Fan, Ruzong; Manga, Prashiela

    2015-01-01

    A central problem in genetic epidemiology is to identify and rank genetic markers involved in a disease. Complex diseases, such as cancer, hypertension, diabetes, are thought to be caused by an interaction of a panel of genetic factors, that can be identified by markers, which modulate environmental factors. Moreover, the effect of each genetic marker may be small. Hence, the association signal may be missed unless a large sample is considered, or a priori biomedical data are used. Recent advances generated a vast variety of a priori information, including linkage maps and information about gene regulatory dependence assembled into curated pathway databases. We propose a genotype-based approach that takes into account linkage disequilibrium (LD) information between genetic markers that are in moderate LD while modeling gene-gene and gene-environment interactions. A major advantage of our method is that the observed genetic information enters a model directly thus eliminating the need to estimate haplotype-phase. Our approach results in an algorithm that is inexpensive computationally and does not suffer from bias induced by haplotype-phase ambiguity. We investigated our model in a series of simulation experiments and demonstrated that the proposed approach results in estimates that are nearly unbiased and have small variability. We applied our method to the analysis of data from a melanoma case-control study and investigated interaction between a set of pigmentation genes and environmental factors defined by age and gender. Furthermore, an application of our method is demonstrated using a study of Alcohol Dependence. PMID:26191336

  19. The role of environmental heterogeneity in meta-analysis of gene-environment interactions with quantitative traits.

    PubMed

    Li, Shi; Mukherjee, Bhramar; Taylor, Jeremy M G; Rice, Kenneth M; Wen, Xiaoquan; Rice, John D; Stringham, Heather M; Boehnke, Michael

    2014-07-01

    With challenges in data harmonization and environmental heterogeneity across various data sources, meta-analysis of gene-environment interaction studies can often involve subtle statistical issues. In this paper, we study the effect of environmental covariate heterogeneity (within and between cohorts) on two approaches for fixed-effect meta-analysis: the standard inverse-variance weighted meta-analysis and a meta-regression approach. Akin to the results in Simmonds and Higgins (), we obtain analytic efficiency results for both methods under certain assumptions. The relative efficiency of the two methods depends on the ratio of within versus between cohort variability of the environmental covariate. We propose to use an adaptively weighted estimator (AWE), between meta-analysis and meta-regression, for the interaction parameter. The AWE retains full efficiency of the joint analysis using individual level data under certain natural assumptions. Lin and Zeng (2010a, b) showed that a multivariate inverse-variance weighted estimator retains full efficiency as joint analysis using individual level data, if the estimates with full covariance matrices for all the common parameters are pooled across all studies. We show consistency of our work with Lin and Zeng (2010a, b). Without sacrificing much efficiency, the AWE uses only univariate summary statistics from each study, and bypasses issues with sharing individual level data or full covariance matrices across studies. We compare the performance of the methods both analytically and numerically. The methods are illustrated through meta-analysis of interaction between Single Nucleotide Polymorphisms in FTO gene and body mass index on high-density lipoprotein cholesterol data from a set of eight studies of type 2 diabetes.

  20. Epigenetic genes and emotional reactivity to daily life events: a multi-step gene-environment interaction study.

    PubMed

    Pishva, Ehsan; Drukker, Marjan; Viechtbauer, Wolfgang; Decoster, Jeroen; Collip, Dina; van Winkel, Ruud; Wichers, Marieke; Jacobs, Nele; Thiery, Evert; Derom, Catherine; Geschwind, Nicole; van den Hove, Daniel; Lataster, Tineke; Myin-Germeys, Inez; van Os, Jim; Rutten, Bart P F; Kenis, Gunter

    2014-01-01

    Recent human and animal studies suggest that epigenetic mechanisms mediate the impact of environment on development of mental disorders. Therefore, we hypothesized that polymorphisms in epigenetic-regulatory genes impact stress-induced emotional changes. A multi-step, multi-sample gene-environment interaction analysis was conducted to test whether 31 single nucleotide polymorphisms (SNPs) in epigenetic-regulatory genes, i.e. three DNA methyltransferase genes DNMT1, DNMT3A, DNMT3B, and methylenetetrahydrofolate reductase (MTHFR), moderate emotional responses to stressful and pleasant stimuli in daily life as measured by Experience Sampling Methodology (ESM). In the first step, main and interactive effects were tested in a sample of 112 healthy individuals. Significant associations in this discovery sample were then investigated in a population-based sample of 434 individuals for replication. SNPs showing significant effects in both the discovery and replication samples were subsequently tested in three other samples of: (i) 85 unaffected siblings of patients with psychosis, (ii) 110 patients with psychotic disorders, and iii) 126 patients with a history of major depressive disorder. Multilevel linear regression analyses showed no significant association between SNPs and negative affect or positive affect. No SNPs moderated the effect of pleasant stimuli on positive affect. Three SNPs of DNMT3A (rs11683424, rs1465764, rs1465825) and 1 SNP of MTHFR (rs1801131) moderated the effect of stressful events on negative affect. Only rs11683424 of DNMT3A showed consistent directions of effect in the majority of the 5 samples. These data provide the first evidence that emotional responses to daily life stressors may be moderated by genetic variation in the genes involved in the epigenetic machinery.

  1. Epigenetic Genes and Emotional Reactivity to Daily Life Events: A Multi-Step Gene-Environment Interaction Study

    PubMed Central

    Pishva, Ehsan; Drukker, Marjan; Viechtbauer, Wolfgang; Decoster, Jeroen; Collip, Dina; van Winkel, Ruud; Wichers, Marieke; Jacobs, Nele; Thiery, Evert; Derom, Catherine; Geschwind, Nicole; van den Hove, Daniel; Lataster, Tineke; Myin-Germeys, Inez; van Os, Jim

    2014-01-01

    Recent human and animal studies suggest that epigenetic mechanisms mediate the impact of environment on development of mental disorders. Therefore, we hypothesized that polymorphisms in epigenetic-regulatory genes impact stress-induced emotional changes. A multi-step, multi-sample gene-environment interaction analysis was conducted to test whether 31 single nucleotide polymorphisms (SNPs) in epigenetic-regulatory genes, i.e. three DNA methyltransferase genes DNMT1, DNMT3A, DNMT3B, and methylenetetrahydrofolate reductase (MTHFR), moderate emotional responses to stressful and pleasant stimuli in daily life as measured by Experience Sampling Methodology (ESM). In the first step, main and interactive effects were tested in a sample of 112 healthy individuals. Significant associations in this discovery sample were then investigated in a population-based sample of 434 individuals for replication. SNPs showing significant effects in both the discovery and replication samples were subsequently tested in three other samples of: (i) 85 unaffected siblings of patients with psychosis, (ii) 110 patients with psychotic disorders, and iii) 126 patients with a history of major depressive disorder. Multilevel linear regression analyses showed no significant association between SNPs and negative affect or positive affect. No SNPs moderated the effect of pleasant stimuli on positive affect. Three SNPs of DNMT3A (rs11683424, rs1465764, rs1465825) and 1 SNP of MTHFR (rs1801131) moderated the effect of stressful events on negative affect. Only rs11683424 of DNMT3A showed consistent directions of effect in the majority of the 5 samples. These data provide the first evidence that emotional responses to daily life stressors may be moderated by genetic variation in the genes involved in the epigenetic machinery. PMID:24967710

  2. Gene-environment interaction in progression of AMD: the CFH gene, smoking and exposure to chronic infection.

    PubMed

    Baird, Paul N; Robman, Luba D; Richardson, Andrea J; Dimitrov, Peter N; Tikellis, Gabriella; McCarty, Catherine A; Guymer, Robyn H

    2008-05-01

    A number of risk factors including the complement factor H (CFH) gene, smoking and Chlamydia pneumoniae have been associated with age-related macular degeneration (AMD). However, the mechanisms underlying how these risk factors might be involved in disease progression and disease aetiology is poorly understood. A cohort series of 233 individuals followed for AMD progression over a mean period of 7 years underwent a full eye examination, blood was taken for DNA and antibody titre and individuals completed a standard medical and general questionnaire. Y402H variants of the CFH gene were assessed with disease progression as well as examination of interaction between Y402H variants and smoking and Y402H variants and the pathogen C. pneumoniae. The CC risk genotype of Y402H was significantly associated with increased AMD progression [odds ratio (OR) 2.43, 95% confidence interval (95% CI) 1.07-5.49] as was smoking (OR 2.28, 95% CI 1.26-4.12). However, the risk of progression was greatly increased to almost 12-fold (OR 11.8, 95% CI 2.1-65.8) when, in addition to having the C risk allele, subjects also presented with the upper tertile of antibodies to the bacterial pathogen C. pneumoniae compared with those with the T allele of Y402H and the lowest antibody tertile. This demonstrates for the first time the existence of a gene environment-interaction between pathogenic load of C. pneumoniae and the CFH gene in the aetiology of AMD.

  3. Gene-environment interactions between ERCC2, ERCC3, XRCC1 and cadmium exposure in nasal polyposis disease.

    PubMed

    Khlifi, Rim; Olmedo, Pablo; Gil, Fernando; Hammami, Boutheina; Hamza-Chaffai, Amel; Rebai, Ahmed

    2016-11-12

    Gene-environment interactions have long been known to play an important role in complex disease aetiology, such as nasal polyposis (NP). The present study supports the concept that DNA repair gene polymorphisms play critical roles in modifying individual susceptibility to environmental diseases. In fact, we investigated the role of polymorphisms in DNA repair genes and cadmium as risk factors for Tunisian patients with NP. To the best of our knowledge, this is the first report on the impact of combined effects of cadmium and ERCC3 7122 A>G (rs4150407), ERCC2 Lys751Gln (rs13181) and XRCC1 Arg399Gln (rs25487) genes in the susceptibility to NP disease. Significant associations between the risk of developing NP disease and ERCC2 [odds ratio (OR) = 2.0, 95 % confidence interval (CI) = 1.1-3.7, p = 0.023] and ERCC3 (OR = 2.2, 95 % CI = 1.2-4.1, p = 0.013) genotypes polymorphisms were observed. Blood concentrations of Cd in NP patients (2.2 μg/L) were significantly higher than those of controls (0.5 μg/L). A significant interaction between ERCC3 (7122 A>G) polymorphism and blood-Cd levels (for the median of blood-Cd levels: OR = 3.8, 95 % CI = 1.3-10.8, p = 0.014 and for the 75th percentiles of blood-Cd levels: OR = 2.7, 95 % CI = 1.1-7.2, p = 0.041) was found in association with the risk of NP disease. In addition, when we stratified ERCC2, ERCC3 and XRCC1 polymorphism genotypes by the median and 75th percentiles of blood-Cd levels, we found also significant interactions between ERCC2 (Lys751Gln) and ERCC3 (7122 A>G) genotypes polymorphism and this metal in association with NP disease. However, no interaction was found between XRCC1 (Arg399Gln) polymorphism genotypes and Cd in association with NP disease.

  4. Enacting the molecular imperative: How gene-environment interaction research links bodies and environments in the Post-Genomic Age

    PubMed Central

    Darling, Katherine Weatherford; Ackerman, Sara L.; Hiatt, Robert H.; Lee, Sandra Soo-Jin; Shim, Janet K.

    2016-01-01

    Despite a proclaimed shift from ‘nature versus nurture’ to ‘genes and environment’ paradigms within biomedical and genomic science, capturing the environment and identifying gene-environment interactions (GEIs) has remained a challenge. What does ‘the environment’ mean in the post-genomic age? In this paper, we present qualitative data from a study of 33 principal investigators funded by the U.S. National Institutes of Health to conduct etiological research on three complex diseases (cancer, cardiovascular disease and diabetes). We examine their research practices and perspectives on the environment through the concept of molecularization: the social processes and transformations through which phenomena (diseases, identities, pollution, food, racial/ethnic classifications) are re-defined in terms of their molecular components and described in the language of molecular biology. We show how GEI researchers’ expansive conceptualizations of the environment ultimately yield to the imperative to molecularize and personalize the environment. They seek to ‘go into the body’ and re-work the boundaries between bodies and environments. In the process, they create epistemic hinges to facilitate a turn from efforts to understand social and environmental exposures outside the body, to quantifying their effects inside the body. GEI researchers respond to these emergent imperatives with a mixture of excitement, ambivalence and frustration. We reflect on how GEI researchers struggle to make meaning of molecules in their work, and how they grapple with molecularization as a methodological and rhetorical imperative as well as a process transforming biomedical research practices. PMID:26994357

  5. Semiparametric Bayesian analysis of gene-environment interactions with error in measurement of environmental covariates and missing genetic data.

    PubMed

    Lobach, Iryna; Mallick, Bani; Carroll, Raymond J

    2011-01-01

    Case-control studies are widely used to detect gene-environment interactions in the etiology of complex diseases. Many variables that are of interest to biomedical researchers are difficult to measure on an individual level, e.g. nutrient intake, cigarette smoking exposure, long-term toxic exposure. Measurement error causes bias in parameter estimates, thus masking key features of data and leading to loss of power and spurious/masked associations. We develop a Bayesian methodology for analysis of case-control studies for the case when measurement error is present in an environmental covariate and the genetic variable has missing data. This approach offers several advantages. It allows prior information to enter the model to make estimation and inference more precise. The environmental covariates measured exactly are modeled completely nonparametrically. Further, information about the probability of disease can be incorporated in the estimation procedure to improve quality of parameter estimates, what cannot be done in conventional case-control studies. A unique feature of the procedure under investigation is that the analysis is based on a pseudo-likelihood function therefore conventional Bayesian techniques may not be technically correct. We propose an approach using Markov Chain Monte Carlo sampling as well as a computationally simple method based on an asymptotic posterior distribution. Simulation experiments demonstrated that our method produced parameter estimates that are nearly unbiased even for small sample sizes. An application of our method is illustrated using a population-based case-control study of the association between calcium intake with the risk of colorectal adenoma development.

  6. Semiparametric Bayesian analysis of gene-environment interactions with error in measurement of environmental covariates and missing genetic data

    PubMed Central

    Mallick, Bani; Carroll, Raymond J.

    2011-01-01

    Case-control studies are widely used to detect gene-environment interactions in the etiology of complex diseases. Many variables that are of interest to biomedical researchers are difficult to measure on an individual level, e.g. nutrient intake, cigarette smoking exposure, long-term toxic exposure. Measurement error causes bias in parameter estimates, thus masking key features of data and leading to loss of power and spurious/masked associations. We develop a Bayesian methodology for analysis of case-control studies for the case when measurement error is present in an environmental covariate and the genetic variable has missing data. This approach offers several advantages. It allows prior information to enter the model to make estimation and inference more precise. The environmental covariates measured exactly are modeled completely nonparametrically. Further, information about the probability of disease can be incorporated in the estimation procedure to improve quality of parameter estimates, what cannot be done in conventional case-control studies. A unique feature of the procedure under investigation is that the analysis is based on a pseudo-likelihood function therefore conventional Bayesian techniques may not be technically correct. We propose an approach using Markov Chain Monte Carlo sampling as well as a computationally simple method based on an asymptotic posterior distribution. Simulation experiments demonstrated that our method produced parameter estimates that are nearly unbiased even for small sample sizes. An application of our method is illustrated using a population-based case-control study of the association between calcium intake with the risk of colorectal adenoma development. PMID:21949562

  7. Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate.

    PubMed

    Wu, Tao; Schwender, Holger; Ruczinski, Ingo; Murray, Jeffrey C; Marazita, Mary L; Munger, Ronald G; Hetmanski, Jacqueline B; Parker, Margaret M; Wang, Ping; Murray, Tanda; Taub, Margaret; Li, Shuai; Redett, Richard J; Fallin, M Daniele; Liang, Kung Yee; Wu-Chou, Yah Huei; Chong, Samuel S; Yeow, Vincent; Ye, Xiaoqian; Wang, Hong; Huang, Shangzhi; Jabs, Ethylin W; Shi, Bing; Wilcox, Allen J; Jee, Sun Ha; Scott, Alan F; Beaty, Terri H

    2014-01-01

    Nonsyndromic cleft palate (CP) is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS) using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP) achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS) among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester). When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10(-6)interaction. SNPs rs3733585 and rs12508991 in SLC2A9 yielded P = 2.26×10(-7) in a test for GxETS interaction. SNPs rs6820756 and rs7699512 in WDR1 also yielded P = 1.79×10(-7) and P = 1.98×10(-7) in a 1 df test for GxE interaction. Although further replication studies are critical to confirming these findings, these results illustrate how genetic associations for nonsyndromic CP can be missed if potential GxE interaction is not taken into account, and this study suggest SLC2A9 and WDR1 should be considered as candidate genes for CP.

  8. Allowing for population stratification in case-only studies of gene-environment interaction, using genomic control.

    PubMed

    Yadav, Pankaj; Freitag-Wolf, Sandra; Lieb, Wolfgang; Dempfle, Astrid; Krawczak, Michael

    2015-10-01

    Gene-environment interactions (G × E) have attracted considerable research interest in the past owing to their scientific and public health implications, but powerful statistical methods are required to successfully track down G × E, particularly at a genome-wide level. Previously, a case-only (CO) design has been proposed as a means to identify G × E with greater efficiency than traditional case-control or cohort studies. However, as with genotype-phenotype association studies themselves, hidden population stratification (PS) can impact the validity of G × E studies using a CO design. Since this problem has been subject to little research to date, we used comprehensive simulation to systematically assess the type I error rate, power and effect size bias of CO studies of G × E in the presence of PS. Three types of PS were considered, namely genetic-only (PSG), environment-only (PSE), and joint genetic and environmental stratification (PSGE). Our results reveal that the type I error rate of an unadjusted Wald test, appropriate for the CO design, would be close to its nominal level (0.05 in our study) as long as PS involves only one interaction partner (i.e., either PSG or PSE). In contrast, if the study population is stratified with respect to both G and E (i.e., if there is PSGE), then the type I error rate is seriously inflated and estimates of the underlying G × E interaction are biased. Comparison of CO to a family-based case-parents design confirmed that the latter is more robust against PSGE, as expected. However, case-parent trios may be particularly unsuitable for G × E studies in view of the fact that they require genotype data from parents and that many diseases with an environmental component are likely to be of late onset. An alternative approach to adjusting for PS is principal component analysis (PCA), which has been widely used for this very purpose in past genome-wide association studies (GWAS). However, resolving genetic PS properly by PCA

  9. Research Review: Gene-Environment Interaction Research in Youth Depression--A Systematic Review with Recommendations for Future Research

    ERIC Educational Resources Information Center

    Dunn, Erin C.; Uddin, Monica; Subramanian, S. V.; Smoller, Jordan W.; Galea, Sandro; Koenen, Karestan C.

    2011-01-01

    Background: Depression is a major public health problem among youth, currently estimated to affect as many as 9% of US children and adolescents. The recognition that both genes (nature) and environments (nurture) are important for understanding the etiology of depression has led to a rapid growth in research exploring gene-environment interactions…

  10. The Interacting Effect of the BDNF Val66Met Polymorphism and Stressful Life Events on Adolescent Depression Is Not an Artifact of Gene-Environment Correlation: Evidence from a Longitudinal Twin Study

    ERIC Educational Resources Information Center

    Chen, Jie; Li, Xinying; McGue, Matt

    2013-01-01

    Background: Confounding introduced by gene-environment correlation (rGE) may prevent one from observing a true gene-environment interaction (G × E) effect on psychopathology. The present study investigated the interacting effect of the BDNF Val66Met polymorphism and stressful life events (SLEs) on adolescent depression while controlling for the…

  11. Rule based classifier for the analysis of gene-gene and gene-environment interactions in genetic association studies

    PubMed Central

    2011-01-01

    Background Several methods have been presented for the analysis of complex interactions between genetic polymorphisms and/or environmental factors. Despite the available methods, there is still a need for alternative methods, because no single method will perform well in all scenarios. The aim of this work was to evaluate the performance of three selected rule based classifier algorithms, RIPPER, RIDOR and PART, for the analysis of genetic association studies. Methods Overall, 42 datasets were simulated with three different case-control models, a varying number of subjects (300, 600), SNPs (500, 1500, 3000) and noise (5%, 10%, 20%). The algorithms were applied to each of the datasets with a set of algorithm-specific settings. Results were further investigated with respect to a) the Model, b) the Rules, and c) the Attribute level. Data analysis was performed using WEKA, SAS and PERL. Results The RIPPER algorithm discovered the true case-control model at least once in >33% of the datasets. The RIDOR and PART algorithm performed poorly for model detection. The RIPPER, RIDOR and PART algorithm discovered the true case-control rules in more than 83%, 83% and 44% of the datasets, respectively. All three algorithms were able to detect the attributes utilized in the respective case-control models in most datasets. Conclusions The current analyses substantiate the utility of rule based classifiers such as RIPPER, RIDOR and PART for the detection of gene-gene/gene-environment interactions in genetic association studies. These classifiers could provide a valuable new method, complementing existing approaches, in the analysis of genetic association studies. The methods provide an advantage in being able to handle both categorical and continuous variable types. Further, because the outputs of the analyses are easy to interpret, the rule based classifier approach could quickly generate testable hypotheses for additional evaluation. Since the algorithms are computationally

  12. Glutamatergic GRIN2B and polyaminergic ODC1 genes in suicide attempts: associations and gene-environment interactions with childhood/adolescent physical assault.

    PubMed

    Sokolowski, M; Ben-Efraim, Y J; Wasserman, J; Wasserman, D

    2013-09-01

    The complex etiology of suicidal behavior has frequently been investigated in relation to monoaminergic neurotransmission, but other neurosystems have shown alterations as well, involving excitatory glutamatergic and inhibitory γ-aminobutyric acid (GABA) molecular components, together with the modulating polyamines. Sufficiently powered and family-based association studies of glutamatergic and GABAergic genes with suicidal behavior are nonexistent, but several studies have been reported for polyamines. We therefore conducted, for the first time ever, an extensive family-based study of 113 candidate single-nucleotide polymorphisms (SNPs) located in 24 glutamatergic and GABA genes, in addition to interrelated polyaminergic genes, on the outcome of severe suicide attempts (SAs). The family-based analysis (n=660 trios) was supplemented with gene-environment interaction (G × E), case-control (n=519 controls) and subgroup analyses. The main observations were the previously unreported association and linkage of SNPs rs2268115 and rs220557 in GRIN2B, as well as of SNPs rs1049500 and rs2302614 in ODC1 (P<10(-2)). Furthermore, GRIN2B haplotypic associations were observed, in particular with a four-SNP AGGC haplotype (rs1805247-rs1806201-rs1805482-rs2268115; P<10(-5)), and a third SNP rs7559979 in ODC1 showed G × E with serious childhood/adolescent physical assault (P<10(-4)). SA subjects were characterized by transdiagnostic trait anger and past year alcohol-drug use disorders, but not by alcohol-drug use at SA, depression, anxiety or psychosis diagnoses. We also discuss a first ever confirmatory observation of SNP rs6526342 (polyaminergic SAT1) in SA, originally identified in completed suicides. The results suggest that specific genetic variants in a subset of glutamatergic (GRIN2B) and polyaminergic (ODC1) neurosystem genes may be of importance in certain suicidal subjects.

  13. Detection of Epistatic and Gene-Environment Interactions Underlying Three Quality Traits in Rice Using High-Throughput Genome-Wide Data

    PubMed Central

    Xu, Haiming; Jiang, Beibei; Cao, Yujie; Zhang, Yingxin; Zhan, Xiaodeng; Shen, Xihong; Cheng, Shihua; Lou, Xiangyang; Cao, Liyong

    2015-01-01

    With development of sequencing technology, dense single nucleotide polymorphisms (SNPs) have been available, enabling uncovering genetic architecture of complex traits by genome-wide association study (GWAS). However, the current GWAS strategy usually ignores epistatic and gene-environment interactions due to absence of appropriate methodology and heavy computational burden. This study proposed a new GWAS strategy by combining the graphics processing unit- (GPU-) based generalized multifactor dimensionality reduction (GMDR) algorithm with mixed linear model approach. The reliability and efficiency of the analytical methods were verified through Monte Carlo simulations, suggesting that a population size of nearly 150 recombinant inbred lines (RILs) had a reasonable resolution for the scenarios considered. Further, a GWAS was conducted with the above two-step strategy to investigate the additive, epistatic, and gene-environment associations between 701,867 SNPs and three important quality traits, gelatinization temperature, amylose content, and gel consistency, in a RIL population with 138 individuals derived from super-hybrid rice Xieyou9308 in two environments. Four significant SNPs were identified with additive, epistatic, and gene-environment interaction effects. Our study showed that the mixed linear model approach combining with the GPU-based GMDR algorithm is a feasible strategy for implementing GWAS to uncover genetic architecture of crop complex traits. PMID:26345334

  14. Detection of Epistatic and Gene-Environment Interactions Underlying Three Quality Traits in Rice Using High-Throughput Genome-Wide Data.

    PubMed

    Xu, Haiming; Jiang, Beibei; Cao, Yujie; Zhang, Yingxin; Zhan, Xiaodeng; Shen, Xihong; Cheng, Shihua; Lou, Xiangyang; Cao, Liyong

    2015-01-01

    With development of sequencing technology, dense single nucleotide polymorphisms (SNPs) have been available, enabling uncovering genetic architecture of complex traits by genome-wide association study (GWAS). However, the current GWAS strategy usually ignores epistatic and gene-environment interactions due to absence of appropriate methodology and heavy computational burden. This study proposed a new GWAS strategy by combining the graphics processing unit- (GPU-) based generalized multifactor dimensionality reduction (GMDR) algorithm with mixed linear model approach. The reliability and efficiency of the analytical methods were verified through Monte Carlo simulations, suggesting that a population size of nearly 150 recombinant inbred lines (RILs) had a reasonable resolution for the scenarios considered. Further, a GWAS was conducted with the above two-step strategy to investigate the additive, epistatic, and gene-environment associations between 701,867 SNPs and three important quality traits, gelatinization temperature, amylose content, and gel consistency, in a RIL population with 138 individuals derived from super-hybrid rice Xieyou9308 in two environments. Four significant SNPs were identified with additive, epistatic, and gene-environment interaction effects. Our study showed that the mixed linear model approach combining with the GPU-based GMDR algorithm is a feasible strategy for implementing GWAS to uncover genetic architecture of crop complex traits.

  15. The Cumulative Effect of Gene-Gene and Gene-Environment Interactions on the Risk of Prostate Cancer in Chinese Men

    PubMed Central

    Liu, Ming; Shi, Xiaohong; Yang, Fan; Wang, Jianye; Xu, Yong; Wei, Dong; Yang, Kuo; Zhang, Yaoguang; Wang, Xin; Liang, Siying; Chen, Xin; Sun, Liang; Zhu, Xiaoquan; Zhao, Chengxiao; Zhu, Ling; Tang, Lei; Zheng, Chenguang; Yang, Ze

    2016-01-01

    Prostate cancer (PCa) is a multifactorial disease involving complex genetic and environmental factors interactions. Gene-gene and gene-environment interactions associated with PCa in Chinese men are less studied. We explored the association between 36 SNPs and PCa in 574 subjects from northern China. Body mass index (BMI), smoking, and alcohol consumption were determined through self-administered questionnaires in 134 PCa patients. Then gene-gene and gene-environment interactions among the PCa-associated SNPs were analyzed using the generalized multifactor dimensionality reduction (GMDR) and logistic regression methods. Allelic and genotypic association analyses showed that six variants were associated with PCa and the cumulative effect suggested men who carried any combination of 1, 2, or ≥3 risk genotypes had a gradually increased PCa risk (odds ratios (ORs) = 1.79–4.41). GMDR analysis identified the best gene-gene interaction model with scores of 10 for both the cross-validation consistency and sign tests. For gene-environment interactions, rs6983561 CC and rs16901966 GG in individuals with a BMI ≥ 28 had ORs of 7.66 (p = 0.032) and 5.33 (p = 0.046), respectively. rs7679673 CC + CA and rs12653946 TT in individuals that smoked had ORs of 2.77 (p = 0.007) and 3.11 (p = 0.024), respectively. rs7679673 CC in individuals that consumed alcohol had an OR of 4.37 (p = 0.041). These results suggest that polymorphisms, either individually or by interacting with other genes or environmental factors, contribute to an increased risk of PCa. PMID:26828504

  16. The Cumulative Effect of Gene-Gene and Gene-Environment Interactions on the Risk of Prostate Cancer in Chinese Men.

    PubMed

    Liu, Ming; Shi, Xiaohong; Yang, Fan; Wang, Jianye; Xu, Yong; Wei, Dong; Yang, Kuo; Zhang, Yaoguang; Wang, Xin; Liang, Siying; Chen, Xin; Sun, Liang; Zhu, Xiaoquan; Zhao, Chengxiao; Zhu, Ling; Tang, Lei; Zheng, Chenguang; Yang, Ze

    2016-01-27

    Prostate cancer (PCa) is a multifactorial disease involving complex genetic and environmental factors interactions. Gene-gene and gene-environment interactions associated with PCa in Chinese men are less studied. We explored the association between 36 SNPs and PCa in 574 subjects from northern China. Body mass index (BMI), smoking, and alcohol consumption were determined through self-administered questionnaires in 134 PCa patients. Then gene-gene and gene-environment interactions among the PCa-associated SNPs were analyzed using the generalized multifactor dimensionality reduction (GMDR) and logistic regression methods. Allelic and genotypic association analyses showed that six variants were associated with PCa and the cumulative effect suggested men who carried any combination of 1, 2, or ≥3 risk genotypes had a gradually increased PCa risk (odds ratios (ORs) = 1.79-4.41). GMDR analysis identified the best gene-gene interaction model with scores of 10 for both the cross-validation consistency and sign tests. For gene-environment interactions, rs6983561 CC and rs16901966 GG in individuals with a BMI ≥ 28 had ORs of 7.66 (p = 0.032) and 5.33 (p = 0.046), respectively. rs7679673 CC + CA and rs12653946 TT in individuals that smoked had ORs of 2.77 (p = 0.007) and 3.11 (p = 0.024), respectively. rs7679673 CC in individuals that consumed alcohol had an OR of 4.37 (p = 0.041). These results suggest that polymorphisms, either individually or by interacting with other genes or environmental factors, contribute to an increased risk of PCa.

  17. Cytochrome P450 1B1, a new keystone in gene-environment interactions related to human head and neck cancer?

    PubMed

    Thier, Ricarda; Brüning, Thomas; Roos, Peter H; Bolt, Hermann M

    2002-06-01

    Alcohol consumption and tobacco smoking are major causes of head and neck cancers, and regional differences point to the importance of research into gene-environment interactions. Much interest has been focused on polymorphisms of CYP1A1 and of GSTM1 and GSTT1, but a number of studies have not demonstrated significant effects. This has mostly been ascribed to small sample sizes. In general, the impact of polymorphisms of metabolic enzymes appears inconsistent, with some reports of weak-to-moderate associations, and with others of no elevation of risks. The classical cytochrome P450 isoenzyme considered for metabolic activation of polycyclic aromatic hydrocarbons (PAH) is CYP1A1. A new member of the CYP1 family, CYP1B1, was cloned in 1994, currently representing the only member of the CYP1B subfamily. A number of single nucleotide polymorphisms of the CYP1B1 gene have been reported. The amino acid substitutions Val432Leu ( CYP1B1*3) and Asn453Ser ( CYP1B1*4), located in the heme binding domain of CYP1B1, appear as likely candidates to be linked with biological effects. CYP1B1 activates a wide range of PAH, aromatic and heterocyclic amines. Very recently, the CYP1B1 codon 432 polymorphism ( CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squamous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has pointed to interactive effects. This provides new molecular evidence that tobacco smoke-specific compounds relevant to head and neck carcinogenesis are metabolically activated through CYP1B1 and is consistent with a major pathogenetic relevance of PAH as ingredients of tobacco smoke.

  18. Is the gene-environment interaction paradigm relevant to genome-wide studies? The case of education and body mass index.

    PubMed

    Boardman, Jason D; Domingue, Benjamin W; Blalock, Casey L; Haberstick, Brett C; Harris, Kathleen Mullan; McQueen, Matthew B

    2014-02-01

    This study uses data from the Framingham Heart Study to examine the relevance of the gene-environment interaction paradigm for genome-wide association studies (GWAS). We use completed college education as our environmental measure and estimate the interactive effect of genotype and education on body mass index (BMI) using 260,402 single-nucleotide polymorphisms (SNPs). Our results highlight the sensitivity of parameter estimates obtained from GWAS models and the difficulty of framing genome-wide results using the existing gene-environment interaction typology. We argue that SNP-environment interactions across the human genome are not likely to provide consistent evidence regarding genetic influences on health that differ by environment. Nevertheless, genome-wide data contain rich information about individual respondents, and we demonstrate the utility of this type of data. We highlight the fact that GWAS is just one use of genome-wide data, and we encourage demographers to develop methods that incorporate this vast amount of information from respondents into their analyses.

  19. Gene environment interaction in periphery and brain converge to modulate behavioral outcomes: Insights from the SP1 transient early in life interference rat model

    PubMed Central

    Asor, Eyal; Ben-Shachar, Dorit

    2016-01-01

    It is generally assumed that behavior results from an interaction between susceptible genes and environmental stimuli during critical life stages. The present article reviews the main theoretical and practical concepts in the research of gene environment interaction, emphasizing the need for models simulating real life complexity. We review a novel approach to study gene environment interaction in which a brief post-natal interference with the expression of multiple genes, by hindering the activity of the ubiquitous transcription factor specificity protein 1 (Sp1) is followed by later-in-life exposure of rats to stress. Finally, this review discusses the role of peripheral processes in behavioral responses, with the Sp1 model as one example demonstrating how specific behavioral patterns are linked to modulations in both peripheral and central physiological processes. We suggest that models, which take into account the tripartite reciprocal interaction between the central nervous system, peripheral systems and environmental stimuli will advance our understanding of the complexity of behavior. PMID:27679768

  20. Enhancing the gene-environment interaction framework through a quasi-experimental research design: evidence from differential responses to September 11.

    PubMed

    Fletcher, Jason M

    2014-01-01

    This article uses a gene-environment interaction framework to examine the differential responses to an objective external stressor based on genetic variation in the production of depressive symptoms. This article advances the literature by utilizing a quasi-experimental environmental exposure design, as well as a regression discontinuity design, to control for seasonal trends, which limit the potential for gene-environment correlation and allow stronger causal claims. Replications are attempted for two prominent genes (5-HTT and MAOA), and three additional genes are explored (DRD2, DRD4, and DAT1). This article provides evidence of a main effect of 9/11 on reports of feelings of sadness and fails to replicate a common finding of interaction using 5-HTT but does show support for interaction with MAOA in men. It also provides new evidence that variation in the DRD4 gene modifies an individual's response to the exposure, with individuals with no 7-repeats found to have a muted response.

  1. Rigorous tests of gene-environment interactions in a lab study of the oxytocin receptor gene (OXTR), alcohol exposure, and aggression.

    PubMed

    LoParo, Devon; Johansson, Ada; Walum, Hasse; Westberg, Lars; Santtila, Pekka; Waldman, Irwin

    2016-07-01

    Naturalistic studies of gene-environment interactions (G X E) have been plagued by several limitations, including difficulty isolating specific environmental risk factors from other correlated aspects of the environment, gene-environment correlation (rGE ), and the use of a single genetic variant to represent the influence of a gene. We present results from 235 Finnish young men in two lab studies of aggression and alcohol challenge that attempt to redress these limitations of the extant G X E literature. Specifically, we use a latent variable modeling approach in an attempt to more fully account for genetic variation across the oxytocin receptor gene (OXTR) and to robustly test its main effects on aggression and its interaction with alcohol exposure. We also modeled aggression as a latent variable comprising various indices, including the average and maximum levels of aggression, the earliest trial on which aggression was expressed, and the proportion of trials on which the minimum and maximum levels of aggression were expressed. The best fitting model for the genetic variation across OXTR included six factors derived from an exploratory factor analysis, roughly corresponding to six haplotype blocks. Aggression levels were higher on trials in which participants were administered alcohol, won, or were provoked. There was a significant main effect of OXTR on aggression across studies after controlling for covariates. The interaction of OXTR and alcohol was also significant across studies, such that OXTR had stronger effects on aggression in the alcohol administration condition. © 2015 Wiley Periodicals, Inc.

  2. SHIELD: Observations of Three Candidate Interacting Systems

    NASA Astrophysics Data System (ADS)

    Ruvolo, Elizabeth; Miazzo, Masao; Cannon, John M.; McNichols, Andrew; Teich, Yaron; Adams, Elizabeth A.; Giovanelli, Riccardo; Haynes, Martha P.; McQuinn, Kristen B.; Salzer, John Joseph; Skillman, Evan D.; Dolphin, Andrew E.; Elson, Edward C.; Haurberg, Nathalie C.; Huang, Shan; Janowiecki, Steven; Jozsa, Gyula; Leisman, Luke; Ott, Juergen; Papastergis, Emmanouil; Rhode, Katherine L.; Saintonge, Amelie; Van Sistine, Angela; Warren, Steven R.

    2017-01-01

    Abstract:The “Survey of HI in Extremely Low-mass Dwarfs” (SHIELD) is a multiwavelength study of local volume low-mass galaxies. Using the now-complete Arecibo Legacy Fast ALFA (ALFALFA) source catalog, 82 systems are identified that meet distance, line width, and HI flux criteria for being gas-rich, low-mass galaxies. These systems harbor neutral gas reservoirs smaller than 3x10^7 M_sun, thus populating the faint end of the HI mass function with statistical confidence for the first time. In a companion poster, we present new Karl G. Jansky Very Large Array D-configuration HI spectral line observations of 32 previously unobserved galaxies. Three galaxies in that study have been discovered to lie in close angular proximity to more massive galaxies. Here we present VLA HI imaging of these candidate interacting systems. We compare the neutral gas morphology and kinematics with optical images from SDSS. We discuss the frequency of low-mass galaxies undergoing tidal interaction in the complete SHIELD sample.Support for this work was provided by NSF grant 1211683 to JMC at Macalester College.

  3. Bayesian inference of gene-environment interaction from incomplete data: what happens when information on environment is disjoint from data on gene and disease?

    PubMed

    Gustafson, Paul; Burstyn, Igor

    2011-04-15

    Inference in gene-environment studies can sometimes exploit the assumption of mendelian randomization that genotype and environmental exposure are independent in the population under study. Moreover, in some such problems it is reasonable to assume that the disease risk for subjects without environmental exposure will not vary with genotype. When both assumptions can be invoked, we consider the prospects for inferring the dependence of disease risk on genotype and environmental exposure (and particularly the extent of any gene-environment interaction), without detailed data on environmental exposure. The data structure envisioned involves data on disease and genotype jointly, but only external information about the distribution of the environmental exposure in the population. This is relevant as for many environmental exposures individual-level measurements are costly and/or highly error-prone. Working in the setting where all relevant variables are binary, we examine the extent to which such data are informative about the interaction, via determination of the large-sample limit of the posterior distribution. The ideas are illustrated using data from a case-control study for bladder cancer involving smoking behaviour and the NAT2 genotype.

  4. Invited commentary: genes, environment, and hybrid vigor.

    PubMed

    Gwinn, Marta; Guessous, Idris; Khoury, Muin J

    2009-09-15

    In the 1950s, case-control studies of smoking and lung cancer established a paradigm for epidemiologic studies of risk factors for chronic diseases. Since then, thousands of case-control studies have examined possible associations of countless risk factors with numerous diseases, rarely finding associations as strong or consistent as that of smoking with lung cancer. Recently, researchers have applied advances in molecular genetics to conduct candidate gene and genome-wide association studies of lung cancer. Skeptics among both epidemiologists and geneticists have argued that genomic research adds little value when most cases of disease can be attributed to a preventable exposure; however, well-conducted studies of gene-environment interactions that draw on data from more than 50 years of research in toxicology, pathophysiology, and behavioral science offer important models for the development of more comprehensive approaches to understanding the etiology of chronic diseases.

  5. Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease.

    PubMed

    Stankovic, Marija; Kojic, Snezana; Djordjevic, Valentina; Tomovic, Andrija; Nagorni-Obradovic, Ljudmila; Petrovic-Stanojevic, Natasa; Mitic-Milikic, Marija; Radojkovic, Dragica

    2016-07-01

    The aetiology of chronic obstructive pulmonary disease (COPD) is complex. While cigarette smoking is a well-established cause of COPD, a myriad of assessed genetic factors has given conflicting data. Since gene-environment interactions are thought to be implicated in aetiopathogenesis of COPD, we aimed to examine the matrix metalloproteinase (MMP) 9 C-1562T (rs3918242) functional variant and cigarette smoke in the pathogenesis of this disease. The distribution of the MMP9 C-1562T variant was analyzed in COPD patients and controls with normal pulmonary function from Serbia. Interaction between the C-1562T genetic variant and cigarette smoking was assessed using a case-control model. The response of the C-1562T promoter variant to cigarette smoke condensate (CSC) exposure was examined using a dual luciferase reporter assay. The frequency of T allele carriers was higher in the COPD group than in smoker controls (38.4% vs. 20%; OR = 2.7, P = 0.027). Interaction between the T allele and cigarette smoking was identified in COPD occurrence (OR = 4.38, P = 0.005) and severity (P = 0.001). A functional analysis of the C-1562T variant demonstrated a dose-dependent and allele-specific response (P < 0.01) to CSC. Significantly higher MMP9 promoter activity following CSC exposure was found for the promoter harboring the T allele compared to the promoter harboring the C allele (P < 0.05). Our study is the first to reveal an interaction between the MMP9-1562T allele and cigarette smoke in COPD, emphasising gene-environment interactions as a possible cause of lung damage in the pathogenesis of COPD. Environ. Mol. Mutagen. 57:447-454, 2016. © 2016 Wiley Periodicals, Inc.

  6. The role of 5-HTT LPR and GNβ3 825C>T polymorphisms and gene-environment interactions in irritable bowel syndrome (IBS)

    PubMed Central

    Saito, Yuri A.; Larson, Joseph J.; Atkinson, Elizabeth J.; Ryu, Euijung; Almazar, Ann E.; Petersen, Gloria M.; Talley, Nicholas J.

    2014-01-01

    Background Smaller studies have evaluated SLC6A4 5-HTTLPR and GNβ3 825C>T polymorphisms in IBS, and interactions between 5-HTT LPR with life events have been reported in the psychiatric literature, but gene-environment studies in IBS are lacking. Aims To assess the association of two polymorphisms with IBS and age of onset; and to assess whether there are gene-environment interactions with IBS. Methods Outpatients with IBS and controls completed a validated questionnaire and provided blood for DNA. Comparisons of genotype/allele frequencies between cases and controls were performed with logistic regression. Linear regression was used to evaluate the association between the variants and age of onset. Environmental variables tested included abuse, parental alcohol abuse, parental psychiatric disorders, and gastrointestinal infections. Results Genotyping was performed in 385 cases and 262 controls with median age of 50 yrs (range: 18.0–70.0) and 498 (77%) females. The IBS subtype distribution among cases was: 102 (26%) D-IBS, 40 (10%) C-IBS, 125 (32%) M-IBS, 118 (31%) other. No association was observed between IBS or age of onset and both variants. Significant interactions were observed between GI infection and the GNβ3 825T allele. For those reporting gastrointestinal infection, the OR for IBS was 3.9 (95%CI: 1.2–12.7) whereas the OR was 0.86 (95% CI: 0.65–1.13) for those without prior infection. Conclusions There was a significant interaction between the GNβ3 polymorphism and infection in the development of IBS, suggesting that its etiology is the result of a combination of specific genetic and environmental risk factors. PMID:22855291

  7. A general test for gene-environment interaction in sib pair-based association analysis of quantitative traits.

    PubMed

    van der Sluis, Sophie; Dolan, Conor V; Neale, Michael C; Posthuma, Danielle

    2008-07-01

    Several association studies support the hypothesis that genetic variants can modify the influence of environmental factors on behavioral outcomes, i.e., G x E interaction. The case-control design used in these studies is powerful, but population stratification with respect to allele frequencies can give rise to false positive or false negative associations. Stratification with respect to the environmental factors can lead to false positives or false negatives with respect to environmental main effects and G x E interaction effects as well. Here we present a model based on Fulker et al. (1999) and Purcell (2002) for the study of G x E interaction in family-based association designs, in which the effects of stratification can be controlled. Simulations illustrate the power to detect genetic and environmental main effects, and G x E interaction effects for the sib pair design. The power to detect interaction was studied in eight different situations, both with and without the presence of population stratification, and for categorical and continuous environmental factors. Results show that the power to detect genetic and environmental main effects, and G x E interaction effects, depends on the allele frequencies and the distribution of the environmental moderator. Admixture effects of realistic effect size lead only to very small stratification effects in the G x E component, so impractically large numbers of sib pairs are required to detect such stratification.

  8. Assessing Gene-Environment Interactions for Common and Rare Variants with Binary Traits Using Gene-Trait Similarity Regression

    PubMed Central

    Zhao, Guolin; Marceau, Rachel; Zhang, Daowen; Tzeng, Jung-Ying

    2015-01-01

    Accounting for gene–environment (G×E) interactions in complex trait association studies can facilitate our understanding of genetic heterogeneity under different environmental exposures, improve the ability to discover susceptible genes that exhibit little marginal effect, provide insight into the biological mechanisms of complex diseases, help to identify high-risk subgroups in the population, and uncover hidden heritability. However, significant G×E interactions can be difficult to find. The sample sizes required for sufficient power to detect association are much larger than those needed for genetic main effects, and interactions are sensitive to misspecification of the main-effects model. These issues are exacerbated when working with binary phenotypes and rare variants, which bear less information on association. In this work, we present a similarity-based regression method for evaluating G×E interactions for rare variants with binary traits. The proposed model aggregates the genetic and G×E information across markers, using genetic similarity, thus increasing the ability to detect G×E signals. The model has a random effects interpretation, which leads to robustness against main-effect misspecifications when evaluating G×E interactions. We construct score tests to examine G×E interactions and a computationally efficient EM algorithm to estimate the nuisance variance components. Using simulations and data applications, we show that the proposed method is a flexible and powerful tool to study the G×E effect in common or rare variant studies with binary traits. PMID:25585620

  9. Epistasis-list.org: A Curated Database of Gene-Gene and Gene-Environment Interactions in Human Epidemiology

    EPA Science Inventory

    The field of human genetics has experienced a paradigm shift in that common diseases are now thought to be due to the complex interactions among numerous genetic and environmental factors. This paradigm shift has prompted the development of myriad novel methods to detect such int...

  10. An investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

    PubMed Central

    Rudolph, Anja; Milne, Roger L.; Truong, Thérèse; Knight, Julia A.; Seibold, Petra; Flesch-Janys, Dieter; Behrens, Sabine; Eilber, Ursula; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dunning, Alison M.; Shah, Mitul; Munday, Hannah R.; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S.; Olson, Janet; Vachon, Celine M.; Hallberg, Emily; Castelao, J. Esteban; Carracedo, Angel; Torres, Maria; Li, Jingmei; Humphreys, Keith; Cordina-Duverger, Emilie; Menegaux, Florence; Flyger, Henrik; Nordestgaard, Børge G.; Nielsen, Sune F.; Yesilyurt, Betul T.; Floris, Giuseppe; Leunen, Karin; Engelhardt, Ellen G.; Broeks, Annegien; Rutgers, Emiel J.; Glendon, Gord; Mulligan, Anna Marie; Cross, Simon; Reed, Malcolm; Gonzalez-Neira, Anna; Perez, José Ignacio Arias; Provenzano, Elena; Apicella, Carmel; Southey, Melissa C.; Spurdle, Amanda; Investigators, kConFab; Group, AOCS; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; McLean, Catriona; Baglietto, Laura; Chanock, Stephen J.; Lissowska, Jolanta; Sherman, Mark E.; Brüning, Thomas; Hamann, Ute; Ko, Yon-Dschun; Orr, Nick; Schoemaker, Minouk; Ashworth, Alan; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M.; Mannermaa, Arto; Swerdlow, Anthony; Giles, Graham G.; Brenner, Hermann; Fasching, Peter A.; Chenevix-Trench, Georgia; Hopper, John; Benítez, Javier; Cox, Angela; Andrulis, Irene L.; Lambrechts, Diether; Gago-Dominguez, Manuela; Couch, Fergus; Czene, Kamila; Bojesen, Stig E.; Easton, Doug F.; Schmidt, Marjanka K.; Guénel, Pascal; Hall, Per; Pharoah, Paul D. P.; Garcia-Closas, Montserrat; Chang-Claude, Jenny

    2014-01-01

    A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint) <1.1×10−3. None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER-negative BC risk in women ≥170cm (OR=1.22, p=0.017), but inversely associated with ER-negative BC risk in women <160cm (OR=0.83, p=0.039, pint=1.9×10−4). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR=0.85, p=2.0×10−4), and absent in women who had had just one (OR=0.96, p=0.19, pint = 6.1×10−4). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR=0.93, p=2.8×10−5), but no association was observed in current smokers (OR=1.07, p=0.14, pint = 3.4×10−4). In conclusion, recently identified breast cancer susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies. PMID:25227710

  11. Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors.

    PubMed

    Rudolph, Anja; Milne, Roger L; Truong, Thérèse; Knight, Julia A; Seibold, Petra; Flesch-Janys, Dieter; Behrens, Sabine; Eilber, Ursula; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dunning, Alison M; Shah, Mitul; Munday, Hannah R; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S; Olson, Janet; Vachon, Celine M; Hallberg, Emily; Castelao, J Esteban; Carracedo, Angel; Torres, Maria; Li, Jingmei; Humphreys, Keith; Cordina-Duverger, Emilie; Menegaux, Florence; Flyger, Henrik; Nordestgaard, Børge G; Nielsen, Sune F; Yesilyurt, Betul T; Floris, Giuseppe; Leunen, Karin; Engelhardt, Ellen G; Broeks, Annegien; Rutgers, Emiel J; Glendon, Gord; Mulligan, Anna Marie; Cross, Simon; Reed, Malcolm; Gonzalez-Neira, Anna; Arias Perez, José Ignacio; Provenzano, Elena; Apicella, Carmel; Southey, Melissa C; Spurdle, Amanda; Häberle, Lothar; Beckmann, Matthias W; Ekici, Arif B; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; McLean, Catriona; Baglietto, Laura; Chanock, Stephen J; Lissowska, Jolanta; Sherman, Mark E; Brüning, Thomas; Hamann, Ute; Ko, Yon-Dschun; Orr, Nick; Schoemaker, Minouk; Ashworth, Alan; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M; Mannermaa, Arto; Swerdlow, Anthony; Giles, Graham G; Brenner, Hermann; Fasching, Peter A; Chenevix-Trench, Georgia; Hopper, John; Benítez, Javier; Cox, Angela; Andrulis, Irene L; Lambrechts, Diether; Gago-Dominguez, Manuela; Couch, Fergus; Czene, Kamila; Bojesen, Stig E; Easton, Doug F; Schmidt, Marjanka K; Guénel, Pascal; Hall, Per; Pharoah, Paul D P; Garcia-Closas, Montserrat; Chang-Claude, Jenny

    2015-03-15

    A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint ) <1.1 × 10(-3) . None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER-negative BC risk in women ≥170 cm (OR = 1.22, p = 0.017), but inversely associated with ER-negative BC risk in women <160 cm (OR = 0.83, p = 0.039, pint = 1.9 × 10(-4) ). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR = 0.85, p = 2.0 × 10(-4) ), and absent in women who had had just one (OR = 0.96, p = 0.19, pint = 6.1 × 10(-4) ). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR = 0.93, p = 2.8 × 10(-5) ), but no association was observed in current smokers (OR = 1.07, p = 0.14, pint = 3.4 × 10(-4) ). In conclusion, recently identified BC susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies.

  12. Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis.

    PubMed

    Naj, Adam C; Scott, William K; Courtenay, Monique D; Cade, William H; Schwartz, Stephen G; Kovach, Jaclyn L; Agarwal, Anita; Wang, Gaofeng; Haines, Jonathan L; Pericak-Vance, Margaret A

    2013-05-01

    Relatively little is known about the interaction between genes and environment in the complex etiology of age-related macular degeneration (AMD). This study aimed to identify novel factors associated with AMD by analyzing gene-smoking interactions in a genome-wide association study of 1207 AMD cases and 686 controls of Caucasian background with genotype data on 668,238 single nucleotide polymorphisms (SNPs) after quality control. Participants' history of smoking at least 100 cigarettes lifetime was determined by a self-administered questionnaire. SNP associations modeled the effect of the minor allele additively on AMD using logistic regression, with adjustment for age, sex, and ever/never smoking. Joint effects of SNPs and smoking were examined comparing a null model containing only age, sex, and smoking against an extended model including genotypic and interaction terms. Genome-wide significant main effects were detected at three known AMD loci: CFH (P = 7.51×10(-30) ), ARMS2 (P = 1.94×10(-23) ), and RDBP/CFB/C2 (P = 4.37×10(-10) ), while joint effects analysis revealed three genomic regions with P < 10(-5) . Analyses stratified by smoking found genetic associations largely restricted to nonsmokers, with one notable exception: the chromosome 18q22.1 intergenic SNP rs17073641 (between SERPINB8 and CDH7), more strongly associated in nonsmokers (OR = 0.57, P = 2.73 × 10(-5) ), with an inverse association among smokers (OR = 1.42, P = 0.00228), suggesting that smoking modifies the effect of some genetic polymorphisms on AMD risk.

  13. Effect of TNF and LTA polymorphisms on biological markers of response to oxidative stimuli in coal miners: a model of gene-environment interaction

    PubMed Central

    Nadif, R; Jedlicka, A; Mintz, M; Bertrand, J; Kleeberger, S; Kauffmann, F

    2003-01-01

    Introduction: Interaction between genetic background and oxidative environmental stimuli in the pathogenesis of human lung disease has been largely unexplored. Methods: A prospective epidemiological study was undertaken in 253 coal miners. Intermediate quantitative phenotypes of response to oxidant exposure, including erythrocyte glutathione peroxidase (GSH-Px) and catalase activities, were studied. Oxidant exposures studied were smoking habits and cumulative dust exposure assessed by job history and ambient measures. Disease phenotypes included subclinical computed tomography score at the first survey and x ray profusion grades twice, five years apart, to assess established coal workers' pneumoconiosis (CWP). Miners were genotyped for common functional polymorphisms in the gene for tumour necrosis factor α (TNF) and lymphotoxin α (LTA), two proinflammatory cytokines that have been implicated in the pathogenesis of chronic lung diseases. Results: Regarding gene-environment interaction on intermediate phenotypes, results showed interaction of a promoter polymorphism at the –308 position in TNF with occupational exposure on erythrocyte GSH-Px activity with a significant association in those with high exposure (p=0.003), whereas no association was observed among those with low exposure (interaction p=0.06). Regarding gene intermediate phenotype interaction on clinical outcome, results showed an association of CWP prevalence with an NcoI polymorphism in LTA in those with low catalase activity (p=0.05), whereas no association was observed in those with high activity (interaction p=0.03). No other significant association was observed. Conclusion: The results suggest that interactions of genetic background with environmental exposure and intermediate response phenotypes are important components in the pathogenesis of CWP. PMID:12566517

  14. Multivariate dimensionality reduction approaches to identify gene-gene and gene-environment interactions underlying multiple complex traits.

    PubMed

    Xu, Hai-Ming; Sun, Xi-Wei; Qi, Ting; Lin, Wan-Yu; Liu, Nianjun; Lou, Xiang-Yang

    2014-01-01

    The elusive but ubiquitous multifactor interactions represent a stumbling block that urgently needs to be removed in searching for determinants involved in human complex diseases. The dimensionality reduction approaches are a promising tool for this task. Many complex diseases exhibit composite syndromes required to be measured in a cluster of clinical traits with varying correlations and/or are inherently longitudinal in nature (changing over time and measured dynamically at multiple time points). A multivariate approach for detecting interactions is thus greatly needed on the purposes of handling a multifaceted phenotype and longitudinal data, as well as improving statistical power for multiple significance testing via a two-stage testing procedure that involves a multivariate analysis for grouped phenotypes followed by univariate analysis for the phenotypes in the significant group(s). In this article, we propose a multivariate extension of generalized multifactor dimensionality reduction (GMDR) based on multivariate generalized linear, multivariate quasi-likelihood and generalized estimating equations models. Simulations and real data analysis for the cohort from the Study of Addiction: Genetics and Environment are performed to investigate the properties and performance of the proposed method, as compared with the univariate method. The results suggest that the proposed multivariate GMDR substantially boosts statistical power.

  15. The Influence of Gene-Environment Interactions on Alcohol Consumption and Alcohol Use Disorders: A Comprehensive Review

    PubMed Central

    Young-Wolff, Kelly C.; Enoch, Mary-Anne; Prescott, Carol A.

    2011-01-01

    Since 2005, a rapidly expanding literature has evaluated whether environmental factors such as socio-cultural context and environmental adversity interact with genetic influences on drinking behaviors. This article critically reviews empirical research on alcohol-related genotype-environment interactions (GxE) and provides a contextual framework for understanding how genetic factors combine with (or are shaped by) environmental influences to influence the development of drinking behaviors and alcohol use disorders. Collectively, evidence from twin, adoption, and molecular genetic studies indicates that the degree of importance of genetic influences on risk for drinking outcomes can vary in different populations and under different environmental circumstances. However, methodological limitations and lack of consistent replications in this literature make it difficult to draw firm conclusions regarding the nature and effect size of alcohol-related GxE. On the basis of this review, we describe several methodological challenges as they relate to current research on GxE in drinking behaviors and provide recommendations to aid future research. PMID:21530476

  16. Influence of 5-HTT variation, childhood trauma and self-efficacy on anxiety traits: a gene-environment-coping interaction study.

    PubMed

    Schiele, Miriam A; Ziegler, Christiane; Holitschke, Karoline; Schartner, Christoph; Schmidt, Brigitte; Weber, Heike; Reif, Andreas; Romanos, Marcel; Pauli, Paul; Zwanzger, Peter; Deckert, Jürgen; Domschke, Katharina

    2016-08-01

    Environmental vulnerability factors such as adverse childhood experiences in interaction with genetic risk variants, e.g., the serotonin transporter gene linked polymorphic region (5-HTTLPR), are assumed to play a role in the development of anxiety and affective disorders. However, positive influences such as general self-efficacy (GSE) may exert a compensatory effect on genetic disposition, environmental adversity, and anxiety traits. We, thus, assessed childhood trauma (Childhood Trauma Questionnaire, CTQ) and GSE in 678 adults genotyped for 5-HTTLPR/rs25531 and their interaction on agoraphobic cognitions (Agoraphobic Cognitions Questionnaire, ACQ), social anxiety (Liebowitz Social Anxiety Scale, LSAS), and trait anxiety (State-Trait Anxiety Inventory, STAI-T). The relationship between anxiety traits and childhood trauma was moderated by self-efficacy in 5-HTTLPR/rs25531 LALA genotype carriers: LALA probands maltreated as children showed high anxiety scores when self-efficacy was low, but low anxiety scores in the presence of high self-efficacy despite childhood maltreatment. Our results extend previous findings regarding anxiety-related traits showing an interactive relationship between 5-HTT genotype and adverse childhood experiences by suggesting coping-related measures to function as an additional dimension buffering the effects of a gene-environment risk constellation. Given that anxiety disorders manifest already early in childhood, this insight could contribute to the improvement of psychotherapeutic interventions by including measures strengthening self-efficacy and inform early targeted preventive interventions in at-risk populations, particularly within the crucial time window of childhood and adolescence.

  17. Classification and Clustering Methods for Multiple Environmental Factors in Gene-Environment Interaction: Application to the Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Ko, Yi-An; Mukherjee, Bhramar; Smith, Jennifer A; Kardia, Sharon L R; Allison, Matthew; Diez Roux, Ana V

    2016-11-01

    There has been an increased interest in identifying gene-environment interaction (G × E) in the context of multiple environmental exposures. Most G × E studies analyze one exposure at a time, but we are exposed to multiple exposures in reality. Efficient analysis strategies for complex G × E with multiple environmental factors in a single model are still lacking. Using the data from the Multiethnic Study of Atherosclerosis, we illustrate a two-step approach for modeling G × E with multiple environmental factors. First, we utilize common clustering and classification strategies (e.g., k-means, latent class analysis, classification and regression trees, Bayesian clustering using Dirichlet Process) to define subgroups corresponding to distinct environmental exposure profiles. Second, we illustrate the use of an additive main effects and multiplicative interaction model, instead of the conventional saturated interaction model using product terms of factors, to study G × E with the data-driven exposure subgroups defined in the first step. We demonstrate useful analytical approaches to translate multiple environmental exposures into one summary class. These tools not only allow researchers to consider several environmental exposures in G × E analysis but also provide some insight into how genes modify the effect of a comprehensive exposure profile instead of examining effect modification for each exposure in isolation.

  18. Conceptual Shifts Needed to Understand the Dynamic Interactions of Genes, Environment, Epigenetics, Social Processes, and Behavioral Choices

    PubMed Central

    Niculescu, Mihai D.; Jackson, Robert T.

    2013-01-01

    Social and behavioral research in public health is often intimately tied to profound, but frequently neglected, biological influences from underlying genetic, environmental, and epigenetic events. The dynamic interplay between the life, social, and behavioral sciences often remains underappreciated and underutilized in addressing complex diseases and disorders and in developing effective remediation strategies. Using a case-study format, we present examples as to how the inclusion of genetic, environmental, and epigenetic data can augment social and behavioral health research by expanding the parameters of such studies, adding specificity to phenotypic assessments, and providing additional internal control in comparative studies. We highlight the important roles of gene–environment interactions and epigenetics as sources of phenotypic change and as a bridge between the life and social and behavioral sciences in the development of robust interdisciplinary analyses. PMID:23927503

  19. Gene--environment interactions influence feeding and anti-predator behavior in wild and transgenic coho salmon.

    PubMed

    Sundström, L F; Löhmus, M; Devlin, R H

    2016-01-01

    Environmental conditions are known to affect phenotypic development in many organisms, making the characteristics of an animal reared under one set of conditions not always representative of animals reared under a different set of conditions. Previous results show that such plasticity can also affect the phenotypes and ecological interactions of different genotypes, including animals anthropogenically generated by genetic modification. To understand how plastic development can affect behavior in animals of different genotypes, we examined the feeding and risk-taking behavior in growth-enhanced transgenic coho salmon (with two- to threefold enhanced daily growth rates compared to wild type) under a range of conditions. When compared to wild-type siblings, we found clear effects of the rearing environment on feeding and risk-taking in transgenic animals and noted that in some cases, this environmental effect was stronger than the effects of the genetic modification. Generally, transgenic fish, regardless of rearing conditions, behaved similar to wild-type fish reared under natural-like conditions. Instead, the more unusual phenotype was associated with wild-type fish reared under hatchery conditions, which possessed an extreme risk averse phenotype compared to the same strain reared in naturalized conditions. Thus, the relative performance of genotypes from one environment (e.g., laboratory) may not always accurately reflect ecological interactions as would occur in a different environment (e.g., nature). Further, when assessing risks of genetically modified organisms, it is important to understand how the environment affects phenotypic development, which in turn may variably influence consequences to ecosystem components across different conditions found in the complexity of nature.

  20. Have studies of the developmental regulation of behavioral phenotypes revealed the mechanisms of gene-environment interactions?

    PubMed Central

    Hall, F. Scott; Perona, Maria T. G.

    2012-01-01

    This review addresses the recent convergence of our long-standing knowledge of the regulation of behavioral phenotypes by developmental experience with recent advances in our understanding of mechanisms regulating gene expression. This review supports a particular perspective on the developmental regulation of behavioral phenotypes: That the role of common developmental experiences (e.g. maternal interactions, peer interactions, exposure to a complex environment, etc.) is to fit individuals to the circumstances of their lives within bounds determined by long-standing (evolutionary) mechanisms that have shaped responses to critical and fundamental types of experience via those aspects of gene structure that regulate gene expression. The phenotype of a given species is not absolute for a given genotype but rather variable within bounds that are determined by mechanisms regulated by experience (e.g. epigenetic mechanisms). This phenotypic variation is not necessarily random, or evenly distributed along a continuum of description or measurement, but often highly disjointed, producing distinct, even opposing, phenotypes. The potentiality for these varying phenotypes is itself the product of evolution, the potential for alternative phenotypes itself conveying evolutionary advantage. Examples of such phenotypic variation, resulting from environmental or experiential influences, have a long history of study in neurobiology, and a number of these will be discussed in this review: neurodevelopmental experiences that produce phenotypic variation in visual perception, cognitive function, and emotional behavior. Although other examples will be discussed, particular emphasis will be made on the role of social behavior on neurodevelopment and phenotypic determination. It will be argued that an important purpose of some aspects of social behavior is regulation of neurobehavioral phenotypes by experience via genetic regulatory mechanisms. PMID:22643448

  1. Environmental and genetic risk factors and gene-environment interactions in the pathogenesis of chronic obstructive lung disease.

    PubMed Central

    Walter, R; Gottlieb, D J; O'Connor, G T

    2000-01-01

    Current understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD), a source of substantial morbidity and mortality in the United States, suggests that chronic inflammation leads to the airways obstruction and parenchymal destruction that characterize this condition. Environmental factors, especially tobacco smoke exposure, are known to accelerate longitudinal decline of lung function, and there is substantial evidence that upregulation of inflammatory pathways plays a vital role in this process. Genetic regulation of both inflammatory responses and anti-inflammatory protective mechanisms likely underlies the heritability of COPD observed in family studies. In alpha-1 protease inhibitor deficiency, the only genetic disorder known to cause COPD, lack of inhibition of elastase activity, results in the parenchymal destruction of emphysema. Other genetic polymorphisms have been hypothesized to alter the risk of COPD but have not been established as causes of this condition. It is likely that multiple genetic factors interacting with each other and with a number of environmental agents will be found to result in the development of COPD. PMID:10931792

  2. Paternal Aging Affects Behavior in Pax6 Mutant Mice: A Gene/Environment Interaction in Understanding Neurodevelopmental Disorders

    PubMed Central

    Kimura, Ryuichi; Tucci, Valter; Kaneda, Hideki; Wakana, Shigeharu; Osumi, Noriko

    2016-01-01

    Neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD) have increased over the last few decades. These neurodevelopmental disorders are characterized by a complex etiology, which involves multiple genes and gene-environmental interactions. Various genes that control specific properties of neural development exert pivotal roles in the occurrence and severity of phenotypes associated with neurodevelopmental disorders. Moreover, paternal aging has been reported as one of the factors that contribute to the risk of ASD and ADHD. Here we report, for the first time, that paternal aging has profound effects on the onset of behavioral abnormalities in mice carrying a mutation of Pax6, a gene with neurodevelopmental regulatory functions. We adopted an in vitro fertilization approach to restrict the influence of additional factors. Comprehensive behavioral analyses were performed in Sey/+ mice (i.e., Pax6 mutant heterozygotes) born from in vitro fertilization of sperm taken from young or aged Sey/+ fathers. No body weight changes were found in the four groups, i.e., Sey/+ and wild type (WT) mice born to young or aged father. However, we found important differences in maternal separation-induced ultrasonic vocalizations of Sey/+ mice born from young father and in the level of hyperactivity of Sey/+ mice born from aged fathers in the open-field test, respectively, compared to WT littermates. Phenotypes of anxiety were observed in both genotypes born from aged fathers compared with those born from young fathers. No significant difference was found in social behavior and sensorimotor gating among the four groups. These results indicate that mice with a single genetic risk factor can develop different phenotypes depending on the paternal age. Our study advocates for serious considerations on the role of paternal aging in breeding strategies for animal studies. PMID:27855195

  3. Paternal Aging Affects Behavior in Pax6 Mutant Mice: A Gene/Environment Interaction in Understanding Neurodevelopmental Disorders.

    PubMed

    Yoshizaki, Kaichi; Furuse, Tamio; Kimura, Ryuichi; Tucci, Valter; Kaneda, Hideki; Wakana, Shigeharu; Osumi, Noriko

    2016-01-01

    Neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD) have increased over the last few decades. These neurodevelopmental disorders are characterized by a complex etiology, which involves multiple genes and gene-environmental interactions. Various genes that control specific properties of neural development exert pivotal roles in the occurrence and severity of phenotypes associated with neurodevelopmental disorders. Moreover, paternal aging has been reported as one of the factors that contribute to the risk of ASD and ADHD. Here we report, for the first time, that paternal aging has profound effects on the onset of behavioral abnormalities in mice carrying a mutation of Pax6, a gene with neurodevelopmental regulatory functions. We adopted an in vitro fertilization approach to restrict the influence of additional factors. Comprehensive behavioral analyses were performed in Sey/+ mice (i.e., Pax6 mutant heterozygotes) born from in vitro fertilization of sperm taken from young or aged Sey/+ fathers. No body weight changes were found in the four groups, i.e., Sey/+ and wild type (WT) mice born to young or aged father. However, we found important differences in maternal separation-induced ultrasonic vocalizations of Sey/+ mice born from young father and in the level of hyperactivity of Sey/+ mice born from aged fathers in the open-field test, respectively, compared to WT littermates. Phenotypes of anxiety were observed in both genotypes born from aged fathers compared with those born from young fathers. No significant difference was found in social behavior and sensorimotor gating among the four groups. These results indicate that mice with a single genetic risk factor can develop different phenotypes depending on the paternal age. Our study advocates for serious considerations on the role of paternal aging in breeding strategies for animal studies.

  4. Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium

    PubMed Central

    Fan, Qiao; Guo, Xiaobo; Tideman, J. Willem L.; Williams, Katie M.; Yazar, Seyhan; Hosseini, S. Mohsen; Howe, Laura D.; Pourcain, Beaté St; Evans, David M.; Timpson, Nicholas J.; McMahon, George; Hysi, Pirro G.; Krapohl, Eva; Wang, Ya Xing; Jonas, Jost B.; Baird, Paul Nigel; Wang, Jie Jin; Cheng, Ching-Yu; Teo, Yik-Ying; Wong, Tien-Yin; Ding, Xiaohu; Wojciechowski, Robert; Young, Terri L.; Pärssinen, Olavi; Oexle, Konrad; Pfeiffer, Norbert; Bailey-Wilson, Joan E.; Paterson, Andrew D.; Klaver, Caroline C. W.; Plomin, Robert; Hammond, Christopher J.; Mackey, David A.; He, Mingguang; Saw, Seang-Mei; Williams, Cathy; Guggenheim, Jeremy A.; Meguro, Akira; Wright, Alan F.; Hewitt, Alex W.; Young, Alvin L.; Veluchamy, Amutha Barathi; Metspalu, Andres; Paterson, Andrew D.; Döring, Angela; Khawaja, Anthony P.; Klein, Barbara E.; Pourcain, Beate St; Fleck, Brian; Klaver, Caroline C. W.; Hayward, Caroline; Williams, Cathy; Delcourt, Cécile; Pang, Chi Pui; Khor, Chiea-Chuen; Cheng, Ching-Yu; Gieger, Christian; Hammond, Christopher J.; Simpson, Claire L.; van Duijn, Cornelia M.; Mackey, David A.; Evans, David M.; Stambolian, Dwight; Chew, Emily; Tai, E-Shyong; Krapohl, Eva; Mihailov, Evelin; Smith, George Davey; McMahon, George; Biino, Ginevra; Campbell, Harry; Rudan, Igor; Seppälä, Ilkka; Kaprio, Jaakko; Wilson, James F.; Craig, Jamie E.; Tideman, J. Willem L.; Ried, Janina S.; Korobelnik, Jean-François; Guggenheim, Jeremy A.; Fondran, Jeremy R.; Wang, Jie Jin; Liao, Jiemin; Zhao, Jing Hua; Xie, Jing; Bailey-Wilson, Joan E.; Kemp, John P.; Lass, Jonathan H.; Jonas, Jost B.; Rahi, Jugnoo S.; Wedenoja, Juho; Mäkelä, Kari-Matti; Burdon, Kathryn P.; Williams, Katie M; Khaw, Kay-Tee; Yamashiro, Kenji; Oexle, Konrad; Howe, Laura D.; Chen, Li Jia; Xu, Liang; Farrer, Lindsay; Ikram, M. Kamran; Deangelis, Margaret M.; Morrison, Margaux; Schache, Maria; Pirastu, Mario; Miyake, Masahiro; Yap, Maurice K. H.; Fossarello, Maurizio; Kähönen, Mika; Tedja, Milly S.; He, Mingguang; Yoshimura, Nagahisa; Martin, Nicholas G.; Timpson, Nicholas J.; Wareham, Nick J.; Mizuki, Nobuhisa; Pfeiffer, Norbert; Pärssinen, Olavi; Raitakari, Olli; Polasek, Ozren; Tam, Pancy O.; Foster, Paul J.; Mitchell, Paul; Baird, Paul Nigel; Chen, Peng; Hysi, Pirro G.; Cumberland, Phillippa; Gharahkhani, Puya; Fan, Qiao; Höhn, René; Fogarty, Rhys D.; Luben, Robert N.; Igo Jr, Robert P.; Plomin, Robert; Wojciechowski, Robert; Klein, Ronald; Mohsen Hosseini, S.; Janmahasatian, Sarayut; Saw, Seang-Mei; Yazar, Seyhan; Ping Yip, Shea; Feng, Sheng; Vaccargiu, Simona; Panda-Jonas, Songhomitra; MacGregor, Stuart; Iyengar, Sudha K.; Rantanen, Taina; Lehtimäki, Terho; Young, Terri L.; Meitinger, Thomas; Wong, Tien-Yin; Aung, Tin; Haller, Toomas; Vitart, Veronique; Nangia, Vinay; Verhoeven, Virginie J. M.; Jhanji, Vishal; Zhao, Wanting; Chen, Wei; Zhou, Xiangtian; Guo, Xiaobo; Ding, Xiaohu; Wang, Ya Xing; Lu, Yi; Teo, Yik-Ying; Vatavuk, Zoran

    2016-01-01

    Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7–15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E–08) and 2.3% (P = 6.9E–21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E–04). PMID:27174397

  5. Using gene-environment interaction analyses to clarify the role of well-done meat and heterocyclic amine exposure in the etiology of colorectal polyps123

    PubMed Central

    Fu, Zhenming; Shrubsole, Martha J; Li, Guoliang; Smalley, Walter E; Hein, David W; Chen, Zhi; Shyr, Yu; Cai, Qiuyin; Ness, Reid M

    2012-01-01

    Background: The role of well-done meat intake and meat-derived mutagen heterocyclic amine (HCA) exposure in the risk of colorectal neoplasm has been suggested but not yet established. Objective: With the use of gene-environment interaction analyses, we sought to clarify the association of HCA exposure with colorectal polyp risk. Design: In a case-control study including 2057 colorectal polyp patients and 3329 controls, we evaluated 16 functional genetic variants to construct an HCA-metabolizing score. To derive dietary HCA-exposure amount, data were collected regarding dietary intake of meat by cooking method and degree of doneness. Results: A 2-fold elevated risk associated with high red meat intake was found for colorectal polyps or adenomas in subjects with a high HCA-metabolizing risk score, whereas the risk was 1.3- to 1.4-fold among those with a low risk score (P-interaction ≤ 0.05). The interaction was stronger for the risk of advanced or multiple adenomas, in which an OR of 2.8 (95% CI: 1.8, 4.6) was observed for those with both a high HCA-risk score and high red meat intake (P-interaction = 0.01). No statistically significant interaction was found in analyses that used specific HCA exposure derived from dietary data. Conclusion: High red meat intake is associated with an elevated risk of colorectal polyps, and this association may be synergistically modified by genetic factors involved in HCA metabolism. PMID:23015320

  6. The immunogenetics of narcolepsy associated with A(H1N1)pdm09 vaccination (Pandemrix) supports a potent gene-environment interaction.

    PubMed

    Bomfim, I L; Lamb, F; Fink, K; Szakács, A; Silveira, A; Franzén, L; Azhary, V; Maeurer, M; Feltelius, N; Darin, N; Hallböök, T; Arnheim-Dahlström, L; Kockum, I; Olsson, T

    2017-03-23

    The influenza A(H1N1)pdm09 vaccination campaign from 2009 to 2010 was associated with a sudden increase in the incidence of narcolepsy in several countries. Narcolepsy with cataplexy is strongly associated with the human leukocyte antigen (HLA) class II DQB1*06:02 allele, and protective associations with the DQB1*06:03 allele have been reported. Several non-HLA gene loci are also associated, such as common variants of the T-cell receptor-α (TRA), the purinergic receptor P2RY11, cathepsin H (CTSH) and TNFSF4/OX40L/CD252. In this retrospective multicenter study, we investigated if these predisposing gene loci were also involved in vaccination-associated narcolepsy. We compared HLA- along with single-nucleotide polymorphism genotypes for non-HLA regions between 42 Pandemrix-vaccinated narcolepsy cases and 1990 population-based controls. The class II gene loci associations supported previous findings. Nominal association (P-value<0.05) with TRA as well as suggestive (P-value<0.1) associations with P2RY11 and CTSH were found. These associations suggest a very strong gene-environment interaction, in which the influenza A(H1N1)pdm09 strain or Pandemrix vaccine can act as potent environmental triggers.Genes and Immunity advance online publication, 23 March 2017; doi:10.1038/gene.2017.1.

  7. Genotype-based association mapping of complex diseases: gene-environment interactions with multiple genetic markers and measurement error in environmental exposures.

    PubMed

    Lobach, Iryna; Fan, Ruzong; Carroll, Raymond J

    2010-12-01

    With the advent of dense single nucleotide polymorphism genotyping, population-based association studies have become the major tools for identifying human disease genes and for fine gene mapping of complex traits. We develop a genotype-based approach for association analysis of case-control studies of gene-environment interactions in the case when environmental factors are measured with error and genotype data are available on multiple genetic markers. To directly use the observed genotype data, we propose two genotype-based models: genotype effect and additive effect models. Our approach offers several advantages. First, the proposed risk functions can directly incorporate the observed genotype data while modeling the linkage disequilibrium information in the regression coefficients, thus eliminating the need to infer haplotype phase. Compared with the haplotype-based approach, an estimating procedure based on the proposed methods can be much simpler and significantly faster. In addition, there is no potential risk due to haplotype phase estimation. Further, by fitting the proposed models, it is possible to analyze the risk alleles/variants of complex diseases, including their dominant or additive effects. To model measurement error, we adopt the pseudo-likelihood method by Lobach et al. [2008]. Performance of the proposed method is examined using simulation experiments. An application of our method is illustrated using a population-based case-control study of association between calcium intake with the risk of colorectal adenoma development.

  8. Genotype-Based Association Mapping of Complex Diseases: Gene-Environment Interactions with Multiple Genetic Markers and Measurement Error in Environmental Exposures

    PubMed Central

    Lobach, Irvna; Fan, Ruzone; Carroll, Raymond T.

    2011-01-01

    With the advent of dense single nucleotide polymorphism genotyping, population-based association studies have become the major tools for identifying human disease genes and for fine gene mapping of complex traits. We develop a genotype-based approach for association analysis of case-control studies of gene-environment interactions in the case when environmental factors are measured with error and genotype data are available on multiple genetic markers. To directly use the observed genotype data, we propose two genotype-based models: genotype effect and additive effect models. Our approach offers several advantages. First, the proposed risk functions can directly incorporate the observed genotype data while modeling the linkage disequihbrium information in the regression coefficients, thus eliminating the need to infer haplotype phase. Compared with the haplotype-based approach, an estimating procedure based on the proposed methods can be much simpler and significantly faster. In addition, there is no potential risk due to haplotype phase estimation. Further, by fitting the proposed models, it is possible to analyze the risk alleles/variants of complex diseases, including their dominant or additive effects. To model measurement error, we adopt the pseudo-likelihood method by Lobach et al. [2008]. Performance of the proposed method is examined using simulation experiments. An application of our method is illustrated using a population-based case-control study of association between calcium intake with the risk of colorectal adenoma development. PMID:21031455

  9. Nevoid basal cell carcinoma syndrome with medulloblastoma in an African-American boy: A rare case illustrating gene-environment interaction

    SciTech Connect

    Korczak, J.F.; Goldstein, A.M.; Kase, R.G.

    1997-03-31

    We present an 8-year-old African-American boy with medulloblastoma and nevoid basal cell carcinoma syndrome (NBCCS) who exhibited the radiosensitive response of basal cell carcinoma (BCC) formation in the area irradiated for medulloblastoma. Such a response is well-documented in Caucasian NBCCS patients with medulloblastoma. The propositus was diagnosed with medulloblastoma at the age of 2 years and underwent surgery, chemotherapy, and craniospinal irradiation. At the age of 6 years, he was diagnosed with NBCCS following his presentation with a large odontogenic keratocyst of the mandible, pits of the palms and soles and numerous BCCs in the area of the back and neck that had been irradiated previously for medulloblastoma. Examination of other relatives showed that the propositus mother also had NBCCS but was more mildly affected; in particular, she had no BCCs. This case illustrates complex gene-environment interaction, in that increased skin pigmentation in African-Americans is presumably protective against ultraviolet, but not ionizing, radiation. This case and other similar cases in the literature show the importance of considering NBCCS in the differential diagnosis of any patient who presents with a medulloblastoma, especially before the age of 5 years, and of examining other close relatives for signs of NBCCS to determine the patient`s at-risk status. Finally, for individuals who are radiosensitive, protocols that utilize chemotherapy in lieu of radiotherapy should be considered. 27 refs., 4 figs.

  10. Escitalopram affects cytoskeleton and synaptic plasticity pathways in a rat gene-environment interaction model of depression as revealed by proteomics. Part II: environmental challenge.

    PubMed

    Piubelli, Chiara; Vighini, Miriam; Mathé, Aleksander A; Domenici, Enrico; Carboni, Lucia

    2011-07-01

    Large-scale investigations aimed at elucidating the molecular mechanism of action of antidepressant treatment are achievable through the application of proteomic technologies. We performed a proteomic study on the Flinders Sensitive Line (FSL), a genetically selected rat model of depression, and the control Flinders Resistant Line (FRL). To evaluate gene-environment interactions, FSL and FRL animals were separated from their mothers for 3 h from postnatal days 2 to 14 (maternal separation; MS), since early-life trauma is considered an important antecedent of depression. All groups received either escitalopram (Esc) admixed to food pellets (25 mg/kg.d) or vehicle for 1 month. Protein extracts from prefrontal/frontal cortex and hippocampus were separated by 2D electrophoresis. Proteins differentially modulated were identified by mass spectrometry. Bioinformatics analyses were performed to discover gene ontology terms associated with the modulated proteins. This paper was focused on the modifications induced by the environmental challenge of MS, both on the predisposed genetic background and on the resistant phenotype. The combination between Esc treatment and MS was investigated by comparing the MS, Esc-treated rats with rats subjected to each single procedure. In MS rats, antidepressant treatment influenced mainly proteins involved in carbohydrate metabolism in FSL rats and in vesicle-mediated transport in FRL rats. When studying the interaction between Esc and MS vs. non-separated rats, proteins playing a role in cytoskeleton organization, neuronal development, vesicle-mediated transport and synaptic plasticity were identified. The results provide further support to the available reports that antidepressant treatment affects intracellular pathways and also suggest new potential targets for future therapeutic intervention.

  11. A systematic gene-gene and gene-environment interaction analysis of DNA repair genes XRCC1, XRCC2, XRCC3, XRCC4, and oral cancer risk.

    PubMed

    Yang, Cheng-Hong; Lin, Yu-Da; Yen, Ching-Yui; Chuang, Li-Yeh; Chang, Hsueh-Wei

    2015-04-01

    Oral cancer is the sixth most common cancer worldwide with a high mortality rate. Biomarkers that anticipate susceptibility, prognosis, or response to treatments are much needed. Oral cancer is a polygenic disease involving complex interactions among genetic and environmental factors, which require multifaceted analyses. Here, we examined in a dataset of 103 oral cancer cases and 98 controls from Taiwan the association between oral cancer risk and the DNA repair genes X-ray repair cross-complementing group (XRCCs) 1-4, and the environmental factors of smoking, alcohol drinking, and betel quid (BQ) chewing. We employed logistic regression, multifactor dimensionality reduction (MDR), and hierarchical interaction graphs for analyzing gene-gene (G×G) and gene-environment (G×E) interactions. We identified a significantly elevated risk of the XRCC2 rs2040639 heterozygous variant among smokers [adjusted odds ratio (OR) 3.7, 95% confidence interval (CI)=1.1-12.1] and alcohol drinkers [adjusted OR=5.7, 95% CI=1.4-23.2]. The best two-factor based G×G interaction of oral cancer included the XRCC1 rs1799782 and XRCC2 rs2040639 [OR=3.13, 95% CI=1.66-6.13]. For the G×E interaction, the estimated OR of oral cancer for two (drinking-BQ chewing), three (XRCC1-XRCC2-BQ chewing), four (XRCC1-XRCC2-age-BQ chewing), and five factors (XRCC1-XRCC2-age-drinking-BQ chewing) were 32.9 [95% CI=14.1-76.9], 31.0 [95% CI=14.0-64.7], 49.8 [95% CI=21.0-117.7] and 82.9 [95% CI=31.0-221.5], respectively. Taken together, the genotypes of XRCC1 rs1799782 and XRCC2 rs2040639 DNA repair genes appear to be significantly associated with oral cancer. These were enhanced by exposure to certain environmental factors. The observations presented here warrant further research in larger study samples to examine their relevance for routine clinical care in oncology.

  12. Gene-environment interactions in the causation of neural tube defects: folate deficiency increases susceptibility conferred by loss of Pax3 function.

    PubMed

    Burren, Katie A; Savery, Dawn; Massa, Valentina; Kok, Robert M; Scott, John M; Blom, Henk J; Copp, Andrew J; Greene, Nicholas D E

    2008-12-01

    Risk of neural tube defects (NTDs) is determined by genetic and environmental factors, among which folate status appears to play a key role. However, the precise nature of the link between low folate status and NTDs is poorly understood, and it remains unclear how folic acid prevents NTDs. We investigated the effect of folate level on risk of NTDs in splotch (Sp(2)(H)) mice, which carry a mutation in Pax3. Dietary folate restriction results in reduced maternal blood folate, elevated plasma homocysteine and reduced embryonic folate content. Folate deficiency does not cause NTDs in wild-type mice, but causes a significant increase in cranial NTDs among Sp(2)(H) embryos, demonstrating a gene-environment interaction. Control treatments, in which intermediate levels of folate are supplied, suggest that NTD risk is related to embryonic folate concentration, not maternal blood folate concentration. Notably, the effect of folate deficiency appears more deleterious in female embryos than males, since defects are not prevented by exogenous folic acid. Folate-deficient embryos exhibit developmental delay and growth retardation. However, folate content normalized to protein content is appropriate for developmental stage, suggesting that folate availability places a tight limit on growth and development. Folate-deficient embryos also exhibit a reduced ratio of s-adenosylmethionine (SAM) to s-adenosylhomocysteine (SAH). This could indicate inhibition of the methylation cycle, but we did not detect any diminution in global DNA methylation, in contrast to embryos in which the methylation cycle was specifically inhibited. Hence, folate deficiency increases the risk of NTDs in genetically predisposed splotch embryos, probably via embryonic growth retardation.

  13. Gene-environment interactions affect long-term depression (LTD) through changes in dopamine receptor affinity in Snap25 deficient mice

    PubMed Central

    Baca, Michael; Allan, Andrea M.; Partridge, L. Donald; Wilson, Michael C.

    2013-01-01

    Genes and environmental conditions interact in the development of cognitive capacities and each plays an important role in neuropsychiatric disorders such as attention deficit/hyperactivity disorder (ADHD) and schizophrenia. Multiple studies have indicated that the gene for the SNARE protein SNAP-25 is a candidate susceptibility gene for ADHD, as well as schizophrenia, while maternal smoking is a candidate environmental risk factor for ADHD. We utilized mice heterozygous for a Snap25 null allele and deficient in SNAP-25 expression to model genetic effects in combination with prenatal exposure to nicotine to explore genetic and environmental interactions in synaptic plasticity and behavior. We show that SNAP-25 deficient mice exposed to prenatal nicotine exhibit hyperactivity and deficits in social interaction. Using a high frequency stimulus electrophysiological paradigm for long-term depression (LTD) induction, we examined the roles of dopaminergic D2 receptors (D2Rs) and cannabinoid CB1 receptors (CB1Rs), both critical for LTD induction in the striatum. We found that prenatal exposure to nicotine in Snap25 heterozygote null mice produced a deficit in the D2R-dependent induction of LTD, although CB1R regulation of plasticity was not impaired. We also show that prenatal nicotine exposure altered the affinity and/or receptor coupling of D2Rs, but not the number of these receptors in heterozygote null Snap25 mutants. These results refine the observations made in the coloboma mouse mutant, a proposed mouse model of ADHD, and illustrate how gene × environmental influences can interact to perturb neural functions that regulate behavior. PMID:23939223

  14. Commentary: Fundamental problems with candidate gene-by-environment interaction studies - reflections on Moore and Thoemmes (2016).

    PubMed

    Border, Richard; Keller, Matthew C

    2017-03-01

    Moore and Thoemmes elaborate on one particular source of difficulty in the study of candidate gene-by-environment interactions (cG × E): how different biologically plausible configurations of gene-environment covariation can bias estimates of cG × E when not explicitly modeled. However, even if cG × E investigators were able to account for the sources of bias Moore and Thoemmes elaborate, it is unlikely that conventional approaches would yield reliable results. Published cG × E findings to date have generally employed inadequate analytic procedures, have relied on samples orders of magnitude too small to detect plausible effects, and have relied on a particular candidate gene approach that has been unfruitful and largely jettisoned in mainstream genetic analyses of complex traits. Analytic procedures for the study of gene-environment interplay must evolve to meet the challenges that the genetic architecture of complex traits presents, and investigators must collaborate on grander scales if we hope to begin to understand how specific genes and environments combine to affect behavior.

  15. Gene-environment studies: any advantage over environmental studies?

    PubMed

    Bermejo, Justo Lorenzo; Hemminki, Kari

    2007-07-01

    Gene-environment studies have been motivated by the likely existence of prevalent low-risk genes that interact with common environmental exposures. The present study assessed the statistical advantage of the simultaneous consideration of genes and environment to investigate the effect of environmental risk factors on disease. In particular, we contemplated the possibility that several genes modulate the environmental effect. Environmental exposures, genotypes and phenotypes were simulated according to a wide range of parameter settings. Different models of gene-gene-environment interaction were considered. For each parameter combination, we estimated the probability of detecting the main environmental effect, the power to identify the gene-environment interaction and the frequency of environmentally affected individuals at which environmental and gene-environment studies show the same statistical power. The proportion of cases in the population attributable to the modeled risk factors was also calculated. Our data indicate that environmental exposures with weak effects may account for a significant proportion of the population prevalence of the disease. A general result was that, if the environmental effect was restricted to rare genotypes, the power to detect the gene-environment interaction was higher than the power to identify the main environmental effect. In other words, when few individuals contribute to the overall environmental effect, individual contributions are large and result in easily identifiable gene-environment interactions. Moreover, when multiple genes interacted with the environment, the statistical benefit of gene-environment studies was limited to those studies that included major contributors to the gene-environment interaction. The advantage of gene-environment over plain environmental studies also depends on the inheritance mode of the involved genes, on the study design and, to some extend, on the disease prevalence.

  16. Gene-environment interactions on the risk of esophageal cancer among Asian populations with the G48A polymorphism in the alcohol dehydrogenase-2 gene: a meta-analysis.

    PubMed

    Zhang, Long; Jiang, Yingjiu; Wu, Qingcheng; Li, Qiang; Chen, Dan; Xu, Ling; Zhang, Cheng; Zhang, Min; Ye, Ling

    2014-05-01

    The aim of this study is to investigate the gene-environment interactions between the G48A polymorphism in the alcohol dehydrogenase-2 (ADH2) gene and environmental factors in determining the risk of esophageal cancer (EC). A literature search was conducted in the PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar databases to indentify eligible studies published before November 1, 2013. We performed a meta-analysis of 18 case-control studies with a total of 8,906 EC patients and 13,712 controls. The overall analysis suggested that individuals with the GG genotype were associated with a 2.77-fold increased risk of EC, compared with carriers of the GA and AA genotypes. In a stratified analysis by ethnic group, Japanese, Mainland Chinese, and Taiwan Chinese with the GG genotype had a significantly higher risk of EC, compared with Thai and Iranian populations, indicating ethnic variance in EC susceptibility. An analysis of combined effect indicated that GG genotype of ADH2 G48A was associated with the highest risk of EC in heavy drinkers and smokers. A striking difference was found to exist between males and females, showing gender variance for the association between ADH2 G48A and EC risk. This meta-analysis shows that the GG genotype of ADH2 G48A may be associated with an increased risk of EC in Asian populations. In addition, significant gene-environment interactions were found. Heavy drinkers, smokers, and males with the GG genotype may have a higher EC risk. Thus, our results shed new light on the complex gene-environment interactions that exist between environmental factors and ADH2 G48A polymorphism in EC risk.

  17. Genes, Environment, and Human Behavior.

    ERIC Educational Resources Information Center

    Bloom, Mark V.; Cutter, Mary Ann; Davidson, Ronald; Dougherty, Michael J.; Drexler, Edward; Gelernter, Joel; McCullough, Laurence B.; McInerney, Joseph D.; Murray, Jeffrey C.; Vogler, George P.; Zola, John

    This curriculum module explores genes, environment, and human behavior. This book provides materials to teach about the nature and methods of studying human behavior, raise some of the ethical and public policy dilemmas emerging from the Human Genome Project, and provide professional development for teachers. An extensive Teacher Background…

  18. Impact of variation in the BDNF gene on social stress sensitivity and the buffering impact of positive emotions: replication and extension of a gene-environment interaction.

    PubMed

    van Winkel, Mark; Peeters, Frenk; van Winkel, Ruud; Kenis, Gunter; Collip, Dina; Geschwind, Nicole; Jacobs, Nele; Derom, Catherine; Thiery, Evert; van Os, Jim; Myin-Germeys, Inez; Wichers, Marieke

    2014-06-01

    A previous study reported that social stress sensitivity is moderated by the brain-derived-neurotrophic-factor(Val66Met) (BDNF rs6265) genotype. Additionally, positive emotions partially neutralize this moderating effect. The current study aimed to: (i) replicate in a new independent sample of subjects with residual depressive symptoms the moderating effect of BDNF(Val66Met) genotype on social stress sensitivity, (ii) replicate the neutralizing impact of positive emotions, (iii) extend these analyses to other variations in the BDNF gene in the new independent sample and the original sample of non-depressed individuals. Previous findings were replicated in an experience sampling method (ESM) study. Negative Affect (NA) responses to social stress were stronger in "Val/Met" carriers of BDNF(Val66Met) compared to "Val/Val" carriers. Positive emotions neutralized the moderating effect of BDNF(Val66Met) genotype on social stress sensitivity in a dose-response fashion. Finally, two of four additional BDNF SNPs (rs11030101, rs2049046) showed similar moderating effects on social stress-sensitivity across both samples. The neutralizing effect of positive emotions on the moderating effects of these two additional SNPs was found in one sample. In conclusion, ESM has important advantages in gene-environment (GxE) research and may attribute to more consistent findings in future GxE research. This study shows how the impact of BDNF genetic variation on depressive symptoms may be explained by its impact on subtle daily life responses to social stress. Further, it shows that the generation of positive affect (PA) can buffer social stress sensitivity and partially undo the genetic susceptibility.

  19. The impact of exposure-biased sampling designs on detection of gene-environment interactions in case-control studies with potential exposure misclassification.

    PubMed

    Stenzel, Stephanie L; Ahn, Jaeil; Boonstra, Philip S; Gruber, Stephen B; Mukherjee, Bhramar

    2015-05-01

    With limited funding and biological specimen availability, choosing an optimal sampling design to maximize power for detecting gene-by-environment (G-E) interactions is critical. Exposure-enriched sampling is often used to select subjects with rare exposures for genotyping to enhance power for tests of G-E effects. However, exposure misclassification (MC) combined with biased sampling can affect characteristics of tests for G-E interaction and joint tests for marginal association and G-E interaction. Here, we characterize the impact of exposure-biased sampling under conditions of perfect exposure information and exposure MC on properties of several methods for conducting inference. We assess the Type I error, power, bias, and mean squared error properties of case-only, case-control, and empirical Bayes methods for testing/estimating G-E interaction and a joint test for marginal G (or E) effect and G-E interaction across three biased sampling schemes. Properties are evaluated via empirical simulation studies. With perfect exposure information, exposure-enriched sampling schemes enhance power as compared to random selection of subjects irrespective of exposure prevalence but yield bias in estimation of the G-E interaction and marginal E parameters. Exposure MC modifies the relative performance of sampling designs when compared to the case of perfect exposure information. Those conducting G-E interaction studies should be aware of exposure MC properties and the prevalence of exposure when choosing an ideal sampling scheme and method for characterizing G-E interactions and joint effects.

  20. The Dopamine Receptor D4 7-Repeat Allele and Prenatal Smoking in ADHD-Affected Children and Their Unaffected Siblings: No Gene-Environment Interaction

    ERIC Educational Resources Information Center

    Altink, Marieke E.; Arias-Vasquez, Alejandro; Franke, Barbara; Slaats-Willemse, Dorine I. E.; Buschgens, Cathelijne J. M.; Rommelse, Nanda N. J.; Fliers, Ellen A.; Anney, Richard; Brookes, Keeley-Joanne; Chen, Wai; Gill, Michael; Mulligan, Aisling; Sonuga-Barke, Edmund; Thompson, Margaret; Sergeant, Joseph A.; Faraone, Stephen V.; Asherson, Philip; Buitelaar, Jan K.

    2008-01-01

    Background: The dopamine receptor D4 ("DRD4") 7-repeat allele and maternal smoking during pregnancy are both considered as risk factors in the aetiology of attention deficit hyperactivity disorder (ADHD), but few studies have been conducted on their interactive effects in causing ADHD. The purpose of this study is to examine the gene by…

  1. Age at onset of psychotic disorder: cannabis, BDNF Val66Met, and sex-specific models of gene-environment interaction.

    PubMed

    Decoster, Jeroen; van Os, Jim; Kenis, Gunter; Henquet, Cecile; Peuskens, Joseph; De Hert, Marc; van Winkel, Ruud

    2011-04-01

    Discovering modifiable predictors for age at onset may help to identify predictors of transition to psychotic disorder in the "at-risk mental state." Inconsistent effects of sex, BDNF Val66Met (rs6265), and cannabis use on age of onset were previously reported. BDNF Val66Met and cannabis use before illness onset were retrospectively assessed in a sample of 585 patients with schizophrenia and their association with age at onset was evaluated. Cannabis use was significantly associated with earlier age at onset of psychotic disorder (AOP; average difference 2.7 years, P < 0.001), showing dose-response effects with higher frequency and earlier age at first use. There was a weak association between BDNF Val66Met genotype and AOP (difference 1.2 years; P = 0.050). No evidence was found for BDNF × cannabis interaction (interaction χ(2) (1) = 0.65, P = 0.420). However, a significant BDNF × cannabis × sex interaction was found (interaction χ(2) (1) = 4.99, P = 0.026). In female patients, cannabis use was associated with earlier AOP in BDNF Met-carriers (difference 7 years), but not in Val/Val-genotypes. In male patients, cannabis use was associated with earlier AOP irrespective of BDNF Val66Met genotype (difference 1.3 years). BDNF Val66Met genotype in the absence of cannabis use did not influence AOP, neither in female or male patients with psychotic disorder. Complex interactions between cannabis and BDNF may shape age at onset in female individuals at risk of psychotic disorder. No compelling evidence was found that BDNF genotype is associated with age at onset of psychotic disorder in the absence of cannabis use.

  2. Narrative review of genes, environment, and cigarettes.

    PubMed

    Do, Elizabeth; Maes, Hermine

    2016-08-01

    Tobacco use remains the leading cause of preventable death in the US, emphasizing the need to understand which genes and environments are involved in the establishment of cigarette use behaviors. However, to date, no comprehensive review of the influence of genes, the environment, and their interaction on cigarette use exists. This narrative review provides a description of gene variants and environmental factors associated with cigarette use, as well as an overview of studies investigating gene-environment interaction (GxE) in cigarette use. GxE studies of cigarette use have been useful in demonstrating that the influence of genes changes as a function of both the phenotype being measured and the environment. However, it is difficult to determine how the effect of genes contributing to different phenotypes of cigarette use changes as a function of the environment. This suggests the need for more studies of GxE, to parse out the effects of genes and the environment across the development of cigarette use phenotypes, which may help to inform potential prevention and intervention efforts aimed at reducing the prevalence of cigarette use. Key Messages No comprehensive reviews of the influence of genes, the environment, and their interaction on cigarette use exist currently. The influence of genes may change as a function of the environment and the phenotype being measured. It is difficult to determine how the effect of genes contributing to different phenotypes of cigarette use changes according to environmental context, suggesting the need for more studies of gene-environment interaction related to cigarette use to parse out effects.

  3. Confluence of Genes, Environment, Development, and Behavior in a Post-GWAS World

    PubMed Central

    Vrieze, Scott I.; Iacono, William G.; McGue, Matt

    2012-01-01

    This article serves to outline a research paradigm to investigate main effects and interactions of genes, environment, and development on behavior and psychiatric illness. We provide a historical context for candidate gene studies and genome-wide association studies, including benefits, limitations, and expected payoff. Using substance use and abuse as our driving example, we then turn to the importance of etiological psychological theory in guiding genetic, environmental, and developmental research, as well as the utility of refined phenotypic measures, such as endophenotypes, in the pursuit of etiological understanding and focused tests of genetic and environmental associations. Phenotypic measurement has received considerable attention and is informed by psychometrics, while the environment remains relatively poorly measured and is often confounded with genetic effects (i.e., gene-environment correlation). Genetically-informed designs which—thanks to ever cheaper genotyping—are no longer are limited to twin and adoption studies, are required to understand environmental influences. Finally, we outline the vast amount of individual differences in structural genomic variation, most of which remains to be leveraged in genetic association tests. While the genetic data can be burdensomely massive (tens of millions of variants per person), we argue that improved understanding of genomic structure and function will provide investigators with new tools to test specific a priori hypotheses derived from etiological psychological theory, much like current candidate gene research, but with less confusion and more payoff than candidate gene research has to date. PMID:23062291

  4. Current research trends in early life stress and depression: review of human studies on sensitive periods, gene-environment interactions, and epigenetics.

    PubMed

    Heim, Christine; Binder, Elisabeth B

    2012-01-01

    Early life stress, such as childhood abuse, neglect and loss, is a well established major risk factor for developing depressive disorders later in life. We here summarize and discuss current developments in human research regarding the link between early life stress and depression. Specifically, we review the evidence for the existence of sensitive periods for the adverse effects of early life stress in humans. We further review the current state of knowledge regarding gene×environment (G×E) interactions in the effects of early life stress. While multiple genes operate in multiple environments to induce risk for depression after early life stress, these same genes also seem to enhance the beneficial effects of a positive early environment. Also, we discuss the epigenetic mechanisms that might underlie these G×E interactions. Finally, we discuss the potential importance of identifying sensitive time periods of opportunity, as well as G×E interactions and epigenetic mechanisms, for early interventions that might prevent or reverse the detrimental outcomes of early life stress and its transmission across generations.

  5. Gene-environment interaction between DRD4 7-repeat VNTR and early child-care experiences predicts self-regulation abilities in prekindergarten.

    PubMed

    Berry, Daniel; McCartney, Kathleen; Petrill, Stephen; Deater-Deckard, Kirby; Blair, Clancy

    2014-04-01

    Intervention studies indicate that children's early child-care experiences can be leveraged to foster their development of effective self-regulation skills. It is less clear whether typical child-care experiences play a similar role. In addition, evidence suggests that children with a common variant of the DRD4 gene (48-bp VNTR, 7-repeat) may be more sensitive to their experiences than those without this variant. Using data from the NICHD Study of Early Child Care and Youth Development, we considered the degree to which children's early child-care experiences-quantity, quality, and type-were associated with their attention and self-regulation abilities in prekindergarten, and, in particular, whether these relations were conditional on DRD4 genotype. G × E interactions were evident across multiple neuropsychological and observational measures of children's attention and self-regulation abilities. Across most outcome measures, DRD4 7+ children spending fewer hours in child care showed more effective attention/self-regulation abilities. For those without a copy of the DRD4 7-repeat allele, such associations were typically null. The results for child-care quality and type indicated no interactions with genotype; the main-effect associations were somewhat inconsistent.

  6. CYP1A1 genetic polymorphism and polycyclic aromatic hydrocarbons on pulmonary function in the elderly: haplotype-based approach for gene-environment interaction.

    PubMed

    Choi, Yoon-Hyeong; Kim, Jin Hee; Hong, Yun-Chul

    2013-08-29

    Lung function may be impaired by environmental pollutants not only acting alone, but working with genetic factors as well. Few epidemiologic studies have been conducted to explore the interplay of polycyclic aromatic hydrocarbons (PAHs) exposure and genetic polymorphism on lung function in the elderly. For genetic polymorphism, haplotype is considered a more informative unit than single nucleotide polymorphism markers. Therefore, we examined the role of haplotype based-CYP1A1 polymorphism in the effect of PAHs exposure on lung function in 422 participants from a community-based panel of elderly adults in Seoul, Korea. Linear mixed effect models were fit to evaluate the association of PAH exposure markers (urinary 1-hydroxypyrene and 2-naphthol) with FVC, FEV₁, FEV₁/FVC, and FEF₂₅₋₇₅, and then the interaction with CYP1A1 haplotype constructed from three single nucleotide polymorphisms of the gene (rs4646421/rs4646422/rs1048943). Urinary 1-hydroxypyrene levels were inversely associated with FEV₁/FVC (p<0.05), whereas urinary 2-naphthol levels failed to show associations with lung function. Urinary 1-hydroxypyrene was significantly associated with decrease in FEV₁/FVC among participants with rs4646421 variants (CT+TT), rs4646422 wild-type (GG), and rs1048943 wild-type (AA). At least one TGA haplotype predicted a 0.88% (95% confidence interval, 0.31-1.45%) reduction in FEV₁/FVC with an interquartile range increase in 1-hydroxypyrene, whereas no relationship was observed in participants without TGA haplotype (p for interaction=0.045). Similar patterns were also observed in FEF₂₅₋₇₅. We did not find any main effects of CYP1A1 genetic polymorphisms on lung functions. Our findings suggest that PAH exposure producing 1-hydroxypyrene as a metabolite compromises lung function in the elderly, and that haplotype-based CYP1A1 polymorphism modifies the risk.

  7. [Gene-environment interaction for the HIF1-A 1772C>T polymorphisms and cigarette smoking increase susceptibility to abdominal aortic aneurysm].

    PubMed

    Strauss, Ewa; Waliszewski, Krzysztof; Oszkinis, Grzegorz; Staniszewski, Ryszard

    2012-01-01

    Pathological changes in the vascular vessels, such as the presence of atherosclerotic plaques or aneurysmal dilatations, are associated with the local conditions of ischemial/hypoxia. Polymorphisms in the HIF1A gene, encoding an oxygen-regulated HIF-1 subunit (HIF-1a), determine inter-individual variability in vascular response to hypoxia. Stimulation of selected pathways, related to this response (i.e. angiogenesis) is impaired by cigarette smoke exposure. In this work, we examined the associations between 1772C>T polymorphism (rs11549465) located in the coding region of HIF1A gene (Pro582-Ser), smoking and the occurrence of abdominal aortic aneurysm (AAA). Moreover, the relations of these factors with the presence of peripheral arterial disease (PAD) in patients with AAA were studied. The case-control study was designed, in which a group of 1060 Caucasian subjects: 535 AAA patients and 525 controls, was analyzed. Data regarding smoking status were collected using questionnaire. Past and current smokers were analyzed together. In the group of 220 AAA subjects the coexistence of PAD was characterized. HIF-1A genotypes were assessed by PCR-RFLP method. Genetic-environmental interactions were examined by a two-by-four tables. In these analyzes, logistic regression models were used to adjusting for the relevant covariates. The frequency of HIF1A 1772T allele in AAA group (0,067) was similar to that observed in the control group (0,070). In the analyses of genetic-environmental interactions was observed that the co-occurrence of HIF1A 1772CT and TT genotypes and exposure to tobacco smoke has a strong multiplicative effect on the susceptibility to the AAA development. The age and gender adjusted odds ratios (ORs) were: 7,6 for smoking alone (p<0,0001); 0,65 for 1772CT and TT genotypes alone (p=0,3) and 14,4for smoking plus 1772CT and TT genotypes (p<0,0001). The proportion of smokers carrying 1772T allele was higher among patients with advanced form of PAD (femoro

  8. The influence of gene-environment interactions on GHR and IGF-1 expression and their association with growth in brook charr, Salvelinus fontinalis (Mitchill)

    PubMed Central

    Côté, Guillaume; Perry, Guy; Blier, Pierre; Bernatchez, Louis

    2007-01-01

    Background Quantitative reaction norm theory proposes that genotype-by-environment interaction (GxE) results from inter-individual differences of expression in adaptive suites of genes in distinct environments. However, environmental norms for actual gene suites are poorly documented. In this study, we investigated the effects of GxE interactions on levels of gene transcription and growth by documenting the impact of rearing environment (freshwater vs. saltwater), sex and genotypic (low vs. high estimated breeding value EBV) effects on the transcription level of insulin-like growth factor (IGF-1) and growth hormone receptor (GHR) in brook charr (Salvelinus fontinalis). Results Males grew faster than females (μ♀ = 1.20 ± 0.07 g·d-1, μ♂ = 1.46 ± 0.06 g·d-1) and high-EBV fish faster than low-EBV fish (μLOW = 0.97 ± 0.05 g·d-1, μHIGH = 1.58 ± 0.07 g·d-1; p < 0.05). However, growth was markedly lower in saltwater-reared fish than freshwater sibs (μFW = 1.52 ± 0.07 g·d-1, μSW = 1.15 ± 0.06 g·d-1), yet GHR mRNA transcription level was significantly higher in saltwater than in freshwater (μSW = 0.85 ± 0.05, μFW = 0.61 ± 0.05). The ratio of actual growth to units in assayed mRNA ('individual transcript efficiency', iTE; g·d-1·u-1) also differed among EBV groups (μLOW = 2.0 ± 0.24 g·d-1·u-1; μHIGH = 3.7 ± 0.24 g·d-1·u-1) and environments (μSW = 2.0 ± 0.25 g·d-1·u-1; μFW = 3.7 ± 0.25 g·d-1·u-1) for GHR. Males had a lower iTE for GHR than females (μ♂ = 2.4 ± 0.29 g·d-1·u-1; μ♀ = 3.1 ± 0.23 g·d-1·u-1). There was no difference in IGF-1 transcription level between environments (p > 0.7) or EBV groups (p > 0.15) but the level of IGF-1 was four times higher in males than females (μ♂ = 2.4 ± 0.11, μ♀ = 0.58 ± 0.09; p < 0.0001). We detected significant sexual differences in iTE (μ♂ = 1.3 ± 0.59 g·d-1·u-1; μ♀ = 3.9 ± 0.47 g·d-1·u-1), salinities (μSW = 2.3 ± 0.52 g·d-1·u-1; μFW = 3.7 ± 0.53 g·d-1·u-1

  9. Can genes play a role in explaining frequent job changes? An examination of gene-environment interaction from human capital theory.

    PubMed

    Chi, Wei; Li, Wen-Dong; Wang, Nan; Song, Zhaoli

    2016-07-01

    This study examined how a dopamine genetic marker, DRD4 7 Repeat allele, interacted with early life environmental factors (i.e., family socioeconomic status, and neighborhood poverty) to influence job change frequency in adulthood using a national representative sample from the United States. The dopamine gene played a moderating role in the relationship between early life environments and later job change behaviors, which was meditated through educational achievement. In particular, higher family socioeconomic status was associated with higher educational achievement, and thereafter higher frequency of voluntary job changes and lower frequency of involuntary job changes; such relationships were stronger (i.e., more positive or negative) for individuals with more DRD4 7R alleles. In contrast, higher neighborhood poverty was associated with lower educational achievement, and thereafter lower frequency of voluntary job change and higher frequency of involuntary job change; such relationships were again stronger (i.e., more positive or negative) for individuals with more DRD4 7R alleles. The results demonstrated that molecular genetics using DNA information, along with early life environmental factors, can bring new insights to enhance our understanding of job change frequency in individuals' early career development. (PsycINFO Database Record

  10. Witnessing Substance Use and Same-Day Antisocial Behavior among At-Risk Adolescents: Gene-Environment Interaction in a 30-Day Ecological Momentary Assessment Study

    PubMed Central

    Russell, Michael A.; Wang, Lin; Odgers, Candice L.

    2017-01-01

    Many young adolescents are embedded in neighborhoods, schools, and homes where alcohol and drugs are frequently used. However, little is known about (a) how witnessing others’ substance use affects adolescents in their daily lives and (b) which adolescents will be most affected. The current study used ecological momentary assessment with 151 young adolescents (ages 11–15) to examine the daily association between witnessing substance use and antisocial behavior across 38 consecutive days. Results from multilevel logistic regression models indicated that adolescents were more likely to engage in antisocial behavior on days when they witnessed others using substances—an association that held both when substance use was witnessed inside the home as well as outside the home (e.g., at school or in their neighborhoods). A significant gene-by-environment interaction suggested that the same-day association between witnessing substance use and antisocial behavior was significantly stronger among adolescents with, versus without, with the DRD4-7R allele. The implications of our findings for theory and research related to adolescent antisocial behavior are discussed. PMID:26648004

  11. Nature, nurture and neurology: gene-environment interactions in neurodegenerative disease. FEBS Anniversary Prize Lecture delivered on 27 June 2004 at the 29th FEBS Congress in Warsaw.

    PubMed

    Spires, Tara L; Hannan, Anthony J

    2005-05-01

    Neurodegenerative disorders, such as Huntington's, Alzheimer's, and Parkinson's diseases, affect millions of people worldwide and currently there are few effective treatments and no cures for these diseases. Transgenic mice expressing human transgenes for huntingtin, amyloid precursor protein, and other genes associated with familial forms of neurodegenerative disease in humans provide remarkable tools for studying neurodegeneration because they mimic many of the pathological and behavioural features of the human conditions. One of the recurring themes revealed by these various transgenic models is that different diseases may share similar molecular and cellular mechanisms of pathogenesis. Cellular mechanisms known to be disrupted at early stages in multiple neurodegenerative disorders include gene expression, protein interactions (manifesting as pathological protein aggregation and disrupted signaling), synaptic function and plasticity. Recent work in mouse models of Huntington's disease has shown that enriching the environment of transgenic animals delays the onset and slows the progression of Huntington's disease-associated motor and cognitive symptoms. Environmental enrichment is known to induce various molecular and cellular changes in specific brain regions of wild-type animals, including altered gene expression profiles, enhanced neurogenesis and synaptic plasticity. The promising effects of environmental stimulation, demonstrated recently in models of neurodegenerative disease, suggest that therapy based on the principles of environmental enrichment might benefit disease sufferers and provide insight into possible mechanisms of neurodegeneration and subsequent identification of novel therapeutic targets. Here, we review the studies of environmental enrichment relevant to some major neurodegenerative diseases and discuss their research and clinical implications.

  12. Gene-environment interaction for polymorphisms in ataxia telangiectasia-mutated gene and radiation exposure in carcinogenesis: results from two literature-based meta-analyses of 27120 participants

    PubMed Central

    Wu, Di; He, Hua; Wang, Mengmeng; Ge, Tingwen; Liu, Yudi; Tian, Huimin; Cui, Jiuwei; Jia, Lin; Wan, Ziqiang; Han, Fujun

    2016-01-01

    Purpose We conducted two meta-analyses of ATM genetic polymorphisms and cancer risk in individuals with or without radiation exposure to determine whether there was a joint effect between the ATM gene and radiation exposure in carcinogenesis. Results rs1801516, which was the only ATM polymorphism investigated by more than 3 studies of radiation exposure, was eligible for the present study. The meta-analysis of 23333 individuals without radiation exposure from 24 studies showed no association between the rs1801516 polymorphism and cancer risk, without heterogeneity across studies. The meta-analysis of 3787 individuals with radiation exposure from 6 studies showed a significant association between the rs1801516 polymorphism and a decreased cancer risk, with heterogeneity across studies. There was a borderline-significant difference between the ORs of the two meta-analyses (P = 0.066), and the difference was significant when only Caucasians were included (P = 0.011). Materials and methods Publications were identified by searching PubMed, EMBASE, Web of Science, and CNKI databases. Odds ratios (ORs) were calculated to estimate the association between ATM genetic polymorphisms and cancer risk. Tests of interaction were used to compare differences between the ORs of the two meta-analyses. Conclusions Our meta-analyses confirmed the presence of a gene-environment interaction between the rs1801516 polymorphism and radiation exposure in carcinogenesis, whereas no association was found between the rs1801516 polymorphism and cancer risk for individuals without radiation exposure. The heterogeneity observed in the meta-analysis of individuals with radiation exposure might be due to gene-ethnicity or gene-gene interactions. Further studies are needed to elucidate sources of the heterogeneity. PMID:27764772

  13. Gene-Environment Interplay between Peer Rejection and Depressive Behavior in Children

    ERIC Educational Resources Information Center

    Brendgen, Mara; Vitaro, Frank; Boivin, Michel; Girard, Alain; Bukowski, William M.; Dionne, Ginette; Tremblay, Richard E.; Perusse, Daniel

    2009-01-01

    Background: Genetic risk for depressive behavior may increase the likelihood of exposure to environmental stressors (gene-environment correlation, rGE). By the same token, exposure to environmental stressors may moderate the effect of genes on depressive behavior (gene-environment interaction, GxE). Relating these processes to a peer-related…

  14. Gene-Environment Interplay between Number of Friends and Prosocial Leadership Behavior in Children

    ERIC Educational Resources Information Center

    Rivizzigno, Alessandra S.; Brendgen, Mara; Feng, Bei; Vitaro, Frank; Dionne, Ginette; Tremblay, Richard E.; Boivin, Michel

    2014-01-01

    Enriched environments may moderate the effect of genetic factors on prosocial leadership (gene-environment interaction, G × E). However, positive environmental experiences may also themselves be influenced by a genetic disposition for prosocial leadership (gene-environment correlation, rGE). Relating these processes to friendships, the present…

  15. Gene-Environment Processes Linking Aggression, Peer Victimization, and the Teacher-Child Relationship

    ERIC Educational Resources Information Center

    Brendgen, Mara; Boivin, Michel; Dionne, Ginette; Barker, Edward D.; Vitaro, Frank; Girard, Alain; Tremblay, Richard; Perusse, Daniel

    2011-01-01

    Aggressive behavior in middle childhood is at least partly explained by genetic factors. Nevertheless, estimations of simple effects ignore possible gene-environment interactions (G x E) or gene-environment correlations (rGE) in the etiology of aggression. The present study aimed to simultaneously test for G x E and rGE processes between…

  16. Gene-environment interplay between cannabis and psychosis.

    PubMed

    Henquet, Cécile; Di Forti, Marta; Morrison, Paul; Kuepper, Rebecca; Murray, Robin M

    2008-11-01

    Cannabis use is considered a contributory cause of schizophrenia and psychotic illness. However, only a small proportion of cannabis users develop psychosis. This can partly be explained by the amount and duration of the consumption of cannabis and by its strength but also by the age at which individuals are first exposed to cannabis. Genetic factors, in particular, are likely to play a role in the short- and the long-term effects cannabis may have on psychosis outcome. This review will therefore consider the interplay between genes and exposure to cannabis in the development of psychotic symptoms and schizophrenia. Studies using genetic, epidemiological, experimental, and observational techniques will be discussed to investigate gene-environment correlation gene-environment interaction, and higher order interactions within the cannabis-psychosis association. Evidence suggests that mechanisms of gene-environment interaction are likely to underlie the association between cannabis and psychosis. In this respect, multiple variations within multiple genes--rather than single genetic polymorphisms--together with other environmental factors (eg, stress) may interact with cannabis to increase the risk of psychosis. Further research on these higher order interactions is needed to better understand the biological pathway by which cannabis use, in some individuals, may cause psychosis in the short- and long term.

  17. Community-Based Participatory Research and Gene-Environment Interaction Methodologies Addressing Environmental Justice among Migrant and Seasonal Farmworker Women and Children in Texas: “From Mother to Child Project”

    PubMed Central

    Hernández-Valero, María A.; Herrera, Angelica P.; Zahm, Sheila H.; Jones, Lovell A.

    2013-01-01

    The “From Mother to Child Project” is a molecular epidemiological study that employs a community- based participatory research (CBPR) approach and gene-environment interaction research to address environmental justice in migrant and seasonal farmworker (MSF) women and children of Mexican origin home-based in Baytown and La Joya, Texas. This paper presents the background and rationale for the study and describes the study design and methodology. Preliminary data showed that MSF women and children in Texas have measurable levels of pesticides in their blood and urine, some of which were banned in the United States decades ago and are possible human carcinogens. Polymorphisms in genes involved in chemical detoxification and DNA repair have been associated with susceptibility to genetic damage and cancer development in populations exposed to environmental toxins. The “From Mother to Child Project” is testing three hypotheses: (1) MSF women and children who are occupationally exposed to pesticides are at higher risk for DNA damage than are non-exposed women and children. (2) Both, the extent of pesticide exposure and type of polymorphisms in chemical detoxification and DNA repair genes contribute to the extent of DNA damage observed in study participants. (3) The mutagenic potency levels measured in the organic compounds extracted from the urine and serum of study participants will correlate with the total concentrations of pesticides and with the measured DNA damage in study participants. The study will enroll 800 participants: 200 MSF mother-child pairs; 200 children (one per family) whose parents have never worked in agriculture, matched with the MSF children by ethnicity, age ± 2 years, gender, and city of residence; and these children’s mothers. Personal interviews with the mothers are used to gather data for both mothers and children on sociodemographic characteristics; pesticide exposure at work and home; medical and reproductive history; dietary

  18. A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations.

    PubMed

    Rai, Rajani; Kim, Jong Joo; Misra, Sanjeev; Kumar, Ashok; Mittal, Balraj

    2015-11-25

    Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR) and Classification and Regression Tree Analysis (CRT) to investigate the gene-gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634); FAS (rs2234767); FASL (rs763110); DCC (rs2229080, rs4078288, rs7504990, rs714); PSCA (rs2294008, rs2978974); ADRA2A (rs1801253); ADRB1 (rs1800544); ADRB3 (rs4994); CYP17 (rs2486758)) involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634), DCC (rs714, rs2229080, rs4078288) and ADRB3 (rs4994) polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994) to be crucial candidate in GBC susceptibility that may act either alone (p < 0.0001, CVC = 10/10) or in combination with DCC (rs714 and rs2229080, p < 0.0001, CVC = 9/10). Our CRT results are in agreement with the above findings. Further, in-silico results of studied SNPs advocated their role in splicing, transcriptional and/or protein coding regulation. Overall, our result suggested complex interactions amongst the studied SNPs and ADRB3 rs4994 as candidate influencing GBC susceptibility.

  19. A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations

    PubMed Central

    Rai, Rajani; Kim, Jong Joo; Misra, Sanjeev; Kumar, Ashok; Mittal, Balraj

    2015-01-01

    Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR) and Classification and Regression Tree Analysis (CRT) to investigate the gene–gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634); FAS (rs2234767); FASL (rs763110); DCC (rs2229080, rs4078288, rs7504990, rs714); PSCA (rs2294008, rs2978974); ADRA2A (rs1801253); ADRB1 (rs1800544); ADRB3 (rs4994); CYP17 (rs2486758)) involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634), DCC (rs714, rs2229080, rs4078288) and ADRB3 (rs4994) polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994) to be crucial candidate in GBC susceptibility that may act either alone (p < 0.0001, CVC = 10/10) or in combination with DCC (rs714 and rs2229080, p < 0.0001, CVC = 9/10). Our CRT results are in agreement with the above findings. Further, in-silico results of studied SNPs advocated their role in splicing, transcriptional and/or protein coding regulation. Overall, our result suggested complex interactions amongst the studied SNPs and ADRB3 rs4994 as candidate influencing GBC susceptibility. PMID:26602921

  20. The Interactive Candidate Assessment Tool: A New Way to Interview Residents.

    PubMed

    Platt, Michael P; Akhtar-Khavari, Vafa; Ortega, Rafael; Schneider, Jeffrey I; Fineberg, Tabitha; Grundfast, Kenneth M

    2017-04-01

    The purpose of the residency interview is to determine the extent to which a well-qualified applicant is a good fit with a residency program. However, questions asked during residency interviews tend to be standard and repetitive, and they may not elicit information that best differentiates one applicant from another. The iCAT (interactive Candidate Assessment Tool) is a novel interview instrument that allows both interviewers and interviewees to learn about each other in a meaningful way. The iCAT uses a tablet computer to enable the candidate to select questions from an array of video and nonvideo vignettes. Vignettes include recorded videos regarding some aspect of the program, while other icons include questions within recognizable categories. Postinterview surveys demonstrated advantages over traditional interview methods, with 93% agreeing that it was an innovative and effective tool for conducting residency program interviews. The iCAT for residency interviews is a technological advancement that facilitates in-depth candidate assessment.

  1. Enhancing Extraction of Drug-Drug Interaction from Literature Using Neutral Candidates, Negation, and Clause Dependency

    PubMed Central

    Bokharaeian, Behrouz; Diaz, Alberto; Chitsaz, Hamidreza

    2016-01-01

    Motivation Supervised biomedical relation extraction plays an important role in biomedical natural language processing, endeavoring to obtain the relations between biomedical entities. Drug-drug interactions, which are investigated in the present paper, are notably among the critical biomedical relations. Thus far many methods have been developed with the aim of extracting DDI relations. However, unfortunately there has been a scarcity of comprehensive studies on the effects of negation, complex sentences, clause dependency, and neutral candidates in the course of DDI extraction from biomedical articles. Results Our study proposes clause dependency features and a number of features for identifying neutral candidates as well as negation cues and scopes. Furthermore, our experiments indicate that the proposed features significantly improve the performance of the relation extraction task combined with other kernel methods. We characterize the contribution of each category of features and finally conclude that neutral candidate features have the most prominent role among all of the three categories. PMID:27695078

  2. Dissecting cause and effect in the pathogenesis of psychiatric disorders: genes, environment and behaviour.

    PubMed

    Gray, Laura; Hannan, Anthiny J

    2007-08-01

    It has long been established that the development of psychiatric illness results from a complex interplay between genetic and environmental factors. Postmortem and genetic linkage studies have identified a number of promising candidate genes which have been reinforced by replication and functional studies. However, the fact that concordance rates for monozygotic twins rarely approach 100% highlights the involvement of environmental factors. Whilst epidemiological studies of psychiatric cohorts have demonstrated potential risk factors, such studies are clearly limited and in many cases the potential mechanism linking a given risk factor with pathogenesis remains unclear. A very powerful method of elucidating the mechanisms underlying gene-environment interactions is the use of appropriate animal models of psychiatric pathology. Whilst animals cannot be used to map the entire complexity of diseases such as schizophrenia, dissecting the symptom profile into more simply encapsulated traits or endophenotypes has proved to be a successful approach. Such endophenotypes provide a measurable link between aetiological factors and phenotypic outcome. Given the potential for the careful control and modification of an experimental animal's environment, the combination of studies of candidate genes with investigations of environmental factors is an effective heuristic tool, allowing examination of behavioural endophenotypes in conjunction with cellular and molecular outcomes. This review will consider the extant genetic, molecular, pharmacological and lesion-based models of psychiatric disorders, and the relevant methods of environmental manipulation appearing in the literature. We will discuss studies where such models have been combined, and the potential for future experimentation in this area.

  3. Gene-Environment-Wide Association Studies: Emerging Approaches

    PubMed Central

    Thomas, Duncan

    2010-01-01

    Despite the yield of recent genome-wide association (GWA) studies, the identified variants explain only a small proportion of the heritability of most complex diseases. This unexplained heritability could be partly due to gene-environment (G×E) interactions or more complex pathways involving multiple genes and exposures. This article provides a tutorial on the available epidemiological designs and statistical analysis approaches for studying specific G×E interactions and choosing the most appropriate methods. I discuss the approaches that are being developed to study entire pathways and available techniques for mining interactions in GWA data. I also explore approaches to marrying hypothesis-driven pathway-based approaches with “agnostic” GWA studies. PMID:20212493

  4. Identifying Novel Candidate Genes Related to Apoptosis from a Protein-Protein Interaction Network

    PubMed Central

    Wang, Baoman; Yuan, Fei; Kong, Xiangyin; Hu, Lan-Dian; Cai, Yu-Dong

    2015-01-01

    Apoptosis is the process of programmed cell death (PCD) that occurs in multicellular organisms. This process of normal cell death is required to maintain the balance of homeostasis. In addition, some diseases, such as obesity, cancer, and neurodegenerative diseases, can be cured through apoptosis, which produces few side effects. An effective comprehension of the mechanisms underlying apoptosis will be helpful to prevent and treat some diseases. The identification of genes related to apoptosis is essential to uncover its underlying mechanisms. In this study, a computational method was proposed to identify novel candidate genes related to apoptosis. First, protein-protein interaction information was used to construct a weighted graph. Second, a shortest path algorithm was applied to the graph to search for new candidate genes. Finally, the obtained genes were filtered by a permutation test. As a result, 26 genes were obtained, and we discuss their likelihood of being novel apoptosis-related genes by collecting evidence from published literature. PMID:26543496

  5. Effects of the Family Environment: Gene-Environment Interaction and Passive Gene-Environment Correlation

    ERIC Educational Resources Information Center

    Price, Thomas S.; Jaffee, Sara R.

    2008-01-01

    The classical twin study provides a useful resource for testing hypotheses about how the family environment influences children's development, including how genes can influence sensitivity to environmental effects. However, existing statistical models do not account for the possibility that children can inherit exposure to family environments…

  6. Interaction of Sr-90 with site candidate soil for demonstration disposal facility at Serpong

    SciTech Connect

    Setiawan, Budi; Mila, Oktri; Safni

    2014-03-24

    Interaction of radiostrontium (Sr-90) with site candidate soil for demonstration disposal facility to be constructed in the near future at Serpong has been done. This activity is to anticipate the interim storage facility at Serpong nuclear area becomes full off condition, and show to the public how radioactive waste can be well managed with the existing technology. To ensure that the location is save, a reliability study of site candidate soil becomes very importance to be conducted through some experiments consisted some affected parameters such as contact time, effect of ionic strength, and effect of Sr{sup +} ion in solution. Radiostrontium was used as a tracer on the experiments and has role as radionuclide reference in low-level radioactive waste due to its long half-live and it's easy to associate with organism in nature. So, interaction of radiostrontium and soil samples from site becomes important to be studied. Experiment was performed in batch method, and soil sample-solution containing radionuclide was mixed in a 20 ml of PE vial. Ratio of solid: liquid was 10{sup −2} g/ml. Objective of the experiment is to collect the specific characteristics data of radionuclide sorption onto soil from site candidate. Distribution coefficient value was used as indicator where the amount of initial and final activities of radiostrontium in solution was compared. Result showed that equilibrium condition was reached after contact time 10 days with Kd values ranged from 1600-2350 ml/g. Increased in ionic strength in solution made decreased of Kd value into soil sample due to competition of background salt and radiostrontium into soil samples, and increased in Sr ion in solution caused decreased of Kd value in soil sample due to limitation of sorption capacity in soil samples. Fast condition in saturated of metal ion into soil samples was reached due to a simple reaction was occurred.

  7. Interaction of Sr-90 with site candidate soil for demonstration disposal facility at Serpong

    NASA Astrophysics Data System (ADS)

    Setiawan, Budi; Mila, Oktri; Safni

    2014-03-01

    Interaction of radiostrontium (Sr-90) with site candidate soil for demonstration disposal facility to be constructed in the near future at Serpong has been done. This activity is to anticipate the interim storage facility at Serpong nuclear area becomes full off condition, and show to the public how radioactive waste can be well managed with the existing technology. To ensure that the location is save, a reliability study of site candidate soil becomes very importance to be conducted through some experiments consisted some affected parameters such as contact time, effect of ionic strength, and effect of Sr+ ion in solution. Radiostrontium was used as a tracer on the experiments and has role as radionuclide reference in low-level radioactive waste due to its long half-live and it's easy to associate with organism in nature. So, interaction of radiostrontium and soil samples from site becomes important to be studied. Experiment was performed in batch method, and soil sample-solution containing radionuclide was mixed in a 20 ml of PE vial. Ratio of solid: liquid was 10-2 g/ml. Objective of the experiment is to collect the specific characteristics data of radionuclide sorption onto soil from site candidate. Distribution coefficient value was used as indicator where the amount of initial and final activities of radiostrontium in solution was compared. Result showed that equilibrium condition was reached after contact time 10 days with Kd values ranged from 1600-2350 ml/g. Increased in ionic strength in solution made decreased of Kd value into soil sample due to competition of background salt and radiostrontium into soil samples, and increased in Sr ion in solution caused decreased of Kd value in soil sample due to limitation of sorption capacity in soil samples. Fast condition in saturated of metal ion into soil samples was reached due to a simple reaction was occurred.

  8. Chromatin interactions and candidate genes at ten prostate cancer risk loci

    PubMed Central

    Du, Meijun; Tillmans, Lori; Gao, Jianzhong; Gao, Ping; Yuan, Tiezheng; Dittmar, Rachel L; Song, Wei; Yang, Yuehong; Sahr, Natasha; Wang, Tao; Wei, Gong-Hong; Thibodeau, Stephen N.; Wang, Liang

    2016-01-01

    Genome-wide association studies have identified more than 100 common single nucleotide polymorphisms (SNPs) that are associated with prostate cancer risk. However, the vast majority of these SNPs lie in noncoding regions of the genome. To test whether these risk SNPs regulate their target genes through long-range chromatin interactions, we applied capture-based 3C sequencing technology to investigate possible cis-interactions at ten prostate cancer risk loci in six cell lines. We identified significant physical interactions between risk regions and their potential target genes including CAPG at 2p11.2, C2orf43 at 2p24.1, RFX6 at 6q22.1, NFASC at 1q32.1, MYC at 8q24.1 and AGAP7P at 10q11.23. Most of the interaction peaks were co-localized to regions of active histone modification and transcription factor binding sites. Expression quantitative trait locus (eQTL) analysis showed suggestive eQTL signals at rs1446669, rs699664 and rs1078004 for CAPG (p < 0.004), rs13394027 for C2orf43 (p = 2.25E-27), rs10993994 and rs4631830 for AGAP7P (p < 8.02E-5). Further analysis revealed an enhancer activity at genomic region surrounding rs4631830 which was expected to disrupt HOXB-like DNA binding affinity. This study identifies a set of candidate genes and their potential regulatory variants, and provides additional evidence showing the role of long-range chromatin interactions in prostate cancer etiology. PMID:26979803

  9. Genes, environments, and developmental research: methods for a multi-site study of early substance abuse.

    PubMed

    Costello, E Jane; Eaves, Lindon; Sullivan, Patrick; Kennedy, Martin; Conway, Kevin; Adkins, Daniel E; Angold, A; Clark, Shaunna L; Erkanli, Alaattin; McClay, Joseph L; Copeland, William; Maes, Hermine H; Liu, Youfang; Patkar, Ashwin A; Silberg, Judy; van den Oord, Edwin

    2013-04-01

    The importance of including developmental and environmental measures in genetic studies of human pathology is widely acknowledged, but few empirical studies have been published. Barriers include the need for longitudinal studies that cover relevant developmental stages and for samples large enough to deal with the challenge of testing gene-environment-development interaction. A solution to some of these problems is to bring together existing data sets that have the necessary characteristics. As part of the National Institute on Drug Abuse-funded Gene-Environment-Development Initiative, our goal is to identify exactly which genes, which environments, and which developmental transitions together predict the development of drug use and misuse. Four data sets were used of which common characteristics include (1) general population samples, including males and females; (2) repeated measures across adolescence and young adulthood; (3) assessment of nicotine, alcohol, and cannabis use and addiction; (4) measures of family and environmental risk; and (5) consent for genotyping DNA from blood or saliva. After quality controls, 2,962 individuals provided over 15,000 total observations. In the first gene-environment analyses, of alcohol misuse and stressful life events, some significant gene-environment and gene-development effects were identified. We conclude that in some circumstances, already collected data sets can be combined for gene-environment and gene-development analyses. This greatly reduces the cost and time needed for this type of research. However, care must be taken to ensure careful matching across studies and variables.

  10. Genes, environments, and developmental GEWIS: Methods for a multi-site study of early substance abuse

    PubMed Central

    Costello, E. J.; Eaves, Lindon; Sullivan, Patrick; Kennedy, Martin; Conway, Kevin; Adkins, Daniel E.; Angold, A.; Clark, Shaunna L; Erkanli, Alaattin; McClay, Joseph L; Copeland, William; Maes, Hermine H.; Liu, Youfang; Patkar, Ashwin A.; Silberg, Judy; van den Oord, Edwin

    2013-01-01

    The importance of including developmental and environmental measures in genetic studies of human pathology is widely acknowledged, but few empirical studies have been published. Barriers include the need for longitudinal studies that cover relevant developmental stages and for samples large enough to deal with the challenge of testing gene-environment-development interaction. A solution to some of these problems is to bring together existing data sets that have the necessary characteristics. As part of the NIDA-funded Gene-Environment-Development Initiative (GEDI) our goal is to identify exactly which genes, which environments, and which developmental transitions together predict the development of drug use and misuse. Four data sets were used whose common characteristics include (1) general population samples including males and females; (2) repeated measures across adolescence and young adulthood; (3) assessment of nicotine, alcohol and cannabis use and addiction; (4) measures of family and environmental risk; and (5) consent for genotyping DNA from blood or saliva. After quality controls, 2,962 individuals provided over 15,000 total observations. In the first gene-environment analyses, of alcohol misuse and stressful life events, some significant gene-environment and gene-development effects were identified. We conclude that in some circumstances, already-collected data sets can be combined for gene-environment and gene-development analyses. This greatly reduces the cost and time needed for this type of research. However, care must be taken to ensure careful matching across studies and variables. PMID:23461817

  11. Commentary: Gene-Environment Interplay in the Context of Genetics, Epigenetics, and Gene Expression.

    ERIC Educational Resources Information Center

    Kramer, Douglas A.

    2005-01-01

    Objective: To comment on the article in this issue of the Journal by Professor Michael Rutter, "Environmentally Mediated Risks for Psychopathology: Research Strategies and Findings," in the context of current research findings on gene-environment interaction, epigenetics, and gene expression. Method: Animal and human studies are reviewed that…

  12. When Chocolate Seeking Becomes Compulsion: Gene-Environment Interplay

    PubMed Central

    Patella, Loris; Andolina, Diego; Valzania, Alessandro; Latagliata, Emanuele Claudio; Felsani, Armando; Pompili, Assunta; Gasbarri, Antonella; Puglisi-Allegra, Stefano; Ventura, Rossella

    2015-01-01

    Background Eating disorders appear to be caused by a complex interaction between environmental and genetic factors, and compulsive eating in response to adverse circumstances characterizes many eating disorders. Materials and Methods We compared compulsion-like eating in the form of conditioned suppression of palatable food-seeking in adverse situations in stressed C57BL/6J and DBA/2J mice, two well-characterized inbred strains, to determine the influence of gene-environment interplay on this behavioral phenotype. Moreover, we tested the hypothesis that low accumbal D2 receptor (R) availability is a genetic risk factor of food compulsion-like behavior and that environmental conditions that induce compulsive eating alter D2R expression in the striatum. To this end, we measured D1R and D2R expression in the striatum and D1R, D2R and α1R levels in the medial prefrontal cortex, respectively, by western blot. Results Exposure to environmental conditions induces compulsion-like eating behavior, depending on genetic background. This behavioral pattern is linked to decreased availability of accumbal D2R. Moreover, exposure to certain environmental conditions upregulates D2R and downregulates α1R in the striatum and medial prefrontal cortex, respectively, of compulsive animals. These findings confirm the function of gene-environment interplay in the manifestation of compulsive eating and support the hypothesis that low accumbal D2R availability is a “constitutive” genetic risk factor for compulsion-like eating behavior. Finally, D2R upregulation and α1R downregulation in the striatum and medial prefrontal cortex, respectively, are potential neuroadaptive responses that parallel the shift from motivated to compulsive eating. PMID:25781028

  13. Genotypes Do Not Confer Risk For Delinquency ut Rather Alter Susceptibility to Positive and Negative Environmental Factors: Gene-Environment Interactions of BDNF Val66Met, 5-HTTLPR, and MAOA-uVNTR

    PubMed Central

    Comasco, Erika; Hodgins, Sheilagh; Oreland, Lars; Åslund, Cecilia

    2015-01-01

    Background: Previous evidence of gene-by-environment interactions associated with emotional and behavioral disorders is contradictory. Differences in findings may result from variation in valence and dose of the environmental factor, and/or failure to take account of gene-by-gene interactions. The present study investigated interactions between the brain-derived neurotrophic factor gene (BDNF Val66Met), the serotonin transporter gene-linked polymorphic region (5-HTTLPR), the monoamine oxidase A (MAOA-uVNTR) polymorphisms, family conflict, sexual abuse, the quality of the child-parent relationship, and teenage delinquency. Methods: In 2006, as part of the Survey of Adolescent Life in Västmanland, Sweden, 1 337 high-school students, aged 17–18 years, anonymously completed questionnaires and provided saliva samples for DNA analyses. Results: Teenage delinquency was associated with two-, three-, and four-way interactions of each of the genotypes and the three environmental factors. Significant four-way interactions were found for BDNF Val66Met × 5-HTTLPR×MAOA-uVNTR × family conflicts and for BDNF Val66Met × 5-HTTLPR×MAOA-uVNTR × sexual abuse. Further, the two genotype combinations that differed the most in expression levels (BDNF Val66Met Val, 5-HTTLPR LL, MAOA-uVNTR LL [girls] and L [boys] vs BDNF Val66Met Val/Met, 5-HTTLPR S/LS, MAOA-uVNTR S/SS/LS) in interaction with family conflict and sexual abuse were associated with the highest delinquency scores. The genetic variants previously shown to confer vulnerability for delinquency (BDNF Val66Met Val/Met × 5-HTTLPR S × MAOA-uVNTR S) were associated with the lowest delinquency scores in interaction with a positive child-parent relationship. Conclusions: Functional variants of the MAOA-uVNTR, 5-HTTLPR, and BDNF Val66Met, either alone or in interaction with each other, may be best conceptualized as modifying sensitivity to environmental factors that confer either risk or protection for teenage delinquency. PMID

  14. Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates

    PubMed Central

    Boloc, Daniel; Castillo-Lara, Sergio; Marfany, Gemma; Gonzàlez-Duarte, Roser; Abril, Josep F.

    2015-01-01

    Background Retinitis pigmentosa (RP) is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA). The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD genes and mutations has been gathered, but a comprehensive view of the RP genes and their interacting partners is still very fragmentary. This is the main gap that needs to be filled in order to understand how mutations relate to progressive blinding disorders and devise effective therapies. Methodology We have built an RP-specific network (RPGeNet) by merging data from different sources: high-throughput data from BioGRID and STRING databases, manually curated data for interactions retrieved from iHOP, as well as interactions filtered out by syntactical parsing from up-to-date abstracts and full-text papers related to the RP research field. The paths emerging when known RP genes were used as baits over the whole interactome have been analysed, and the minimal number of connections among the RP genes and their close neighbors were distilled in order to simplify the search space. Conclusions In contrast to the analysis of single isolated genes, finding the networks linking disease genes renders powerful etiopathological insights. We here provide an interactive interface, RPGeNet, for the molecular biologist to explore the network centered on the non-syndromic and syndromic RP and LCA causative genes. By integrating tissue-specific expression levels and phenotypic data on top of that network, a more comprehensive biological view will highlight key molecular players of retinal degeneration and unveil new RP disease candidates. PMID:26267445

  15. Discovery of new candidate genes related to brain development using protein interaction information.

    PubMed

    Chen, Lei; Chu, Chen; Kong, Xiangyin; Huang, Tao; Cai, Yu-Dong

    2015-01-01

    Human brain development is a dramatic process composed of a series of complex and fine-tuned spatiotemporal gene expressions. A good comprehension of this process can assist us in developing the potential of our brain. However, we have only limited knowledge about the genes and gene functions that are involved in this biological process. Therefore, a substantial demand remains to discover new brain development-related genes and identify their biological functions. In this study, we aimed to discover new brain-development related genes by building a computational method. We referred to a series of computational methods used to discover new disease-related genes and developed a similar method. In this method, the shortest path algorithm was executed on a weighted graph that was constructed using protein-protein interactions. New candidate genes fell on at least one of the shortest paths connecting two known genes that are related to brain development. A randomization test was then adopted to filter positive discoveries. Of the final identified genes, several have been reported to be associated with brain development, indicating the effectiveness of the method, whereas several of the others may have potential roles in brain development.

  16. Gene-Environment Interplay in the Link of Friends' and Nonfriends' Behaviors with Children's Social Reticence in a Competitive Situation

    ERIC Educational Resources Information Center

    Guimond, Fanny-Alexandra; Brendgen, Mara; Vitaro, Frank; Forget-Dubois, Nadine; Dionne, Ginette; Tremblay, Richard E.; Boivin, Michel

    2014-01-01

    This study used a genetically informed design to assess the effects of friends' and nonfriends' reticent and dominant behaviors on children's observed social reticence in a competitive situation. Potential gene-environment correlations (rGE) and gene-environment interactions (GxE) in the link between (a) friends' and…

  17. Dopaminergic, Serotonergic, and Oxytonergic Candidate Genes Associated with Infant Attachment Security and Disorganization? In Search of Main and Interaction Effects

    ERIC Educational Resources Information Center

    Luijk, Maartje P. C. M.; Roisman, Glenn I.; Haltigan, John D.; Tiemeier, Henning; Booth-LaForce, Cathryn; van IJzendoorn, Marinus H.; Belsky, Jay; Uitterlinden, Andre G.; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; Tharner, Anne; Bakermans-Kranenburg, Marian J.

    2011-01-01

    Background and methods: In two birth cohort studies with genetic, sensitive parenting, and attachment data of more than 1,000 infants in total, we tested main and interaction effects of candidate genes involved in the dopamine, serotonin, and oxytocin systems ("DRD4", "DRD2", "COMT", "5-HTT", "OXTR") on attachment security and disorganization.…

  18. Integrating nutrigenomics data to identify cardiometabolic gene-environment interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutrition is a key factor in health and in many age-related diseases. This is particularly the case for cardiometabolic diseases such as cardiovascular disease, type 2 diabetes and hypertension, and is often precluded by obesity, glucose impairment and metabolic syndrome. Our research objectives are...

  19. Prioritizing disease candidate proteins in cardiomyopathy-specific protein-protein interaction networks based on "guilt by association" analysis.

    PubMed

    Li, Wan; Chen, Lina; He, Weiming; Li, Weiguo; Qu, Xiaoli; Liang, Binhua; Gao, Qianping; Feng, Chenchen; Jia, Xu; Lv, Yana; Zhang, Siya; Li, Xia

    2013-01-01

    The cardiomyopathies are a group of heart muscle diseases which can be inherited (familial). Identifying potential disease-related proteins is important to understand mechanisms of cardiomyopathies. Experimental identification of cardiomyophthies is costly and labour-intensive. In contrast, bioinformatics approach has a competitive advantage over experimental method. Based on "guilt by association" analysis, we prioritized candidate proteins involving in human cardiomyopathies. We first built weighted human cardiomyopathy-specific protein-protein interaction networks for three subtypes of cardiomyopathies using the known disease proteins from Online Mendelian Inheritance in Man as seeds. We then developed a method in prioritizing disease candidate proteins to rank candidate proteins in the network based on "guilt by association" analysis. It was found that most candidate proteins with high scores shared disease-related pathways with disease seed proteins. These top ranked candidate proteins were related with the corresponding disease subtypes, and were potential disease-related proteins. Cross-validation and comparison with other methods indicated that our approach could be used for the identification of potentially novel disease proteins, which may provide insights into cardiomyopathy-related mechanisms in a more comprehensive and integrated way.

  20. Amphiphilic Nature of New Antitubercular Drug Candidates and Their Interaction With Lipid Monolayer

    NASA Astrophysics Data System (ADS)

    Hill, K.; Pénzes, C. B.; Vértessy, B. G.; Szabadka, Z.; Grolmusz, V.; Kiss, É.

    Tuberculosis remains a major problem throughout the world causing large number of deaths, more than that from any other single infectious disease [1]. The treatment of the chronic inflammatory caused by Mycobacterium tuberculosis (Mtb) requires prolonged chemotherapy often associated with unwanted side effects and developing resistant bacterium strains [2]. Introduction of new in silico identified drug candidates which are expected to be specific inhibitor of dUTPase [3] a vital enzyme of Mtb presents a novel approach in the combat with the disease. Three of those drug candidates - ligand 3, 4 and 69 - were compared in the present study considering their interfacial properties, polarity, amphipatic character and lipid affinity which are relevant in pharmaceutical function.

  1. Candidate gene–environment interactions and their relationships with timing of breeding in a wild bird population

    PubMed Central

    Bourret, Audrey; Garant, Dany

    2015-01-01

    Monitoring and predicting evolutionary changes underlying current environmental modifications are complex challenges. Recent approaches to achieve these objectives include assessing the genetic variation and effects of candidate genes on traits indicating adaptive potential. In birds, for example, short tandem repeat polymorphism at four candidate genes (CLOCK, NPAS2, ADCYAP1, and CREB1) has been linked to variation in phenological traits such as laying date and timing of migration. However, our understanding of their importance as evolutionary predictors is still limited, mainly because the extent of genotype–environment interactions (GxE) related to these genes has yet to be assessed. Here, we studied a population of Tree swallow (Tachycineta bicolor) over 4 years in southern Québec (Canada) to assess the relationships between those four candidate genes and two phenological traits related to reproduction (laying date and incubation duration) and also determine the importance of GxE in this system. Our results showed that NPAS2 female genotypes were nonrandomly distributed across the study system and formed a longitudinal cline with longer genotypes located to the east. We observed relationships between length polymorphism at all candidate genes and laying date and/or incubation duration, and most of these relationships were affected by environmental variables (breeding density, latitude, or temperature). In particular, the positive relationships detected between laying date and both CLOCK and NPAS2 female genotypes were variable depending on breeding density. Our results suggest that all four candidate genes potentially affect timing of breeding in birds and that GxE are more prevalent and important than previously reported in this context. PMID:26380692

  2. Gene-Environment Interplay, Family Relationships, and Child Adjustment

    ERIC Educational Resources Information Center

    Horwitz, Briana N.; Neiderhiser, Jenae M.

    2011-01-01

    This paper reviews behavioral genetic research from the past decade that has moved beyond simply studying the independent influences of genes and environments. The studies considered in this review have instead focused on understanding gene-environment interplay, including genotype-environment correlation (rGE) and genotype x environment…

  3. Gene-environment correlations in the stress-depression relationship.

    PubMed

    Schnittker, Jason

    2010-09-01

    A critical feature of the social stress model is the apparent relationship between stress and depression. Although many studies have demonstrated a connection between the two, the relationship may be contaminated by genes affecting both stress and depression. Using a sample of identical and fraternal twins, this study explores genetic influences on depression and assorted sources of stress while explicitly estimating, and thereby controlling for, gene-environment correlations. I consider both stress and depression in a fine-grained fashion. For the former, the study explores assorted sources of stress, including health and disability, family, unemployment, discrimination, and perceived neighborhood safety, as gene-environment correlations may be stronger for some forms of stress than others. For the latter, the study explores both depressive symptoms and major depressive disorders, as each may entail a different epidemiological process, especially with respect to genes. The results reveal that most, but not all, measures of stress have moderate heritabilities, suggesting that genes influence exposure to the environment in a broad fashion. Yet, despite this, the relationship between stress and depression is generally robust to gene-environment correlations. There are some notable exceptions. For example, allowing for gene-environment correlations, marital conflict is generally unrelated to depression. Moreover, gene-environment correlations are generally stronger for major depression than for depressive symptoms, encouraging further elaboration of the distinction between the onset of depression and its recurrence, especially in the context of genes. These exceptions do not put limits on environmental influence, but do suggest that genes operate in a complex life-course fashion.

  4. Gene-environment interplay in attention-deficit hyperactivity disorder and the importance of a developmental perspective.

    PubMed

    Thapar, Anita; Langley, Kate; Asherson, Philip; Gill, Michael

    2007-01-01

    Attention-deficit hyperactivity disorder (ADHD) varies in its clinical presentation and course. Susceptibility gene variants for ADHD and associated antisocial behaviour are being identified with emerging evidence of gene-environment interaction. Genes and environmental factors that influence the origins of disorder are not necessarily the same as those that contribute to its course and outcome.

  5. Gene-gene interaction between tuberculosis candidate genes in a South African population.

    PubMed

    de Wit, Erika; van der Merwe, Lize; van Helden, Paul D; Hoal, Eileen G

    2011-02-01

    In a complex disease such as tuberculosis (TB) it is increasingly evident that gene-gene interactions play a far more important role in an individual's susceptibility to develop the disease than single polymorphisms on their own, as one gene can enhance or hinder the expression of another gene. Gene-gene interaction analysis is a new approach to elucidate susceptibility to TB. The possibility of gene-gene interactions was assessed, focusing on 11 polymorphisms in nine genes (DC-SIGN, IFN-γ, IFNGR1, IL-8, IL-1Ra, MBL, NRAMP1, RANTES, and SP-D) that have been associated with TB, some repeatedly. An optimal model, which best describes and predicts TB case-control status, was constructed. Significant interactions were detected between eight pairs of variants. The models fitted the observed data extremely well, with p < 0.0001 for all eight models. A highly significant interaction was detected between INFGR1 and NRAMP1, which is not surprising because macrophage activation is greatly enhanced by IFN-γ and IFN-γ response elements that are present in the human NRAMP1 promoter region, providing further evidence for their interaction. This study enabled us to test the theory that disease outcome may be due to interaction of several gene effects. With eight instances of statistically significant gene-gene interactions, the importance of epistasis is clearly identifiable in this study. Methods for studying gene-gene interactions are based on a multilocus and multigene approach, consistent with the nature of complex-trait diseases, and may provide the paradigm for future genetic studies of TB.

  6. Microbial interactions in crude oils: Possible impact on biochemical versatility on the choice of microbial candidates

    SciTech Connect

    Premuzic, E.T.; Lin, M.S.; Lian, H.

    1995-10-01

    Experimental data gathered over the past several years show that the interactions of microorganisms with crude oils are variable and depend on the microbial species and the chemical composition of crude oils. The variations can be observed in terms of the extent of emulsification, changes in the hydrocarbon composition of crude oils, and duration of biotreatment. All of these factors indicate that the interaction of microbes with crude oils involves multiple chemical reactions resulting from the biochemical interactions between microbes and oils. Different interactions may influence the efficiency of processes in which single or mixed microbial species are used for the oil treatment and may also suggest possible combinations of biological and chemical technologies. Some of these concepts will be discussed in this paper.

  7. Identification of new candidate drugs for lung cancer using chemical-chemical interactions, chemical-protein interactions and a K-means clustering algorithm.

    PubMed

    Lu, Jing; Chen, Lei; Yin, Jun; Huang, Tao; Bi, Yi; Kong, Xiangyin; Zheng, Mingyue; Cai, Yu-Dong

    2016-01-01

    Lung cancer, characterized by uncontrolled cell growth in the lung tissue, is the leading cause of global cancer deaths. Until now, effective treatment of this disease is limited. Many synthetic compounds have emerged with the advancement of combinatorial chemistry. Identification of effective lung cancer candidate drug compounds among them is a great challenge. Thus, it is necessary to build effective computational methods that can assist us in selecting for potential lung cancer drug compounds. In this study, a computational method was proposed to tackle this problem. The chemical-chemical interactions and chemical-protein interactions were utilized to select candidate drug compounds that have close associations with approved lung cancer drugs and lung cancer-related genes. A permutation test and K-means clustering algorithm were employed to exclude candidate drugs with low possibilities to treat lung cancer. The final analysis suggests that the remaining drug compounds have potential anti-lung cancer activities and most of them have structural dissimilarity with approved drugs for lung cancer.

  8. Pathway Analysis Incorporating Protein-Protein Interaction Networks Identified Candidate Pathways for the Seven Common Diseases

    PubMed Central

    Lin, Peng-Lin; Yu, Ya-Wen

    2016-01-01

    Pathway analysis has become popular as a secondary analysis strategy for genome-wide association studies (GWAS). Most of the current pathway analysis methods aggregate signals from the main effects of single nucleotide polymorphisms (SNPs) in genes within a pathway without considering the effects of gene-gene interactions. However, gene-gene interactions can also have critical effects on complex diseases. Protein-protein interaction (PPI) networks have been used to define gene pairs for the gene-gene interaction tests. Incorporating the PPI information to define gene pairs for interaction tests within pathways can increase the power for pathway-based association tests. We propose a pathway association test, which aggregates the interaction signals in PPI networks within a pathway, for GWAS with case-control samples. Gene size is properly considered in the test so that genes do not contribute more to the test statistic simply due to their size. Simulation studies were performed to verify that the method is a valid test and can have more power than other pathway association tests in the presence of gene-gene interactions within a pathway under different scenarios. We applied the test to the Wellcome Trust Case Control Consortium GWAS datasets for seven common diseases. The most significant pathway is the chaperones modulate interferon signaling pathway for Crohn’s disease (p-value = 0.0003). The pathway modulates interferon gamma, which induces the JAK/STAT pathway that is involved in Crohn’s disease. Several other pathways that have functional implications for the seven diseases were also identified. The proposed test based on gene-gene interaction signals in PPI networks can be used as a complementary tool to the current existing pathway analysis methods focusing on main effects of genes. An efficient software implementing the method is freely available at http://puppi.sourceforge.net. PMID:27622767

  9. Vavien: An Algorithm for Prioritizing Candidate Disease Genes Based on Topological Similarity of Proteins in Interaction Networks

    PubMed Central

    Bebek, Gurkan; Koyutürk, Mehmet

    2011-01-01

    Abstract Genome-wide linkage and association studies have demonstrated promise in identifying genetic factors that influence health and disease. An important challenge is to narrow down the set of candidate genes that are implicated by these analyses. Protein-protein interaction (PPI) networks are useful in extracting the functional relationships between known disease and candidate genes, based on the principle that products of genes implicated in similar diseases are likely to exhibit significant connectivity/proximity. Information flow–based methods are shown to be very effective in prioritizing candidate disease genes. In this article, we utilize the topology of PPI networks to infer functional information in the context of disease association. Our approach is based on the assumption that PPI networks are organized into recurrent schemes that underlie the mechanisms of cooperation among different proteins. We hypothesize that proteins associated with similar diseases would exhibit similar topological characteristics in PPI networks. Utilizing the location of a protein in the network with respect to other proteins (i.e., the “topological profile” of the proteins), we develop a novel measure to assess the topological similarity of proteins in a PPI network. We then use this measure to prioritize candidate disease genes based on the topological similarity of their products and the products of known disease genes. We test the resulting algorithm, Vavien, via systematic experimental studies using an integrated human PPI network and the Online Mendelian Inheritance in Man (OMIM) database. Vavien outperforms other network-based prioritization algorithms as shown in the results and is available at www.diseasegenes.org. PMID:22035267

  10. Stochastic Dynamics of the Multi-State Voter Model Over a Network Based on Interacting Cliques and Zealot Candidates

    NASA Astrophysics Data System (ADS)

    Palombi, Filippo; Toti, Simona

    2014-07-01

    The stochastic dynamics of the multi-state voter model is investigated on a class of complex networks made of non-overlapping cliques, each hosting a political candidate and interacting with the others via Erdős-Rényi links. Numerical simulations of the model are interpreted in terms of an ad-hoc mean field theory, specifically tuned to resolve the inter/intra-clique interactions. Under a proper definition of the thermodynamic limit (with the average degree of the agents kept fixed while increasing the network size), the model is found to display the empirical scaling discovered by Fortunato and Castellano (Phys Rev Lett 99(13):138701, 2007) , while the vote distribution resembles roughly that observed in Brazilian elections.

  11. Candidate Cell and Matrix Interaction Domains on the Collagen Fibril, the Predominant Protein of Vertebrates

    SciTech Connect

    Sweeney, Shawn M.; Orgel, Joseph P.; Fertala, Andrzej; McAuliffe, Jon D.; Turner, Kevin R.; Di Lullo, Gloria A.; Chen, Steven; Antipova, Olga; Perumal, Shiamalee; Ala-Kokko, Leena; Forlinoi, Antonella; Cabral, Wayne A.; Barnes, Aileen M.; Marini, Joan C.; San Antonio, James D.

    2008-07-18

    Type I collagen, the predominant protein of vertebrates, polymerizes with type III and V collagens and non-collagenous molecules into large cable-like fibrils, yet how the fibril interacts with cells and other binding partners remains poorly understood. To help reveal insights into the collagen structure-function relationship, a data base was assembled including hundreds of type I collagen ligand binding sites and mutations on a two-dimensional model of the fibril. Visual examination of the distribution of functional sites, and statistical analysis of mutation distributions on the fibril suggest it is organized into two domains. The 'cell interaction domain' is proposed to regulate dynamic aspects of collagen biology, including integrin-mediated cell interactions and fibril remodeling. The 'matrix interaction domain' may assume a structural role, mediating collagen cross-linking, proteoglycan interactions, and tissue mineralization. Molecular modeling was used to superimpose the positions of functional sites and mutations from the two-dimensional fibril map onto a three-dimensional x-ray diffraction structure of the collagen microfibril in situ, indicating the existence of domains in the native fibril. Sequence searches revealed that major fibril domain elements are conserved in type I collagens through evolution and in the type II/XI collagen fibril predominant in cartilage. Moreover, the fibril domain model provides potential insights into the genotype-phenotype relationship for several classes of human connective tissue diseases, mechanisms of integrin clustering by fibrils, the polarity of fibril assembly, heterotypic fibril function, and connective tissue pathology in diabetes and aging.

  12. A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions

    PubMed Central

    Hostetler, Jessica B.; Sharma, Sumana; Bartholdson, S. Josefin; Wright, Gavin J.; Fairhurst, Rick M.; Rayner, Julian C.

    2015-01-01

    Background A vaccine targeting Plasmodium vivax will be an essential component of any comprehensive malaria elimination program, but major gaps in our understanding of P. vivax biology, including the protein-protein interactions that mediate merozoite invasion of reticulocytes, hinder the search for candidate antigens. Only one ligand-receptor interaction has been identified, that between P. vivax Duffy Binding Protein (PvDBP) and the erythrocyte Duffy Antigen Receptor for Chemokines (DARC), and strain-specific immune responses to PvDBP make it a complex vaccine target. To broaden the repertoire of potential P. vivax merozoite-stage vaccine targets, we exploited a recent breakthrough in expressing full-length ectodomains of Plasmodium proteins in a functionally-active form in mammalian cells and initiated a large-scale study of P. vivax merozoite proteins that are potentially involved in reticulocyte binding and invasion. Methodology/Principal Findings We selected 39 P. vivax proteins that are predicted to localize to the merozoite surface or invasive secretory organelles, some of which show homology to P. falciparum vaccine candidates. Of these, we were able to express 37 full-length protein ectodomains in a mammalian expression system, which has been previously used to express P. falciparum invasion ligands such as PfRH5. To establish whether the expressed proteins were correctly folded, we assessed whether they were recognized by antibodies from Cambodian patients with acute vivax malaria. IgG from these samples showed at least a two-fold change in reactivity over naïve controls in 27 of 34 antigens tested, and the majority showed heat-labile IgG immunoreactivity, suggesting the presence of conformation-sensitive epitopes and native tertiary protein structures. Using a method specifically designed to detect low-affinity, extracellular protein-protein interactions, we confirmed a predicted interaction between P. vivax 6-cysteine proteins P12 and P41, further

  13. A gene-environment study of the paraoxonase 1 gene and pesticides in amyotrophic lateral sclerosis.

    PubMed

    Morahan, Julia M; Yu, Bing; Trent, Ronald J; Pamphlett, Roger

    2007-05-01

    Sporadic amyotrophic lateral sclerosis (SALS) causes progressive muscle weakness because of the loss of motor neurons. SALS has been associated with exposure to environmental toxins, including pesticides and chemical warfare agents, many of which are organophosphates. The enzyme paraoxonase 1 (PON1) detoxifies organophosphates and the efficacy of this enzyme varies with polymorphisms in the PON1 gene. To determine if an impaired ability to break down organophosphates underlies some cases of SALS, we compared the frequencies of PON1 polymorphisms in SALS patients and controls and investigated gene-environment interactions with self-reported pesticide/herbicide exposure. The PON1 coding polymorphisms L55M, Q192R and I102V, and the promoter polymorphisms -909c>g, -832g>a, -162g>a and -108c>t, were genotyped in 143 SALS patients and 143 matched controls. Statistical comparisons were carried out at allele, genotype and haplotype levels. The PON1 promoter allele -108t, which reduces PON1 expression, was strongly associated with SALS. Overall, promoter haplotypes that decrease PON1 expression were associated with SALS, whereas haplotypes that increase expression were associated with controls. Coding polymorphisms did not correlate with SALS. Gene-environment interactions were identified at the allele level for some promoter SNPs and pesticide/herbicide exposure, but not at the genotype or haplotype level. In conclusion, some PON1 promoter polymorphisms may predispose to SALS, possibly by making motor neurons more susceptible to organophosphate-containing toxins.

  14. Evidence of reactive gene-environment correlation in preschoolers' prosocial play with unfamiliar peers.

    PubMed

    DiLalla, Lisabeth Fisher; Bersted, Kyle; John, Sufna Gheyara

    2015-10-01

    The development of prosocial behaviors during the preschool years is essential for children's positive interactions with peers in school and other social situations. Although there is some evidence of genetic influences on prosocial behaviors, very little is known about how genes and environment, independently and in concert, affect prosocial behaviors in young children. This study of 126 twin and sibling pairs examined 5-year-old preschool children's positive behaviors (prosocial and easy-going) while playing freely with an unfamiliar, same-age, same-sex peer. Children were randomly paired, allowing us to rule out passive (parent-influenced environment) and active (child-driven peer choices) gene-environment correlations as potential influences on the results. We found evidence of reactive gene-environment correlation, demonstrating that children who are genetically more likely to act prosocially and to be temperamentally outgoing appear to evoke more prosocial and easy-going behaviors from an unfamiliar peer. We also found that both dominant genetic and nonshared environmental factors were significant influences on preschoolers' prosocial play behaviors, but that neither genetic nor shared environmental factors were significant for easy-going play behaviors. These findings shed important light on influences of prosocial behaviors in preschoolers. Via inherited tendencies, preschool children's positive behaviors evoke similar positive behaviors from their play peers. Given that prosocial behaviors are preludes to a large range of important socially appropriate behaviors, prosocial children should be encouraged to interact with their peers to potentially create a more positive atmosphere within social contexts.

  15. Child dopamine active transporter 1 genotype and parenting: evidence for evocative gene-environment correlations.

    PubMed

    Hayden, Elizabeth P; Hanna, Brigitte; Sheikh, Haroon I; Laptook, Rebecca S; Kim, Jiyon; Singh, Shiva M; Klein, Daniel N

    2013-02-01

    The dopamine active transporter 1 (DAT1) gene is implicated in psychopathology risk. Although the processes by which this gene exerts its effects on risk are poorly understood, a small body of research suggests that the DAT1 gene influences early emerging negative emotionality, a marker of children's psychopathology risk. As child negative emotionality evokes negative parenting practices, the DAT1 gene may also play a role in gene-environment correlations. To test this model, children (N = 365) were genotyped for the DAT1 gene and participated in standardized parent-child interaction tasks with their primary caregiver. The DAT1 gene 9-repeat variant was associated with child negative affect expressed toward the parent during parent-child interactions, and parents of children with a 9-repeat allele exhibited more hostility and lower guidance/engagement than parents of children without a 9-repeat allele. These gene-environment associations were partially mediated by child negative affect toward the parent. The findings implicate a specific polymorphism in eliciting negative parenting, suggesting that evocative associations play a role in elevating children's risk for emotional trajectories toward psychopathology risk.

  16. The developmental origins of externalizing behavioral problems: parental disengagement and the role of gene-environment interplay.

    PubMed

    Boutwell, Brian B; Beaver, Kevin M; Barnes, James C; Vaske, Jamie

    2012-05-30

    A line of research has revealed that the influence of genes on behavioral development is closely tied to environmental experiences. Known as gene-environment interaction, research in this area is beginning to reveal that variation in parenting behaviors may moderate genetic influences on antisocial behaviors in children. Despite growing interest in gene-environment interaction research, little evidence exists concerning the role of maternal disengagement in the conditioning of genetic influences on childhood behavioral problems. The current study is intended to address this gap in the literature by analyzing a sample of twin pairs drawn from the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B). Analysis of the ECLS-B provided evidence that maternal disengagement moderates genetic influences on the development of externalizing problems.

  17. Multilocus analyses of seven candidate genes suggest interacting pathways for obesity-related traits in Brazilian populations.

    PubMed

    Angeli, Cláudia B; Kimura, Lilian; Auricchio, Maria T; Vicente, João P; Mattevi, Vanessa S; Zembrzuski, Verônica M; Hutz, Mara H; Pereira, Alexandre C; Pereira, Tiago V; Mingroni-Netto, Regina C

    2011-06-01

    We investigated whether variants in major candidate genes for food intake and body weight regulation contribute to obesity-related traits under a multilocus perspective. We studied 375 Brazilian subjects from partially isolated African-derived populations (quilombos). Seven variants displaying conflicting results in previous reports and supposedly implicated in the susceptibility of obesity-related phenotypes were investigated: β2-adrenergic receptor (ADRB2) (Arg16Gly), insulin induced gene 2 (INSIG2) (rs7566605), leptin (LEP) (A19G), LEP receptor (LEPR) (Gln223Arg), perilipin (PLIN) (6209T > C), peroxisome proliferator-activated receptor-γ (PPARG) (Pro12Ala), and resistin (RETN) (-420 C > G). Regression models as well as generalized multifactor dimensionality reduction (GMDR) were employed to test the contribution of individual effects and higher-order interactions to BMI and waist-hip ratio (WHR) variation and risk of overweight/obesity. The best multilocus association signal identified in the quilombos was further examined in an independent sample of 334 Brazilian subjects of European ancestry. In quilombos, only the PPARG polymorphism displayed significant individual effects (WHR variation, P = 0.028). No association was observed either with the risk of overweight/obesity (BMI ≥ 25 kg/m2), risk of obesity alone (BMI ≥ 30 kg/m2) or BMI variation. However, GMDR analyses revealed an interaction between the LEPR and ADRB2 polymorphisms (P = 0.009) as well as a third-order effect involving the latter two variants plus INSIG2 (P = 0.034) with overweight/obesity. Assessment of the LEPR-ADRB2 interaction in the second sample indicated a marginally significant association (P = 0.0724), which was further verified to be limited to men (P = 0.0118). Together, our findings suggest evidence for a two-locus interaction between the LEPR Gln223Arg and ADRB2 Arg16Gly variants in the risk of overweight/obesity, and highlight further the importance of multilocus effects in

  18. Prioritization of candidate genes for cattle reproductive traits, based on protein-protein interactions, gene expression, and text-mining.

    PubMed

    Hulsegge, Ina; Woelders, Henri; Smits, Mari; Schokker, Dirkjan; Jiang, Li; Sørensen, Peter

    2013-05-15

    Reproduction is of significant economic importance in dairy cattle. Improved understanding of mechanisms that control estrous behavior and other reproduction traits could help in developing strategies to improve and/or monitor these traits. The objective of this study was to predict and rank genes and processes in brain areas and pituitary involved in reproductive traits in cattle using information derived from three different data sources: gene expression, protein-protein interactions, and literature. We identified 59, 89, 53, 23, and 71 genes in bovine amygdala, dorsal hypothalamus, hippocampus, pituitary, and ventral hypothalamus, respectively, potentially involved in processes underlying estrus and estrous behavior. Functional annotation of the candidate genes points to a number of tissue-specific processes of which the "neurotransmitter/ion channel/synapse" process in the amygdala, "steroid hormone receptor activity/ion binding" in the pituitary, "extracellular region" in the ventral hypothalamus, and "positive regulation of transcription/metabolic process" in the dorsal hypothalamus are most prominent. The regulation of the functional processes in the various tissues operate at different biological levels, including transcriptional, posttranscriptional, extracellular, and intercellular signaling levels.

  19. An attachment perspective on borderline personality disorder: advances in gene-environment considerations.

    PubMed

    Steele, Howard; Siever, Larry

    2010-02-01

    Accumulating evidence points to severe relationship dysfunction as the core epigenetic expression of borderline personality disorder (BPD). In adulthood, BPD is typified by disorganization within and across interpersonal domains of functioning. When interacting with their infants, mothers with BPD show marked withdrawal and frightening or frightened behavior, leading to disorganized infant-mother attachments. Linked to both infant disorganization and BPD is a maternal state of mind typified by unresolved mourning regarding past loss or trauma. Early risk factors for BPD in adulthood include maternal withdrawal in infancy and separation of 1 month or more from mother in the first 5 years of life. Likely contributing biological factors include genes linked to dopamine, serotonin, the hypothalamic-pituitary-adrenal axis, and neuropeptides. The complex gene-environment picture emerging confers risk or protection against BPD pathology in ways consistent with infants varying biological sensitivity to context. This line of research may refine early risk assessment and preventive mental health services.

  20. Interactions between a Candidate Gene for Migration (ADCYAP1), Morphology and Sex Predict Spring Arrival in Blackcap Populations.

    PubMed

    Mettler, Raeann; Segelbacher, Gernot; Schaefer, H Martin

    2015-01-01

    Avian research has begun to reveal associations between candidate genes and migratory behaviors of captive birds, yet few studies utilize genotypic, morphometric, and phenological data from wild individuals. Previous studies have identified an association between ADCYAP1 polymorphism and autumn migratory behavior (restlessness, or zugunruhe), but little is known about the relationship between ADCYAP1 and spring migratory behavior. The timing of spring migration and arrival to the breeding ground are phenological traits which could be particularly favorable for establishing territories and acquiring mates, thus important to fitness and reproductive success. Here, we investigated how individual genotypic ADCYAP1 variation and phenotypic variation (wing length and shape) of blackcaps (Sylvia atricapilla) affect spring arrival date across nine natural populations in Europe. We hypothesized that longer alleles should be associated with earlier spring arrival dates and expected the effect on arrival date to be stronger for males as they arrive earlier. However, we found that longer wings were associated with earlier spring arrival to the breeding grounds for females, but not for males. Another female-specific effect indicated an interaction between ADCYAP1 allele size and wing pointedness on the response of spring arrival: greater allele size had a positive effect on spring arrival date for females with rounder wings, while a negative effect was apparent for females with more pointed wings. Also, female heterozygotes with pointed wing tips arrived significantly earlier than both homozygotes with pointed wings and heterozygotes with round wings. Stable isotope ratios (δ2H) of a subset of blackcaps captured in Freiburg in 2011 allowed us also to assign individuals to their main overwintering areas in northwest (NW) and southwest (SW) Europe. NW males arrived significantly earlier to the Freiburg breeding site than both SW males and females in 2011. NW females had more

  1. Interactions between a Candidate Gene for Migration (ADCYAP1), Morphology and Sex Predict Spring Arrival in Blackcap Populations

    PubMed Central

    2015-01-01

    Avian research has begun to reveal associations between candidate genes and migratory behaviors of captive birds, yet few studies utilize genotypic, morphometric, and phenological data from wild individuals. Previous studies have identified an association between ADCYAP1 polymorphism and autumn migratory behavior (restlessness, or zugunruhe), but little is known about the relationship between ADCYAP1 and spring migratory behavior. The timing of spring migration and arrival to the breeding ground are phenological traits which could be particularly favorable for establishing territories and acquiring mates, thus important to fitness and reproductive success. Here, we investigated how individual genotypic ADCYAP1 variation and phenotypic variation (wing length and shape) of blackcaps (Sylvia atricapilla) affect spring arrival date across nine natural populations in Europe. We hypothesized that longer alleles should be associated with earlier spring arrival dates and expected the effect on arrival date to be stronger for males as they arrive earlier. However, we found that longer wings were associated with earlier spring arrival to the breeding grounds for females, but not for males. Another female-specific effect indicated an interaction between ADCYAP1 allele size and wing pointedness on the response of spring arrival: greater allele size had a positive effect on spring arrival date for females with rounder wings, while a negative effect was apparent for females with more pointed wings. Also, female heterozygotes with pointed wing tips arrived significantly earlier than both homozygotes with pointed wings and heterozygotes with round wings. Stable isotope ratios (δ2H) of a subset of blackcaps captured in Freiburg in 2011 allowed us also to assign individuals to their main overwintering areas in northwest (NW) and southwest (SW) Europe. NW males arrived significantly earlier to the Freiburg breeding site than both SW males and females in 2011. NW females had more

  2. Identification and Characterization of a Candidate Wolbachia pipientis Type IV Effector That Interacts with the Actin Cytoskeleton

    PubMed Central

    Sheehan, Kathy B.; Martin, MaryAnn; Lesser, Cammie F.; Isberg, Ralph R.

    2016-01-01

    ABSTRACT Many bacteria live as intracellular symbionts, causing persistent infections within insects. One extraordinarily common infection is that of Wolbachia pipientis, which infects 40% of insect species and induces reproductive effects. The bacteria are passed from generation to generation both vertically (through the oocyte) and horizontally (by environmental transmission). Maintenance of the infection within Drosophila melanogaster is sensitive to the regulation of actin, as Wolbachia inefficiently colonizes strains hemizygous for the profilin or villin genes. Therefore, we hypothesized that Wolbachia must depend on the host actin cytoskeleton. In this study, we identify and characterize a Wolbachia protein (WD0830) that is predicted to be secreted by the bacterial parasite. Expression of WD0830 in a model eukaryote (the yeast Saccharomyces cerevisiae) induces a growth defect associated with the appearance of aberrant, filamentous structures which colocalize with rhodamine-phalloidin-stained actin. Purified WD0830 bundles actin in vitro and cosediments with actin filaments, suggesting a direct interaction of the two proteins. We characterized the expression of WD0830 throughout Drosophila development and found it to be upregulated in third-instar larvae, peaking in early pupation, during the critical formation of adult tissues, including the reproductive system. In transgenic flies, heterologously expressed WD0830 localizes to the developing oocyte. Additionally, overexpression of WD0830 results in increased Wolbachia titers in whole flies, in stage 9 and 10 oocytes, and in embryos, compared to controls, suggesting that the protein may facilitate Wolbachia’s replication or transmission. Therefore, this candidate secreted effector may play a role in Wolbachia’s infection of and persistence within host niches. PMID:27381293

  3. Dual RNA-seq reveals Meloidogyne graminicola transcriptome and candidate effectors during the interaction with rice plants.

    PubMed

    Petitot, Anne-Sophie; Dereeper, Alexis; Agbessi, Mawusse; Da Silva, Corinne; Guy, Julie; Ardisson, Morgane; Fernandez, Diana

    2016-08-01

    Root-knot nematodes secrete proteinaceous effectors into plant tissues to facilitate infection by suppressing host defences and reprogramming the host metabolism to their benefit. Meloidogyne graminicola is a major pest of rice (Oryza sativa) in Asia and Latin America, causing important crop losses. The goal of this study was to identify M. graminicola pathogenicity genes expressed during the plant-nematode interaction. Using the dual RNA-sequencing (RNA-seq) strategy, we generated transcriptomic data of M. graminicola samples covering the pre-parasitic J2 stage and five parasitic stages in rice plants, from the parasitic J2 to the adult female. In the absence of a reference genome, a de novo M. graminicola transcriptome of 66 396 contigs was obtained from those reads that were not mapped on the rice genome. Gene expression profiling across the M. graminicola life cycle revealed key genes involved in nematode development and provided insights into the genes putatively associated with parasitism. The development of a 'secreted protein prediction' pipeline revealed a typical set of proteins secreted by nematodes, as well as a large number of cysteine-rich proteins and putative nuclear proteins. Combined with expression data, this pipeline enabled the identification of 15 putative effector genes, including two homologues of well-characterized effectors from cyst nematodes (CLE-like and VAP1) and a metallothionein. The localization of gene expression was assessed by in situ hybridization for a subset of candidates. All of these data represent important molecular resources for the elucidation of M. graminicola biology and for the selection of potential targets for the development of novel control strategies for this nematode species.

  4. Prioritizing Disease Candidate Proteins in Cardiomyopathy-Specific Protein-Protein Interaction Networks Based on “Guilt by Association” Analysis

    PubMed Central

    He, Weiming; Li, Weiguo; Qu, Xiaoli; Liang, Binhua; Gao, Qianping; Feng, Chenchen; Jia, Xu; Lv, Yana; Zhang, Siya; Li, Xia

    2013-01-01

    The cardiomyopathies are a group of heart muscle diseases which can be inherited (familial). Identifying potential disease-related proteins is important to understand mechanisms of cardiomyopathies. Experimental identification of cardiomyophthies is costly and labour-intensive. In contrast, bioinformatics approach has a competitive advantage over experimental method. Based on “guilt by association” analysis, we prioritized candidate proteins involving in human cardiomyopathies. We first built weighted human cardiomyopathy-specific protein-protein interaction networks for three subtypes of cardiomyopathies using the known disease proteins from Online Mendelian Inheritance in Man as seeds. We then developed a method in prioritizing disease candidate proteins to rank candidate proteins in the network based on “guilt by association” analysis. It was found that most candidate proteins with high scores shared disease-related pathways with disease seed proteins. These top ranked candidate proteins were related with the corresponding disease subtypes, and were potential disease-related proteins. Cross-validation and comparison with other methods indicated that our approach could be used for the identification of potentially novel disease proteins, which may provide insights into cardiomyopathy-related mechanisms in a more comprehensive and integrated way. PMID:23940716

  5. Gene-Environment Interplay and Psychopathology: Multiple Varieties but Real Effects

    ERIC Educational Resources Information Center

    Rutter, Michael; Moffitt, Terrie E.; Caspi, Avshalom

    2006-01-01

    Gene-environment interplay is a general term that covers several divergent concepts with different meanings and different implications. In this review, we evaluate research evidence on four varieties of gene-environment interplay. First, we consider epigenetic mechanisms by which environmental influences alter the effects of genes. Second, we…

  6. Candidate Genes for Cannabis Use Disorders: Findings, Challenges and Directions

    PubMed Central

    Agrawal, Arpana; Lynskey, Michael T.

    2009-01-01

    Aim Twin studies have shown that cannabis use disorders (abuse/dependence) are highly heritable. This review aims to: (i) review existing linkage studies of cannabis use disorders and (ii) review gene association studies, to identify potential candidate genes, including those that have been tested for composite substance use disorders, and (iii) to highlight challenges in the genomic study of cannabis use disorders. Methods Peer-reviewed linkage and candidate gene association studies are reviewed. Results Four linkage studies are reviewed: results from these have homed in on regions on chromosomes 1, 3, 4, 9, 14, 17 and 18, which harbor candidates of predicted biological relevance, such as monoglyceride lipase (MGL) on chromosome 3, but also novel genes, including ELTD1 (EGF, latrophilin and seven transmembrane domain containing 1) on chromosome 1. Gene association studies are presented for (a) genes posited to have specific influences on cannabis use disorders: CNR1, CB2, FAAH, MGL, TRPV1 and GPR55 and (b) genes from various neurotransmitter systems that are likely to exert a non-specific influence on risk of cannabis use disorders e.g. GABRA2, DRD2 and OPRM1. Conclusions There are challenges associated with (i) understanding biological complexity underlying cannabis use disorders (including the need to study gene-gene and gene-environment interactions), (ii) using diagnostic versus quantitative phenotypes, (iii) delineating which stage of cannabis involvement (e.g. use vs. misuse) genes influence and (iv) problems of sample ascertainment. PMID:19335651

  7. Identification of novel candidate drivers connecting different dysfunctional levels for lung adenocarcinoma using protein-protein interactions and a shortest path approach

    PubMed Central

    Chen, Lei; Huang, Tao; Zhang, Yu-Hang; Jiang, Yang; Zheng, Mingyue; Cai, Yu-Dong

    2016-01-01

    Tumors are formed by the abnormal proliferation of somatic cells with disordered growth regulation under the influence of tumorigenic factors. Recently, the theory of “cancer drivers” connects tumor initiation with several specific mutations in the so-called cancer driver genes. According to the differentiation of four basic levels between tumor and adjacent normal tissues, the cancer drivers can be divided into the following: (1) Methylation level, (2) microRNA level, (3) mutation level, and (4) mRNA level. In this study, a computational method is proposed to identify novel lung adenocarcinoma drivers based on dysfunctional genes on the methylation, microRNA, mutation and mRNA levels. First, a large network was constructed using protein-protein interactions. Next, we searched all of the shortest paths connecting dysfunctional genes on different levels and extracted new candidate genes lying on these paths. Finally, the obtained candidate genes were filtered by a permutation test and an additional strict selection procedure involving a betweenness ratio and an interaction score. Several candidate genes remained, which are deemed to be related to two different levels of cancer. The analyses confirmed our assertions that some have the potential to contribute to the tumorigenesis process on multiple levels. PMID:27412431

  8. Identification of novel candidate drivers connecting different dysfunctional levels for lung adenocarcinoma using protein-protein interactions and a shortest path approach

    NASA Astrophysics Data System (ADS)

    Chen, Lei; Huang, Tao; Zhang, Yu-Hang; Jiang, Yang; Zheng, Mingyue; Cai, Yu-Dong

    2016-07-01

    Tumors are formed by the abnormal proliferation of somatic cells with disordered growth regulation under the influence of tumorigenic factors. Recently, the theory of “cancer drivers” connects tumor initiation with several specific mutations in the so-called cancer driver genes. According to the differentiation of four basic levels between tumor and adjacent normal tissues, the cancer drivers can be divided into the following: (1) Methylation level, (2) microRNA level, (3) mutation level, and (4) mRNA level. In this study, a computational method is proposed to identify novel lung adenocarcinoma drivers based on dysfunctional genes on the methylation, microRNA, mutation and mRNA levels. First, a large network was constructed using protein-protein interactions. Next, we searched all of the shortest paths connecting dysfunctional genes on different levels and extracted new candidate genes lying on these paths. Finally, the obtained candidate genes were filtered by a permutation test and an additional strict selection procedure involving a betweenness ratio and an interaction score. Several candidate genes remained, which are deemed to be related to two different levels of cancer. The analyses confirmed our assertions that some have the potential to contribute to the tumorigenesis process on multiple levels.

  9. Evocative gene-environment correlation in the mother-child relationship: a twin study of interpersonal processes.

    PubMed

    Klahr, Ashlea M; Thomas, Katherine M; Hopwood, Christopher J; Klump, Kelly L; Burt, S Alexandra

    2013-02-01

    The behavior genetic literature suggests that genetically influenced characteristics of the child elicit specific behaviors from the parent. However, little is known about the processes by which genetically influenced child characteristics evoke parental responses. Interpersonal theory provides a useful framework for identifying reciprocal behavioral processes between children and mothers. The theory posits that, at any given moment, interpersonal behavior varies along the orthogonal dimensions of warmth and control and that the interpersonal behavior of one individual tends to elicit corresponding or contrasting behavior from the other (i.e., warmth elicits warmth, whereas control elicits submission). The current study thus examined these dimensions of interpersonal behavior as they relate to the parent-child relationship in 546 twin families. A computer joystick was used to rate videos of mother-child interactions in real time, yielding information on mother and child levels of warmth and control throughout the interaction. Analyses indicated that maternal control, but not maternal warmth, was influenced by evocative gene-environment correlational processes, such that genetic influences on maternal control and child control were largely overlapping. Moreover, these common genetic influences were present both cross-sectionally and over the course of the interaction. Such findings not only confirm the presence of evocative gene-environment correlational processes in the mother-child relationship but also illuminate at least one of the specific interpersonal behaviors that underlie this evocative process.

  10. Identification of New Candidate Genes and Chemicals Related to Esophageal Cancer Using a Hybrid Interaction Network of Chemicals and Proteins.

    PubMed

    Gao, Yu-Fei; Yuan, Fei; Liu, Junbao; Li, Li-Peng; He, Yi-Chun; Gao, Ru-Jian; Cai, Yu-Dong; Jiang, Yang

    2015-01-01

    Cancer is a serious disease responsible for many deaths every year in both developed and developing countries. One reason is that the mechanisms underlying most types of cancer are still mysterious, creating a great block for the design of effective treatments. In this study, we attempted to clarify the mechanism underlying esophageal cancer by searching for novel genes and chemicals. To this end, we constructed a hybrid network containing both proteins and chemicals, and generalized an existing computational method previously used to identify disease genes to identify new candidate genes and chemicals simultaneously. Based on jackknife test, our generalized method outperforms or at least performs at the same level as those obtained by a widely used method--the Random Walk with Restart (RWR). The analysis results of the final obtained genes and chemicals demonstrated that they highly shared gene ontology (GO) terms and KEGG pathways with direct and indirect associations with esophageal cancer. In addition, we also discussed the likelihood of selected candidate genes and chemicals being novel genes and chemicals related to esophageal cancer.

  11. "We're Not Alone": An Analysis of the Relationship between Program Design and Teacher Candidate Interaction and Support in a Teacher Education Program Employing a Cohort System

    ERIC Educational Resources Information Center

    Levin, Jason

    2012-01-01

    There is very little evidence regarding the specifics of how teacher candidates in preservice teacher education programs employing a cohort system interact and support one another. Similarly, there have been calls for more evidence of the specifics of the socialization process of teacher candidates, especially as it relates to the relationship…

  12. Gene-environment interplay in Drosophila melanogaster: chronic nutritional deprivation in larval life affects adult fecal output.

    PubMed

    Urquhart-Cronish, Mackenzie; Sokolowski, Marla B

    2014-10-01

    Life history consequences of stress in early life are varied and known to have lasting impacts on the fitness of an organism. Gene-environment interactions play a large role in how phenotypic differences are mediated by stressful conditions during development. Here we use natural allelic 'rover/sitter' variants of the foraging (for) gene and chronic early life nutrient deprivation to investigate gene-environment interactions on excretion phenotypes. Excretion assay analysis and a fully factorial nutritional regimen encompassing the larval and adult life cycle of Drosophila melanogaster were used to assess the effects of larval and adult nutritional stress on adult excretion phenotypes. Natural allelic variants of for exhibited differences in the number of fecal spots when they were nutritionally deprived as larvae and well fed as adults. for mediates the excretion response to chronic early-life nutritional stress in mated female, virgin female, and male rovers and sitters. Transgenic manipulations of for in a sitter genetic background under larval but not adult food deprivation increases the number of fecal spots. Our study shows that food deprivation early in life affects adult excretion phenotypes and these excretion differences are mediated by for.

  13. Nuclear Localization of the Autism Candidate Gene Neurobeachin and Functional Interaction with the NOTCH1 Intracellular Domain Indicate a Role in Regulating Transcription

    PubMed Central

    Tuand, Krizia; Stijnen, Pieter; Volders, Karolien; Declercq, Jeroen; Nuytens, Kim; Meulemans, Sandra; Creemers, John

    2016-01-01

    Background Neurobeachin (NBEA) is an autism spectrum disorders (ASD) candidate gene. NBEA deficiency affects regulated secretion, receptor trafficking, synaptic architecture and protein kinase A (PKA)-mediated phosphorylation. NBEA is a large multidomain scaffolding protein. From N- to C-terminus, NBEA has a concanavalin A-like lectin domain flanked by armadillo repeats (ACA), an A-kinase anchoring protein domain that can bind to PKA, a domain of unknown function (DUF1088) and a BEACH domain, preceded by a pleckstrin homology-like domain and followed by WD40 repeats (PBW). Although most of these domains mediate protein-protein interactions, no interaction screen has yet been performed. Methods Yeast two-hybrid screens with the ACA and PBW domain modules of NBEA gave a list of interaction partners, which were analyzed for Gene Ontology (GO) enrichment. Neuro-2a cells were used for confocal microscopy and nuclear extraction analysis. NOTCH-mediated transcription was studied with luciferase reporter assays and qRT-PCR, combined with NBEA knockdown or overexpression. Results Both domain modules showed a GO enrichment for the nucleus. PBW almost exclusively interacted with transcription regulators, while ACA interacted with a number of PKA substrates. NBEA was partially localized in the nucleus of Neuro-2a cells, albeit much less than in the cytoplasm. A nuclear localization signal was found in the DUF1088 domain, which was shown to contribute to the nuclear localization of an EGFP-DPBW fusion protein. Yeast two-hybrid identified the Notch1 intracellular domain as a physical interactor of the PBW domain and a role for NBEA as a negative regulator in Notch-mediated transcription was demonstrated. Conclusion Defining novel interaction partners of conserved NBEA domain modules identified a role for NBEA as transcriptional regulator in the nucleus. The physical interaction of NBEA with NOTCH1 is most relevant for ASD pathogenesis because NOTCH signaling is essential for

  14. Tracing the Optical Imprints of AN Intermediate-Mass Black Hole Candidate in AN Interacting Galaxy Pair

    NASA Astrophysics Data System (ADS)

    Fuentes-Carrera, I.; Rosado, M.; Flores, H.; Borissova, J.

    We present observations of the extended optical counterpart of the bright, elongated ULX in the interacting galaxy pair NGC 5953/54 using the FLAMES-ARGUS integral field spectrograph on the VLT. We describe spectroscopic and spatial information of the ionized surroundings of this ULX in order to distinguish between two possible scenarios: a stellar-mass black hole binary or an intermediate-mass ( 50 solar masses) black hole.

  15. Identification of Sirtuin4 (SIRT4) Protein Interactions: Uncovering Candidate Acyl-Modified Mitochondrial Substrates and Enzymatic Regulators

    PubMed Central

    Mathias, Rommel A.; Greco, Todd M.; Cristea, Ileana M.

    2016-01-01

    Recent studies have highlighted the three mitochondrial human sirtuins (SIRT3, SIRT4, and SIRT5) as critical regulators of a wide range of cellular metabolic pathways. A key factor to understanding their impact on metabolism has been the discovery that, in addition to their ability to deacetylate substrates, mitochondrial sirtuins can have other prominent enzymatic activities. SIRT4, one of the least characterized mitochondrial sirtuins, was shown to be the first known cellular lipoamidase, removing lipoyl modifications from lysine residues of substrates. Specifically, SIRT4 was found to delipoylate and modulate the activity of the pyruvate dehydrogenase complex (PDH), a protein complex critical for the production of acetyl-CoA. Furthermore, SIRT4 is well known to have ADP-ribosyltransferase activity and to regulate the activity of the glutamate dehydrogenase complex (GDH). Adding to its impressive range of enzymatic activities are its ability to deacetylate malonyl-CoA decarboxylase (MCD) to regulate lipid catabolism, and its newly recognized ability to remove biotinyl groups from substrates that remain to be defined. Given the wide range of enzymatic activities and the still limited knowledge of its substrates, further studies are needed to characterize its protein interactions and its impact on metabolic pathways. Here, we present several proven protocols for identifying SIRT4 protein interaction networks within the mitochondria. Specifically, we describe methods for generating human cell lines expressing SIRT4, purifying mitochondria from crude organelles, and effectively capturing SIRT4 with its interactions and substrates. PMID:27246218

  16. Breast Cancer Risk – Genes, Environment and Clinics

    PubMed Central

    Fasching, P. A.; Ekici, A. B.; Adamietz, B. R.; Wachter, D. L.; Hein, A.; Bayer, C. M.; Häberle, L.; Loehberg, C. R.; Jud, S. M.; Heusinger, K.; Rübner, M.; Rauh, C.; Bani, M. R.; Lux, M. P.; Schulz-Wendtland, R.; Hartmann, A.; Beckmann, M. W.

    2011-01-01

    The information available about breast cancer risk factors has increased dramatically during the last 10 years. In particular, studies of low-penetrance genes and mammographic density have improved our understanding of breast cancer risk. In addition, initial steps have been taken in investigating interactions between genes and environmental factors. This review concerns with actual data on this topic. Several genome-wide association studies (GWASs) with a case–control design, as well as large-scale validation studies, have identified and validated more than a dozen single nucleotide polymorphisms (SNPs) associated with breast cancer risk. They are located not only in or close to genes known to be involved in cancer pathogenesis, but also in genes not previously associated with breast cancer pathogenesis, or may even not be related to any genes. SNPs have also been identified that alter the lifetime risk in BRCA mutation carriers. With regard to nongenetic risk factors, studies of postmenopausal hormone replacement therapy (HRT) have revealed important information on how to weigh up the risks and benefits of HRT. Mammographic density (MD) has become an accepted and important breast cancer risk factor. Lifestyle and nutritional considerations have become an integral part of most studies of breast cancer risk, and some improvements have been made in this field as well. More than 10 years after the publication of the first breast cancer prevention studies with tamoxifen, other substances such as raloxifene and aromatase inhibitors have been investigated and have also been shown to have preventive potential. Finally, mammographic screening systems have been implemented in most Western countries during the last decade. These may be developed further by including more individualized methods of predicting the patientʼs breast cancer risk. PMID:25253900

  17. De novo Transcriptome Sequencing to Dissect Candidate Genes Associated with Pearl Millet-Downy Mildew (Sclerospora graminicola Sacc.) Interaction

    PubMed Central

    Kulkarni, Kalyani S.; Zala, Harshvardhan N.; Bosamia, Tejas C.; Shukla, Yogesh M.; Kumar, Sushil; Fougat, Ranbir S.; Patel, Mruduka S.; Narayanan, Subhash; Joshi, Chaitanya G.

    2016-01-01

    Understanding the plant-pathogen interactions is of utmost importance to design strategies for minimizing the economic deficits caused by pathogens in crops. With an aim to identify genes underlying resistance to downy mildew, a major disease responsible for productivity loss in pearl millet, transcriptome analysis was performed in downy mildew resistant and susceptible genotypes upon infection and control on 454 Roche NGS platform. A total of ~685 Mb data was obtained with 1 575 290 raw reads. The raw reads were pre-processed into high-quality (HQ) reads making to ~82% with an average of 427 bases. The assembly was optimized using four assemblers viz. Newbler, MIRA, CLC and Trinity, out of which MIRA with a total of 14.10 Mb and 90118 transcripts proved to be the best for assembling reads. Differential expression analysis depicted 1396 and 936 and 1000 and 1591 transcripts up and down regulated in resistant inoculated/resistant control and susceptible inoculated/susceptible control respectively with a common of 3644 transcripts. The pathways for secondary metabolism, specifically the phenylpropanoid pathway was up-regulated in resistant genotype. Transcripts up-regulated as a part of defense response included classes of R genes, PR proteins, HR induced proteins and plant hormonal signaling transduction proteins. The transcripts for skp1 protein, purothionin, V type proton ATPase were found to have the highest expression in resistant genotype. Ten transcripts, selected on the basis of their involvement in defense mechanism were validated with qRT-PCR and showed positive co-relation with transcriptome data. Transcriptome analysis evoked potentials of hypersensitive response and systemic acquired resistance as possible mechanism operating in defense mechanism in pearl millet against downy mildew infection. PMID:27446100

  18. Biometric Modeling of Gene-Environment Interplay: The Intersection of Theory and Method and Applications for Social Inequality.

    PubMed

    South, Susan C; Hamdi, Nayla R; Krueger, Robert F

    2017-02-01

    For more than a decade, biometric moderation models have been used to examine whether genetic and environmental influences on individual differences might vary within the population. These quantitative Gene × Environment interaction models have the potential to elucidate not only when genetic and environmental influences on a phenotype might differ, but also why, as they provide an empirical test of several theoretical paradigms that serve as useful heuristics to explain etiology-diathesis-stress, bioecological, differential susceptibility, and social control. In the current article, we review how these developmental theories align with different patterns of findings from statistical models of gene-environment interplay. We then describe the extant empirical evidence, using work by our own research group and others, to lay out genetically informative plausible accounts of how phenotypes related to social inequality-physical health and cognition-might relate to these theoretical models.

  19. Satiety and the Self-Regulation of Food Take in Children: a Potential Role for Gene-Environment Interplay.

    PubMed

    Hughes, Sheryl O; Frazier-Wood, Alexis C

    2016-03-01

    Child eating self-regulation refers to behaviors that enable children to start and stop eating in a manner consistent with maintaining energy balance. Perturbations in these behaviors, manifesting as poorer child eating self-regulation, are associated with higher child weight status. Initial research into child eating self-regulation focused on the role of parent feeding styles and behaviors. However, we argue that child eating self-regulation is better understood as arising from a complex interplay between the child and their feeding environment, and highlight newer research into the heritable child characteristics, such as cognitive ability, that play an important role in this dynamic. Therefore, child eating self-regulation arises from gene-environment interactions. Identifying the genes and environmental influences contributing to these will help us tailor our parental feeding advice to the unique nature of the child. In this way, we will devise more effective advice for preventing childhood obesity.

  20. Satiety and the self-regulation of food take in children: A potential role for gene-environment interplay

    PubMed Central

    Hughes, Sheryl O.

    2016-01-01

    Child eating self-regulation refers to behaviors that enable children to start and stop eating in a manner consistent with maintaining energy balance. Perturbations in these behaviors, manifesting as poorer child eating self-regulation, are associated with higher child weight status. Initial research into child eating self-regulation focused on the role of parent feeding styles and behaviors. However, we argue that child eating self-regulation is better understood as arising from a complex interplay between the child and their feeding environment, and highlight newer research into the heritable child characteristics, such as cognitive ability, that play an important role in this dynamic. Therefore, child eating self-regulation arises from gene-environment interactions. Identifying the genes and environmental influences contributing to these will help us tailor our parental feeding advice to the unique nature of the child. In this way, we will devise more effective advice for preventing childhood obesity. PMID:26847550

  1. The Gene, Environment Association Studies consortium (GENEVA): maximizing the knowledge obtained from GWAS by collaboration across studies of multiple conditions.

    PubMed

    Cornelis, Marilyn C; Agrawal, Arpana; Cole, John W; Hansel, Nadia N; Barnes, Kathleen C; Beaty, Terri H; Bennett, Siiri N; Bierut, Laura J; Boerwinkle, Eric; Doheny, Kimberly F; Feenstra, Bjarke; Feingold, Eleanor; Fornage, Myriam; Haiman, Christopher A; Harris, Emily L; Hayes, M Geoffrey; Heit, John A; Hu, Frank B; Kang, Jae H; Laurie, Cathy C; Ling, Hua; Manolio, Teri A; Marazita, Mary L; Mathias, Rasika A; Mirel, Daniel B; Paschall, Justin; Pasquale, Louis R; Pugh, Elizabeth W; Rice, John P; Udren, Jenna; van Dam, Rob M; Wang, Xiaojing; Wiggs, Janey L; Williams, Kayleen; Yu, Kai

    2010-05-01

    Genome-wide association studies (GWAS) have emerged as powerful means for identifying genetic loci related to complex diseases. However, the role of environment and its potential to interact with key loci has not been adequately addressed in most GWAS. Networks of collaborative studies involving different study populations and multiple phenotypes provide a powerful approach for addressing the challenges in analysis and interpretation shared across studies. The Gene, Environment Association Studies (GENEVA) consortium was initiated to: identify genetic variants related to complex diseases; identify variations in gene-trait associations related to environmental exposures; and ensure rapid sharing of data through the database of Genotypes and Phenotypes. GENEVA consists of several academic institutions, including a coordinating center, two genotyping centers and 14 independently designed studies of various phenotypes, as well as several Institutes and Centers of the National Institutes of Health led by the National Human Genome Research Institute. Minimum detectable effect sizes include relative risks ranging from 1.24 to 1.57 and proportions of variance explained ranging from 0.0097 to 0.02. Given the large number of research participants (N>80,000), an important feature of GENEVA is harmonization of common variables, which allow analyses of additional traits. Environmental exposure information available from most studies also enables testing of gene-environment interactions. Facilitated by its sizeable infrastructure for promoting collaboration, GENEVA has established a unified framework for genotyping, data quality control, analysis and interpretation. By maximizing knowledge obtained through collaborative GWAS incorporating environmental exposure information, GENEVA aims to enhance our understanding of disease etiology, potentially identifying opportunities for intervention.

  2. Gene-Environment Correlation Underlying the Association between Parental Negativity and Adolescent Externalizing Problems

    ERIC Educational Resources Information Center

    Marceau, Kristine; Horwitz, Briana N.; Narusyte, Jurgita; Ganiban, Jody M.; Spotts, Erica L.; Reiss, David; Neiderhiser, Jenae M.

    2013-01-01

    Studies of adolescent or parent-based twins suggest that gene-environment correlation (rGE) is an important mechanism underlying parent-adolescent relationships. However, information on how parents' and children's genes and environments influence correlated parent "and" child behaviors is needed to distinguish types of rGE. The present…

  3. Gene-Environment Interplay in Internalizing Disorders: Consistent Findings across Six Environmental Risk Factors

    ERIC Educational Resources Information Center

    Hicks, Brian M.; Dirago, Ana C.; Iacono, William G.; McGue, Matt

    2009-01-01

    Background: Behavior genetic methods can help to elucidate gene-environment (G-E) interplay in the development of internalizing (INT) disorders (i.e., major depression and anxiety disorders). To date, however, no study has conducted a comprehensive analysis examining multiple environmental risk factors with the purpose of delineating general…

  4. Gene Environment Risk Assessment and Colorectal Cancer Screening in an Average Risk Population: A Randomized, Controlled Trial

    PubMed Central

    Weinberg, David S.; Myers, Ronald E.; Keenan, Eileen; Ruth, Karen; Sifri, Randa; Ziring, Barry; Ross, Eric; Manne, Sharon L.

    2015-01-01

    Background New methods are needed to improve health behaviors such as adherence to colorectal cancer (CRC) screening. There is increasing availability of personalized genetic information to inform medical decisions. It is not known if such information motivates behavioral change. Objective To determine, in average risk persons, if individualized gene-environment risk assessment about CRC susceptibility improves adherence to screening. Design Two-arm, randomized, controlled trial Setting Four medical school affiliated primary care practices Patients 783 patients at average risk for CRC, but not adherent with screening at study entry Intervention Patients were randomized to usual care or to receipt of Gene Environmental Risk Assessment (GERA), which assessed Methylene Tetrahydrofolate Reductase (MTHFR) polymorphisms and serum folate level. Based on pre-specified polymorphism/folate level combinations, GERA participants were told they were at either “elevated” or at “average” risk for CRC. Measurements The primary outcome was receipt of CRC screening within 6 months of study entry. Results CRC screening rates were not statistically significantly different between usual care (35.7%) and GERA (33.1%) arms overall. After adjustment for baseline participant factors, the odds ratio (OR) for screening completion for GERA vs usual care was 0.88 (95% CI 0.64 - 1.22). Within the GERA arm, there was no significant difference in screening rates between GERA average risk (38.1%) and GERA elevated risk (26.9%) groups. Odds ratios for elevated vs. average risk remained non-significant after adjustment for covariates (OR=0.75, 95% CI 0.39 - 1.42). Limitations Only one personalized, gene-environment interaction and only one health behavior, colorectal cancer screening, were assessed. Conclusion In average risk persons, there was no positive association between CRC screening uptake and feedback of a single personalized gene-environment risk assessment (GERA). Additional

  5. Identification of candidates for interacting partners of the tail domain of DcNMCP1, a major component of the Daucus carota nuclear lamina-like structure.

    PubMed

    Mochizuki, Ryota; Tsugama, Daisuke; Yamazaki, Michihiro; Fujino, Kaien; Masuda, Kiyoshi

    2017-02-01

    NMCP/CRWN (NUCLEAR MATRIX CONSTITUENT PROTEIN/CROWDED NUCLEI) is a major component of a protein fibrous meshwork (lamina-like structure) on the plant inner nuclear membrane. NMCP/CRWN contributes to regulating nuclear shape and nuclear functions. An NMCP/CRWN protein in Daucus carota (DcNMCP1) is localized to the nuclear periphery in interphase cells, and surrounds chromosomes in cells in metaphase and anaphase. The N-terminal region and the C-terminal region of DcNMCP1 are both necessary for localizing DcNMCP1 to the nuclear periphery. Here candidate interacting partners of the amino acid position 975-1053 of DcNMCP1 (T975-1053), which is present in the C-terminal region and contains a conserved sequence that plays a role in localizing DcNMCP1 to the nuclear periphery, are screened for. Arabidopsis thaliana nuclear proteins were subjected to far-Western blotting with GST-fused T975-1053 as a probe, and signals were detected at the positions corresponding to ∼70, ∼40, and ∼18 kDa. These ∼70, ∼40, and ∼18 kDa nuclear proteins were identified by mass spectrometry, and subjected to a yeast 2-hybrid (Y2H) analysis with T975-1053 as bait. In this analysis, the ∼40 kDa protein ARP7, which is a nuclear actin-related protein possibly involved in regulating chromatin structures, was confirmed to interact with T975-1053. Independently of the far-Western blotting, a Y2H screen was performed using T975-1053 as bait. Targeted Y2H assays confirmed that 3 proteins identified in the screen, MYB3, SINAT1, and BIM1, interact with T975-1053. These proteins might have roles in NMCP/CRWN protein-mediated biologic processes.

  6. Gene-environment interactions and the impact on obesity and lipid profile phenotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sequencing the human genome provided the data, human intellectual capital and technology, particularly in terms of infrastructure and methodologies, to begin discovering genes involved in a wide range of human diseases and afflictions. This has led to a resurgence in genetics with the advent of geno...

  7. Heritability for Adolescent Antisocial Behavior Differs with Socioeconomic Status: Gene-Environment Interaction

    ERIC Educational Resources Information Center

    Tuvblad, Catherine; Grann, Martin; Lichtenstein, Paul

    2006-01-01

    Background: Socioeconomic status is often assumed to be of importance for the development of antisocial behavior, yet it explains only a fraction of the variance. One explanation for this paradox could be that socioeconomic status moderates the influence of genetic and environmental effects on antisocial behavior. Method: TCHAD is a Swedish…

  8. Gene-Gene and Gene-Environment Interactions in the Etiology of Breast Cancer

    DTIC Science & Technology

    2007-06-01

    Egusi Vegetable 1 2 3 4 5 67. Egusi Tomato Vegetable 1 2 3 4 5 68. Egusi Okra 1 2 3 4 5 69. Okra soup 1 2 3 4 5 Disclaimer: This is...unpublished 70. Okra Tomato 1 2 3 4 5 71. Okra Vegetable 1 2 3 4 5 72. Okra Tomato Vegetable 1 2 3 4 5 73. Ogbolo Tomato 1 2 3 4 5 74. Ogbolo... Okra 1 2 3 4 5 75. Ogbolo Vegetable 1 2 3 4 5 76. Ewedu Tomato 1 2 3 4 5 77. Banga ( Palm Sauce) 1 2 3 4 5 78. Banga Tomato 1 2 3 4 5 79

  9. Gene-environment interactions of circadian-related genes for cardiometabolic traits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Common circadian-related gene variants associate with increased risk for metabolic alterations including type 2 diabetes. However, little is known about whether diet and sleep could modify associations between circadian-related variants (CLOCK-rs1801260, CRY2-rs11605924, MTNR1B-rs1387153, MTNR1B-rs1...

  10. Gene environment interaction of GALNT2 and APOE gene with hypertension in the Chinese Han Population.

    PubMed

    Zhang, Xuejuan; Zhao, Haiping; Zhang, Jietao; Han, Di; Zheng, Yu; Guo, Xiaozi; He, Dian; Guo, Jin; Wang, Yingcui

    2015-01-01

    In some GWAs studies, GALNT2 and APOE polymorphisms have been identified to be related to alterations of plasma or serum HDL-C and TG concentrations. The purpose of our study is to assess the contribution of GALNT2 rs4846914, APOE rs429358, rs7412, rs405509 variants, and several environmental factors to the development of hypertension disease in the China Han population. A hospital-based case-control study was conducted. Cases were hypertension (n=211) and controls were normal participants (n=434). The AA, AG, and GG genotype frequencies of GALNT2 rs4846914 were 22.8%, 43.1%, and 34.1% in hypertension subjects, and 35.3%, 44.2%, and 20.5% in controls (P<0.05), respectively. The OR of the AG genotype adjusted for all risk factors compared to the AA genotype was 1.61 (95%CI: 1.02 to 2.56) and to the GG genotype 2.67 (95%CI: 1.59 to 4.488). There was no significant difference between the APOE rs429358, rs7412, and rs405509 genotype frequencies in hypertension and control subjects. The present work indicates that SNP rs4846914 in GALNT2 gene is related to an increased risk of hypertension in China Han population, but the APOE gene is not.

  11. Gene-environment interactions in susceptibility to fumonisin-induced neural tube defects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisin B1 (FB1) is a mycotoxin produced by a common fungal contaminant of corn. In populations that rely on maize-based foods as a dietary staple, consumption of FB1-contaminated food during early pregnancy is associated with increased risk for neural tube defects (NTDs). Administration of FB1 ...

  12. Gene-environment interactions in asthma: with apologies to William of Ockham.

    PubMed

    Martinez, Fernando D

    2007-01-01

    Many environmental factors and a large number of genetic polymorphisms have been reported to be associated with asthma risk in different locales and at different ages. It seems that what we call asthma is a heterogeneous set of conditions for which the only common feature is recurrent airway obstruction that is at least partially responsive to usual asthma therapy. Recent studies in which environmental factors and genetic variants were studied concomitantly have suggested a potential unifying concept for the disease. It seems that asthma is a genetically mediated development dysregulation of diverse immune and airway responses to a variety of specific and nonspecific exposures. It thus seems improbable that most genetic variants associated with asthma influence the disease regardless of which environmental factors trigger it and at which lifetime phase they are present. More likely, the most important gene variants for asthma are polymorphisms that exert their influence on the network system controlling biological responses to asthma-related exposures.

  13. Gene-Environment Interaction and Breast Cancer on Long Island, NY

    DTIC Science & Technology

    2008-05-01

    present in many consumer products as well as many common household materials such as plastics and fragrances . Given the rising rates of asthma and...Prevention, Atlanta, GA , USA cDepartment of Pediatrics, Mount Sinai School of Medicine, New York, NY, USA Received 30 March 2007; received in revised form...purposes such as adding flexibility to plastics and making fragrances last ARTICLE IN PRESS S.L. Teitelbaum et al. / Environmental Research 106 (2008) 257

  14. Histone Deacetylases and Mood Disorders: Epigenetic Programming in Gene-Environment Interactions

    PubMed Central

    Machado-Vieira, Rodrigo; Ibrahim, Lobna; Zarate, Carlos A.

    2010-01-01

    Epigenetics involves molecular mechanisms related to gene expression independent of DNA sequence, mostly mediated by modification of chromatin histones. It has recently been suggested that these transcriptional changes may be implicated in the pathophysiology of mood disorders. In addition, histone deacetylase (HDAC) inhibitors have been shown to control epigenetic programming associated with the regulation of cognition and behavior, and may reverse dysfunctional epigenetic regulation associated with early life events in preclinical models. In this context, the active and continuous adaptation of chromatin, and the access of gene promoters to transcription factor mechanisms may represent a potential therapeutic target in the treatment of mood disorders such as bipolar disorder (BD) and major depressive disorder (MDD). Notably, the standard mood stabilizer valproate (VPA) has been shown to modulate the epigenome by inhibiting HDACs. However, several potential limitations are associated with this class of agents, including lack of selectivity for specific HDAC isoforms as well as risk of potentially serious side effects. Further studies regarding the potential role of chromatin remodeling in the mechanism of action of antidepressants and mood stabilizers are necessary to clarify the potential role of this class of agents as therapeutics for mood disorders. PMID:20961400

  15. Gene Environment Interactions in Women With Breast and Secondary Lung Cancer

    DTIC Science & Technology

    2005-07-01

    expression is correlated with benzo [ a ] pyrene -DNA adducts in carcinoma cell lines. Carcinogenesis 1995; 16:2117-2124. 16. Phillips, E.N., et al...with Breast and Secondary Lung Cancer PRINCIPAL INVESTIGATOR: Meredith A . Tennis Peter G...Secondary Lung Cancer 5b. GRANT NUMBER DAMD17-03-1-0300 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Meredith A . Tennis 5d. PROJECT NUMBER Peter G

  16. Functional Analysis of the Early Development of Self-Injurious Behavior: Incorporating Gene-Environment Interactions

    ERIC Educational Resources Information Center

    Langthorne, Paul; McGill, Peter

    2008-01-01

    The analysis of the early development of self-injurious behavior (SIB) has, to date, reflected the wider distinction between nature and nurture. Despite the status of genetic factors as risk markers for the later development of SIB, a model that accounts for their influence on early behavior-environment relations is lacking. In the current paper…

  17. Gene-Environment Interaction and Breast Cancer on Long Island, NY

    DTIC Science & Technology

    2005-05-01

    essential for primary prevention. 14. SUBJECT TERMS 15. NUMBER OF PAGES Epidemiology, environmental exposure, endocrine disruptors , estrogen 7 receptor...residential pesticide use on Long Island, NY" 4 W81XWH-04-1-0507 o American Association for Cancer Research (AACR) and co-chaired mini-symposium on "The...estrogens, including bisphenol A, phthalates and pyrethroid pesticides . "o The collection of serial urine samples will be completed in April 2005. "o

  18. Gene--Environment Interplay and Delinquent Involvement: Evidence of Direct, Indirect, and Interactive Effects

    ERIC Educational Resources Information Center

    Beaver, Kevin M.; DeLisi, Matt; Wright, John Paul; Vaughn, Michael G.

    2009-01-01

    Behavioral genetic research has revealed that biogenic factors play a role in the development of antisocial behaviors. Much of this research has also explicated the way in which the environment and genes may combine to create different phenotypes. The authors draw heavily from this literature and use data from the National Longitudinal Study of…

  19. GENE-ENVIRONMENT INTERACTIONS: A REVIEW OF EFFECTS ON REPRODUCTION AND DEVELOPMENT

    EPA Science Inventory

    Polymorphisms in genes can lead to differences in the level of susceptibility of individuals to potentially adverse effects of environmental influences, such as chemical exposure, on prenatal development or male or female reproductive function. We have reviewed the literature in ...

  20. Analysis of the Interaction between Globular Head Modules of Human C1q and Its Candidate Receptor gC1qR

    PubMed Central

    Pednekar, Lina; Pathan, Ansar A.; Paudyal, Basudev; Tsolaki, Anthony G.; Kaur, Anuvinder; Abozaid, Suhair M.; Kouser, Lubna; Khan, Haseeb A.; Peerschke, Ellinor I.; Shamji, Mohamed H.; Stenbeck, Gudrun; Ghebrehiwet, Berhane; Kishore, Uday

    2016-01-01

    The heterotrimeric globular head (gC1q) domain of human C1q is made up of the C-terminal ends of the three individual chains, ghA, ghB, and ghC. A candidate receptor for the gC1q domain is a multi-functional pattern recognition protein, gC1qR. Since understanding of gC1qR and gC1q interaction could provide an insight into the pleiotropic functions of gC1qR, this study was undertaken to identify the gC1qR-binding site on the gC1q domain, using the recombinant ghA, ghB, and ghC modules and their substitution mutants. Our results show that ghA, ghB, and ghC modules can interact with gC1qR independently, thus reinforcing the notion of modularity within the gC1q domain of human C1q. Mutational analysis revealed that while Arg162 in the ghA module is central to interaction between gC1qR and C1q, a single amino acid substitution (arginine to glutamate) in residue 114 of the ghB module resulted in enhanced binding. Expression of gC1qR and C1q in adherent monocytes with or without pro-inflammatory stimuli was also analyzed by qPCR; it showed an autocrine/paracrine basis of C1q and gC1qR interaction. Microscopic studies revealed that C1q and gC1qR are colocalized on PBMCs. Cell proliferation assays indicated that ghA, ghB, and ghC modules were able to attenuate phytohemagglutinin-stimulated proliferation of PBMCs. Addition of gC1qR had an additive effect on the anti-proliferative effect of globular head modules. In summary, our results identify residues involved in C1q-gC1qR interaction and explain, to a certain level, their involvement on the immune cell surface, which is relevant for C1q-induced functions including inflammation, infection, and immunity. PMID:28018340

  1. Analysis of the Interaction between Globular Head Modules of Human C1q and Its Candidate Receptor gC1qR.

    PubMed

    Pednekar, Lina; Pathan, Ansar A; Paudyal, Basudev; Tsolaki, Anthony G; Kaur, Anuvinder; Abozaid, Suhair M; Kouser, Lubna; Khan, Haseeb A; Peerschke, Ellinor I; Shamji, Mohamed H; Stenbeck, Gudrun; Ghebrehiwet, Berhane; Kishore, Uday

    2016-01-01

    The heterotrimeric globular head (gC1q) domain of human C1q is made up of the C-terminal ends of the three individual chains, ghA, ghB, and ghC. A candidate receptor for the gC1q domain is a multi-functional pattern recognition protein, gC1qR. Since understanding of gC1qR and gC1q interaction could provide an insight into the pleiotropic functions of gC1qR, this study was undertaken to identify the gC1qR-binding site on the gC1q domain, using the recombinant ghA, ghB, and ghC modules and their substitution mutants. Our results show that ghA, ghB, and ghC modules can interact with gC1qR independently, thus reinforcing the notion of modularity within the gC1q domain of human C1q. Mutational analysis revealed that while Arg162 in the ghA module is central to interaction between gC1qR and C1q, a single amino acid substitution (arginine to glutamate) in residue 114 of the ghB module resulted in enhanced binding. Expression of gC1qR and C1q in adherent monocytes with or without pro-inflammatory stimuli was also analyzed by qPCR; it showed an autocrine/paracrine basis of C1q and gC1qR interaction. Microscopic studies revealed that C1q and gC1qR are colocalized on PBMCs. Cell proliferation assays indicated that ghA, ghB, and ghC modules were able to attenuate phytohemagglutinin-stimulated proliferation of PBMCs. Addition of gC1qR had an additive effect on the anti-proliferative effect of globular head modules. In summary, our results identify residues involved in C1q-gC1qR interaction and explain, to a certain level, their involvement on the immune cell surface, which is relevant for C1q-induced functions including inflammation, infection, and immunity.

  2. Genes, environment and gene expression in colon tissue: a pathway approach to determining functionality.

    PubMed

    Slattery, Martha L; Pellatt, Daniel F; Wolff, Roger K; Lundgreen, Abbie

    2016-01-01

    Genetic and environmental factors have been shown to work together to alter cancer risk. In this study we evaluate previously identified gene and lifestyle interactions in a candidate pathway that were associated with colon cancer risk to see if these interactions altered gene expression. We analyzed non-tumor RNA-seq data from 144 colon cancer patients who had genotype, recent cigarette smoking, diet, body mass index (BMI), and recent aspirin/non-steroidal anti-inflammatory use data. Using a false discovery rate of 0.1, we evaluated differential gene expression between high and low levels of lifestyle exposure and genotypes using DESeq2. Thirteen pathway genes and 17 SNPs within those genes were associated with altered expression of other genes in the pathway. BMI, NSAIDs use and dietary components of the oxidative balance score (OBS) also were associated with altered gene expression. SNPs previously identified as interacting with these lifestyle factors, altered expression of pathway genes. NSAIDs interacted with 10 genes (15 SNPs) within those genes to alter expression of 28 pathway genes; recent cigarette smoking interacted with seven genes (nine SNPs) to alter expression of 27 genes. BMI interacted with FLT1, KDR, SEPN1, TERT, TXNRD2, and VEGFA to alter expression of eight genes. Three genes (five SNPs) interacted with OBS to alter expression of 12 genes. These data provide support for previously identified lifestyle and gene interactions associated with colon cancer in that they altered expression of key pathway genes. The need to consider lifestyle factors in conjunction with genetic factors is illustrated.

  3. Gene-environment interplay in the link of friends' and nonfriends' behaviors with children's social reticence in a competitive situation.

    PubMed

    Guimond, Fanny-Alexandra; Brendgen, Mara; Vitaro, Frank; Forget-Dubois, Nadine; Dionne, Ginette; Tremblay, Richard E; Boivin, Michel

    2014-03-01

    This study used a genetically informed design to assess the effects of friends' and nonfriends' reticent and dominant behaviors on children's observed social reticence in a competitive situation. Potential gene-environment correlations (rGE) and gene-environment interactions (GxE) in the link between (a) friends' and nonfriends' behaviors and (b) children's social reticence were examined. The sample comprised 466 twin children (i.e., the target children), each of whom was assessed in kindergarten together with a same-sex friend and two nonfriend classmates of either sex. Multilevel regression analyses revealed that children with a genetic disposition for social reticence showed more reticent behavior in the competitive situation and were more likely to affiliate with reticent friends (i.e., rGE). Moreover, a higher level of children's reticent behavior was predicted by their friends' higher social reticence (particularly for girls) and their friends' higher social dominance, independently of children's genetic disposition. Children's social reticence was also predicted by their nonfriends' behaviors. Specifically, children were less reticent when male nonfriends showed high levels of social reticence in the competitive situation, and this was particularly true for children with a genetic disposition for social reticence (i.e., GxE). Moreover, children genetically vulnerable for social reticence seemed to foster dominant behavior in their female nonfriend peers (i.e., rGE). In turn, male nonfriends seemed to be more dominant as soon as the target children were reticent, even if the target children did not have a stable genetic disposition for this behavior.

  4. Social defeat interacts with Disc1 mutations in the mouse to affect behavior.

    PubMed

    Haque, F Nipa; Lipina, Tatiana V; Roder, John C; Wong, Albert H C

    2012-08-01

    DISC1 (Disrupted-in-schizophrenia 1) is a strong candidate susceptibility gene for psychiatric disease that was originally discovered in a family with a chromosomal translocation severing this gene. Although the family members with the translocation had an identical genetic mutation, their clinical diagnosis and presentation varied significantly. Gene-environment interactions have been proposed as a mechanism underlying the complex heritability and variable phenotype of psychiatric disorders such as major depressive disorder and schizophrenia. We hypothesized that gene-environment interactions would affect behavior in a mutant Disc1 mouse model. We examined the effect of chronic social defeat (CSD) as an environmental stressor in two lines of mice carrying different Disc1 point mutations, on behaviors relevant to psychiatric illness: locomotion in a novel open field (OF), pre-pulse inhibition (PPI) of the acoustic startle response, latent inhibition (LI), elevated plus maze (EPM), forced swim test (FST), sucrose consumption (SC), and the social interaction task for sociability and social novelty (SSN). We found that Disc1-L100P +/- and wild-type mice have similar anxiety responses to CSD, while Q31L +/- mice had a very different response. We also found evidence of significant gene-environment interactions in the OF, EPM and SSN.

  5. The First Pilot Genome-Wide Gene-Environment Study of Depression in the Japanese Population

    PubMed Central

    Otowa, Takeshi; Kawamura, Yoshiya; Tsutsumi, Akizumi; Kawakami, Norito; Kan, Chiemi; Shimada, Takafumi; Umekage, Tadashi; Kasai, Kiyoto; Tokunaga, Katsushi; Sasaki, Tsukasa

    2016-01-01

    Stressful events have been identified as a risk factor for depression. Although gene–environment (G × E) interaction in a limited number of candidate genes has been explored, no genome-wide search has been reported. The aim of the present study is to identify genes that influence the association of stressful events with depression. Therefore, we performed a genome-wide G × E interaction analysis in the Japanese population. A genome-wide screen with 320 subjects was performed using the Affymetrix Genome-Wide Human Array 6.0. Stressful life events were assessed using the Social Readjustment Rating Scale (SRRS) and depression symptoms were assessed with self-rating questionnaires using the Center for Epidemiologic Studies Depression (CES-D) scale. The p values for interactions between single nucleotide polymorphisms (SNPs) and stressful events were calculated using the linear regression model adjusted for sex and age. After quality control of genotype data, a total of 534,848 SNPs on autosomal chromosomes were further analyzed. Although none surpassed the level of the genome-wide significance, a marginal significant association of interaction between SRRS and rs10510057 with depression were found (p = 4.5 × 10−8). The SNP is located on 10q26 near Regulators of G-protein signaling 10 (RGS10), which encodes a regulatory molecule involved in stress response. When we investigated a similar G × E interaction between depression (K6 scale) and work-related stress in an independent sample (n = 439), a significant G × E effect on depression was observed (p = 0.015). Our findings suggest that rs10510057, interacting with stressors, may be involved in depression risk. Incorporating G × E interaction into GWAS can contribute to find susceptibility locus that are potentially missed by conventional GWAS. PMID:27529621

  6. DrugE-Rank: improving drug–target interaction prediction of new candidate drugs or targets by ensemble learning to rank

    PubMed Central

    Yuan, Qingjun; Gao, Junning; Wu, Dongliang; Zhang, Shihua; Mamitsuka, Hiroshi; Zhu, Shanfeng

    2016-01-01

    Motivation: Identifying drug–target interactions is an important task in drug discovery. To reduce heavy time and financial cost in experimental way, many computational approaches have been proposed. Although these approaches have used many different principles, their performance is far from satisfactory, especially in predicting drug–target interactions of new candidate drugs or targets. Methods: Approaches based on machine learning for this problem can be divided into two types: feature-based and similarity-based methods. Learning to rank is the most powerful technique in the feature-based methods. Similarity-based methods are well accepted, due to their idea of connecting the chemical and genomic spaces, represented by drug and target similarities, respectively. We propose a new method, DrugE-Rank, to improve the prediction performance by nicely combining the advantages of the two different types of methods. That is, DrugE-Rank uses LTR, for which multiple well-known similarity-based methods can be used as components of ensemble learning. Results: The performance of DrugE-Rank is thoroughly examined by three main experiments using data from DrugBank: (i) cross-validation on FDA (US Food and Drug Administration) approved drugs before March 2014; (ii) independent test on FDA approved drugs after March 2014; and (iii) independent test on FDA experimental drugs. Experimental results show that DrugE-Rank outperforms competing methods significantly, especially achieving more than 30% improvement in Area under Prediction Recall curve for FDA approved new drugs and FDA experimental drugs. Availability: http://datamining-iip.fudan.edu.cn/service/DrugE-Rank Contact: zhusf@fudan.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307615

  7. Cognitive change in aging: identifying gene-environment correlation and nonshared environment mechanisms.

    PubMed

    Deater-Deckard, Kirby; Mayr, Ulrich

    2005-03-01

    We describe gene-environment processes that may help account for individual differences in successful aging. Our emphasis is on successful aging in the cognitive domain, wherein individuals come to use a variety of strategies to cope with changes in cognitive capacities. We focus on the role of executive control in particular and define gene-environment correlation and nonshared environmental mechanisms. The quantitative genetic methods used to identify these mechanisms are described, with examples from research in childhood, where such studies are now common. Future work will be most effective if it is guided by life-span development frameworks that address these processes, such as the developmental genotype-->environment theory of Scarr and McCartney and the selection/optimization/compensation theory of Baltes and Baltes.

  8. Gene-environment interplay in Drosophila melanogaster: chronic food deprivation in early life affects adult exploratory and fitness traits.

    PubMed

    Burns, James Geoffrey; Svetec, Nicolas; Rowe, Locke; Mery, Frederic; Dolan, Michael J; Boyce, W Thomas; Sokolowski, Marla B

    2012-10-16

    Early life adversity has known impacts on adult health and behavior, yet little is known about the gene-environment interactions (GEIs) that underlie these consequences. We used the fruit fly Drosophila melanogaster to show that chronic early nutritional adversity interacts with rover and sitter allelic variants of foraging (for) to affect adult exploratory behavior, a phenotype that is critical for foraging, and reproductive fitness. Chronic nutritional adversity during adulthood did not affect rover or sitter adult exploratory behavior; however, early nutritional adversity in the larval period increased sitter but not rover adult exploratory behavior. Increasing for gene expression in the mushroom bodies, an important center of integration in the fly brain, changed the amount of exploratory behavior exhibited by sitter adults when they did not experience early nutritional adversity but had no effect in sitters that experienced early nutritional adversity. Manipulation of the larval nutritional environment also affected adult reproductive output of sitters but not rovers, indicating GEIs on fitness itself. The natural for variants are an excellent model to examine how GEIs underlie the biological embedding of early experience.

  9. Significant interactions between maternal PAH exposure and haplotypes in candidate genes on B[a]P-DNA adducts in a NYC cohort of non-smoking African-American and Dominican mothers and newborns.

    PubMed

    Iyer, Shoba; Perera, Frederica; Zhang, Bingzhi; Chanock, Stephen; Wang, Shuang; Tang, Deliang

    2014-01-01

    Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[a]pyrene (B[a]P) is a well-studied PAH that is classified as a probable human carcinogen. Within our New York City-based cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn haplotypes (and in one case, a single-nucleotide polymorphism) in key B[a]P metabolism genes on B[a]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking African-American (n = 132) and Dominican (n = 235) women with available data on maternal PAH exposure, paired cord adducts and genetic data who resided in the Washington Heights, Central Harlem and South Bronx neighborhoods of New York City. We selected seven maternal and newborn genes related to B[a]P metabolism, detoxification and repair for our analyses: CYP1A1, CYP1A2, CYP1B1, GSTM3, GSTT2, NQO1 and XRCC1. We found significant interactions between maternal PAH exposure and haplotype on cord B[a]P-DNA adducts in the following genes: maternal CYP1B1, XRCC1 and GSTM3, and newborn CYP1A2 and XRCC1 in African-Americans; and maternal XRCC1 and newborn NQO1 in Dominicans. These novel findings highlight differences in maternal and newborn genetic contributions to B[a]P-DNA adduct formation, as well as ethnic differences in gene-environment interactions, and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[a]P.

  10. Axenic culture of a candidate division TM7 bacterium from the human oral cavity and biofilm interactions with other oral bacteria.

    PubMed

    Soro, Valeria; Dutton, Lindsay C; Sprague, Susan V; Nobbs, Angela H; Ireland, Anthony J; Sandy, Jonathan R; Jepson, Mark A; Micaroni, Massimo; Splatt, Peter R; Dymock, David; Jenkinson, Howard F

    2014-10-01

    The diversity of bacterial species in the human oral cavity is well recognized, but a high proportion of them are presently uncultivable. Candidate division TM7 bacteria are almost always detected in metagenomic studies but have not yet been cultivated. In this paper, we identified candidate division TM7 bacterial phylotypes in mature plaque samples from around orthodontic bonds in subjects undergoing orthodontic treatment. Successive rounds of enrichment in laboratory media led to the isolation of a pure culture of one of these candidate division TM7 phylotypes. The bacteria formed filaments of 20 to 200 μm in length within agar plate colonies and in monospecies biofilms on salivary pellicle and exhibited some unusual morphological characteristics by transmission electron microscopy, including a trilaminated cell surface layer and dense cytoplasmic deposits. Proteomic analyses of cell wall protein extracts identified abundant polypeptides predicted from the TM7 partial genomic sequence. Pleiomorphic phenotypes were observed when the candidate division TM7 bacterium was grown in dual-species biofilms with representatives of six different oral bacterial genera. The TM7 bacterium formed long filaments in dual-species biofilm communities with Actinomyces oris or Fusobacterium nucleatum. However, the TM7 isolate grew as short rods or cocci in dual-species biofilms with Porphyromonas gingivalis, Prevotella intermedia, Parvimonas micra, or Streptococcus gordonii, forming notably robust biofilms with the latter two species. The ability to cultivate TM7 axenically should majorly advance understanding of the physiology, genetics, and virulence properties of this novel candidate division oral bacterium.

  11. Interpretations of education about gene-environment influences on health in rural Ethiopia: the context of a neglected tropical disease

    PubMed Central

    Tora, Abebayehu; Ayode, Desta; Tadele, Getnet; Farrell, David; Davey, Gail; McBride, Colleen M.

    2016-01-01

    Background Misunderstandings of the role of genetics in disease development are associated with stigmatizing behaviors and fatalistic attitudes about prevention. This report describes an evaluation of community understanding of an educational module about genetic and environmental influences on the development of podoconiosis, a neglected tropical disease endemic in highland Ethiopia. Methods A qualitative process assessment was conducted as part of a large prospective intervention trial in August 2013, in Wolaita Zone, southern Ethiopia. Sixty five participants were purposively selected from 600 households randomized to receive the inherited susceptibility module. The educational module used pictorial representations and oral explanations of the interaction of inherited sensitivity and soil exposure and was delivered by lay health educators in participants' homes. Data were collected using semi-structured individual interviews (IDIs) or focus group discussions (FGDs). Results Qualitative analyses showed that most participants improved their understanding of inherited soil sensitivity and susceptibility to podoconiosis. Participants linked their new understanding to decreased stigma-related attitudes. The module also corrected misconceptions that the condition was contagious, again diminishing stigmatizing attitudes. Lastly, these improvements in understanding increased the perceived value of foot protection. Conclusions Taken together, these improvements support the acceptability, feasibility and potential benefits of implementing gene-environment education in low and middle income countries. PMID:27114426

  12. Gene-Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood: Is APOE a Variability Gene?

    PubMed

    Reynolds, Chandra A; Gatz, Margaret; Christensen, Kaare; Christiansen, Lene; Dahl Aslan, Anna K; Kaprio, Jaakko; Korhonen, Tellervo; Kremen, William S; Krueger, Robert; McGue, Matt; Neiderhiser, Jenae M; Pedersen, Nancy L

    2016-01-01

    Despite emerging interest in gene-environment interaction (GxE) effects, there is a dearth of studies evaluating its potential relevance apart from specific hypothesized environments and biometrical variance trends. Using a monozygotic within-pair approach, we evaluated evidence of G×E for body mass index (BMI), depressive symptoms, and cognition (verbal, spatial, attention, working memory, perceptual speed) in twin studies from four countries. We also evaluated whether APOE is a 'variability gene' across these measures and whether it partly represents the 'G' in G×E effects. In all three domains, G×E effects were pervasive across country and gender, with small-to-moderate effects. Age-cohort trends were generally stable for BMI and depressive symptoms; however, they were variable-with both increasing and decreasing age-cohort trends-for different cognitive measures. Results also suggested that APOE may represent a 'variability gene' for depressive symptoms and spatial reasoning, but not for BMI or other cognitive measures. Hence, additional genes are salient beyond APOE.

  13. Determination of Perceptions of the Teacher Candidates Studying in the Computer and Instructional Technology Department towards Human-Computer Interaction and Related Basic Concepts

    ERIC Educational Resources Information Center

    Kiyici, Mubin

    2011-01-01

    HCI is a field which has an increasing popularity by virtue of the spread of the computers and internet and gradually contributes to the production of the user-friendlier software and hardware with the contribution of the scientists from different disciplines. Teacher candidates studying at the computer and instructional technologies department…

  14. Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases.

    PubMed

    Harris, Philip A; Berger, Scott B; Jeong, Jae U; Nagilla, Rakesh; Bandyopadhyay, Deepak; Campobasso, Nino; Capriotti, Carol A; Cox, Julie A; Dare, Lauren; Dong, Xiaoyang; Eidam, Patrick M; Finger, Joshua N; Hoffman, Sandra J; Kang, James; Kasparcova, Viera; King, Bryan W; Lehr, Ruth; Lan, Yunfeng; Leister, Lara K; Lich, John D; MacDonald, Thomas T; Miller, Nathan A; Ouellette, Michael T; Pao, Christina S; Rahman, Attiq; Reilly, Michael A; Rendina, Alan R; Rivera, Elizabeth J; Schaeffer, Michelle C; Sehon, Clark A; Singhaus, Robert R; Sun, Helen H; Swift, Barbara A; Totoritis, Rachel D; Vossenkämper, Anna; Ward, Paris; Wisnoski, David D; Zhang, Daohua; Marquis, Robert W; Gough, Peter J; Bertin, John

    2017-02-23

    RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-molecule inhibitors of RIP1 kinase that are suitable for advancement into the clinic have yet to be described. Herein, we report our lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and profile of clinical candidate GSK2982772 (compound 5), currently in phase 2a clinical studies for psoriasis, rheumatoid arthritis, and ulcerative colitis. Compound 5 potently binds to RIP1 with exquisite kinase specificity and has excellent activity in blocking many TNF-dependent cellular responses. Highlighting its potential as a novel anti-inflammatory agent, the inhibitor was also able to reduce spontaneous production of cytokines from human ulcerative colitis explants. The highly favorable physicochemical and ADMET properties of 5, combined with high potency, led to a predicted low oral dose in humans.

  15. Synthetic lethal genetic interactions that decrease somatic cell proliferation in Caenorhabditis elegans identify the alternative RFC CTF18 as a candidate cancer drug target.

    PubMed

    McLellan, Jessica; O'Neil, Nigel; Tarailo, Sanja; Stoepel, Jan; Bryan, Jennifer; Rose, Ann; Hieter, Philip

    2009-12-01

    Somatic mutations causing chromosome instability (CIN) in tumors can be exploited for selective killing of cancer cells by knockdown of second-site genes causing synthetic lethality. We tested and statistically validated synthetic lethal (SL) interactions between mutations in six Saccharomyces cerevisiae CIN genes orthologous to genes mutated in colon tumors and five additional CIN genes. To identify which SL interactions are conserved in higher organisms and represent potential chemotherapeutic targets, we developed an assay system in Caenorhabditis elegans to test genetic interactions causing synthetic proliferation defects in somatic cells. We made use of postembryonic RNA interference and the vulval cell lineage of C. elegans as a readout for somatic cell proliferation defects. We identified SL interactions between members of the cohesin complex and CTF4, RAD27, and components of the alternative RFC(CTF18) complex. The genetic interactions tested are highly conserved between S. cerevisiae and C. elegans and suggest that the alternative RFC components DCC1, CTF8, and CTF18 are ideal therapeutic targets because of their mild phenotype when knocked down singly in C. elegans. Furthermore, the C. elegans assay system will contribute to our knowledge of genetic interactions in a multicellular animal and is a powerful approach to identify new cancer therapeutic targets.

  16. Links between Friends' Physical Aggression and Adolescents' Physical Aggression: What Happens If Gene-Environment Correlations are Controlled?

    ERIC Educational Resources Information Center

    Vitaro, Frank; Brendgen, Mara; Girard, Alain; Dionne, Ginette; Tremblay, Richard E.; Boivin, Michel

    2016-01-01

    Exposure to deviant friends has been found to be a powerful source of influence on children's and adolescents' aggressive behavior. However, the contribution of deviant friends may have been overestimated because of a possible non-accounted gene-environment correlation (rGE). In this study, we used a cross-lagged design to test whether friends'…

  17. Recent advances in candidate-gene and whole-genome approaches to the discovery of anthelmintic resistance markers and the description of drug/receptor interactions.

    PubMed

    Kotze, Andrew C; Hunt, Peter W; Skuce, Philip; von Samson-Himmelstjerna, Georg; Martin, Richard J; Sager, Heinz; Krücken, Jürgen; Hodgkinson, Jane; Lespine, Anne; Jex, Aaron R; Gilleard, John S; Beech, Robin N; Wolstenholme, Adrian J; Demeler, Janina; Robertson, Alan P; Charvet, Claude L; Neveu, Cedric; Kaminsky, Ronald; Rufener, Lucien; Alberich, Melanie; Menez, Cecile; Prichard, Roger K

    2014-12-01

    Anthelmintic resistance has a great impact on livestock production systems worldwide, is an emerging concern in companion animal medicine, and represents a threat to our ongoing ability to control human soil-transmitted helminths. The Consortium for Anthelmintic Resistance and Susceptibility (CARS) provides a forum for scientists to meet and discuss the latest developments in the search for molecular markers of anthelmintic resistance. Such markers are important for detecting drug resistant worm populations, and indicating the likely impact of the resistance on drug efficacy. The molecular basis of resistance is also important for understanding how anthelmintics work, and how drug resistant populations arise. Changes to target receptors, drug efflux and other biological processes can be involved. This paper reports on the CARS group meeting held in August 2013 in Perth, Australia. The latest knowledge on the development of molecular markers for resistance to each of the principal classes of anthelmintics is reviewed. The molecular basis of resistance is best understood for the benzimidazole group of compounds, and we examine recent work to translate this knowledge into useful diagnostics for field use. We examine recent candidate-gene and whole-genome approaches to understanding anthelmintic resistance and identify markers. We also look at drug transporters in terms of providing both useful markers for resistance, as well as opportunities to overcome resistance through the targeting of the transporters themselves with inhibitors. Finally, we describe the tools available for the application of the newest high-throughput sequencing technologies to the study of anthelmintic resistance.

  18. Early-life stress and antidepressant treatment involve synaptic signaling and Erk kinases in a gene-environment model of depression.

    PubMed

    Musazzi, Laura; Mallei, Alessandra; Tardito, Daniela; Gruber, Susanne H M; El Khoury, Aram; Racagni, Giorgio; Mathé, Aleksander A; Popoli, Maurizio

    2010-06-01

    Stress has been shown to interact with genetic vulnerability in pathogenesis of psychiatric disorders. Here we investigated the outcome of interaction between genetic vulnerability and early-life stress, by employing a rodent model that combines an inherited trait of vulnerability in Flinders Sensitive Line (FSL) rats, with early-life stress (maternal separation). Basal differences in synaptic signaling between FSL rats and their controls were studied, as well as the consequences of early-life stress in adulthood, and their response to chronic antidepressant treatment (escitalopram). FSL rats showed basal differences in the activation of synapsin I and Erk1/2, as well as in alpha CaM kinase II/syntaxin-1 and alpha CaM kinase II/NMDA-receptor interactions in purified hippocampal synaptosomes. In addition, FSL rats displayed a blunted response of Erk-MAP kinases and other differences in the outcome of early-life stress in adulthood. Escitalopram treatment restored some but not all alterations observed in FSL rats after early-life stress. The marked alterations found in key regulators of presynaptic release/neurotransmission in the basal FSL rats, and as a result of early-life stress, suggest synaptic dysfunction. These results show that early gene-environment interaction may cause life-long synaptic changes affecting the course of depressive-like behavior and response to drugs.

  19. Molecular interaction studies of green tea catechins as multitarget drug candidates for the treatment of Parkinson's disease: computational and structural insights.

    PubMed

    Azam, Faizul; Mohamed, Najah; Alhussen, Fatma

    2015-01-01

    Green tea catechins have extensively been studied for their imminent role in reducing the risk of various neurodegenerative diseases such as Parkinson's disease (PD). Understanding the molecular interaction of these compounds with various anti-Parkinsonian drug targets is of interest. The present study is intended to explore binding modes of catechins with molecular targets having potential role in PD. Lamarckian genetic algorithm methodology was adopted for molecular docking simulations employing AutoDock 4.2 program. Toxicity potential and molecular properties responsible for good pharmacokinetic profile were calculated by Osiris property explorer and Molinspiration online toolkit, respectively. A strong correlation coefficient (r(2) = 0.893) was obtained between experimentally reported and docking predicted activities of native co-crystallized ligands of the 18 target receptors used in current study. Analysis of docked conformations revealed monoamine oxidase-B as most promising, while N-methyl-D-aspartate receptor was recognized as the least favorable target for catechins. Benzopyran skeleton with a phenyl group substituted at the 2-position and a hydroxyl (or ester) function at the 3-position has been identified as common structural requirements at majority of the targets. The present findings suggest that epigallocatechin gallate is the most promising lead to be developed as multitarget drug for the design and development of novel anti-Parkinsonian agents.

  20. What's wrong with my mouse cage? Methodological considerations for modeling lifestyle factors and gene-environment interactions in mice.

    PubMed

    Mo, Christina; Renoir, Thibault; Hannan, Anthony J

    2016-05-30

    The mechanistic understanding of lifestyle contributions to disease has been largely driven by work in laboratory rodent models using environmental interventions. These interventions show an array of methodologies and sometimes unclear collective conclusions, hampering clinical interpretations. Here we discuss environmental enrichment, exercise and stress interventions to illustrate how different protocols can affect the interpretations of environmental factors in disease. We use Huntington's disease (HD) as an example because its mouse models exhibit excellent validity and HD was the first genetic animal model in which environmental stimulation was found to be beneficial. We make a number of observations and recommendations. Firstly, environmental enrichment and voluntary exercise generally show benefits across laboratories and mouse models. However, the extent to which these environmental interventions have beneficial effects depends on parameters such as the structural complexity of the cage in the case of enrichment, the timing of the intervention and the nature of the control conditions. In particular, clinical interpretations should consider deprived control living conditions and the ethological relevance of the enrichment. Secondly, stress can have negative effects on the phenotype in mouse models of HD and other brain disorders. When modeling stress, the effects of more than one type of experimental stressor should be investigated due to the heterogeneity and complexity of stress responses. With stress in particular, but ideally in all studies, both sexes should be used and the randomized group sizes need to be sufficiently powered to detect any sex effects. Opportunities for clinical translation will be guided by the 'environmental construct validity' of the preclinical data, including the culmination of complementary protocols across multiple animal models. Environmental interventions in mouse models of HD provide illustrative examples of how valid preclinical studies can lead to conclusions relevant to clinical populations.

  1. A Twin and Adoption Study of Reading Achievement: Exploration of Shared-Environmental and Gene-Environment-Interaction Effects

    ERIC Educational Resources Information Center

    Kirkpatrick, Robert M.; Legrand, Lisa N.; Iacono, William G.; McGue, Matt

    2011-01-01

    Existing behavior-genetic research implicates substantial influence of heredity and modest influence of shared environment on reading achievement and reading disability. Applying DeFries-Fulker analysis to a combined sample of twins and adoptees (N = 4886, including 266 reading-disabled probands), the present study replicates prior findings of…

  2. The Dopamine D2 Receptor Gene, Perceived Parental Support, and Adolescent Loneliness: Longitudinal Evidence for Gene-Environment Interactions

    ERIC Educational Resources Information Center

    van Roekel, Eeske; Goossens, Luc; Scholte, Ron H. J.; Engels, Rutger C. M. E.; Verhagen, Maaike

    2011-01-01

    Background: Loneliness is a common problem in adolescence. Earlier research focused on genes within the serotonin and oxytocin systems, but no studies have examined the role of dopamine-related genes in loneliness. In the present study, we focused on the dopamine D2 receptor gene (DRD2). Methods: Associations among the DRD2, sex, parental support,…

  3. Gene-Environment Contributions to the Development of Infant Vagal Reactivity: The Interaction of Dopamine and Maternal Sensitivity

    ERIC Educational Resources Information Center

    Propper, Cathi; Moore, Ginger A.; Mills-Koonce, W. Roger; Halpern, Carolyn Tucker; Hill-Soderlund, Ashley L.; Calkins, Susan D.; Carbone, Mary Anna; Cox, Martha

    2008-01-01

    This study investigated dopamine receptor genes ("DRD2" and "DRD4") and maternal sensitivity as predictors of infant respiratory sinus arrhythmia (RSA) and RSA reactivity, purported indices of vagal tone and vagal regulation, in a challenge task at 3, 6, and 12 months in 173 infant-mother dyads. Hierarchical linear modeling (HLM) revealed that at…

  4. Neuronal connectivity as a convergent target of gene-environment interactions that confer risk for Autism Spectrum Disorders

    PubMed Central

    Stamou, Marianna; Streifel, Karin M.; Goines, Paula E.; Lein, Pamela J.

    2013-01-01

    Evidence implicates environmental factors in the pathogenesis of Autism Spectrum Disorders (ASD). However, the identity of specific environmental chemicals that influence ASD risk, severity or treatment outcome remains elusive. The impact of any given environmental exposure likely varies across a population according to individual genetic substrates, and this increases the difficulty of identifying clear associations between exposure and ASD diagnoses. Heritable genetic vulnerabilities may amplify adverse effects triggered by environmental exposures if genetic and environmental factors converge to dysregulate the same signaling systems at critical times of development. Thus, one strategy for identifying environmental risk factors for ASD is to screen for environmental factors that modulate the same signaling pathways as ASD susceptibility genes. Recent advances in defining the molecular and cellular pathology of ASD point to altered patterns of neuronal connectivity in the developing brain as the neurobiological basis of these disorders. Studies of syndromic ASD and rare highly penetrant mutations or CNVs in ASD suggest that ASD risk genes converge on several major signaling pathways linked to altered neuronal connectivity in the developing brain. This review briefly summarizes the evidence implicating dysfunctional signaling via Ca2+-dependent mechanisms, extracellular signal-regulated kinases (ERK)/phosphatidylinositol-3-kinases (PI3K) and neuroligin-neurexin-SHANK as convergent molecular mechanisms in ASD, and then discusses examples of environmental chemicals for which there is emerging evidence of their potential to interfere with normal neuronal connectivity via perturbation of these signaling pathways. PMID:23269408

  5. Linkages between Children's and Their Friends' Social and Physical Aggression: Evidence for a Gene-Environment Interaction?

    ERIC Educational Resources Information Center

    Brendgen, Mara; Boivin, Michel; Vitaro, Frank; Bukowski, William M.; Dionne, Ginette; Tremblay, Richard E.; Perusse, Daniel

    2008-01-01

    Based on a sample of 406 seven-year-old twins, this study examined whether exposure to friends' social or physical aggression, respectively, moderates the effect of heritability on children's own social and physical aggression. Univariate analyses showed that children's own social and physical aggression were significantly explained by genetic…

  6. Detection and characterization of gene-gene and gene-environment interactions in common human diseases and complex clinical endpoints

    EPA Science Inventory

    Biological organisms are complex systems that dynamically integrate inputs from a multitude of physiological and environmental factors. Therefore, in addressing questions concerning the etiology of complex health outcomes, it is essential that the systemic nature of biology be ta...

  7. Chronic and Acute Stress, Gender, and Serotonin Transporter Gene-Environment Interactions Predicting Depression Symptoms in Youth

    ERIC Educational Resources Information Center

    Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle; Hazel, Nicholas A.; Najman, Jake M.

    2010-01-01

    Background: Many recent studies of serotonin transporter gene by environment effects predicting depression have used stress assessments with undefined or poor psychometric methods, possibly contributing to wide variation in findings. The present study attempted to distinguish between effects of acute and chronic stress to predict depressive…

  8. Candidate CDTI procedures study

    NASA Technical Reports Server (NTRS)

    Ace, R. E.

    1981-01-01

    A concept with potential for increasing airspace capacity by involving the pilot in the separation control loop is discussed. Some candidate options are presented. Both enroute and terminal area procedures are considered and, in many cases, a technologically advanced Air Traffic Control structure is assumed. Minimum display characteristics recommended for each of the described procedures are presented. Recommended sequencing of the operational testing of each of the candidate procedures is presented.

  9. Remodelling by early-life stress of NMDA receptor-dependent synaptic plasticity in a gene-environment rat model of depression.

    PubMed

    Ryan, Ben; Musazzi, Laura; Mallei, Alessandra; Tardito, Daniela; Gruber, Suzanne H M; El Khoury, Aram; Anwyl, Roger; Racagni, Giorgio; Mathé, Aleksander A; Rowan, Michael J; Popoli, Maurizio

    2009-05-01

    An animal model of depression combining genetic vulnerability and early-life stress (ELS) was prepared by submitting the Flinders Sensitive Line (FSL) rats to a standard paradigm of maternal separation. We analysed hippocampal synaptic transmission and plasticity in vivo and ionotropic receptors for glutamate in FSL rats, in their controls Flinders Resistant Line (FRL) rats, and in both lines subjected to ELS. A strong inhibition of long-term potentiation (LTP) and lower synaptic expression of NR1 subunit of the NMDA receptor were found in FSL rats. Remarkably, ELS induced a remodelling of synaptic plasticity only in FSL rats, reducing inhibition of LTP; this was accompanied by marked increase of synaptic NR1 subunit and GluR2/3 subunits of AMPA receptors. Chronic treatment with escitalopram inhibited LTP in FRL rats, but this effect was attenuated by prior ELS. The present results suggest that early gene-environment interactions cause lifelong synaptic changes affecting functional and molecular aspects of plasticity, partly reversed by antidepressant treatments.

  10. Evidence of Reactive Gene-Environment Correlation in Preschoolers' Prosocial Play with Unfamiliar Peers

    ERIC Educational Resources Information Center

    DiLalla, Lisabeth Fisher; Bersted, Kyle; John, Sufna Gheyara

    2015-01-01

    The development of prosocial behaviors during the preschool years is essential for children's positive interactions with peers in school and other social situations. Although there is some evidence of genetic influences on prosocial behaviors, very little is known about how genes and environment, independently and in concert, affect prosocial…

  11. Observed positive parenting behaviors and youth genotype: evidence for gene-environment correlations and moderation by parent personality traits.

    PubMed

    Oppenheimer, Caroline W; Hankin, Benjamin L; Jenness, Jessica L; Young, Jami F; Smolen, Andrew

    2013-02-01

    Gene-environment correlations (rGE) have been demonstrated in behavioral genetic studies, but rGE have proven elusive in molecular genetic research. Significant gene-environment correlations may be difficult to detect because potential moderators could reduce correlations between measured genetic variants and the environment. Molecular genetic studies investigating moderated rGE are lacking. This study examined associations between child catechol-O-methyltransferase genotype and aspects of positive parenting (responsiveness and warmth), and whether these associations were moderated by parental personality traits (neuroticism and extraversion) among a general community sample of third, sixth, and ninth graders (N = 263) and their parents. Results showed that parent personality traits moderated the rGE association between youths' genotype and coded observations of positive parenting. Parents with low levels of neuroticism and high levels of extraversion exhibited greater sensitive responsiveness and warmth, respectively, to youth with the valine/valine genotype. Moreover, youth with this genotype exhibited lower levels of observed anger. There was no association between the catechol-O-methyltransferase genotype and parenting behaviors for parents high on neuroticism and low on extraversion. Findings highlight the importance of considering moderating variables that may influence child genetic effects on the rearing environment. Implications for developmental models of maladaptive and adaptive child outcomes, and interventions for psychopathology, are discussed within a developmental psychopathology framework.

  12. Boys' serotonin transporter genotype affects maternal behavior through self-control: a case of evocative gene-environment correlation.

    PubMed

    Pener-Tessler, Roni; Avinun, Reut; Uzefovsky, Florina; Edelman, Shany; Ebstein, Richard P; Knafo, Ariel

    2013-02-01

    Self-control, involving processes such as delaying gratification, concentrating, planning, following instructions, and adapting emotions and behavior to situational requirements and social norms, may have a profound impact on children's adjustment. The importance of self-control suggests that parents are likely to modify their parenting based on children's ability for self-control. We study the effect of children's self-control, a trait partially molded by genetics, on their mothers' parenting, a process of evocative gene-environment correlation. Israeli 3.5-year-old twins (N = 320) participated in a lab session in which their mothers' parenting was observed. DNA was available from most children (N = 228). Mothers described children's self-control in a questionnaire. Boys were lower in self-control and received less positive parenting from their mothers, in comparison with girls. For boys, and not for girls, the serotonin transporter linked polymorphic region gene predicted mothers' levels of positive parenting, an effect mediated by boys' self-control. The implications of this evocative gene-environment correlation and the observed sex differences are discussed.

  13. CANDID: A flexible method for prioritizing candidate genes for complex human traits

    PubMed Central

    Hutz, Janna E.; Kraja, Aldi T.; McLeod, Howard L.; Province, Michael A.

    2015-01-01

    Genomewide studies and localized candidate gene approaches have become everyday study designs for identifying polymorphisms in genes that influence complex human traits. Yet, in general, the number of significant findings and the need to focus in smaller regions require a prioritization of genes for further study. Some candidate gene identification algorithms have been proposed in recent years to attempt to streamline this prioritization, but many suffer from limitations imposed by the source data or are difficult to use and understand. CANDID is a prioritization algorithm designed to produce impartial, accurate rankings of candidate genes that influence complex human traits. CANDID can use information from publications, protein domain descriptions, cross-species conservation measures, gene expression profiles, and protein-protein interactions in its analysis. Additionally, users may supplement these data sources with results from linkage, association and other studies. CANDID was tested on well-known complex trait genes using data from the Online Mendelian Inheritance in Man (OMIM) database. Additionally, CANDID was evaluated in a modeled gene discovery environment, where it ranked genes whose trait associations were published after CANDID’s databases were compiled. In all settings, CANDID exhibited high sensitivity and specificity, indicating an improvement upon previously published algorithms. Its accuracy and ease of use make CANDID a highly useful tool in study design and analysis for complex human traits. PMID:18613097

  14. Significant interactions between maternal PAH exposure and single nucleotide polymorphisms in candidate genes on B[a]P-DNA adducts in a cohort of non-smoking Polish mothers and newborns.

    PubMed

    Iyer, Shoba; Wang, Ya; Xiong, Wei; Tang, Deliang; Jedrychowski, Wieslaw; Chanock, Stephen; Wang, Shuang; Stigter, Laura; Mróz, Elzbieta; Perera, Frederica

    2016-08-26

    Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[a]pyrene (B[a]P) is a well-studied PAH that is classified as a known human carcinogen. Within our Polish cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn single nucleotide polymorphisms (SNPs) in plausible B[a]P metabolism genes on B[a]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking women (n = 368) with available data on maternal PAH exposure, paired cord adducts, and genetic data who resided in Krakow, Poland. We selected eight common variants in maternal and newborn candidate genes related to B[a]P metabolism, detoxification, and repair for our analyses: CYP1A1, CYP1A2, CYP1B1, GSTM1, GSTT2, NQO1, and XRCC1 We observed significant interactions between maternal PAH exposure and SNPs on cord B[a]P-DNA adducts in the following genes: maternal CYP1A1 and GSTT2, and newborn CYP1A1 and CYP1B1 These novel findings highlight differences in maternal and newborn genetic contributions to B[a]P-DNA adduct formation and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[a]P.

  15. ALA Candidates: Presidential Timbre

    ERIC Educational Resources Information Center

    Berry, John N., III

    2010-01-01

    This article presents an interview with two effective spokespeople, notable school librarian Sara Kelly Johns and retired public library administrator Molly Raphael, who compete to be American Library Association (ALA) president. One of them will be elected president of ALA for a year's term beginning in July 2011. Each candidate comes from a…

  16. Ageing, genes, environment and epigenetics: what twin studies tell us now, and in the future.

    PubMed

    Steves, Claire Joanne; Spector, Timothy D; Jackson, Stephen H D

    2012-09-01

    Compared with younger people, older people are much more variable in their organ function, and these large individual differences contribute to the complexity of geriatric medicine. What determines this variability? Is it due to the accumulation of different life experiences, or because of the variation in the genes we are born with, or an interaction of both? This paper reviews key findings from ageing twin cohorts probing these questions. Twin studies are the perfect natural experiment to dissect out genes and life experiences. We discuss the paradox that ageing is strongly determined by heritable factors (an influence that often gets stronger with time), yet longevity and lifespan seem not to be so heritable. We then focus on the intriguing question of why DNA sequence-identical twins might age differently. Animal studies are increasingly showing that epigenetic modifications occurring in early development and adulthood, might be key to ageing phenomena but this is difficult to investigate longitudinally in human populations, due to ethical problems of intervention and long lifespan. We propose that identical twin studies using new and existing cohorts may be useful human models in which to investigate the interaction between the environment and genetics, mediated by epigenetic modifications.

  17. Genes, environment and sport performance: why the nature-nurture dualism is no longer relevant.

    PubMed

    Davids, Keith; Baker, Joseph

    2007-01-01

    The historical debate on the relative influences of genes (i.e. nature) and environment (i.e. nurture) on human behaviour has been characterised by extreme positions leading to reductionist and polemic conclusions. Our analysis of research on sport and exercise behaviours shows that currently there is little support for either biologically or environmentally deterministic perspectives on elite athletic performance. In sports medicine, recent molecular biological advances in genomic studies have been over-interpreted, leading to a questionable 'single-gene-as-magic-bullet' philosophy adopted by some practitioners. Similarly, although extensive involvement in training and practice is needed at elite levels, it has become apparent that the acquisition of expertise is not merely about amassing a requisite number of practice hours. Although an interactionist perspective has been mooted over the years, a powerful explanatory framework has been lacking. In this article, we propose how the complementary nature of degenerate neurobiological systems might provide the theoretical basis for explaining the interactive influence of genetic and environmental constraints on elite athletic performance. We argue that, due to inherent human degeneracy, there are many different trajectories to achieving elite athletic performance. While the greatest training responses may be theoretically associated with the most favourable genotypes being exposed to highly specialised training environments, this is a rare and complex outcome. The concept of degeneracy provides us with a basis for understanding why each of the major interacting constraints might act in a compensatory manner on the acquisition of elite athletic performance.

  18. Genes, Environment and Sport Performance : Why the Nature-Nurture Dualism is no Longer Relevant.

    PubMed

    Davids, Keith; Baker, Joseph

    2007-11-01

    The historical debate on the relative influences of genes (i.e. nature) and environment (i.e. nurture) on human behaviour has been characterised by extreme positions leading to reductionist and polemic conclusions. Our analysis of research on sport and exercise behaviours shows that currently there is little support for either biologically or environmentally deterministic perspectives on elite athletic performance. In sports medicine, recent molecular biological advances in genomic studies have been over-interpreted, leading to a questionable 'single-gene-as-magic-bullet' philosophy adopted by some practitioners. Similarly, although extensive involvement in training and practice is needed at elite levels, it has become apparent that the acquisition of expertise is not merely about amassing a requisite number of practice hours. Although an interactionist perspective has been mooted over the years, a powerful explanatory framework has been lacking. In this article, we propose how the complementary nature of degenerate neurobiological systems might provide the theoretical basis for explaining the interactive influence of genetic and environmental constraints on elite athletic performance. We argue that, due to inherent human degeneracy, there are many different trajectories to achieving elite athletic performance. While the greatest training responses may be theoretically associated with the most favourable genotypes being exposed to highly specialised training environments, this is a rare and complex outcome. The concept of degeneracy provides us with a basis for understanding why each of the major interacting constraints might act in a compensatory manner on the acquisition of elite athletic performance.

  19. Physical punishment and childhood aggression: the role of gender and gene-environment interplay.

    PubMed

    Boutwell, Brian B; Franklin, Cortney A; Barnes, J C; Beaver, Kevin M

    2011-01-01

    A large body of research has linked spanking with a range of adverse outcomes in children, including aggression, psychopathology, and criminal involvement. Despite evidence concerning the association of spanking with antisocial behavior, not all children who are spanked develop antisocial traits. Given the heterogeneous effects of spanking on behavior, it is possible that a third variable may condition the influence of corporal punishment on child development. We test this possibility using data drawn from a nationally representative dataset of twin siblings. Our findings suggest that genetic risk factors condition the effects of spanking on antisocial behavior. Moreover, our results provide evidence that the interaction between genetic risk factors and corporal punishment may be particularly salient for males.

  20. Correcting Systematic Inflation in Genetic Association Tests That Consider Interaction Effects

    PubMed Central

    Almli, Lynn M.; Duncan, Richard; Feng, Hao; Ghosh, Debashis; Binder, Elisabeth B.; Bradley, Bekh; Ressler, Kerry J.; Conneely, Karen N.; Epstein, Michael P.

    2015-01-01

    IMPORTANCE Genetic association studies of psychiatric outcomes often consider interactions with environmental exposures and, in particular, apply tests that jointly consider gene and gene-environment interaction effects for analysis. Using a genome-wide association study (GWAS) of posttraumatic stress disorder (PTSD), we report that heteroscedasticity (defined as variability in outcome that differs by the value of the environmental exposure) can invalidate traditional joint tests of gene and gene-environment interaction. OBJECTIVES To identify the cause of bias in traditional joint tests of gene and gene-environment interaction in a PTSD GWAS and determine whether proposed robust joint tests are insensitive to this problem. DESIGN, SETTING, AND PARTICIPANTS The PTSD GWAS data set consisted of 3359 individuals (978 men and 2381 women) from the Grady Trauma Project (GTP), a cohort study from Atlanta, Georgia. The GTP performed genome-wide genotyping of participants and collected environmental exposures using the Childhood Trauma Questionnaire and Trauma Experiences Inventory. MAIN OUTCOMES AND MEASURES We performed joint interaction testing of the Beck Depression Inventory and modified PTSD Symptom Scale in the GTP GWAS. We assessed systematic bias in our interaction analyses using quantile-quantile plots and genome-wide inflation factors. RESULTS Application of the traditional joint interaction test to the GTP GWAS yielded systematic inflation across different outcomes and environmental exposures (inflation-factor estimates ranging from 1.07 to 1.21), whereas application of the robust joint test to the same data set yielded no such inflation (inflation-factor estimates ranging from 1.01 to 1.02). Simulated data further revealed that the robust joint test is valid in different heteroscedasticity models, whereas the traditional joint test is invalid. The robust joint test also has power similar to the traditional joint test when heteroscedasticity is not an issue

  1. Validating Kepler Planet Candidates

    NASA Astrophysics Data System (ADS)

    Lissauer, Jack J.; Torres, G.; Marcy, G.; Brown, T.; Gilliland, R.; Gautier, T. N.; Isaacson, H.; Dupree, A.; Kepler Science Team

    2011-01-01

    The Kepler Science Team has identified more than 700 transit-like signatures in the first 43 days of data returned from the spacecraft (Borucki et al. 2010, arXiv1006.2799B). However, only 7 of these candidates have been confirmed as planets as of late September 2010. The number of true planets in this sample is clearly far larger than 7, but the sample is also 'contaminated' with false-positives, including many from eclipsing binary stars. Separating the wheat from the chaff requires a careful study of individual candidates using both Kepler photometry and spectroscopic and imaging data from the ground. Techniques that the Science Team is developing to address these issues, which include detailed analysis of the photometric data and follow-up observations with ground-based telescopes, will be presented. Kepler was selected as the 10th mission of the Discovery Program. Funding for this mission is provided by NASA, Science Mission Directorate.

  2. Dark matter candidates

    SciTech Connect

    Turner, M.S.

    1989-01-01

    One of the simplest, yet most profound, questions we can ask about the Universe is, how much stuff is in it, and further what is that stuff composed of. Needless to say, the answer to this question has very important implications for the evolution of the Universe, determining both the ultimate fate and the course of structure formation. Remarkably, at this late date in the history of the Universe we still do not have a definitive answer to this simplest of questions---although we have some very intriguing clues. It is known with certainty that most of the material in the Universe is dark, and we have the strong suspicion that the dominant component of material in the Cosmos is not baryons, but rather is exotic relic elementary particles left over from the earliest, very hot epoch of the Universe. If true, the Dark Matter question is a most fundamental one facing both particle physics and cosmology. The leading particle dark matter candidates are: the axion, the neutralino, and a light neutrino species. All three candidates are accessible to experimental tests, and experiments are now in progress. In addition, there are several dark horse, long shot, candidates, including the superheavy magnetic monopole and soliton stars. 13 refs.

  3. The Autism Birth Cohort: a paradigm for gene-environment-timing research.

    PubMed

    Stoltenberg, C; Schjølberg, S; Bresnahan, M; Hornig, M; Hirtz, D; Dahl, C; Lie, K K; Reichborn-Kjennerud, T; Schreuder, P; Alsaker, E; Øyen, A-S; Magnus, P; Surén, P; Susser, E; Lipkin, W I

    2010-07-01

    The reported prevalence of autism spectrum disorders (ASDs) has increased by 5- to 10-fold over the past 20 years. Whether ASDs are truly more frequent is controversial; nonetheless, the burden is profound in human and economic terms. Although autism is among the most heritable of mental disorders, its pathogenesis remains obscure. Environmental factors are proposed; however, none is implicated. Furthermore, there are no biomarkers to screen for ASD or risk of ASD. The Autism Birth Cohort (ABC) was initiated to analyze gene x environment x timing interactions and enable early diagnosis. It uses a large, unselected birth cohort in which cases are prospectively ascertained through population screening. Samples collected serially through pregnancy and childhood include parental blood, maternal urine, cord blood, milk teeth and rectal swabs. More than 107,000 children are continuously screened through questionnaires, referral, and a national registry. Cases are compared with a control group from the same cohort in a 'nested case-control' design. Early screening and diagnostic assessments and re-assessments are designed to provide a rich view of longitudinal trajectory. Genetic, proteomic, immunologic, metagenomic and microbiological tools will be used to exploit unique biological samples. The ABC is a paradigm for analyzing the role of genetic and environmental factors in complex disorders.

  4. Use of the Twin Design to Examine Evocative Gene-Environment Effects within a Conversational Context

    PubMed Central

    DeThorne, Laura Segebart; Hart, Sara Ann

    2010-01-01

    The purpose of this study was to highlight the role of twin designs in understanding children’s conversational interactions. Specifically, we (a) attempted to replicate the findings of genetic effects on children’s conversational language use reported in DeThorne et al. (2008), and (b) examined whether the language used by examiners in their conversation with twins reflected differences in the children’s genetic similarity. Behavioral genetic analyses included intraclass correlations and model fitting procedures applied to 514 same-sex twins (202 MZ, 294 DZ, 10 unknown zygosity) from the Western Reserve Reading Project (Petrill, Deater-Deckard, Thompson, DeThorne, & Schatschneider, 2006). Analyses focused on child and examiner measures of talkativeness, average utterance length, vocabulary diversity, and grammatical complexity from a fifteen-minute conversational exchange. Substantial genetic effects on children’s conversational language measures replicated results from DeThorne et al. (2008) using an expanded sample. However, no familiality was reflected in the examiner language measures. Modest phenotypic correlations between child and examiner language measures suggested that differences in examiner language use may elicit differences in child language use, but evidence of evocative rGE in which genetic differences across children evoke differences in examiner language use, was not found. The discussion focuses on a comparison of findings to previous studies and implications for future research. PMID:22102850

  5. Detection of SNP-SNP interactions in trios of parents with schizophrenic children.

    PubMed

    Li, Qing; Fallin, M Daniele; Louis, Thomas A; Lasseter, Virginia K; McGrath, John A; Avramopoulos, Dimitri; Wolyniec, Paula S; Valle, David; Liang, Kung-Yee; Pulver, Ann E; Ruczinski, Ingo

    2010-07-01

    Schizophrenia (SZ) is a heritable and complex psychiatric disorder with an estimated worldwide prevalence of about 1%. Research on the risk factors for SZ has thus far yielded few clues to causes, but has pointed to a heterogeneous etiology that likely involves multiple genes and gene-environment interactions. In this manuscript, we apply a novel method (trio logic regression, Li et al., 2009) to case-parent trio data from a SZ candidate gene study conducted on families of Ashkenazi Jewish descent, and demonstrate the method's ability to detect multi-gene models for SZ risk in the family-based design. In particular, we demonstrate how this method revealed a genotype-phenotype association that includes an allele without marginal effect.

  6. Gene-physical activity interactions in the etiology of obesity: behavioral considerations.

    PubMed

    Dishman, Rod K

    2008-12-01

    Understanding how genes, environment, and personal motivation operate to influence physical activity will require (i) inclusion of properly validated measures of putative mediators (e.g., cultural values, efficacy and control beliefs, goals, intentions, enjoyment, and self-management skills) and moderators (e.g., age or maturation, personality, race/ethnicity, fitness, fatness, skill, and competing behaviors) of physical activity, (ii) a search for candidate genes involved with motivational systems of energy expenditure in addition to energy intake pathways, (iii) assessment of specific features physical activity exposure (i.e., type, intensity, timing, and context), (iv) manipulation of physical activity or prospective observation of change in physical activity at multiple times, rather than cross-sectional association and linkage studies, and (v) use of statistical procedures that permit multilevel modeling (i.e., personal and group-level variables) of direct, indirect (i.e., mediated), and moderated (i.e., interactions of mediators with external factors) relations with physical activity within theoretical gene-environment networks.

  7. Kernel Approach for Modeling Interaction Effects in Genetic Association Studies of Complex Quantitative Traits

    PubMed Central

    Broadaway, K. Alaine; Duncan, Richard; Conneely, Karen N.; Almli, Lynn M.; Bradley, Bekh; Ressler, Kerry J.; Epstein, Michael P.

    2015-01-01

    The etiology of complex traits likely involves the effects of genetic and environmental factors, along with complicated interaction effects between them. Consequently, there has been interest in applying genetic association tests of complex traits that account for potential modification of the genetic effect in the presence of an environmental factor. One can perform such an analysis using a joint test of gene and gene-environment interaction. An optimal joint test would be one that remains powerful under a variety of models ranging from those of strong gene-environment interaction effect to those of little or no gene-environment interaction effect. To fill this demand, we have extended a kernel-machine based approach for association mapping of multiple SNPs to consider joint tests of gene and gene-environment interaction. The kernel-based approach for joint testing is promising, since it incorporates linkage disequilibrium information from multiple SNPs simultaneously in analysis and permits flexible modeling of interaction effects. Using simulated data, we show that our kernel-machine approach typically outperforms the traditional joint test under strong gene-environment interaction models and further outperforms the traditional main-effect association test under models of weak or no gene-environment interaction effects. We illustrate our test using genome-wide association data from the Grady Trauma Project, a cohort of highly traumatized, at-risk individuals, which has previously been investigated for interaction effects. PMID:25885490

  8. Organochlorine Pesticides Exposure and Bladder Cancer: Evaluation from a Gene-Environment Perspective in a Hospital-Based Case-Control Study in the Canary Islands (Spain).

    PubMed

    Boada, L D; Henríquez-Hernández, L A; Zumbado, M; Almeida-González, M; Álvarez-León, E E; Navarro, P; Luzardo, O P

    2016-01-01

    The incidence of bladder cancer has increased significantly since the 1950s. Pesticide exposure has been linked with increasing bladder cancer incidence, although the evidence is inconclusive. However, most epidemiological studies did not evaluate the potential role played by the organochlorine pesticides, the most widely used pesticides in Western countries from the 1940s to the 1970s. Organochlorine pesticides were banned in the late 1970s because of their persistence in the environment and their carcinogenic and mutagenic effects. Organochlorine pesticides were employed in huge amounts in the Spanish archipelago of the Canary Islands; the authors, therefore, evaluated the role played by organochlorine pesticides exposure on bladder cancer. Serum levels of the most prevalent organochlorine pesticides used in the agriculture of these Islands (dichlorodiphenyltrichloroethane [p,p'-DDT], and its metabolites dichlorodiphenyldichloroethylene [p,p'-DDE] and dichlorodiphenyldichloroethane [p,p'-DDD], hexachlorobenzene, hexachlorocyclohexane isomers, aldrin, dieldrin, endrin, heptachlor, cis-chlordane, trans-chlordane, α- and β-endosulfan, endosulfan sulfate, methoxychlor, and mirex) were measured in 140 bladder cancer cases and 206 controls. GST-M1 and GST-T1 gene polymorphisms were genotyped by polymerase chain reaction (PCR)-based methods. These results showed that serum levels of organochlorine pesticides did not increase bladder cancer risk. On the contrary, total burden of hexachlorocyclohexanes was found to be negatively associated to bladder cancer (odds ratio [OR] = 0.929, 95% confidence interval [CI]: 0.865-0.997; P = .041). This effect disappeared when the distribution of the gluthathione S-transferase polymorphisms was introduced in the statistical model. These results indicate that organochlorine pesticides are not a risk factor for bladder cancer. However, these findings provide additional evidence of gene-environment interactions for organochlorine

  9. The Internal-Candidate Syndrome

    ERIC Educational Resources Information Center

    Barden, Dennis M.

    2008-01-01

    In this article, the author explains the complications involved when an internal candidate is included in an open search for a leadership position in an academic institution. Internal-candidate syndrome is a dilemma faced by institutions when they have to choose between an internal candidate and an external one. There are two reasons why…

  10. The Influence of Major Life Events on Economic Attitudes in a World of Gene-Environment Interplay

    PubMed Central

    Hatemi, Peter K.

    2014-01-01

    The role of “genes” on political attitudes has gained attention across disciplines. However, person-specific experiences have yet to be incorporated into models that consider genetic influences. Relying on a gene-environment interplay approach, this study explicates how life-events, such as losing one’s job or suffering a financial loss, influence economic policy attitudes. The results indicate genetic and environmental variance on support for unions, immigration, capitalism, socialism and property tax is moderated by financial risks. Changes in the magnitude of genetic influences, however, are temporary. After two years, the phenotypic effects of the life events remain on most attitudes, but changes in the sources of individual differences do not. Univariate twin models that estimate the independent contributions of genes and environment on the variation of attitudes appear to provide robust baseline indicators of sources of individual differences. These estimates, however, are not event or day specific. In this way, genetic influences add stability, while environment cues change, and this process is continually updated. PMID:24860199

  11. The Influence of Major Life Events on Economic Attitudes in a World of Gene-Environment Interplay.

    PubMed

    Hatemi, Peter K

    2013-10-01

    The role of "genes" on political attitudes has gained attention across disciplines. However, person-specific experiences have yet to be incorporated into models that consider genetic influences. Relying on a gene-environment interplay approach, this study explicates how life-events, such as losing one's job or suffering a financial loss, influence economic policy attitudes. The results indicate genetic and environmental variance on support for unions, immigration, capitalism, socialism and property tax is moderated by financial risks. Changes in the magnitude of genetic influences, however, are temporary. After two years, the phenotypic effects of the life events remain on most attitudes, but changes in the sources of individual differences do not. Univariate twin models that estimate the independent contributions of genes and environment on the variation of attitudes appear to provide robust baseline indicators of sources of individual differences. These estimates, however, are not event or day specific. In this way, genetic influences add stability, while environment cues change, and this process is continually updated.

  12. Temperament and peer problems from early to middle childhood: Gene-environment correlations with negative emotionality and sociability.

    PubMed

    Hasenfratz, Liat; Benish-Weisman, Maya; Steinberg, Tami; Knafo-Noam, Ariel

    2015-11-01

    Based in a transactional framework in which children's own characteristics and the social environment influence each other to produce individual differences in social adjustment, we investigated relationships between children's peer problems and their temperamental characteristics, using a longitudinal and genetically informed study of 939 pairs of Israeli twins followed from early to middle childhood (ages 3, 5, and 6.5). Peer problems were moderately stable within children over time, such that children who appeared to have more peer problems at age 3 tended to have also more peer problems at age 6.5. Children's temperament accounted for 10%-22% of the variance in their peer problems measured at the same age and for 2%-7% of the variance longitudinally. It is important that genetic factors accounted for the association between temperament and peer problems and were in line with a gene-environment correlation process, providing support for the proposal that biologically predisposed characteristics, particularly negative emotionality and sociability, have an influence on children's early experiences of peer problems. The results highlight the need for early and continuous interventions that are specifically tailored to address the interpersonal difficulties of children with particular temperamental profiles.

  13. Genetic variants determining survival and fertility in an adverse African environment: a population-based large-scale candidate gene association study

    PubMed Central

    Koopman, Jacob J.E.; Pijpe, Jeroen; Böhringer, Stefan; van Bodegom, David; Eriksson, Ulrika K.; Sanchez-Faddeev, Hernando; Ziem, Juventus B.; Zwaan, Bas; Slagboom, P. Eline; de Knijff, Peter; Westendorp, Rudi G.J.

    2016-01-01

    Human survival probability and fertility decline strongly with age. These life history traits have been shaped by evolution. However, research has failed to uncover a consistent genetic determination of variation in survival and fertility. As an explanation, such genetic determinants have been selected in adverse environments, in which humans have lived during most of their history, but are almost exclusively studied in populations in modern affluent environments. Here, we present a large-scale candidate gene association study in a rural African population living in an adverse environment. In 4387 individuals, we studied 4052 SNPs in 148 genes that have previously been identified as possible determinants of survival or fertility in animals or humans. We studied their associations with survival comparing newborns, middle-age adults, and old individuals. In women, we assessed their associations with reported and observed numbers of children. We found no statistically significant associations of these SNPs with survival between the three age groups nor with women's reported and observed fertility. Population stratification was unlikely to explain these results. Apart from a lack of power, we hypothesise that genetic heterogeneity of complex phenotypes and gene-environment interactions prevent the identification of genetic variants explaining variation in survival and fertility in humans. PMID:27356285

  14. 2009 Elections: The Candidates Statements

    ERIC Educational Resources Information Center

    TechTrends: Linking Research and Practice to Improve Learning, 2009

    2009-01-01

    This article presents the candidates for the 2009 Association for Educational Communications and Technology (AECT) election and their statements. The candidates are: (1) Andy Gibbons (President-Elect); (2) Barbara B. Lockee (President-Elect); (3) Mary Jean Bishop (At-Large Representative); and (4) Deepak Subramony (At-Large Representative). In…

  15. A gene-environment investigation on personality traits in two independent clinical sets of adult patients with personality disorder and attention deficit/hyperactive disorder.

    PubMed

    Jacob, Christian P; Nguyen, Thuy Trang; Dempfle, Astrid; Heine, Monika; Windemuth-Kieselbach, Christine; Baumann, Katarina; Jacob, Florian; Prechtl, Julian; Wittlich, Maike; Herrmann, Martin J; Gross-Lesch, Silke; Lesch, Klaus-Peter; Reif, Andreas

    2010-06-01

    While an interactive effect of genes with adverse life events is increasingly appreciated in current concepts of depression etiology, no data are presently available on interactions between genetic and environmental (G x E) factors with respect to personality and related disorders. The present study therefore aimed to detect main effects as well as interactions of serotonergic candidate genes (coding for the serotonin transporter, 5-HTT; the serotonin autoreceptor, HTR1A; and the enzyme which synthesizes serotonin in the brain, TPH2) with the burden of life events (#LE) in two independent samples consisting of 183 patients suffering from personality disorders and 123 patients suffering from adult attention deficit/hyperactivity disorder (aADHD). Simple analyses ignoring possible G x E interactions revealed no evidence for associations of either #LE or of the considered polymorphisms in 5-HTT and TPH2. Only the G allele of HTR1A rs6295 seemed to increase the risk of emotional-dramatic cluster B personality disorders (p = 0.019, in the personality disorder sample) and to decrease the risk of anxious-fearful cluster C personality disorders (p = 0.016, in the aADHD sample). We extended the initial simple model by taking a G x E interaction term into account, since this approach may better fit the data indicating that the effect of a gene is modified by stressful life events or, vice versa, that stressful life events only have an effect in the presence of a susceptibility genotype. By doing so, we observed nominal evidence for G x E effects as well as main effects of 5-HTT-LPR and the TPH2 SNP rs4570625 on the occurrence of personality disorders. Further replication studies, however, are necessary to validate the apparent complexity of G x E interactions in disorders of human personality.

  16. Dark matter candidates

    NASA Technical Reports Server (NTRS)

    Turner, Michael S.

    1989-01-01

    The types of particles which may provide the nonluminous mass required by big-bang cosmological models are listed and briefly characterized. The observational evidence for the existence of dark matter (outweighing the luminous component by at least a factor of 10) is reviewed; the theoretical arguments favoring mainly nonbaryonic dark matter are summarized; and particular attention is given to weakly interacting massive particles (WIMPs) remaining as relics from the early universe. The WIMPs are classified as thermal relics (heavy stable neutrinos and lighter neutralinos), asymmetric relics (including baryons), nonthermal relics (superheavy magnetic monopoles, axions, and soliton stars), and truly exotic relics (relativistic debris or vacuum energy). Explanations for the current apparent baryon/exotica ratio of about 0.1 in different theoretical scenarios are considered, and the problems of experimental and/or observational dark-matter detection are examined.

  17. Gene-Lifestyle Interactions in Complex Diseases: Design and Description of the GLACIER and VIKING Studies

    PubMed Central

    Kurbasic, Azra; Poveda, Alaitz; Chen, Yan; Ågren, Åsa; Engberg, Elisabeth; Hu, Frank B.; Johansson, Ingegerd; Barroso, Ines; Brändström, Anders; Hallmans, Göran; Renström, Frida; Franks, Paul W.

    2014-01-01

    Most complex diseases have well-established genetic and non-genetic risk factors. In some instances, these risk factors are likely to interact, whereby their joint effects convey a level of risk that is either significantly more or less than the sum of these risks. Characterizing these gene-environment interactions may help elucidate the biology of complex diseases, as well as to guide strategies for their targeted prevention. In most cases, the detection of gene-environment interactions will require sample sizes in excess of those needed to detect the marginal effects of the genetic and environmental risk factors. Although many consortia have been formed, comprising multiple diverse cohorts to detect gene-environment interactions, few robust examples of such interactions have been discovered. This may be because combining data across studies, usually through meta-analysis of summary data from the contributing cohorts, is often a statistically inefficient approach for the detection of gene-environment interactions. Ideally, single, very large and well-genotyped prospective cohorts, with validated measures of environmental risk factor and disease outcomes should be used to study interactions. The presence of strong founder effects within those cohorts might further strengthen the capacity to detect novel genetic effects and gene-environment interactions. Access to accurate genealogical data would also aid in studying the diploid nature of the human genome, such as genomic imprinting (parent-of-origin effects). Here we describe two studies from northern Sweden (the GLACIER and VIKING studies) that fulfill these characteristics. PMID:25396097

  18. Gene-Lifestyle Interactions in Complex Diseases: Design and Description of the GLACIER and VIKING Studies.

    PubMed

    Kurbasic, Azra; Poveda, Alaitz; Chen, Yan; Agren, Asa; Engberg, Elisabeth; Hu, Frank B; Johansson, Ingegerd; Barroso, Ines; Brändström, Anders; Hallmans, Göran; Renström, Frida; Franks, Paul W

    2014-12-01

    Most complex diseases have well-established genetic and non-genetic risk factors. In some instances, these risk factors are likely to interact, whereby their joint effects convey a level of risk that is either significantly more or less than the sum of these risks. Characterizing these gene-environment interactions may help elucidate the biology of complex diseases, as well as to guide strategies for their targeted prevention. In most cases, the detection of gene-environment interactions will require sample sizes in excess of those needed to detect the marginal effects of the genetic and environmental risk factors. Although many consortia have been formed, comprising multiple diverse cohorts to detect gene-environment interactions, few robust examples of such interactions have been discovered. This may be because combining data across studies, usually through meta-analysis of summary data from the contributing cohorts, is often a statistically inefficient approach for the detection of gene-environment interactions. Ideally, single, very large and well-genotyped prospective cohorts, with validated measures of environmental risk factor and disease outcomes should be used to study interactions. The presence of strong founder effects within those cohorts might further strengthen the capacity to detect novel genetic effects and gene-environment interactions. Access to accurate genealogical data would also aid in studying the diploid nature of the human genome, such as genomic imprinting (parent-of-origin effects). Here we describe two studies from northern Sweden (the GLACIER and VIKING studies) that fulfill these characteristics.

  19. Interactions between Obesity-Related Copy Number Variants and Dietary Behaviors in Childhood Obesity

    PubMed Central

    Zhang, Dandan; Li, Zhenli; Wang, Hao; Yang, Min; Liang, Li; Fu, Junfen; Wang, Chunling; Ling, Jie; Zhang, Yan; Zhang, Shuai; Xu, Yuyang; Zhu, Yimin; Lai, Maode

    2015-01-01

    Copy number variants (CNVs) have been implicated as an important genetic marker of obesity, and gene-environment interaction has been found to modulate risk of obesity. To evaluate the associations between CNVs and childhood obesity, as well as the interactions between CNVs and dietary behaviors, we recruited 534 obese children and 508 controls from six cities in China and six candidate CNVs were screened through published genome-wide studies (GWAS) on childhood obesity. We found three loci (10q11.22, 4q25 and 11q11) to be significantly associated with obesity after false discovery rate (FDR) correction (all the p ≤ 0.05). Cumulative effect of the three positive loci was measured by the genetic risk score (GRS), showing a significant relationship with the risk of obesity (Ptrend < 0.001). The OR of obesity increased to 21.38 (95% CI = 21.19–21.55) among the 10q11.22 deletion carriers who had meat-based diets, indicating prominent multiplicative interaction (MI) between deletions of 10q11.22 and preference for a meat-based diet. Simultaneous deletions of 5q13.2 and duplications of 6q14.1 had significant MI with a preference for salty foods. Our results suggested that CNVs may contribute to the genetic susceptibility of childhood obesity, and the CNV-diet interactions modulate the risk of obesity. PMID:25912042

  20. Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility--Reykjavik study.

    PubMed

    Mitchell, Gary F; van Buchem, Mark A; Sigurdsson, Sigurdur; Gotal, John D; Jonsdottir, Maria K; Kjartansson, Ólafur; Garcia, Melissa; Aspelund, Thor; Harris, Tamara B; Gudnason, Vilmundur; Launer, Lenore J

    2011-11-01

    Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid-femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility--Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69-93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta-carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta-carotid reflection coefficient (R = -0.66, P<0.001). Carotid pulse pressure, pulsatility index and carotid-femoral pulse wave velocity were each associated with increased risk for silent subcortical infarcts (hazard ratios of 1.62-1.71 per standard deviation, P<0.002). Carotid-femoral pulse wave velocity was associated with higher white matter hyperintensity volume (0.108 ± 0.045 SD/SD, P = 0.018). Pulsatility index was associated with lower whole brain (-0.127 ± 0.037 SD/SD, P<0.001), grey matter (-0.079 ± 0.038 SD/SD, P = 0.038) and white matter (-0.128 ± 0.039 SD/SD, P<0.001) volumes. Carotid-femoral pulse

  1. 5 CFR 412.302 - Criteria for a Senior Executive Service candidate development program (SESCDP).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... all groups of qualified individuals within the civil service, or all groups of qualified individuals... interaction with senior employees outside the candidate's department or agency to foster a broader perspective... include interaction with senior employees outside the candidate's department or agency; (3)...

  2. 76 FR 4896 - Call for Candidates

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-27

    ... From the Federal Register Online via the Government Publishing Office FEDERAL ACCOUNTING STANDARDS ADVISORY BOARD Call for Candidates AGENCY: Federal Accounting Standards Advisory Board. ACTION: Notice... Federal Accounting Standards Advisory Board (FASAB) is currently seeking candidates (candidates must...

  3. 11 CFR 9002.4 - Eligible candidates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... FINANCING DEFINITIONS § 9002.4 Eligible candidates. Eligible candidates means those Presidential and Vice Presidential candidates who have met all applicable conditions for eligibility to receive payments from...

  4. A direct molecular link between the autism candidate gene RORa and the schizophrenia candidate MIR137

    NASA Astrophysics Data System (ADS)

    Devanna, Paolo; Vernes, Sonja C.

    2014-02-01

    Retinoic acid-related orphan receptor alpha gene (RORa) and the microRNA MIR137 have both recently been identified as novel candidate genes for neuropsychiatric disorders. RORa encodes a ligand-dependent orphan nuclear receptor that acts as a transcriptional regulator and miR-137 is a brain enriched small non-coding RNA that interacts with gene transcripts to control protein levels. Given the mounting evidence for RORa in autism spectrum disorders (ASD) and MIR137 in schizophrenia and ASD, we investigated if there was a functional biological relationship between these two genes. Herein, we demonstrate that miR-137 targets the 3'UTR of RORa in a site specific manner. We also provide further support for MIR137 as an autism candidate by showing that a large number of previously implicated autism genes are also putatively targeted by miR-137. This work supports the role of MIR137 as an ASD candidate and demonstrates a direct biological link between these previously unrelated autism candidate genes.

  5. Gene × environment interaction on intergroup bias: the role of 5-HTTLPR and perceived outgroup threat.

    PubMed

    Cheon, Bobby K; Livingston, Robert W; Hong, Ying-Yi; Chiao, Joan Y

    2014-09-01

    Perceived threat from outgroups is a consistent social-environmental antecedent of intergroup bias (i.e. prejudice, ingroup favoritism). The serotonin transporter gene polymorphism (5-HTTLPR) has been associated with individual variations in sensitivity to context, particularly stressful and threatening situations. Here, we examined how 5-HTTLPR and environmental factors signaling potential outgroup threat dynamically interact to shape intergroup bias. Across two studies, we provide novel evidence for a gene-environment interaction on the acquisition of intergroup bias and prejudice. Greater exposure to signals of outgroup threat, such as negative prior contact with outgroups and perceived danger from the social environment, were more predictive of intergroup bias among participants possessing at least one short allele (vs two long alleles) of 5-HTTLPR. Furthermore, this gene x environment interaction was observed for biases directed at diverse ethnic and arbitrarily-defined outgroups across measures reflecting intergroup biases in evaluation and discriminatory behavior. These findings reveal a candidate genetic mechanism for the acquisition of intergroup bias, and suggest that intergroup bias is dually inherited and transmitted through the interplay of social (i.e. contextual cues of outgroup threat) and biological mechanisms (i.e. genetic sensitivity toward threatening contexts) that regulate perceived intergroup threats.

  6. Quantitative gene-gene and gene-environment mapping for leaf shape variation using tree-based models

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leaf shape traits have long been a focus of many disciplines, but searching for complex genetic and environmental interactive mechanisms regulating leaf shape variation has not yet been well developed. The question of the respective roles of gene and environment and how they interplay to modulate l...

  7. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.

    PubMed

    Fan, Qiao; Verhoeven, Virginie J M; Wojciechowski, Robert; Barathi, Veluchamy A; Hysi, Pirro G; Guggenheim, Jeremy A; Höhn, René; Vitart, Veronique; Khawaja, Anthony P; Yamashiro, Kenji; Hosseini, S Mohsen; Lehtimäki, Terho; Lu, Yi; Haller, Toomas; Xie, Jing; Delcourt, Cécile; Pirastu, Mario; Wedenoja, Juho; Gharahkhani, Puya; Venturini, Cristina; Miyake, Masahiro; Hewitt, Alex W; Guo, Xiaobo; Mazur, Johanna; Huffman, Jenifer E; Williams, Katie M; Polasek, Ozren; Campbell, Harry; Rudan, Igor; Vatavuk, Zoran; Wilson, James F; Joshi, Peter K; McMahon, George; St Pourcain, Beate; Evans, David M; Simpson, Claire L; Schwantes-An, Tae-Hwi; Igo, Robert P; Mirshahi, Alireza; Cougnard-Gregoire, Audrey; Bellenguez, Céline; Blettner, Maria; Raitakari, Olli; Kähönen, Mika; Seppala, Ilkka; Zeller, Tanja; Meitinger, Thomas; Ried, Janina S; Gieger, Christian; Portas, Laura; van Leeuwen, Elisabeth M; Amin, Najaf; Uitterlinden, André G; Rivadeneira, Fernando; Hofman, Albert; Vingerling, Johannes R; Wang, Ya Xing; Wang, Xu; Tai-Hui Boh, Eileen; Ikram, M Kamran; Sabanayagam, Charumathi; Gupta, Preeti; Tan, Vincent; Zhou, Lei; Ho, Candice E H; Lim, Wan'e; Beuerman, Roger W; Siantar, Rosalynn; Tai, E-Shyong; Vithana, Eranga; Mihailov, Evelin; Khor, Chiea-Chuen; Hayward, Caroline; Luben, Robert N; Foster, Paul J; Klein, Barbara E K; Klein, Ronald; Wong, Hoi-Suen; Mitchell, Paul; Metspalu, Andres; Aung, Tin; Young, Terri L; He, Mingguang; Pärssinen, Olavi; van Duijn, Cornelia M; Jin Wang, Jie; Williams, Cathy; Jonas, Jost B; Teo, Yik-Ying; Mackey, David A; Oexle, Konrad; Yoshimura, Nagahisa; Paterson, Andrew D; Pfeiffer, Norbert; Wong, Tien-Yin; Baird, Paul N; Stambolian, Dwight; Wilson, Joan E Bailey; Cheng, Ching-Yu; Hammond, Christopher J; Klaver, Caroline C W; Saw, Seang-Mei; Rahi, Jugnoo S; Korobelnik, Jean-François; Kemp, John P; Timpson, Nicholas J; Smith, George Davey; Craig, Jamie E; Burdon, Kathryn P; Fogarty, Rhys D; Iyengar, Sudha K; Chew, Emily; Janmahasatian, Sarayut; Martin, Nicholas G; MacGregor, Stuart; Xu, Liang; Schache, Maria; Nangia, Vinay; Panda-Jonas, Songhomitra; Wright, Alan F; Fondran, Jeremy R; Lass, Jonathan H; Feng, Sheng; Zhao, Jing Hua; Khaw, Kay-Tee; Wareham, Nick J; Rantanen, Taina; Kaprio, Jaakko; Pang, Chi Pui; Chen, Li Jia; Tam, Pancy O; Jhanji, Vishal; Young, Alvin L; Döring, Angela; Raffel, Leslie J; Cotch, Mary-Frances; Li, Xiaohui; Yip, Shea Ping; Yap, Maurice K H; Biino, Ginevra; Vaccargiu, Simona; Fossarello, Maurizio; Fleck, Brian; Yazar, Seyhan; Tideman, Jan Willem L; Tedja, Milly; Deangelis, Margaret M; Morrison, Margaux; Farrer, Lindsay; Zhou, Xiangtian; Chen, Wei; Mizuki, Nobuhisa; Meguro, Akira; Mäkelä, Kari Matti

    2016-03-29

    Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.

  8. Gene-environment interactions in the pre-Industrial Era: the cancer of King Ferrante I of Aragon (1431-1494).

    PubMed

    Ottini, Laura; Falchetti, Mario; Marinozzi, Silvia; Angeletti, Luciana Rita; Fornaciari, Gino

    2011-03-01

    King Ferrante I of Aragon, leading figure of the Italian Renaissance, died in 1494. The autopsy of his mummy revealed a tumor infiltrating the small pelvis. We examined the histologic and molecular features of this ancient tumor to investigate its primary origin. Hematoxylin-eosin, Van Gieson, and Alcian Blue staining showed neoplastic cells infiltrating muscular fibers and forming pseudo-glandular lumina disseminated in fibrous stroma with scarce mucus. A strong immunoreactivity of the neoplastic cells was shown for pancytokeratins and proliferating cell nuclear antigen. Molecular fingerprints were investigated by examining K-ras, BRAF, and microsatellite instability in ancient tumor DNA. Sequencing analysis showed G-to-A transition in codon 12 of K-ras. BRAF mutations and microsatellite instability were not observed. Because the presence of K-ras codon 12 mutation could be associated with exposure to chemical carcinogens, possibly present in some food items, paleodietary reconstruction of the King Ferrante I was carried out by carbon (δ(13)C ) and nitrogen (δ(15)N) stable isotopes analysis. δ(13)C and δ(15)N values found in bone collagen of the King were consistent with a massive intake of animal proteins. Overall, our data show that the tumor of Ferrante I was a mucinous adenocarcinoma with molecular fingerprints characteristic of colorectal carcinogenesis linked to K-ras pathway. Paleodietary reconstruction and historical chronicles indicate a strong consumption of meat by the King. The possible abundance of dietary carcinogens, related to meat consumption, could explain the K-ras mutation causing the colorectal tumor that killed Ferrante I more than 5 centuries ago.

  9. Gene-Environment Interaction in Teacher-Rated Internalizing and Externalizing Problem Behavior in 7- to 12-Year-Old Twins

    ERIC Educational Resources Information Center

    Lamb, Diane J.; Middeldorp, Christel M.; Van Beijsterveldt, Catarina E. M.; Boomsma, Dorret I.

    2012-01-01

    Background: Internalizing and externalizing problem behavior at school can have major consequences for a child and is predictive for disorders later in life. Teacher ratings are important to assess internalizing and externalizing problems at school. Genetic epidemiological studies on teacher-rated problem behavior are relatively scarce and the…

  10. Gene-environment interactions: the potential role of contaminants in somatic growth and the development of the reproductive system of the American alligator.

    PubMed

    Moore, Brandon C; Roark, Alison M; Kohno, Satomi; Hamlin, Heather J; Guillette, Louis J

    2012-05-06

    Developing organisms interpret and integrate environmental signals to produce adaptive phenotypes that are prospectively suited for probable demands in later life. This plasticity can be disrupted when embryos are impacted by exogenous contaminants, such as environmental pollutants, producing potentially deleterious and long-lasting mismatches between phenotype and the future environment. We investigated the ability for in ovo environmental contaminant exposure to alter the growth trajectory and ovarian function of alligators at five months after hatching. Alligators collected as eggs from polluted Lake Apopka, FL, hatched with smaller body masses but grew faster during the first five months after hatching, as compared to reference-site alligators. Further, ovaries from Lake Apopka alligators displayed lower basal expression levels of inhibin beta A mRNA as well as decreased responsiveness of aromatase and follistatin mRNA expression levels to treatment with follicle stimulating hormone. We posit that these differences predispose these animals to increased risks of disease and reproductive dysfunction at adulthood.

  11. Nutrigenomics, the microbiome, and gene environment interactions: new directions in cardiovascular disease research, prevention, and treatment. A scientific statement From the American Heart Association

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cardiometabolic diseases are the leading cause of death worldwide and are strongly linked to both genetic and nutritional factors. The field of nutrigenomics encompasses multiple approaches aimed at understanding the effects of diet on health or disease development, including nutrigenetic studies in...

  12. Replication of a gene-environment interaction Via Multimodel inference: additive-genetic variance in adolescents' general cognitive ability increases with family-of-origin socioeconomic status.

    PubMed

    Kirkpatrick, Robert M; McGue, Matt; Iacono, William G

    2015-03-01

    The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES-an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research.

  13. Replication of a Gene-Environment Interaction via Multimodel Inference: Additive-Genetic Variance in Adolescents’ General Cognitive Ability Increases with Family-of-Origin Socioeconomic Status

    PubMed Central

    Kirkpatrick, Robert M.; McGue, Matt; Iacono, William G.

    2015-01-01

    The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES—an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research. PMID:25539975

  14. Candidate Exercise Technologies and Prescriptions

    NASA Technical Reports Server (NTRS)

    Loerch, Linda H.

    2010-01-01

    This slide presentation reviews potential exercise technologies to counter the effects of space flight. It includes a overview of the exercise countermeasures project, a review of some of the candidate exercise technologies being considered and a few of the analog exercise hardware devices, and a review of new studies that are designed to optimize the current and future exercise protocols.

  15. Teacher Candidate Applications of Telecommunications.

    ERIC Educational Resources Information Center

    Crawford, Caroline M.; Hilburn, Sue; Willis, Jana

    Telecommunications offers teacher candidates an environment through which to delve into higher order thinking skills within the methods coursework, student teaching internship experience, as well as within the PreK-12 classroom environment. Modeling of appropriate uses of technology within the learning environment as the teacher candidate…

  16. SAO RAS SN candidates classifications

    NASA Astrophysics Data System (ADS)

    Fatkhullin, T. A.; Moskvitin, A. S.

    2016-08-01

    We observed SN candidates (AT 2016eow, AT 2016enu and AT 2016enf) with the BTA/Scorpio-I on August, 4. Direct images in the R band and long-slit spectra in the range of 3600-7600AA (resolution FWHM = 10A) were obtained.

  17. Candidate Cave Entrances on Mars

    NASA Astrophysics Data System (ADS)

    Cushing, Glen

    2012-04-01

    This paper presents newly discovered candidate cave entrances into Martian near-surface lava tubes, volcano-tectonic fracture systems, and pit craters and describes their characteristics and exploration possibilities. These candidates are all collapse features that occur either intermittently along laterally continuous trench-like depressions or in the floors of sheer-walled atypical pit craters. As viewed from orbit, locations of most candidates are visibly consistent with known terrestrial features such as tube-fed lava flows, volcano-tectonic fractures, and pit craters, each of which forms by mechanisms that can produce caves. Although we cannot determine subsurface extents of the Martian features discussed here, some may continue unimpeded for many kilometers if terrestrial examples are indeed analogous. The features presented here were identified in images acquired by the Mars Odyssey's Thermal Emission Imaging System visiblewavelength camera, and by the Mars Reconnaissance Orbiter's Context Camera. Select candidates have since been targeted by the High-Resolution Imaging Science Experiment. Martian caves are promising potential sites for future human habitation and astrobiology investigations; understanding their characteristics is critical for long-term mission planning and for developing the necessary exploration technologies.

  18. Candidate gene prioritization with Endeavour.

    PubMed

    Tranchevent, Léon-Charles; Ardeshirdavani, Amin; ElShal, Sarah; Alcaide, Daniel; Aerts, Jan; Auboeuf, Didier; Moreau, Yves

    2016-07-08

    Genomic studies and high-throughput experiments often produce large lists of candidate genes among which only a small fraction are truly relevant to the disease, phenotype or biological process of interest. Gene prioritization tackles this problem by ranking candidate genes by profiling candidates across multiple genomic data sources and integrating this heterogeneous information into a global ranking. We describe an extended version of our gene prioritization method, Endeavour, now available for six species and integrating 75 data sources. The performance (Area Under the Curve) of Endeavour on cross-validation benchmarks using 'gold standard' gene sets varies from 88% (for human phenotypes) to 95% (for worm gene function). In addition, we have also validated our approach using a time-stamped benchmark derived from the Human Phenotype Ontology, which provides a setting close to prospective validation. With this benchmark, using 3854 novel gene-phenotype associations, we observe a performance of 82%. Altogether, our results indicate that this extended version of Endeavour efficiently prioritizes candidate genes. The Endeavour web server is freely available at https://endeavour.esat.kuleuven.be/.

  19. Email Journaling for Teacher Candidates

    ERIC Educational Resources Information Center

    Jenny, Geraldine Covert

    2005-01-01

    This paper discusses email journaling for those hoping to become a teacher. The author discusses an innovative format she designed for journal entries that revolutionized her field experience supervision practices and those of other supervisors with whom she has shared this format. It has vastly improved the quality of the teacher-candidate's…

  20. Candidate cave entrances on Mars

    USGS Publications Warehouse

    Cushing, Glen E.

    2012-01-01

    This paper presents newly discovered candidate cave entrances into Martian near-surface lava tubes, volcano-tectonic fracture systems, and pit craters and describes their characteristics and exploration possibilities. These candidates are all collapse features that occur either intermittently along laterally continuous trench-like depressions or in the floors of sheer-walled atypical pit craters. As viewed from orbit, locations of most candidates are visibly consistent with known terrestrial features such as tube-fed lava flows, volcano-tectonic fractures, and pit craters, each of which forms by mechanisms that can produce caves. Although we cannot determine subsurface extents of the Martian features discussed here, some may continue unimpeded for many kilometers if terrestrial examples are indeed analogous. The features presented here were identified in images acquired by the Mars Odyssey's Thermal Emission Imaging System visible-wavelength camera, and by the Mars Reconnaissance Orbiter's Context Camera. Select candidates have since been targeted by the High-Resolution Imaging Science Experiment. Martian caves are promising potential sites for future human habitation and astrobiology investigations; understanding their characteristics is critical for long-term mission planning and for developing the necessary exploration technologies.

  1. Child-evoked maternal negativity from 9 to 27 months: evidence of gene-environment correlation and its moderation by marital distress

    PubMed Central

    Fearon, R.M. Pasco; Reiss, David; Leve, Leslie D.; Shaw, Daniel S.; Scaramella, Laura V.; Ganiban, Jody M.; Neiderhiser, Jenae M.

    2014-01-01

    Past research has documented pervasive genetic influences on emotional and behavioral disturbance across the lifespan and on liability to adult psychiatric disorder. Increasingly, interest is turning to mechanisms of gene-environment interplay in attempting to understand the earliest manifestations of genetic risk. We report findings from a prospective adoption study, which aimed to test the role of evocative gene-environment correlation in early development. 561 infants adopted at birth were studied between 9 and 27 months with their adoptive parents and birth mothers. Birth mother psychiatric diagnoses and symptoms scales were used as indicators of genetic influence, and multiple self-report measures were used to index adoptive mother parental negativity. We hypothesized that birth parent psychopathology would be associated with greater adoptive parent negativity, and that such evocative effects would be amplified under conditions of high family adversity. The findings suggested that genetic factors linked to birth mother externalizing psychopathology may evoke negative reactions in adoptive mothers in the first year of life, but primarily when the adoptive family environment was characterized by marital problems. The observed maternal negativity mediated the effects of genetic risk on child adjustment at 27 months. The results underline the importance of genetically-influenced evocative processes in early development. PMID:25216383

  2. Significant interactions between maternal PAH exposure and haplotypes in candidate genes on B[a]P-DNA adducts in a NYC cohort of non-smoking African-American and Dominican mothers and newborns

    PubMed Central

    Tang, Deliang

    2014-01-01

    Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[a]pyrene (B[a]P) is a well-studied PAH that is classified as a probable human carcinogen. Within our New York City-based cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn haplotypes (and in one case, a single-nucleotide polymorphism) in key B[a]P metabolism genes on B[a]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking African-American (n = 132) and Dominican (n = 235) women with available data on maternal PAH exposure, paired cord adducts and genetic data who resided in the Washington Heights, Central Harlem and South Bronx neighborhoods of New York City. We selected seven maternal and newborn genes related to B[a]P metabolism, detoxification and repair for our analyses: CYP1A1, CYP1A2, CYP1B1, GSTM3, GSTT2, NQO1 and XRCC1. We found significant interactions between maternal PAH exposure and haplotype on cord B[a]P-DNA adducts in the following genes: maternal CYP1B1, XRCC1 and GSTM3, and newborn CYP1A2 and XRCC1 in African-Americans; and maternal XRCC1 and newborn NQO1 in Dominicans. These novel findings highlight differences in maternal and newborn genetic contributions to B[a]P-DNA adduct formation, as well as ethnic differences in gene–environment interactions, and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[a]P. PMID:24177223

  3. Age-dependent role of pre- and perinatal factors in interaction with genes on ADHD symptoms across adolescence.

    PubMed

    Brinksma, Djûke M; Hoekstra, Pieter J; van den Hoofdakker, Barbara; de Bildt, Annelies; Buitelaar, Jan K; Hartman, Catharina A; Dietrich, Andrea

    2017-02-21

    Little is known about the effects of risk factors on attention-deficit/hyperactivity disorder (ADHD) symptom over time. Here, we longitudinally studied the role of candidate genes, pre- and perinatal factors, and their interactions on ADHD symptoms between ages 10 and 18 years. Subjects were part of the general population or clinic-referred cohort of the TRacking Adolescents' Individual Lives Survey (n = 1667). At mean ages of 11.1 (T1), 13.4 (T2), and 16.2 years (T3), ADHD symptoms were assessed with the Child Behavior Checklist. Linear Mixed Models were used to examine the association of candidate genes (i.e., DRD4, DRD2, 5-HTTLPR, COMT, and MAOA), pre- and perinatal factors (i.e., index measure of various pregnancy and delivery complications, maternal smoking, maternal drinking, and low birth weight), and their interactions with ADHD symptoms across adolescence. Pregnancy and delivery complications were associated with a higher level of ADHD symptoms across all time points, but with a significantly declining influence over time (p = 0.006). We found no main effects of the candidate genes on ADHD symptoms throughout adolescence. The simultaneous presence of the low activity MAOA genotype and low birth weight (p < 0.001) and of the 5-HTTLPR LL-allele and respectively pregnancy and delivery complications (p = 0.04) and maternal smoking (p = 0.04) were associated with more ADHD symptoms particularly during early adolescence, and these influences significantly decreased over time. Findings suggest an age-dependent role of gene-environment interactions on ADHD symptoms across adolescence.

  4. An environmental analysis of genes associated with schizophrenia: hypoxia and vascular factors as interacting elements in the neurodevelopmental model.

    PubMed

    Schmidt-Kastner, R; van Os, J; Esquivel, G; Steinbusch, H W M; Rutten, B P F

    2012-12-01

    Investigating and understanding gene-environment interaction (G × E) in a neurodevelopmentally and biologically plausible manner is a major challenge for schizophrenia research. Hypoxia during neurodevelopment is one of several environmental factors related to the risk of schizophrenia, and links between schizophrenia candidate genes and hypoxia regulation or vascular expression have been proposed. Given the availability of a wealth of complex genetic information on schizophrenia in the literature without knowledge on the connections to environmental factors, we now systematically collected genes from candidate studies (using SzGene), genome-wide association studies (GWAS) and copy number variation (CNV) analyses, and then applied four criteria to test for a (theoretical) link to ischemia-hypoxia and/or vascular factors. In all, 55% of the schizophrenia candidate genes (n=42 genes) met the criteria for a link to ischemia-hypoxia and/or vascular factors. Genes associated with schizophrenia showed a significant, threefold enrichment among genes that were derived from microarray studies of the ischemia-hypoxia response (IHR) in the brain. Thus, the finding of a considerable match between genes associated with the risk of schizophrenia and IHR and/or vascular factors is reproducible. An additional survey of genes identified by GWAS and CNV analyses suggested novel genes that match the criteria. Findings for interactions between specific variants of genes proposed to be IHR and/or vascular factors with obstetric complications in patients with schizophrenia have been reported in the literature. Therefore, the extended gene set defined here may form a reasonable and evidence-based starting point for hypothesis-based testing of G × E interactions in clinical genetic and translational neuroscience studies.

  5. Enthalpy screen of drug candidates.

    PubMed

    Schön, Arne; Freire, Ernesto

    2016-11-15

    The enthalpic and entropic contributions to the binding affinity of drug candidates have been acknowledged to be important determinants of the quality of a drug molecule. These quantities, usually summarized in the thermodynamic signature, provide a rapid assessment of the forces that drive the binding of a ligand. Having access to the thermodynamic signature in the early stages of the drug discovery process will provide critical information towards the selection of the best drug candidates for development. In this paper, the Enthalpy Screen technique is presented. The enthalpy screen allows fast and accurate determination of the binding enthalpy for hundreds of ligands. As such, it appears to be ideally suited to aid in the ranking of the hundreds of hits that are usually identified after standard high throughput screening.

  6. Leishmaniasis: vaccine candidates and perspectives.

    PubMed

    Singh, Bhawana; Sundar, Shyam

    2012-06-06

    Leishmania is a protozoan parasite and a causative agent of the various clinical forms of leishmaniasis. High cost, resistance and toxic side effects of traditional drugs entail identification and development of therapeutic alternatives. The sound understanding of parasite biology is key for identifying novel drug targets, that can induce the cell mediated immunity (mainly CD4+ and CD8+ IFN-gamma mediated responses) polarized towards a Th1 response. These aspects are important in designing a new vaccine along with the consideration of the candidates with respect to their ability to raise memory response in order to improve the vaccine performance. This review is an effort to identify molecules according to their homology with the host and their ability to be used as potent vaccine candidates.

  7. Theoretical Comparison Between Candidates for Dark Matter

    NASA Astrophysics Data System (ADS)

    McKeough, James; Hira, Ajit; Valdez, Alexandra

    2017-01-01

    Since the generally-accepted view among astrophysicists is that the matter component of the universe is mostly dark matter, the search for dark matter particles continues unabated. The Large Underground Xenon (LUX) improvements, aided by advanced computer simulations at the U.S. Department of Energy's Lawrence Berkeley National Laboratory's (Berkeley Lab) National Energy Research Scientific Computing Center (NERSC) and Brown University's Center for Computation and Visualization (CCV), can potentially eliminate some particle models of dark matter. Generally, the proposed candidates can be put in three categories: baryonic dark matter, hot dark matter, and cold dark matter. The Lightest Supersymmetric Particle(LSP) of supersymmetric models is a dark matter candidate, and is classified as a Weakly Interacting Massive Particle (WIMP). Similar to the cosmic microwave background radiation left over from the Big Bang, there is a background of low-energy neutrinos in our Universe. According to some researchers, these may be the explanation for the dark matter. One advantage of the Neutrino Model is that they are known to exist. Dark matter made from neutrinos is termed ``hot dark matter''. We formulate a novel empirical function for the average density profile of cosmic voids, identified via the watershed technique in ΛCDM N-body simulations. This function adequately treats both void size and redshift, and describes the scale radius and the central density of voids. We started with a five-parameter model. Our research is mainly on LSP and Neutrino models.

  8. OPTOPUS observations of quasar candidates.

    NASA Astrophysics Data System (ADS)

    Cristiani, S.

    1987-06-01

    OPTOPUS is a fiber-optic instrument for multiple-object spectroscopy with the Boiler & Chivens spectrograph and a CCD detector at the 3.6-m telescope. The system has been described in detail by the Optical Instrumentation Group (1985, The Messenger 41,25). Its application for observing Halley's comet has been reported by Lund and Surdej (1986, The Messenger 43, 1). Here another "classical" use of multiple-object spectroscopy is presented: followup observations of quasar candidates.

  9. Synaptoproteomic Analysis of a Rat Gene-Environment Model of Depression Reveals Involvement of Energy Metabolism and Cellular Remodeling Pathways

    PubMed Central

    Failler, Marion; Corna, Stefano; Racagni, Giorgio; Mathé, Aleksander A.; Popoli, Maurizio

    2015-01-01

    Background: Major depression is a severe mental illness that causes heavy social and economic burdens worldwide. A number of studies have shown that interaction between individual genetic vulnerability and environmental risk factors, such as stress, is crucial in psychiatric pathophysiology. In particular, the experience of stressful events in childhood, such as neglect, abuse, or parental loss, was found to increase the risk for development of depression in adult life. Here, to reproduce the gene x environment interaction, we employed an animal model that combines genetic vulnerability with early-life stress. Methods: The Flinders Sensitive Line rats (FSL), a validated genetic animal model of depression, and the Flinders Resistant Line (FRL) rats, their controls, were subjected to a standard protocol of maternal separation (MS) from postnatal days 2 to 14. A basal comparison between the two lines for the outcome of the environmental manipulation was performed at postnatal day 73, when the rats were into adulthood. We carried out a global proteomic analysis of purified synaptic terminals (synaptosomes), in order to study a subcellular compartment enriched in proteins involved in synaptic function. Two-dimensional gel electrophoresis (2-DE), mass spectrometry, and bioinformatic analysis were used to analyze proteins and related functional networks that were modulated by genetic susceptibility (FSL vs. FRL) or by exposure to early-life stress (FRL + MS vs. FRL and FSL + MS vs. FSL). Results: We found that, at a synaptic level, mainly proteins and molecular pathways related to energy metabolism and cellular remodeling were dysregulated. Conclusions: The present results, in line with previous works, suggest that dysfunction of energy metabolism and cytoskeleton dynamics at a synaptic level could be features of stress-related pathologies, in particular major depression. PMID:25522407

  10. Dark matter candidates and methods for detecting them

    NASA Technical Reports Server (NTRS)

    Raffelt, G. G.

    1992-01-01

    A number of experiments employing Ge and Si ionization detectors have excluded large regions in the plane of masses and scattering cross-sections for weakly-interacting dark matter (DM) candidates. It is judged that, before a realistic detection experiment for supersymmetric DM candidates can be conducted, significant development efforts will have to be completed for suitable cryogenic or ionization detectors. Pilot experiments have demonstrated the feasibility of axion searches with microwave cavities, but these are at least two orders of magnitude too low in sensitivity.

  11. Polymorphisms in nucleotide excision repair genes and risk of multiple primary melanoma: the Genes Environment and Melanoma Study.

    PubMed

    Millikan, Robert C; Hummer, Amanda; Begg, Colin; Player, Jon; de Cotret, Allan René; Winkel, Scott; Mohrenweiser, Harvey; Thomas, Nancy; Armstrong, Bruce; Kricker, Anne; Marrett, Loraine D; Gruber, Stephen B; Culver, Hoda Anton; Zanetti, Roberto; Gallagher, Richard P; Dwyer, Terence; Rebbeck, Timothy R; Busam, Klaus; From, Lynn; Mujumdar, Urvi; Berwick, Marianne

    2006-03-01

    Polymorphisms in six genes involved in nucleotide excision repair of DNA were examined in a large population-based case-control study of melanoma. Genotyping was conducted for 2485 patients with a single primary melanoma (controls) and 1238 patients with second or higher order primary melanomas (cases). Patients were ascertained from nine geographic regions in Australia, Canada, Italy and the United States. Positive associations were observed for XPD 312 Asn/Asn versus Asp/Asp [odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.2-1.9] and XPD 751 Gln/Gln versus Lys/Lys (OR = 1.4, 95% CI 1.1-1.7) genotypes and melanoma. The combined XPD Asn (A) 312 + Gln (C) 751 haplotype was significantly more frequent in cases (32%) compared with controls (29%) (P = 0.003) and risk of melanoma increased significantly with one and two copies of the haplotype (ORs 1.2, 95% CI 1.0-1.4, and 1.6, 95% CI 1.2-2.0, trend P = 0.002). No significant associations were observed for HR23B codon 249, XPG codon 1104, XPC codon 939, XPF codon 415, XPF nt 2063, ERCC6 codon 1213 or ERCC6 codon 1230. ORs for XPD and XPC genotypes were stronger for melanoma diagnosed at an early age, but tests for interaction were not statistically significant. The results provide further evidence for a role of XPD in the etiology of melanoma.

  12. Genetic Interactions with Prenatal Social Environment: Effects on Academic and Behavioral Outcomes

    ERIC Educational Resources Information Center

    Conley, Dalton; Rauscher, Emily

    2013-01-01

    Numerous studies report gene-environment interactions, suggesting that specific alleles have different effects on social outcomes depending on environment. In all these studies, however, environmental conditions are potentially endogenous to unmeasured genetic characteristics. That is, it could be that the observed interaction effects actually…

  13. 11 CFR 9032.2 - Candidate.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... FUND DEFINITIONS § 9032.2 Candidate. Candidate means an individual who seeks nomination for election to the office of President of the United States. An individual is considered to seek nomination...

  14. Kepler Discovers Earth-size Planet Candidates

    NASA Video Gallery

    NASA's Kepler mission has discovered its first Earth-size planet candidates and its first candidates in the habitable zone, a region where liquid water could exist on a planet's surface. Five of th...

  15. Teacher Candidate Dispositions: Perspectives of Professional Expectations

    ERIC Educational Resources Information Center

    Wake, Donna; Bunn, Gary

    2016-01-01

    This study describes a programmatic effort to examine dispositions perceptions of teacher candidates entering the profession. Study participants included 114 master's level teaching candidates in their first semester of a nontraditional teacher education program. Teacher candidates scored themselves on a department disposition rubric designed to…

  16. 11 CFR 100.154 - Candidate debates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate debates. 100.154 Section 100.154 Federal Elections FEDERAL ELECTION COMMISSION GENERAL SCOPE AND DEFINITIONS (2 U.S.C. 431) Exceptions to Expenditures § 100.154 Candidate debates. Funds used to defray costs incurred in staging candidate debates...

  17. 11 CFR 110.13 - Candidate debates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate debates. 110.13 Section 110.13... PROHIBITIONS § 110.13 Candidate debates. (a) Staging organizations. (1) Nonprofit organizations described in 26... political parties may stage candidate debates in accordance with this section and 11 CFR 114.4(f)....

  18. 11 CFR 100.92 - Candidate debates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate debates. 100.92 Section 100.92 Federal Elections FEDERAL ELECTION COMMISSION GENERAL SCOPE AND DEFINITIONS (2 U.S.C. 431) Exceptions to Contributions § 100.92 Candidate debates. Funds provided to defray costs incurred in staging candidate...

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

    PubMed

    O'Brien, Katie M; Orlow, Irene; Antonescu, Cristina R; Ballman, Karla; McCall, Linda; DeMatteo, Ronald; Engel, Lawrence S

    2013-01-01

    provides a starting point for future candidate gene or gene-environment research.

  20. Gastrointestinal Stromal Tumors, Somatic Mutations and Candidate Genetic Risk Variants

    PubMed Central

    O'Brien, Katie M.; Orlow, Irene; Antonescu, Cristina R.; Ballman, Karla; McCall, Linda; DeMatteo, Ronald; Engel, Lawrence S.

    2013-01-01

    and provides a starting point for future candidate gene or gene-environment research. PMID:23637977

  1. CRISPLD2: a novel NSCLP candidate gene.

    PubMed

    Chiquet, Brett T; Lidral, Andrew C; Stal, Samuel; Mulliken, John B; Moreno, Lina M; Arcos-Burgos, Mauricio; Arco-Burgos, Mauricio; Valencia-Ramirez, Consuelo; Blanton, Susan H; Hecht, Jacqueline T

    2007-09-15

    Non-syndromic cleft lip with or without cleft palate (NSCLP) results from the complex interaction between genes and environmental factors. Candidate gene analysis and genome scans have been employed to identify the genes contributing to NSCLP. In this study, we evaluated the 16q24.1 chromosomal region, which has been identified by multiple genome scans as an NSCLP region of interest. Two candidate genes were found in the region: interferon regulatory factor 8 (IRF8) and cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2). Initially, Caucasian and Hispanic NSCLP multiplex families and simplex parent-child trios were genotyped for single nucleotide polymorphisms (SNPs) in both IRF8 and CRISPLD2. CRISPLD2 was subsequently genotyped in a data set comprised of NSCLP families from Colombia, South America. Linkage disequilibrium analysis identified a significant association between CRISPLD2 and NSCLP in both our Caucasian and Hispanic NSCLP cohorts. SNP rs1546124 and haplotypes between rs1546124 and either rs4783099 or rs16974880 were significant in the Caucasian multiplex population (P=0.01, P=0.002 and P=0.001, respectively). An altered transmission of CRISPLD2 SNPs rs8061351 (P=0.02) and rs2326398 (P=0.06) was detected in the Hispanic population. No association was found between CRISPLD2 and our Colombian population or IRF8 and NSCLP. In situ hybridization showed that CRISPLD2 is expressed in the mandible, palate and nasopharynx regions during craniofacial development at E13.5-E17.5, respectively. Altogether, these data suggest that genetic variation in CRISPLD2 has a role in the etiology of NSCLP.

  2. SN candidate in NGC 3106

    NASA Astrophysics Data System (ADS)

    Drake, A. J.; Djorgovski, S. G.; Mahabal, A. A.; Graham, M. J.; Williams, R.; Catelan, M.; Beshore, E. C.; Larson, S. M.; Gibbs, A.; Christensen, E.

    2009-06-01

    We report the discovery of a SN candidate found by the Catalina Real-time Transient Survey (CRTS) in NGC 3106.

    IDDateRADecMagMag hostz host
    CSS090625:100407+311229 2009-06-25 UT 04:03:46 10:04:06.78 31:12:29.0 16.1 12.7 0.021
    For finding charts, discovery images, lightcurves, etc., please see: http://voeventnet.cacr.caltech.edu/feeds/ATEL/CRTS.

  3. Candidate Gene Identification Approach: Progress and Challenges

    PubMed Central

    Zhu, Mengjin; Zhao, Shuhong

    2007-01-01

    Although it has been widely applied in identification of genes responsible for biomedically, economically, or even evolutionarily important complex and quantitative traits, traditional candidate gene approach is largely limited by its reliance on the priori knowledge about the physiological, biochemical or functional aspects of possible candidates. Such limitation results in a fatal information bottleneck, which has apparently become an obstacle for further applications of traditional candidate gene approach on many occasions. While the identification of candidate genes involved in genetic traits of specific interest remains a challenge, significant progress in this subject has been achieved in the last few years. Several strategies have been developed, or being developed, to break the barrier of information bottleneck. Recently, being a new developing method of candidate gene approach, digital candidate gene approach (DigiCGA) has emerged and been primarily applied to identify potential candidate genes in some studies. This review summarizes the progress, application software, online tools, and challenges related to this approach. PMID:17998950

  4. Advising Doctorate Candidates and Candidates' Views during the Dissertation Process

    ERIC Educational Resources Information Center

    Hilliard, Ann T.

    2013-01-01

    In order to provide candidates with effective advisement, it is important for the advisor to continue to practice positive professional relationships and provide relevant academic support to candidates. The advisor should work closely with other faculty members and need to listen to the voices of candidates to ensure candidates' success. What…

  5. Computational selection and prioritization of candidate genes for Fetal Alcohol Syndrome

    PubMed Central

    Lombard, Zané; Tiffin, Nicki; Hofmann, Oliver; Bajic, Vladimir B; Hide, Winston; Ramsay, Michèle

    2007-01-01

    Background Fetal alcohol syndrome (FAS) is a serious global health problem and is observed at high frequencies in certain South African communities. Although in utero alcohol exposure is the primary trigger, there is evidence for genetic- and other susceptibility factors in FAS development. No genome-wide association or linkage studies have been performed for FAS, making computational selection and -prioritization of candidate disease genes an attractive approach. Results 10174 Candidate genes were initially selected from the whole genome using a previously described method, which selects candidate genes according to their expression in disease-affected tissues. Hereafter candidates were prioritized for experimental investigation by investigating criteria pertinent to FAS and binary filtering. 29 Criteria were assessed by mining various database sources to populate criteria-specific gene lists. Candidate genes were then prioritized for experimental investigation using a binary system that assessed the criteria gene lists against the candidate list, and candidate genes were scored accordingly. A group of 87 genes was prioritized as candidates and for future experimental validation. The validity of the binary prioritization method was assessed by investigating the protein-protein interactions, functional enrichment and common promoter element binding sites of the top-ranked genes. Conclusion This analysis highlighted a list of strong candidate genes from the TGF-β, MAPK and Hedgehog signalling pathways, which are all integral to fetal development and potential targets for alcohol's teratogenic effect. We conclude that this novel bioinformatics approach effectively prioritizes credible candidate genes for further experimental analysis. PMID:17961254

  6. Gene-environment correlation in the development of adolescent substance abuse: selection effects of child personality and mediation via contextual risk factors.

    PubMed

    Hicks, Brian M; Johnson, Wendy; Durbin, C Emily; Blonigen, Daniel M; Iacono, William G; McGue, Matt

    2013-02-01

    We used a longitudinal twin design to examine selection effects of personality traits at age 11 on high-risk environmental contexts at age 14 and the extent to which these contexts mediated risk for substance abuse at age 17. Socialization at age 11 (willingness to follow rules and endorse conventional values) predicted exposure to contextual risk at age 14. Contextual risk partially mediated the effect of socialization on substance abuse, though socialization also had a direct effect. In contrast, boldness at age 11 (social engagement and assurance, thrill seeking, and stress resilience) also predicted substance abuse directly but was unrelated to contextual risk. There was substantial overlap in the genetic and shared environmental influences on socialization and contextual risk, and genetic risk in socialization contributed to substance abuse indirectly via increased exposure to contextual risk. This suggests that active gene-environment correlations related to individual differences in socialization contributed to an early, high-risk developmental trajectory for adolescent substance abuse. In contrast, boldness appeared to index an independent and direct genetic risk factor for adolescent substance abuse.

  7. Newly identified YSO candidates towards LDN 1188

    NASA Astrophysics Data System (ADS)

    Marton , G.; Verebélyi, E.; Kiss, Cs.; Smidla, J.

    2013-11-01

    We present an analysis of young stellar object (YSO) candidates towards the LDN 1188 molecular cloud. The YSO candidates were selected from the WISE all-sky catalogue, based on a statistical method. We found 601 candidates in the region, and classified them as Class I, Flat, and Class II YSOs. Groups were identified and described with the Minimal Spanning Tree (MST) method. Previously identified molecular cores show evidence of ongoing star formation at different stages throughout the cloud complex.

  8. Gene x environment interactions in conduct disorder: Implications for future treatments.

    PubMed

    Holz, Nathalie E; Zohsel, Katrin; Laucht, Manfred; Banaschewski, Tobias; Hohmann, Sarah; Brandeis, Daniel

    2016-08-18

    Conduct disorder (CD) causes high financial and social costs, not only in affected families but across society, with only moderately effective treatments so far. There is consensus that CD is likely caused by the convergence of many different factors, including genetic and adverse environmental factors. There is ample evidence of gene-environment interactions in the etiology of CD on a behavioral level regarding genetically sensitive designs and candidate gene-driven approaches, most prominently and consistently represented by MAOA. However, conclusive indications of causal GxE patterns are largely lacking. Inconsistent findings, lack of replication and methodological limitations remain a major challenge. Likewise, research addressing the identification of affected brain pathways which reflect plausible biological mechanisms underlying GxE is still very sparse. Future research will have to take multilevel approaches into account, which combine genetic, environmental, epigenetic, personality, neural and hormone perspectives. A better understanding of relevant GxE patterns in the etiology of CD might enable researchers to design customized treatment options (e.g. biofeedback interventions) for specific subgroups of patients.

  9. Interactions of early adversity with stress-related gene polymorphisms impact regional brain structure in females

    PubMed Central

    Gupta, Arpana; Labus, Jennifer; Kilpatrick, Lisa A.; Bonyadi, Mariam; Ashe-McNalley, Cody; Heendeniya, Nuwanthi; Bradesi, Sylvie; Chang, Lin; Mayer, Emeran A.

    2015-01-01

    Early adverse life events (EALs) have been associated with regional thinning of the subgenual cingulate cortex (sgACC), a brain region implicated in the development of disorders of mood and affect, and often comorbid functional pain disorders, such as irritable bowel syndrome (IBS). Regional neuroinflammation related to chronic stress system activation has been suggested as a possible mechanism underlying these neuroplastic changes. However, the interaction of genetic and environmental factors in these changes is poorly understood. The current study aimed to evaluate the interactions of EALs and candidate gene polymorphisms in influencing thickness of the sgACC. 210 female subjects (137 healthy controls; 73 IBS) were genotyped for stress and inflammation-related gene polymorphisms. Genetic variation with EALs, and diagnosis on sgACC thickness was examined, while controlling for race, age, and total brain volume. Compared to HCs, IBS had significantly reduced sgACC thickness (p = 0.03). Regardless of disease group (IBS vs. HC), thinning of the left sgACC was associated with a significant gene-gene environment interaction between the IL-1β genotype, the NR3C1 haplotype, and a history of EALs (p = 0.05). Reduced sgACC thickness in women with the minor IL-1β allele, was associated with EAL total scores regardless of NR3C1 haplotype status (p = 0.02). In subjects homozygous for the major IL-1β allele, reduced sgACC with increasing levels of EALs was seen only with the less common NR3C1 haplotype (p = 0.02). These findings support an interaction between polymorphisms related to stress and inflammation and early adverse life events in modulating a key region of the emotion arousal circuit. PMID:25630611

  10. Candidate Chemosensory Genes in the Stemborer Sesamia nonagrioides

    PubMed Central

    Glaser, Nicolas; Gallot, Aurore; Legeai, Fabrice; Montagné, Nicolas; Poivet, Erwan; Harry, Myriam; Calatayud, Paul-André; Jacquin-Joly, Emmanuelle

    2013-01-01

    The stemborer Sesamia nonagrioides is an important pest of maize in the Mediterranean Basin. Like other moths, this noctuid uses its chemosensory system to efficiently interact with its environment. However, very little is known on the molecular mechanisms that underlie chemosensation in this species. Here, we used next-generation sequencing (454 and Illumina) on different tissues from adult and larvae, including chemosensory organs and female ovipositors, to describe the chemosensory transcriptome of S. nonagrioides and identify key molecular components of the pheromone production and detection systems. We identified a total of 68 candidate chemosensory genes in this species, including 31 candidate binding-proteins and 23 chemosensory receptors. In particular, we retrieved the three co-receptors Orco, IR25a and IR8a necessary for chemosensory receptor functioning. Focusing on the pheromonal communication system, we identified a new pheromone-binding protein in this species, four candidate pheromone receptors and 12 carboxylesterases as candidate acetate degrading enzymes. In addition, we identified enzymes putatively involved in S. nonagrioides pheromone biosynthesis, including a ∆11-desaturase and different acetyltransferases and reductases. RNAseq analyses and RT-PCR were combined to profile gene expression in different tissues. This study constitutes the first large scale description of chemosensory genes in S. nonagrioides. PMID:23781142

  11. Harnessing gene expression networks to prioritize candidate epileptic encephalopathy genes.

    PubMed

    Oliver, Karen L; Lukic, Vesna; Thorne, Natalie P; Berkovic, Samuel F; Scheffer, Ingrid E; Bahlo, Melanie

    2014-01-01

    We apply a novel gene expression network analysis to a cohort of 182 recently reported candidate Epileptic Encephalopathy genes to identify those most likely to be true Epileptic Encephalopathy genes. These candidate genes were identified as having single variants of likely pathogenic significance discovered in a large-scale massively parallel sequencing study. Candidate Epileptic Encephalopathy genes were prioritized according to their co-expression with 29 known Epileptic Encephalopathy genes. We utilized developing brain and adult brain gene expression data from the Allen Human Brain Atlas (AHBA) and compared this to data from Celsius: a large, heterogeneous gene expression data warehouse. We show replicable prioritization results using these three independent gene expression resources, two of which are brain-specific, with small sample size, and the third derived from a heterogeneous collection of tissues with large sample size. Of the nineteen genes that we predicted with the highest likelihood to be true Epileptic Encephalopathy genes, two (GNAO1 and GRIN2B) have recently been independently reported and confirmed. We compare our results to those produced by an established in silico prioritization approach called Endeavour, and finally present gene expression networks for the known and candidate Epileptic Encephalopathy genes. This highlights sub-networks of gene expression, particularly in the network derived from the adult AHBA gene expression dataset. These networks give clues to the likely biological interactions between Epileptic Encephalopathy genes, potentially highlighting underlying mechanisms and avenues for therapeutic targets.

  12. Retinopathy in old persons with and without diabetes mellitus: the Age, Gene/Environment Susceptibility—Reykjavik Study (AGES-R)

    PubMed Central

    Gunnlaugsdottir, E.; Halldorsdottir, S.; Klein, R.; Eiriksdottir, G.; Klein, B. E.; Benediktsson, R.; Harris, T. B.; Launer, L. J.; Aspelund, T.; Gudnason, V.

    2012-01-01

    Aims/hypothesis We aimed to describe the prevalence of retinopathy in an aged cohort of Icelanders with and without diabetes mellitus. Methods The study population consisted of 4,994 persons aged ≥67 years, who participated in the Age, Gene/Environment Susceptibility—Reykjavik Study (AGES-R). Type 2 diabetes mellitus was defined as HbA1c ≥6.5% (>48 mmol/mol). Retinopathy was assessed by grading fundus photographs using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Associations between retinopathy and risk factors were estimated using odds ratios obtained from multivariate analyses. Results The overall prevalence of retinopathy in AGES-R was 12.4%. Diabetes mellitus was present in 516 persons (10.3%), for 512 of whom gradable fundus photos were available, including 138 persons (27.0%, 95% CI 23.2, 31.0) with any retinopathy. Five persons (1.0%, 95% CI 0.3, 2.3) had proliferative retinopathy. Clinically significant macular oedema was present in five persons (1.0%, 95% CI 0.3, 2.3). Independent risk factors for retinopathy in diabetic patients in a multivariate model included HbA1c, insulin use and use of oral hypoglycaemic agents, the last two being indicators of longer disease duration. In 4478 participants without diabetes mellitus, gradable fundus photos were available for 4,453 participants, with retinopathy present in 476 (10.7%, 95% CI 9.8, 11.6) and clinically significant macular oedema in three persons. Independent risk factors included increasing age and microalbuminuria. Conclusions/interpretation Over three-quarters (78%) of retinopathy cases were found in persons without diabetes and a strong association between microalbuminuria and non-diabetic retinopathy was found. These results may have implications for patient management of the aged. PMID:22134840

  13. Tumor-Infiltrating Lymphocyte Grade in Primary Melanomas Is Independently Associated With Melanoma-Specific Survival in the Population-Based Genes, Environment and Melanoma Study

    PubMed Central

    Thomas, Nancy E.; Busam, Klaus J.; From, Lynn; Kricker, Anne; Armstrong, Bruce K.; Anton-Culver, Hoda; Gruber, Stephen B.; Gallagher, Richard P.; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Venn, Alison; Kanetsky, Peter A.; Groben, Pamela A.; Hao, Honglin; Orlow, Irene; Reiner, Anne S.; Luo, Li; Paine, Susan; Ollila, David W.; Wilcox, Homer; Begg, Colin B.; Berwick, Marianne

    2013-01-01

    Purpose Although most hospital-based studies suggest more favorable survival with tumor-infiltrating lymphocytes (TILs) present in primary melanomas, it is uncertain whether TILs provide prognostic information beyond existing melanoma staging definitions. We addressed the issue in an international population-based study of patients with single and multiple primary melanomas. Patients and Methods On the basis of the Genes, Environment and Melanoma (GEM) study, we conducted follow-up of 2,845 patients diagnosed from 1998 to 2003 with 3,330 invasive primary melanomas centrally reviewed for TIL grade (absent, nonbrisk, or brisk). The odds of TIL grades associated with clinicopathologic features and survival by TIL grade were examined. Results Independent predictors (P < .05) for nonbrisk TIL grade were site, histologic subtype, and Breslow thickness, and for brisk TIL grade, they were age, site, Breslow thickness, and radial growth phase. Nonbrisk and brisk TIL grades were each associated with lower American Joint Committee on Cancer (AJCC) tumor stage compared with TIL absence (Ptrend < .001). Death as a result of melanoma was 30% less with nonbrisk TIL grade (hazard ratio [HR], 0.7; 95% CI, 0.5 to 1.0) and 50% less with brisk TIL grade (HR, 0.5; 95% CI, 0.3 to 0.9) relative to TIL absence, adjusted for age, sex, site, and AJCC tumor stage. Conclusion At the population level, higher TIL grade of primary melanoma is associated with a lower risk of death as a result of melanoma independently of tumor characteristics currently used for AJCC tumor stage. We conclude that TIL grade deserves further prospective investigation to determine whether it should be included in future AJCC staging revisions. PMID:24127443

  14. 47 CFR 76.206 - Candidate rates.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Candidate rates. 76.206 Section 76.206 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cablecasting § 76.206 Candidate rates. (a) Charges for use of cable...

  15. 47 CFR 76.206 - Candidate rates.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 4 2012-10-01 2012-10-01 false Candidate rates. 76.206 Section 76.206 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cablecasting § 76.206 Candidate rates. (a) Charges for use of cable...

  16. 47 CFR 76.206 - Candidate rates.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 4 2014-10-01 2014-10-01 false Candidate rates. 76.206 Section 76.206 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cablecasting § 76.206 Candidate rates. (a) Charges for use of cable...

  17. 47 CFR 76.206 - Candidate rates.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 4 2013-10-01 2013-10-01 false Candidate rates. 76.206 Section 76.206 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cablecasting § 76.206 Candidate rates. (a) Charges for use of cable...

  18. 11 CFR 9034.1 - Candidate entitlements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Federal Elections FEDERAL ELECTION COMMISSION PRESIDENTIAL ELECTION CAMPAIGN FUND: PRESIDENTIAL PRIMARY... the amount of each matchable campaign contribution received by the candidate, except that a candidate... the date of deposit of the underlying contributions if he or she has no net outstanding...

  19. Critical Thinking Tendencies among Teacher Candidates

    ERIC Educational Resources Information Center

    Genc, Salih Zeki

    2008-01-01

    The study aims to determine critical thinking tendencies among teacher candidates. 720 students from primary school teaching department (Primary School Teaching Programme, Science Teaching Programme and Pre-School Teaching Programme) form the sample of the study. When the gender and age distributions were investigated, 253 candidates are males and…

  20. 11 CFR 9003.2 - Candidate certifications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... perjury, that such candidate will not knowingly make expenditures from his or her personal funds, or the personal funds of his or her immediate family, in connection with his or her campaign for the office of...-sister of the candidate, and the spouses of such persons. (2) Expenditures from personal funds made...

  1. Portfolio Development for Teacher Candidates. ERIC Digest.

    ERIC Educational Resources Information Center

    Takona, James P.

    This Digest is intended to help teacher candidates systematically gauge their progress toward the teaching profession by developing a portfolio. Portfolios are one way to assess teacher candidates, and they are a major requirement for experienced teachers seeking board certification from the National Board for Professional Teaching Standards. The…

  2. Special Education Teacher Candidate Assessment: A Review

    ERIC Educational Resources Information Center

    McCall, Zach; McHatton, Patricia Alvarez; Shealey, Monika Williams

    2014-01-01

    Teacher preparation has been under intense scrutiny in recent years. In order for preparation of special education teacher candidates to remain viable, candidate assessment practices must apply practices identified in the extant literature base, while special education teacher education researchers must extend this base with rigorous efforts to…

  3. 29 CFR 452.28 - Unopposed candidates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Unopposed candidates. 452.28 Section 452.28 Labor Regulations Relating to Labor OFFICE OF LABOR-MANAGEMENT STANDARDS, DEPARTMENT OF LABOR LABOR-MANAGEMENT... DISCLOSURE ACT OF 1959 Frequency and Kinds of Elections § 452.28 Unopposed candidates. An election...

  4. Candidate pathway based analysis for cleft lip with or without cleft palate.

    PubMed

    Zhang, Tian-Xiao; Beaty, Terri H; Ruczinski, Ingo

    2012-01-06

    The objective of this research was to identify potential biological pathways associated with non-syndromic cleft lip with or without cleft palate (NSCL/P), and to explore the potential biological mechanisms underlying these associated pathways on risk of NSCL/P. This project was based on the dataset of a previously published genome-wide association (GWA) study on NSCL/P (Beaty et al. 2010). Case-parent trios used here originated from an international consortium (The Gene, Environment Association Studies consortium, GENEVA) formed in 2007. A total of 5,742 individuals from 1,908 CL/P case-parents trios (1,591 complete trios and 317 incomplete trios where one parent was missing) were collected and genotyped using the Illumina Human610-Quad array. Candidate pathways were selected using a list of 356 genes that may be related to oral clefts. In total, 42 candidate pathways, which included 1,564 genes and 40,208 SNPs were tested. Using a pathway-based analysis approach proposed by Wang et al (2007), we conducted a permutation-based test to assess the statistical significance of the nominal p-values of 42 candidate pathways. The analysis revealed several pathways yielding nominally significant p-values. However, controlling for the family wise error rate, none of these pathways could retain statistical significance. Nominal p-values of these pathways were concentrated at the lower tail of the distribution, with more than expected low p-values. A permutation based test for examining this type of distribution pattern yielded an overall p-value of 0.029. Thus, while this pathway-based analysis did not yield a clear significant result for any particular pathway, we conclude that one or more of the genes and pathways considered here likely do play a role in oral clefting.

  5. LPHN3 and Attention-Deficit/Hyperactivity Disorder: Interaction with Maternal Stress during Pregnancy

    ERIC Educational Resources Information Center

    Choudhry, Zia; Sengupta, Sarojini M.; Grizenko, Natalie; Fortier, Marie-Eve; Thakur, Geeta A.; Bellingham, Johanne; Joober, Ridha

    2012-01-01

    Background: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous behavioral disorder, complex both in etiology and clinical expression. Both genetic and environmental factors have been implicated, and it has been suggested that gene-environment interactions may play a pivotal role in the disorder. Recently, a significant association…

  6. Family Conflict Interacts with Genetic Liability in Predicting Childhood and Adolescent Depression

    ERIC Educational Resources Information Center

    Rice, Frances; Harold, Gordon T.; Shelton, Katherine H.; Thapar, Anita

    2006-01-01

    Objective: To test for gene-environment interaction with depressive symptoms and family conflict. Specifically, to first examine whether the influence of family conflict in predicting depressive symptoms is increased in individuals at genetic risk of depression. Second, to test whether the genetic component of variance in depressive symptoms…

  7. Genetic variants implicated in personality: a review of the more promising candidates.

    PubMed

    Savitz, Jonathan B; Ramesar, Rajkumar S

    2004-11-15

    Alleles of the serotonin transporter gene (SERT) and the dopamine 4 receptor gene (DRD4) were first associated with anxiety-related and novelty-seeking personality traits, respectively, in 1996. These early successes precipitated a flood of research into the genetic basis of personality; a quest that has yet to yield decisive answers. Here, both the theoretical and the empirical evidence implicating specific loci-in particular SERT and DRD4-in the development of personality is evaluated. Despite a paucity of statistically significant results following post-hoc analysis, and an excess of positive results derived from studies with small sample sizes, the existence of a genuine effect is argued for: a gene-personality relationship rendered periodically latent through genetic epistasis, gene-environment interactions, variation in genetic background, and the presence of other confounding variables.

  8. Chromosomes Emission of Planet Candidate Host Stars: A Way to Identify False Positives

    NASA Astrophysics Data System (ADS)

    Karoff, Christoffer; Albrecht, Simon; Bonanno, Alfio; Faurschou Knudsen, Mads

    2016-10-01

    It has been hypothesized that the presence of closely orbiting giant planets is associated with enhanced chromospheric emission of their host stars. The main cause for such a relation would likely be enhanced dynamo action induced by the planet. We present measurements of chromospheric emission in 234 planet candidate systems from the Kepler mission. This ensemble includes 37 systems with giant-planet candidates, which show a clear emission enhancement. The enhancement, however, disappears when systems that are also identified as eclipsing binary candidates are removed from the ensemble. This suggests that a large fraction of the giant-planet candidate systems with chromospheric emission stronger than the Sun are not giant-planet systems, but false positives. Such false-positive systems could be tidally interacting binaries with strong chromospheric emission. This hypothesis is supported by an analysis of 188 eclipsing binary candidates that show increasing chromospheric emission as function of decreasing orbital period.

  9. An INTEGRAL Archival Search for Microquasar Candidates

    NASA Astrophysics Data System (ADS)

    Walker, L. M.; Larson, K. L.; Boone, L. M.

    2005-12-01

    We present the status of an ongoing effort to complete a systematic search of the INTEGRAL archive for possible microquasar candidates. Source screening follows the methodology of Motch et al. (1998), but employs current versions of the NRAO/VLA and X-ray catalogs for positional cross--correlation studies. Candidate source fluxes are evaluated with respect to the sensitivities of the the instruments on board the INTEGRAL satellite, and a preliminary analysis of ISGRI and JEM--X data for appropriate candidate sources is presented. This work was funded in part by The College of Wooster's NSF supported REU program (DMR-0243811).

  10. Updated candidate list for engineered barrier materials

    SciTech Connect

    McCright, R.D.

    1995-10-01

    This report describes candidate materials to be evaluated over the next several years during advanced design phases for the waste package to be used for the underground disposal of high-level radioactive wastes at the Yucca Mountain facility.

  11. New Zika Vaccine Candidate Provides Powerful Protection

    MedlinePlus

    ... medlineplus.gov/news/fullstory_163384.html New Zika Vaccine Candidate Provides Powerful Protection Made without live virus, ... News) -- A single dose of an experimental Zika vaccine protected mice and monkeys from the virus, researchers ...

  12. Candidate preferences and expectations of election outcomes.

    PubMed

    Delavande, Adeline; Manski, Charles F

    2012-03-06

    Analysis of data from the American Life Panel shows that in the presidential election of 2008 and in multiple statewide elections in 2010, citizens exhibited large differences in their expectations of election outcomes. Expectations were strongly positively associated with candidate preferences, persons tending to believe that their preferred candidate is more likely to win the election. Committed supporters of opposing candidates regularly differed by 20-30% in their assessments of the likelihood that each candidate would win. These findings contribute evidence on the false consensus effect, the empirical regularity that own preferences tend to be positively associated with perceptions of social preferences. We used unique measures of preferences and perceptions that enabled respondents to express uncertainty flexibly. We studied a setting that would a priori seem inhospitable to false consensus--one where persons have little private information on social preferences but substantial common knowledge provided by media reports of election polls.

  13. Triton stellar occultation candidates - 1992-1994

    NASA Technical Reports Server (NTRS)

    Mcdonald, S. W.; Elliot, J. T.

    1992-01-01

    A search for Triton stellar occultation candidates for the period 1992-1994 has been completed with CCD strip-scanning observations. The search reached an R magnitude of about 17.4 and found 129 candidates within 1.5 arcsec of Triton's ephemeris during this period. Of these events, around 30 occultations are expected to be visible from the earth, indicating that a number of Triton occultation events should be visible from major observatories. Even the faintest of the present candidate events could produce useful occultation data if observed with a large enough telescope. The present astrometric accuracy is inadequate to identify which of these appulse events will produce occultations on the earth; further astrometry is needed to refine the predictions for positive occultation identification. To aid in selecting candidates for additional astrometric and photometric studies, finder charts and earth-based visibility charts for each event are included.

  14. Study Of Candidate Architectures For Data Processor

    NASA Technical Reports Server (NTRS)

    Mcroberts, Lou

    1991-01-01

    Report discusses candidate architectures for digital computer system, part of communication system in spacecraft. Primary issues in analysis; performance, rates of bit errors attributable to single-event upsets (caused by ionizing radiation), reliability, size, and dissipation of power.

  15. Suitable Candidates for Monte Carlo Solutions.

    ERIC Educational Resources Information Center

    Lewis, Jerome L.

    1998-01-01

    Discusses Monte Carlo methods, powerful and useful techniques that rely on random numbers to solve deterministic problems whose solutions may be too difficult to obtain using conventional mathematics. Reviews two excellent candidates for the application of Monte Carlo methods. (ASK)

  16. Towards Treating Chemistry Teacher Candidates as Human

    NASA Astrophysics Data System (ADS)

    Lewthwaite, Brian Ellis

    2008-05-01

    This research inquiry investigates the factors influencing chemistry teacher candidates’ development during their extended practica in the second and final year of an After-Degree Bachelor of Education at a university in central Canada. A variety of data sources are used to identify the risk and protective factors impeding and contributing to the achievement of their chemistry pedagogical aspirations. Two theoretical frameworks, both having their origins in the pioneering work of Kurt Lewin, are used to conceptualize how a complex amalgam of personal attribute and environmental factors and the interplay among these factors influence teacher candidate developmental trajectories. The tenets of both Bronfenbrenner’s bioecological model and Learning Environment research provide insights into how the factors influencing teacher candidate development can be understood and systematically documented to provide a template for reflective consideration of the practicum experience for both teacher candidates and those involved in fostering the development of chemistry teacher candidates.

  17. Seven Democratic Presidential Candidates Debate Educational Issues.

    ERIC Educational Resources Information Center

    Equity and Excellence, 1988

    1988-01-01

    Provides the transcript of a debate on educational issues among Democratic presidential candidates Paul Simon, Albert Gore, Joseph Biden, Jesse Jackson, Bruce Babbitt, Richard Gephart, and Michael Dukakis. (BJV)

  18. Vaccine candidates for malaria: what's new?

    PubMed

    Takashima, Eizo; Morita, Masayuki; Tsuboi, Takafumi

    2016-01-01

    Although it is more than a decade since the parasite genome information was obtained, standardized novel genome-wide selection/prioritization strategies for candidacy of malaria vaccine antigens are still sought. In the quest to systematically identify candidates, it is impossible to overemphasize the usefulness of wheat germ cell-free technology in expressing quality proteins for the post-genome vaccine candidate discovery.

  19. Teacher Candidates Learning from English Learners: Constructing Concepts of Language and Culture in Tuesday's Tutors After-School Program

    ERIC Educational Resources Information Center

    Fitts, Shanan; Gross, Lisa A.

    2012-01-01

    In teacher preparation programs across the United States, early field experiences are considered to be an effective method of providing teacher candidates with opportunities to observe and interact with children (National Council for Accreditation for Teacher Education (NCATE, 2010). These practicum arrangements assist candidates in developing…

  20. A New Way to Confirm Planet Candidates

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-05-01

    What was the big deal behind the Kepler news conference yesterday? Its not just that the number of confirmed planets found by Kepler has more than doubled (though thats certainly exciting news!). Whats especially interesting is the way in which these new planets were confirmed.Number of planet discoveries by year since 1995, including previous non-Kepler discoveries (blue), previous Kepler discoveries (light blue) and the newly validated Kepler planets (orange). [NASA Ames/W. Stenzel; Princeton University/T. Morton]No Need for Follow-UpBefore Kepler, the way we confirmed planet candidates was with follow-up observations. The candidate could be validated either by directly imaging (which is rare) or obtaining a large number radial-velocity measurements of the wobble of the planets host star due to the planets orbit. But once Kepler started producing planet candidates, these approaches to validation became less feasible. A lot of Kepler candidates are small and orbit faint stars, making follow-up observations difficult or impossible.This problem is what inspired the development of whats known as probabilistic validation, an analysis technique that involves assessing the likelihood that the candidates signal is caused by various false-positive scenarios. Using this technique allows astronomers to estimate the likelihood of a candidate signal being a true planet detection; if that likelihood is high enough, the planet candidate can be confirmed without the need for follow-up observations.A breakdown of the catalog of Kepler Objects of Interest. Just over half had previously been identified as false positives or confirmed as candidates. 1284 are newly validated, and another 455 have FPP of1090%. [Morton et al. 2016]Probabilistic validation has been used in the past to confirm individual planet candidates in Kepler data, but now Timothy Morton (Princeton University) and collaborators have taken this to a new level: they developed the first code thats designed to do fully

  1. SBERIA: Set Based gene EnviRonment InterAction test for rare and common variants in complex diseases

    PubMed Central

    Jiao, Shuo; Hsu, Li; Bézieau, Stéphane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Le Marchand, Loic; Lemire, Mathieu; Newcomb, Polly A.; Slattery, Martha L.; Peters, Ulrike

    2013-01-01

    Identification of gene-environment interaction (GxE) is important in understanding the etiology of complex diseases. However, partially due to the lack of power, there have been very few replicated GxE findings compared to the success in marginal association studies. The existing GxE testing methods mainly focus on improving the power for individual markers. In this paper, we took a different strategy and proposed a Set Based gene EnviRonment InterAction test (SBERIA), which can improve the power by reducing the multiple testing burdens and aggregating signals within a set. The major challenge of the signal aggregation within a set is how to tell signals from noise and how to determine the direction of the signals. SBERIA takes advantage of the established correlation screening for GxE to guide the aggregation of genotypes within a marker set. The correlation screening has been shown to be an efficient way of selecting potential GxE candidate SNPs in case-control studies for complex diseases. Importantly, the correlation screening in case-control combined samples is independent of the interaction test. With this desirable feature, SBERIA maintains the correct type I error level and can be easily implemented in a regular logistic regression setting. We showed that SBERIA had higher power than benchmark methods in various simulation scenarios, both for common and rare variants. We also applied SBERIA to real GWAS data of 10,729 colorectal cancer cases and 13,328 controls and found evidence of interaction between the set of known colorectal cancer susceptibility loci and smoking. PMID:23720162

  2. Candidate genes for individual recognition in Polistes fuscatus paper wasps.

    PubMed

    Berens, A J; Tibbetts, E A; Toth, A L

    2016-02-01

    Few animals are known to individually recognize conspecifics, i.e. learn and recall unique individuals during subsequent encounters, and nearly all are social vertebrates. Remarkably, the social paper wasp Polistes fuscatus has recently been discovered to possess this ability, which is useful for remembering identities during competitive social interactions. We analyzed brain gene expression in staged encounters between pairs of individuals to explore potential mechanisms underlying wasps' ability to recall familiar individuals using real-time qRT-PCR. We identified four candidate genes (IP3K, IP3R, Nckx30C and Su(var)2-10) that were down-regulated in the presence of familiar individuals compared to single wasps and pairs of wasps meeting for the first time. These candidate genes are related to calcium signaling, therefore, we treated wasps with lithium chloride, a pharmacological agent that inhibits calcium signaling in neurons. This treatment decreased aggression in paper wasps, but did not affect expression of genes related to calcium signaling. The results suggest calcium signaling differences may be related to individual memory recall in wasps, and we present four promising candidate genes for future study. These data suggest genes associated with dominance behavior may be co-opted for individual recognition, but further work is needed to establish a causal association with the behavior.

  3. Mapping candidate QTLs related to plant persistency in red clover.

    PubMed

    Klimenko, Irina; Razgulayeva, Nadejda; Gau, Mitsuru; Okumura, Kenji; Nakaya, Akihiro; Tabata, Satoshi; Kozlov, Nicolay N; Isobe, Sachiko

    2010-04-01

    Red clover (Trifolium pratense L.) is a diploid (2n = 14), self-incompatible legume that is widely cultivated as a forage legume in cold geographical regions. Because it is a short-lived perennial species, improvement of plant persistency is the most important objective for red clover breeding. To develop a marker-assisted selection (MAS) approach for red clover, we identified candidate QTLs related to plant persistency. Two full-sib mapping populations, 272 x WF1680 and HR x R130, were used for QTL identification. Resistance to Sclerotinia trifoliorum and Fusarium species, as well as to winter hardiness, was investigated in the laboratory and in field experiments in Moscow region (Russia), and Sapporo (Japan). With the genotype data derived from microsatellite and other DNA markers, candidate QTLs were identified by simple interval mapping (SIM), Kruskal-Wallis analysis (KW analysis) and genotype matrix mapping (GMM). A total of 10 and 23 candidate QTL regions for plant persistency were identified in the 272 x WF1680 and the HR x R130 mapping populations, respectively. The QTLs identified by multiple mapping approaches were mapped on linkage group (LG) 3 and LG6. The significant QTL interactions identified by GMM explained the higher phenotypic variation than single effect QTLs. Identification of haplotypes having positive effect QTLs in each parent were first demonstrated in this study for pseudo-testcross mapping populations in plant species using experimental data.

  4. Five Kepler target stars that show multiple transiting exoplanet candidates

    SciTech Connect

    Steffen, Jason H.; Batalha, Natalie M.; Borucki, William J.; Buchhave, Lars A.; Caldwell, Douglas A.; Cochran, William D.; Endl, Michael; Fabrycky, Daniel C.; Fressin, Francois; Ford, Eric B.; Fortney, Jonathan J.; /UC, Santa Cruz, Phys. Dept. /NASA, Ames

    2010-06-01

    We present and discuss five candidate exoplanetary systems identified with the Kepler spacecraft. These five systems show transits from multiple exoplanet candidates. Should these objects prove to be planetary in nature, then these five systems open new opportunities for the field of exoplanets and provide new insights into the formation and dynamical evolution of planetary systems. We discuss the methods used to identify multiple transiting objects from the Kepler photometry as well as the false-positive rejection methods that have been applied to these data. One system shows transits from three distinct objects while the remaining four systems show transits from two objects. Three systems have planet candidates that are near mean motion commensurabilities - two near 2:1 and one just outside 5:2. We discuss the implications that multitransiting systems have on the distribution of orbital inclinations in planetary systems, and hence their dynamical histories; as well as their likely masses and chemical compositions. A Monte Carlo study indicates that, with additional data, most of these systems should exhibit detectable transit timing variations (TTV) due to gravitational interactions - though none are apparent in these data. We also discuss new challenges that arise in TTV analyses due to the presence of more than two planets in a system.

  5. FIVE KEPLER TARGET STARS THAT SHOW MULTIPLE TRANSITING EXOPLANET CANDIDATES

    SciTech Connect

    Steffen, Jason H.; Batalha, Natalie M.; Borucki, William J.; Caldwell, Douglas A.; Haas, Michael J.; Jenkins, Jon M.; Koch, David; Lissauer, Jack J.; Buchhave, Lars A.; Fabrycky, Daniel C.; Fressin, Francois; Holman, Matthew J.; Latham, David W.; Cochran, William D.; Endl, Michael; Ford, Eric B.; Moorhead, Althea V.; Fortney, Jonathan J.; Howell, Steve B.; Isaacson, Howard

    2010-12-10

    We present and discuss five candidate exoplanetary systems identified with the Kepler spacecraft. These five systems show transits from multiple exoplanet candidates. Should these objects prove to be planetary in nature, then these five systems open new opportunities for the field of exoplanets and provide new insights into the formation and dynamical evolution of planetary systems. We discuss the methods used to identify multiple transiting objects from the Kepler photometry as well as the false-positive rejection methods that have been applied to these data. One system shows transits from three distinct objects while the remaining four systems show transits from two objects. Three systems have planet candidates that are near mean motion commensurabilities-two near 2:1 and one just outside 5:2. We discuss the implications that multi-transiting systems have on the distribution of orbital inclinations in planetary systems, and hence their dynamical histories, as well as their likely masses and chemical compositions. A Monte Carlo study indicates that, with additional data, most of these systems should exhibit detectable transit timing variations (TTVs) due to gravitational interactions, though none are apparent in these data. We also discuss new challenges that arise in TTV analyses due to the presence of more than two planets in a system.

  6. Spectroscopy of Kepler Candidate Exoplanet Host Stars

    NASA Astrophysics Data System (ADS)

    Everett, Mark E.; Howell, Steve B.; Silva, David R.; Szkody, Paula

    2014-02-01

    Currently the NASA Kepler Mission has identified 3449 exoplanet candidates, one third with estimated radii R_p<2.5R_oplus and orbiting faint (m_Kep>14.5) host stars. The NASA sponsored Kepler Follow-up Program is focusing on small exoplanet candidates (R_p<2.5R_oplus) and those in habitable zone orbits. Planet radii estimates depend on estimates of host star radii. Based on spectra previously obtained at the KPNO Mayall 4-m for 220 stars with candidate exoplanets, Everett et al. (2013) have shown that many host stars are larger than originally assumed (up to factor of 2). Therefore, the exoplanet candidates they host must be larger than originally assumed, which conversely reduces the number of known Earth- sized exoplanet candidates. Determination of the frequency of such Earth-sized planets is a cornerstone Kepler mission objective and of keen general interest. These Mayall spectra were also used to confirm the Buchhave et al. (2012) result that exoplanet candidates larger than 4R_oplus in short-period orbits are preferentially associated with host stars with solar or higher metallicity, using a fainter and larger sample of stars than Buchhave et al. In short, followup Mayall optical spectroscopy is critical to confirming the detection of Earth-sized exoplanets, a Kepler cornerstone goal, as well as characterizing the relationship between host star properties and planetary system properties. Here, we propose to continue our reconnaissance survey with a focus on the smallest (most rare) exoplanet candidates orbiting the faintest Kepler host stars.

  7. JELLYFISH GALAXY CANDIDATES AT LOW REDSHIFT

    SciTech Connect

    Poggianti, B. M.; Fasano, G.; Omizzolo, A.; Gullieuszik, M.; Bettoni, D.; Paccagnella, A.; Moretti, A.; D’Onofrio, M.; Jaffé, Y. L.; Vulcani, B.; Fritz, J.; Couch, W.

    2016-03-15

    Galaxies that are being stripped of their gas can sometimes be recognized from their optical appearance. Extreme examples of stripped galaxies are the so-called “jellyfish galaxies” that exhibit tentacles of debris material with a characteristic jellyfish morphology. We have conducted the first systematic search for galaxies that are being stripped of their gas at low-z (z = 0.04−0.07) in different environments, selecting galaxies with varying degrees of morphological evidence for stripping. We have visually inspected B- and V-band images and identified 344 candidates in 71 galaxy clusters of the OMEGAWINGS+WINGS sample and 75 candidates in groups and lower mass structures in the PM2GC sample. We present the atlas of stripping candidates and a first analysis of their environment and their basic properties, such as morphologies, star formation rates and galaxy stellar masses. Candidates are found in all clusters and at all clustercentric radii, and their number does not correlate with the cluster velocity dispersion σ or X-ray luminosity L{sub X}. Interestingly, convincing cases of candidates are also found in groups and lower mass halos (10{sup 11}−10{sup 14}M{sub ⊙}), although the physical mechanism at work needs to be securely identified. All the candidates are disky, have stellar masses ranging from log M/M{sub ⊙} < 9 to > 11.5 and the majority of them form stars at a rate that is on average a factor of 2 higher (2.5σ) compared to non-stripped galaxies of similar mass. The few post-starburst and passive candidates have weak stripping evidence. We conclude that disturbed morphologies suggestive of stripping phenomena are ubiquitous in clusters and could be present even in groups and low mass halos. Further studies will reveal the physics of the gas stripping and clarify the mechanisms at work.

  8. Jellyfish Galaxy Candidates at Low Redshift

    NASA Astrophysics Data System (ADS)

    Poggianti, B. M.; Fasano, G.; Omizzolo, A.; Gullieuszik, M.; Bettoni, D.; Moretti, A.; Paccagnella, A.; Jaffé, Y. L.; Vulcani, B.; Fritz, J.; Couch, W.; D'Onofrio, M.

    2016-03-01

    Galaxies that are being stripped of their gas can sometimes be recognized from their optical appearance. Extreme examples of stripped galaxies are the so-called “jellyfish galaxies” that exhibit tentacles of debris material with a characteristic jellyfish morphology. We have conducted the first systematic search for galaxies that are being stripped of their gas at low-z (z = 0.04-0.07) in different environments, selecting galaxies with varying degrees of morphological evidence for stripping. We have visually inspected B- and V-band images and identified 344 candidates in 71 galaxy clusters of the OMEGAWINGS+WINGS sample and 75 candidates in groups and lower mass structures in the PM2GC sample. We present the atlas of stripping candidates and a first analysis of their environment and their basic properties, such as morphologies, star formation rates and galaxy stellar masses. Candidates are found in all clusters and at all clustercentric radii, and their number does not correlate with the cluster velocity dispersion σ or X-ray luminosity LX. Interestingly, convincing cases of candidates are also found in groups and lower mass halos (1011-1014M⊙), although the physical mechanism at work needs to be securely identified. All the candidates are disky, have stellar masses ranging from log M/M⊙ < 9 to > 11.5 and the majority of them form stars at a rate that is on average a factor of 2 higher (2.5σ) compared to non-stripped galaxies of similar mass. The few post-starburst and passive candidates have weak stripping evidence. We conclude that disturbed morphologies suggestive of stripping phenomena are ubiquitous in clusters and could be present even in groups and low mass halos. Further studies will reveal the physics of the gas stripping and clarify the mechanisms at work.

  9. A genetic ensemble approach for gene-gene interaction identification

    PubMed Central

    2010-01-01

    Background It has now become clear that gene-gene interactions and gene-environment interactions are ubiquitous and fundamental mechanisms for the development of complex diseases. Though a considerable effort has been put into developing statistical models and algorithmic strategies for identifying such interactions, the accurate identification of those genetic interactions has been proven to be very challenging. Methods In this paper, we propose a new approach for identifying such gene-gene and gene-environment interactions underlying complex diseases. This is a hybrid algorithm and it combines genetic algorithm (GA) and an ensemble of classifiers (called genetic ensemble). Using this approach, the original problem of SNP interaction identification is converted into a data mining problem of combinatorial feature selection. By collecting various single nucleotide polymorphisms (SNP) subsets as well as environmental factors generated in multiple GA runs, patterns of gene-gene and gene-environment interactions can be extracted using a simple combinatorial ranking method. Also considered in this study is the idea of combining identification results obtained from multiple algorithms. A novel formula based on pairwise double fault is designed to quantify the degree of complementarity. Conclusions Our simulation study demonstrates that the proposed genetic ensemble algorithm has comparable identification power to Multifactor Dimensionality Reduction (MDR) and is slightly better than Polymorphism Interaction Analysis (PIA), which are the two most popular methods for gene-gene interaction identification. More importantly, the identification results generated by using our genetic ensemble algorithm are highly complementary to those obtained by PIA and MDR. Experimental results from our simulation studies and real world data application also confirm the effectiveness of the proposed genetic ensemble algorithm, as well as the potential benefits of combining identification

  10. Sensitive radio survey of obscured quasar candidates

    NASA Astrophysics Data System (ADS)

    Alexandroff, Rachael M.; Zakamska, Nadia L.; van Velzen, Sjoert; Greene, Jenny E.; Strauss, Michael A.

    2016-12-01

    We study the radio properties of moderately obscured quasars in samples at both low (z ˜ 0.5) and high (z ˜ 2.5) redshift to understand the role of radio activity in accretion, using the Karl G. Jansky Very Large Array (VLA) at 6.0 GHz and 1.4 GHz. Our z ˜ 2.5 sample consists of optically selected obscured quasar candidates, all of which are radio-quiet, with typical radio luminosities of νLν[1.4 GHz] ≲ 1040 erg s-1. Only a single source is individually detected in our deep (rms˜10 μJy) exposures. This population would not be identified by radio-based selection methods used for distinguishing dusty star-forming galaxies and obscured active nuclei. In our pilot A-array study of z ˜ 0.5 radio-quiet quasars, we spatially resolve four of five objects on scales ˜5 kpc and find they have steep spectral indices with an average value of α = -0.75. Therefore, radio emission in these sources could be due to jet-driven or radiatively driven bubbles interacting with interstellar material on the scale of the host galaxy. Finally, we also study the additional population of ˜200 faint ( ˜ 40 μJy-40 mJy) field radio sources observed over ˜120 arcmin2 of our data. 60 per cent of these detections (excluding our original targets) are matched in the Sloan Digital Sky Survey (SDSS) and/or Wide-Field Infrared Survey Explorer (WISE) and are, in roughly equal shares, active galactic nuclei (AGN) at a broad range of redshifts, passive galaxies with no other signs of nuclear activity and infrared-bright but optically faint sources. Spectroscopically or photometrically confirmed star-forming galaxies constitute only a small minority of the matches. Such sensitive radio surveys allow us to address important questions of AGN evolution and evaluate the AGN contribution to the radio-quiet sky.

  11. Phenoscape: Identifying Candidate Genes for Evolutionary Phenotypes

    PubMed Central

    Edmunds, Richard C.; Su, Baofeng; Balhoff, James P.; Eames, B. Frank; Dahdul, Wasila M.; Lapp, Hilmar; Lundberg, John G.; Vision, Todd J.; Dunham, Rex A.; Mabee, Paula M.; Westerfield, Monte

    2016-01-01

    Phenotypes resulting from mutations in genetic model organisms can help reveal candidate genes for evolutionarily important phenotypic changes in related taxa. Although testing candidate gene hypotheses experimentally in nonmodel organisms is typically difficult, ontology-driven information systems can help generate testable hypotheses about developmental processes in experimentally tractable organisms. Here, we tested candidate gene hypotheses suggested by expert use of the Phenoscape Knowledgebase, specifically looking for genes that are candidates responsible for evolutionarily interesting phenotypes in the ostariophysan fishes that bear resemblance to mutant phenotypes in zebrafish. For this, we searched ZFIN for genetic perturbations that result in either loss of basihyal element or loss of scales phenotypes, because these are the ancestral phenotypes observed in catfishes (Siluriformes). We tested the identified candidate genes by examining their endogenous expression patterns in the channel catfish, Ictalurus punctatus. The experimental results were consistent with the hypotheses that these features evolved through disruption in developmental pathways at, or upstream of, brpf1 and eda/edar for the ancestral losses of basihyal element and scales, respectively. These results demonstrate that ontological annotations of the phenotypic effects of genetic alterations in model organisms, when aggregated within a knowledgebase, can be used effectively to generate testable, and useful, hypotheses about evolutionary changes in morphology. PMID:26500251

  12. Evaluating historical candidate genes for schizophrenia.

    PubMed

    Farrell, M S; Werge, T; Sklar, P; Owen, M J; Ophoff, R A; O'Donovan, M C; Corvin, A; Cichon, S; Sullivan, P F

    2015-05-01

    Prior to the genome-wide association era, candidate gene studies were a major approach in schizophrenia genetics. In this invited review, we consider the current status of 25 historical candidate genes for schizophrenia (for example, COMT, DISC1, DTNBP1 and NRG1). The initial study for 24 of these genes explicitly evaluated common variant hypotheses about schizophrenia. Our evaluation included a meta-analysis of the candidate gene literature, incorporation of the results of the largest genomic study yet published for schizophrenia, ratings from informed researchers who have published on these genes, and ratings from 24 schizophrenia geneticists. On the basis of current empirical evidence and mostly consensual assessments of informed opinion, it appears that the historical candidate gene literature did not yield clear insights into the genetic basis of schizophrenia. A likely reason why historical candidate gene studies did not achieve their primary aims is inadequate statistical power. However, the considerable efforts embodied in these early studies unquestionably set the stage for current successes in genomic approaches to schizophrenia.

  13. SOPHIE velocimetry of Kepler transit candidates

    NASA Astrophysics Data System (ADS)

    Santerne, A.; Moutou, C.; Bouchy, F.; Hébrard, G.; Deleuil, M.; Díaz, R. F.; Bonomo, A. S.; Almenara, J.-M.

    2011-10-01

    As CoRoT, the Kepler space mission found a large amount of planetary transit candidates for which radial velocity follow-up is necessary in order to establish the planetary nature and then, to characterize the mass of the transiting companion. We are following up some interesting Kepler candidates with the SOPHIE spectrograph mounted at the 1.93-m telescope in Observatoire de Haute Provence (France). More than one year after the first Kepler release, we will present the strategy used to select the most promising Kepler candidates, within reach of a detection with SOPHIE, using the experience of more than 4 years of CoRoT, SWASP and HAT radial velocity follow-up. We will also highlight the results of the first year of observations that led to the discovery of several new transiting exoplanets and help the understanding of the false positive rate of the Kepler mission.

  14. Isolated dextrocardia in a commercial pilot candidate.

    PubMed

    Syburra, Thomas; Sütsch, Gabor; Huber, Samuel; Schnüriger, Hans; Lachat, Mario; Suter, Jost

    2005-02-01

    Positional anomalies of the heart are rare and are seldom found during routine physical examinations. We describe the case of a 25-yr-old Swiss airline pilot candidate whose aeromedical examination was normal except that an unusual ECG raised suspicion, leading to a diagnosis of dextrocardia with a normal arrangement of atria and abdominal viscera. This diagnosis in a pilot candidate should raise concern because a high percentage of such individuals have congenital heart defects. Further tests were conducted to rule out associated cardiac malformations, conduction anomalies, or rhythm disturbances. Testing also excluded other associated diseases such as primary ciliary dyskinesia and Kartagener's syndrome. Dextrocardia is not listed as a disqualifying condition in the applicable aeromedical regulations (Joint Aviation Authorities Medical Manual, Joint Aviation Requirements-Flight Crew Licensing guidelines). Therefore, after demonstrating that there were no physical, hemodynamic, or electrophysiological abnormalities, the candidate was allowed to enroll in civilian pilot training without restrictions.

  15. Candidate Genes in Ocular Dominance Plasticity

    PubMed Central

    Rietman, M. Liset; Sommeijer, J.-P.; Levelt, Christiaan N.; Heimel, J. Alexander

    2012-01-01

    Many studies have been devoted to the identification of genes involved in experience-dependent plasticity in the visual cortex. To discover new candidate genes, we have reexamined data from one such study on ocular dominance (OD) plasticity in recombinant inbred BXD mouse strains. We have correlated the level of plasticity with the gene expression data in the neocortex that have become available for these same strains. We propose that genes with a high correlation are likely to play a role in OD plasticity. We have tested this hypothesis for genes whose inactivation is known to affect OD plasticity. The expression levels of these genes indeed correlated with OD plasticity if their levels showed strong differences between the BXD strains. To narrow down our candidate list of correlated genes, we have selected only those genes that were previously found to be regulated by visual experience and associated with pathways implicated in OD plasticity. This resulted in a list of 32 candidate genes. The list contained unproven, but not unexpected candidates such as the genes for IGF-1, NCAM1, NOGO-A, the gamma2 subunit of the GABA(A) receptor, acetylcholine esterase, and the catalytic subunit of cAMP-dependent protein kinase A. This demonstrates the viability of our approach. More interestingly, the following novel candidate genes were identified: Akap7, Akt1, Camk2d, Cckbr, Cd44, Crim1, Ctdsp2, Dnajc5, Gnai1, Itpka, Mapk8, Nbea, Nfatc3, Nlk, Npy5r, Phf21a, Phip, Ppm1l, Ppp1r1b, Rbbp4, Slc1a3, Slit2, Socs2, Spock3, St8sia1, Zfp207. Whether all these novel candidates indeed function in OD plasticity remains to be established, but possible roles of some of them are discussed in the article. PMID:22347157

  16. Design, Utility, and History of the Colorado Adoption Project: Examples Involving Adjustment Interactions1

    PubMed Central

    Rhea, Sally Ann; Bricker, Josh B.; Corley, Robin P.; DeFries, John C.; Wadsworth, Sally J.

    2013-01-01

    This paper describes the Colorado Adoption Project (CAP), a longitudinal study in behavioral development, and discusses how adoption studies may be used to assess genetic and environmental etiologies of individual differences for important developmental outcomes. Previous CAP research on adjustment outcomes in childhood and adolescence which found significant interactions, including gene-environment interactions, is reviewed. New research suggests mediating effects of menarche and religiosity on age at first sex in this predominantly middle-class, Caucasian sample. PMID:23833552

  17. The Angstrom Project: a new microlensing candidate

    NASA Astrophysics Data System (ADS)

    Kerins, E.; Darnley, M. J.; Newsam, A. M.; Duke, J. P.; Gould, A.; Street, C. Han B.-G. Park R. A.

    2008-12-01

    We report the discovery of a new microlensing candidate in M31 by the Angstrom Project M31 bulge microlensing survey using the Liverpool Telescope (La Palma). The candidate was discovered using difference imaging techniques by the Angstrom Project Alert System (APAS) in a series of Sloan i'-band images of the bulge of M31.

  18. DOE candidate site meteorological measurement program

    SciTech Connect

    Renne, D. S.; Sandusky, W. F.

    1980-01-01

    In March 1976, DOE issued an RFP to acquire, on a competitive basis, a group of candidate sites, proposed by utilities interested in the field testing program. A total of 17 candidate sites were selected from the 64 proposals submitted in response to the RFP. From these sites, five have been chosen thus far to receive turbines for field testing. This paper discusses the meteorological measurement activities at these sites and provides details of the measurement program as it exists in late 1979. In addition, the paper briefly discusses the directions this program will take in the near future, and the options interested electric service organizations have for participating in the program.

  19. Issue-Advocacy versus Candidate Advertising: Effects on Candidate Preferences and Democratic Process.

    ERIC Educational Resources Information Center

    Pfau, Michael; Holbert, R. Lance; Szabo, Erin Alison; Kaminski, Kelly

    2002-01-01

    Examines the influence of soft-money-sponsored issue-advocacy advertising in U.S. House and Senate campaigns, comparing its effects against candidate-sponsored positive advertising and contrast advertising on viewers' candidate preferences and on their attitude that reflect democratic values. Reveals no main effects for advertising approach on…

  20. Computer Teacher Candidates' Metaphors about the Internet

    ERIC Educational Resources Information Center

    Saban, Aslihan

    2010-01-01

    The purpose of this study was to examine the metaphors of exit-level Turkish computer teacher candidates about the concept of "internet". Participants included 45 seniors (23 boys and 22 girls) majoring in the Department of Computer and Instructional Technologies at Selcuk University, Ahmet Kelesoglu Faculty of Education. They were asked…

  1. Secondary Teacher Candidates' Lesson Planning Learning

    ERIC Educational Resources Information Center

    Santoyo, Christina; Zhang, Shaoan

    2016-01-01

    Teacher candidates (TCs) use clinical experiences to enact concepts taught in their university courses; therefore field experiences may be the most important component of teacher preparation (Hammerness et al., 2005). TCs require support and guidance as they learn to adapt curriculum materials for effective use in the classroom (Davis, 2006). They…

  2. 11 CFR 9002.2 - Candidate.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate. 9002.2 Section 9002.2 Federal Elections FEDERAL ELECTION COMMISSION PRESIDENTIAL ELECTION CAMPAIGN FUND: GENERAL ELECTION FINANCING... accordance with 11 CFR 9002.15. (b) An individual who is no longer actively conducting campaigns in more...

  3. 76 FR 36130 - Call for Candidates

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-21

    ... From the Federal Register Online via the Government Publishing Office FEDERAL ACCOUNTING STANDARDS ADVISORY BOARD Call for Candidates AGENCY: Federal Accounting Standards Advisory Board. ACTION: Request for... Accounting Standards Advisory Board (FASAB or the Board) with the requested materials in response to...

  4. Gallium-67 imaging in candidal esophagitis

    SciTech Connect

    Rundback, J.H.; Goldfarb, C.R.; Ongseng, F. )

    1990-01-01

    Ga-67 scanning has been used to evaluate esophageal carcinoma. It has demonstrated candidal infection in other body sites and, in one previous case, in the esophagus. The authors present a case of diffuse esophageal uptake of Ga-67 in esophageal candidiasis.

  5. Promoting Team Leadership Skills in Doctoral Candidates

    ERIC Educational Resources Information Center

    Suleiman, Mahmoud; Whetton, Danny

    2014-01-01

    Doctoral programs can serve as an optimal opportunity for candidates to engage in tasks and activities to transform them and their schools. The paradigm shifts in such preparation involve moving from sitting and getting to making and taking. Most importantly, it requires building leadership skills and styles necessary to bring about desired change…

  6. Query by image example: The CANDID approach

    SciTech Connect

    Kelly, P.M.; Cannon, M.; Hush, D.R.

    1995-02-01

    CANDID (Comparison Algorithm for Navigating Digital Image Databases) was developed to enable content-based retrieval of digital imagery from large databases using a query-by-example methodology. A user provides an example image to the system, and images in the database that are similar to that example are retrieved. The development of CANDID was inspired by the N-gram approach to document fingerprinting, where a ``global signature`` is computed for every document in a database and these signatures are compared to one another to determine the similarity between any two documents. CANDID computes a global signature for every image in a database, where the signature is derived from various image features such as localized texture, shape, or color information. A distance between probability density functions of feature vectors is then used to compare signatures. In this paper, the authors present CANDID and highlight two results from their current research: subtracting a ``background`` signature from every signature in a database in an attempt to improve system performance when using inner-product similarity measures, and visualizing the contribution of individual pixels in the matching process. These ideas are applicable to any histogram-based comparison technique.

  7. Towards Treating Chemistry Teacher Candidates as Human

    ERIC Educational Resources Information Center

    Lewthwaite, Brian Ellis

    2008-01-01

    This research inquiry investigates the factors influencing chemistry teacher candidates' development during their extended practica in the second and final year of an After-Degree Bachelor of Education at a university in central Canada. A variety of data sources are used to identify the risk and protective factors impeding and contributing to the…

  8. Candidal endophthalmitis: a manifestation of systemic candidiasis.

    PubMed Central

    Patel, B. C.; Kaye, S. B.; Morgan, L. H.

    1987-01-01

    Two patients on total parenteral nutrition who developed endophthalmitis secondary to Candida albicans are described. Candidal endophthalmitis as a manifestation of systemic candidiasis is discussed and its early diagnosis by bedside fundal examination in patients at risk is stressed. Images Figure 1 Figure 2 PMID:3116523

  9. Emotional Intelligence and Beginning Teacher Candidates

    ERIC Educational Resources Information Center

    Justice, Madeline; Espinoza, Sue

    2007-01-01

    According to the Bureau of Labor Statistics, Texas will need over 82,000 new teachers by 2008. Many teachers are leaving the profession within 5 years of being employed. Closing a revolving door, teacher preparation programs are discussing this phenomenon. One hundred sixty beginning teacher candidates were surveyed using the Emotional Skills…

  10. FAME's Search for Extrasolar Planet Candidates

    NASA Astrophysics Data System (ADS)

    Johnston, K.

    FAME is a five year survey mission to observe the positions, proper motions, and parallaxes of 40,000,000 stars down to 15th magnitude with accuracies of 50 microarcseconds at 9th magnitude. In addition to producing an astrometric and photometric catalog unparalleled for its accuracy and size, the survey will provide significant astrophysics results and search for extrasolar planet candidates.

  11. Teacher Candidate Disposition: Moral Judgement or Regurgitation?

    ERIC Educational Resources Information Center

    Johnson, Lisa E.

    2008-01-01

    Developing teacher candidates who are able to make moral judgements to equitably resolve classroom dilemmas, conduct student assessment and allocate resources is critical for today's diverse classrooms and should be part of fostering professional disposition. However, one challenge of incorporating dispositions in teacher education and a valid…

  12. Glycosaminoglycan derivatives: promising candidates for the design of functional biomaterials.

    PubMed

    Scharnweber, Dieter; Hübner, Linda; Rother, Sandra; Hempel, Ute; Anderegg, Ulf; Samsonov, Sergey A; Pisabarro, M Teresa; Hofbauer, Lorenz; Schnabelrauch, Matthias; Franz, Sandra; Simon, Jan; Hintze, Vera

    2015-09-01

    Numerous biological processes (tissue formation, remodelling and healing) are strongly influenced by the cellular microenvironment. Glycosaminoglycans (GAGs) are important components of the native extracellular matrix (ECM) able to interact with biological mediator proteins. They can be chemically functionalized and thereby modified in their interaction profiles. Thus, they are promising candidates for functional biomaterials to control healing processes in particular in health-compromised patients. Biophysical studies show that the interaction profiles between mediator proteins and GAGs are strongly influenced by (i) sulphation degree, (ii) sulphation pattern, and (iii) composition and structure of the carbohydrate backbone. Hyaluronan derivatives demonstrate a higher binding strength in their interaction with biological mediators than chondroitin sulphate for a comparable sulphation degree. Furthermore sulphated GAG derivatives alter the interaction profile of mediator proteins with their cell receptors or solute native interaction partners. These results are in line with biological effects on cells relevant for wound healing processes. This is valid for solute GAGs as well as those incorporated in collagen-based artificial ECM (aECMs). Prominent effects are (i) anti-inflammatory, immunomodulatory properties towards macrophages/dendritic cells, (ii) enhanced osteogenic differentiation of human mesenchymal stromal cells, (iii) altered differentiation of fibroblasts to myofibroblasts, (iv) reduced osteoclast activity and (v) improved osseointegration of dental implants in minipigs. The findings of our consortium Transregio 67 contribute to an improved understanding of structure-function relationships of GAG derivatives in their interaction with mediator proteins and cells. This will enable the design of bioinspired, functional biomaterials to selectively control and promote bone and skin regeneration.

  13. 22 CFR 11.8 - Travel expenses of candidates.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Travel expenses of candidates. 11.8 Section 11... Travel expenses of candidates. The travel and other personal expenses of candidates incurred in... Department may issue round-trip invitational travel orders to bring candidates to Washington at...

  14. 22 CFR 11.8 - Travel expenses of candidates.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Travel expenses of candidates. 11.8 Section 11... Travel expenses of candidates. The travel and other personal expenses of candidates incurred in... Department may issue round-trip invitational travel orders to bring candidates to Washington at...

  15. 22 CFR 11.8 - Travel expenses of candidates.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Travel expenses of candidates. 11.8 Section 11... Travel expenses of candidates. The travel and other personal expenses of candidates incurred in... Department may issue round-trip invitational travel orders to bring candidates to Washington at...

  16. 22 CFR 11.8 - Travel expenses of candidates.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Travel expenses of candidates. 11.8 Section 11... Travel expenses of candidates. The travel and other personal expenses of candidates incurred in... Department may issue round-trip invitational travel orders to bring candidates to Washington at...

  17. 22 CFR 11.8 - Travel expenses of candidates.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Travel expenses of candidates. 11.8 Section 11... Travel expenses of candidates. The travel and other personal expenses of candidates incurred in... Department may issue round-trip invitational travel orders to bring candidates to Washington at...

  18. 14 CFR 91.321 - Carriage of candidates in elections.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Carriage of candidates in elections. 91.321 Section 91.321 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... for carrying a candidate, agent of a candidate, or person traveling on behalf of a candidate,...

  19. 32 CFR 901.6 - Candidate fitness test requirement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 6 2014-07-01 2014-07-01 false Candidate fitness test requirement. 901.6... Requirements § 901.6 Candidate fitness test requirement. Before being offered an appointment, candidates must take a Candidate Fitness Test (CFT) which consists of exercises designed to measure muscular...

  20. 32 CFR 901.6 - Candidate fitness test requirement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false Candidate fitness test requirement. 901.6... Requirements § 901.6 Candidate fitness test requirement. Before being offered an appointment, candidates must take a Candidate Fitness Test (CFT) which consists of exercises designed to measure muscular...

  1. 32 CFR 901.6 - Candidate fitness test requirement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 6 2011-07-01 2011-07-01 false Candidate fitness test requirement. 901.6... Requirements § 901.6 Candidate fitness test requirement. Before being offered an appointment, candidates must take a Candidate Fitness Test (CFT) which consists of exercises designed to measure muscular...

  2. 32 CFR 901.6 - Candidate fitness test requirement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Candidate fitness test requirement. 901.6... Requirements § 901.6 Candidate fitness test requirement. Before being offered an appointment, candidates must take a Candidate Fitness Test (CFT) which consists of exercises designed to measure muscular...

  3. 32 CFR 901.6 - Candidate fitness test requirement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 6 2012-07-01 2012-07-01 false Candidate fitness test requirement. 901.6... Requirements § 901.6 Candidate fitness test requirement. Before being offered an appointment, candidates must take a Candidate Fitness Test (CFT) which consists of exercises designed to measure muscular...

  4. 14 CFR 91.321 - Carriage of candidates in elections.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Carriage of candidates in elections. 91.321 Section 91.321 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... for carrying a candidate, agent of a candidate, or person traveling on behalf of a candidate,...

  5. Candidate marketing takes the guessing game out of choosing employers.

    PubMed

    Russell, Judith; Havel, Stacey

    2010-01-01

    Candidate marketing builds a foundation for relationships between employers and potential employees. Additionally, candidate marketing differentiates organizations in the marketplace. Organizations using candidate marketing to communicate the employer brand can expect a higher quality of candidates, and new employees are better prepared for the work environment and culture. Today, organizations can use a variety of integrated tools and techniques to communicate and build relationships with candidates. Candidate marketing demonstrates an organization's willingness towards transparency, and ability to invite open conversations between candidates and members of the organizations.

  6. "Reflecting on the Reflection…": Exploring Teacher Candidates' Assumptions of Self and Others through Facilitated Reflection

    ERIC Educational Resources Information Center

    Smith, Michael D.; Glenn, Tristan L.

    2016-01-01

    The literature on culturally responsive pedagogy suggests an interaction between teachers' biases and subsequent encounters with students. To gain perspective on these (un)conscious biases, teacher candidates are encouraged to (re)consider their assumptions about "the other" through reflection. This article presents findings from a study…

  7. Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)

    PubMed Central

    Darabi, Hatef; Beesley, Jonathan; Droit, Arnaud; Kar, Siddhartha; Nord, Silje; Moradi Marjaneh, Mahdi; Soucy, Penny; Michailidou, Kyriaki; Ghoussaini, Maya; Fues Wahl, Hanna; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Alonso, M. Rosario; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W.; Benitez, Javier; Bogdanova, Natalia V.; Bojesen, Stig E.; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Choi, Ji-Yeob; Conroy, Don M.; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Devilee, Peter; Dörk, Thilo; Easton, Douglas F.; Fasching, Peter A.; Figueroa, Jonine; Fletcher, Olivia; Flyger, Henrik; Galle, Eva; García-Closas, Montserrat; Giles, Graham G.; Goldberg, Mark S.; González-Neira, Anna; Guénel, Pascal; Haiman, Christopher A.; Hallberg, Emily; Hamann, Ute; Hartman, Mikael; Hollestelle, Antoinette; Hopper, John L.; Ito, Hidemi; Jakubowska, Anna; Johnson, Nichola; Kang, Daehee; Khan, Sofia; Kosma, Veli-Matti; Kriege, Mieke; Kristensen, Vessela; Lambrechts, Diether; Le Marchand, Loic; Lee, Soo Chin; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Mayes, Rebecca; McKay, James; Meindl, Alfons; Milne, Roger L.; Muir, Kenneth; Neuhausen, Susan L.; Nevanlinna, Heli; Olswold, Curtis; Orr, Nick; Peterlongo, Paolo; Pita, Guillermo; Pylkäs, Katri; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C.; Stram, Daniel O.; Surowy, Harald; Swerdlow, Anthony; Teo, Soo H.; Tessier, Daniel C.; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine M.; Vincent, Daniel; Winqvist, Robert; Wu, Anna H.; Wu, Pei-Ei; Yip, Cheng Har; Zheng, Wei; Pharoah, Paul D. P.; Hall, Per; Edwards, Stacey L.; Simard, Jacques; French, Juliet D.; Chenevix-Trench, Georgia; Dunning, Alison M.

    2016-01-01

    Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90–0.94; P = 8.96 × 10−15)) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10−09, r2 = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10−11, r2 = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus. PMID:27600471

  8. Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs).

    PubMed

    Darabi, Hatef; Beesley, Jonathan; Droit, Arnaud; Kar, Siddhartha; Nord, Silje; Moradi Marjaneh, Mahdi; Soucy, Penny; Michailidou, Kyriaki; Ghoussaini, Maya; Fues Wahl, Hanna; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Alonso, M Rosario; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W; Benitez, Javier; Bogdanova, Natalia V; Bojesen, Stig E; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Choi, Ji-Yeob; Conroy, Don M; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Devilee, Peter; Dörk, Thilo; Easton, Douglas F; Fasching, Peter A; Figueroa, Jonine; Fletcher, Olivia; Flyger, Henrik; Galle, Eva; García-Closas, Montserrat; Giles, Graham G; Goldberg, Mark S; González-Neira, Anna; Guénel, Pascal; Haiman, Christopher A; Hallberg, Emily; Hamann, Ute; Hartman, Mikael; Hollestelle, Antoinette; Hopper, John L; Ito, Hidemi; Jakubowska, Anna; Johnson, Nichola; Kang, Daehee; Khan, Sofia; Kosma, Veli-Matti; Kriege, Mieke; Kristensen, Vessela; Lambrechts, Diether; Le Marchand, Loic; Lee, Soo Chin; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Mayes, Rebecca; McKay, James; Meindl, Alfons; Milne, Roger L; Muir, Kenneth; Neuhausen, Susan L; Nevanlinna, Heli; Olswold, Curtis; Orr, Nick; Peterlongo, Paolo; Pita, Guillermo; Pylkäs, Katri; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Marjanka K; Schmutzler, Rita K; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C; Stram, Daniel O; Surowy, Harald; Swerdlow, Anthony; Teo, Soo H; Tessier, Daniel C; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine M; Vincent, Daniel; Winqvist, Robert; Wu, Anna H; Wu, Pei-Ei; Yip, Cheng Har; Zheng, Wei; Pharoah, Paul D P; Hall, Per; Edwards, Stacey L; Simard, Jacques; French, Juliet D; Chenevix-Trench, Georgia; Dunning, Alison M

    2016-09-07

    Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 × 10(-15))) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10(-09), r(2) = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10(-11), r(2) = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.

  9. Dark Matter Candidates: A Status Report

    SciTech Connect

    Bergstroem, Lars

    2010-06-23

    A brief review is given of various dark matter candidates. In particular, some of the most studied candidates like axions, inert Higgs doublet, sterile neutrinos, supersymmetric particles and Kaluza-Klein particles are discussed. In particular, indirect detection methods are reviewed, with gamma-ray detection being a particularly important method. The situation also for indirect detection through antimatter cosmic rays has recently become quite interesting with new results having dark matter as one of the possible explanations. Problems of this explanation and possible solutions are discussed, and the importance of new measurements is emphasized. If the explanation is indeed dark matter, some unusual and unexpected properties would be needed. One should always keep the possible 'conventional' astrophysical explanations, like electron and positron radiation from pulsars in mind. To get a conclusive case for dark matter, detection in other channels will likely be needed, such as direct detection or detection of angular and spectral signatures in gamma-rays.

  10. Candidate Species Selection: Cultural and Photosynthetic Aspects

    NASA Technical Reports Server (NTRS)

    Mitchell, C. A.

    1982-01-01

    Cultural information is provided for a data base that will be used to select candidate crop species for a controlled ecological life support system (CELSS). Lists of food crops which will satisfy most nutritional requirements of humans and also fit within the scope of cultural restrictions that logically would apply to a closed, regenerating system were generated. Cultural and environmental conditions that will allow the most rapid production of edible biomass from candidate species in the shortest possible time are identified. Cultivars which are most productive in terms of edible biomass production by (CE) conditions, and which respond to the ever-closed approach to optimization realized by each shortened production cycle are selected. The experimental approach with lettuce was to grow the crop hydroponically in a growth chamber and to manipulate such variables as light level and duration, day/night temperature, and nutrient form and level in the solution culture.

  11. Warm Debris Disk Candidates from WISE

    NASA Technical Reports Server (NTRS)

    Padgett, Deborah; Stapelfeldt, Karl; Liu, Wilson; Leisawitz, David

    2011-01-01

    The Wide Field Infrared Survey Explorer (WISE) has just completed a sensitive all-sky survey in photometric bands at 3.4, 4.6, 12, and 22 microns. We report on a preliminary investigation of main sequence Hipparcos and Tycho catalog stars with 22 micron emission in excess of photospheric levels. This warm excess emission traces material in the circumstellar region likely to host terrestrial planets and is preferentially found in young systems with ages < 1 Gyr. Nearly a hundred new warm debris disk candidates are detected among FGK stars and 150 A stars within 120 pc. We are in the process of obtaining spectra to determine spectral types and activity level of these stars and are using HST, Herschel and Keck to characterize the dust, multiplicity, and substellar companions of these systems. In this contribution, we will discuss source selection methods and individual examples from among the WISE debris disk candidates.

  12. Presidential candidates focus on energy policy

    SciTech Connect

    Lessard, P.; Belcher, J.

    1996-09-01

    When gasoline prices skyrocketed this past spring, sparking outcries from both the American public and lawmakers on Capitol Hill, the need for a national energy policy suddenly was pushed to the forefront. The attention the higher gasoline prices received has helped focus debate on an even more pressing issue-the real threat to the U.S. economy and national security when Americans cannot get enough oil, regardless of price, to fuel their industrial and transportation needs and, in some parts of the country, to heat their homes. While presidential candidates Bill Clinton and Bob Dole disagree with each other in many areas, with energy policy being no exception, both have expressed the opinion that the U.S. needs to be less reliant on foreign, and often unstable, countries for sources of fuel, such as oil. An exclusive interview with the candidates` respective campaigns about their views on issues facing the domestic oil and natural gas industry is presented.

  13. SAO RAS spectral classification of SN candidates

    NASA Astrophysics Data System (ADS)

    Fatkhullin, T. A.; Moskvitin, A. S.

    2016-08-01

    We observed five SN candidates (AT 2016eld, AT 2016eku, MASTER OT J225939.54+020859.6, AT 2016ekw and AT 2016elw) with the BTA/Scorpio-I on the night of August, 2/3. Direct images in the V band and long-slit spectra in the range of 3600-7600AA (resolution FWHM = 10A) were obtained.

  14. New Young Star Candidates in BRC 27

    NASA Astrophysics Data System (ADS)

    Novatne, Lauren J.; Mattrocce, G.; Milan, T.; Quinonez, A.; Rebull, L. M.; Barge, J.; Amayo, R.; Bieber, H.; Block, L.; Cheung, E.; Cruz, A.; Elkin, D.; Figueroa, A.; Jakus, M.; Kelo, A.; Larson, O.; Lemma, B.; Li, Y.; Loe, C.; Maciag, V.; Moreno, N.; Nevels, M.; Pezanoski-Cohen, G.; Short, M.; Skatchke, K.; Tur-Kaspa, A.; Zegeye, D.; Armstrong, J.; Bonadurer, R.; French, D.; Free, B.; Miller, C.; Scherich, H.; Willis, T.; Koenig, X.; Laher, R.; Padgett, D.; Piper, M.; Pavlak, A.; Piper, M.; Venezio, E.; Ali, B.

    2013-01-01

    All stars originate from clouds of interstellar gas that collapse either under their own gravity or with external help. In triggered star formation, the collapse of a cloud is initiated by pressure, e.g., from nearby star(s). When the external source is bright stars, it can illuminate the rims of the cloud, creating bright-rimmed clouds (BRCs) to be visible at optical and infrared (IR) wavelengths. We searched for new candidate young stellar objects (YSOs) primarily using the March 2012 all-sky release of Wide-field Infrared Survey Explorer (WISE) data in BRC 27, which is part of CMa R1, a region of known star formation. Spitzer data of a 5’x5’ region centered on BRC 27 were presented by Johnson et al. 2012 and Rebull et al. 2012. We investigated WISE data within a 20 arcminute radius of BRC 27 0.35 sq. deg), combining it with Spitzer data serendipitously obtained in this region, 2MASS data, and optical data. We started from nearly 4000 WISE sources and identified about 200 candidate YSOs via a series of color cuts (Koenig et al. 2012) to identify objects with WISE colors consistent with other YSOs, e.g., having an apparent IR excess. There are about 100 objects in this region already identified in the literature as possible YSOs, about 40 of which we recovered with the color cuts. We investigated these literature YSOs and YSO candidates in all available images, and created spectral energy distributions (SEDs) and color-magnitude diagrams for further analysis of each object. We will present an analysis of our selected sub-sample of YSO candidates. This research was made possible through the NASA/IPAC Teacher Archive Research Project (NITARP) and was funded by NASA Astrophysics Data Program and Archive Outreach funds. Our education results are described in a companion education poster, Bonadurer et al.

  15. Database of cattle candidate genes and genetic markers for milk production and mastitis

    PubMed Central

    Ogorevc, J; Kunej, T; Razpet, A; Dovc, P

    2009-01-01

    A cattle database of candidate genes and genetic markers for milk production and mastitis has been developed to provide an integrated research tool incorporating different types of information supporting a genomic approach to study lactation, udder development and health. The database contains 943 genes and genetic markers involved in mammary gland development and function, representing candidates for further functional studies. The candidate loci were drawn on a genetic map to reveal positional overlaps. For identification of candidate loci, data from seven different research approaches were exploited: (i) gene knockouts or transgenes in mice that result in specific phenotypes associated with mammary gland (143 loci); (ii) cattle QTL for milk production (344) and mastitis related traits (71); (iii) loci with sequence variations that show specific allele-phenotype interactions associated with milk production (24) or mastitis (10) in cattle; (iv) genes with expression profiles associated with milk production (207) or mastitis (107) in cattle or mouse; (v) cattle milk protein genes that exist in different genetic variants (9); (vi) miRNAs expressed in bovine mammary gland (32) and (vii) epigenetically regulated cattle genes associated with mammary gland function (1). Fourty-four genes found by multiple independent analyses were suggested as the most promising candidates and were further in silico analysed for expression levels in lactating mammary gland, genetic variability and top biological functions in functional networks. A miRNA target search for mammary gland expressed miRNAs identified 359 putative binding sites in 3′UTRs of candidate genes. PMID:19508288

  16. A computational method for the identification of new candidate carcinogenic and non-carcinogenic chemicals.

    PubMed

    Chen, Lei; Chu, Chen; Lu, Jing; Kong, Xiangyin; Huang, Tao; Cai, Yu-Dong

    2015-09-01

    Cancer is one of the leading causes of human death. Based on current knowledge, one of the causes of cancer is exposure to toxic chemical compounds, including radioactive compounds, dioxin, and arsenic. The identification of new carcinogenic chemicals may warn us of potential danger and help to identify new ways to prevent cancer. In this study, a computational method was proposed to identify potential carcinogenic chemicals, as well as non-carcinogenic chemicals. According to the current validated carcinogenic and non-carcinogenic chemicals from the CPDB (Carcinogenic Potency Database), the candidate chemicals were searched in a weighted chemical network constructed according to chemical-chemical interactions. Then, the obtained candidate chemicals were further selected by a randomization test and information on chemical interactions and structures. The analyses identified several candidate carcinogenic chemicals, while those candidates identified as non-carcinogenic were supported by a literature search. In addition, several candidate carcinogenic/non-carcinogenic chemicals exhibit structural dissimilarity with validated carcinogenic/non-carcinogenic chemicals.

  17. Molecular candidates of MTV in air

    NASA Astrophysics Data System (ADS)

    Dam, Nico; Mirzaei, Mehrnoosh; van de Water, Willem

    2011-11-01

    In molecular tagging velocimetry (MTV), the molecules of a gas are used as flow tracers. These tracers can be produced at will by illumination with a laser which promotes molecules to a long- lived excited state, fuses N2 and N2 to NO, or makes molecules phosphoresce. A while later these tagged molecules can be visualized by laser-induced fluorescence, or by just watching them while they phosphoresce. Candidates for MTV in turbulence research must be arranged in structures narrower than the Kolmogorov scale, which remain narrow as time progresses, and must live longer than the Kolmogorov time. These requirements invalidate many candidates, candidates once deemed successful. They do so in various surprising manners that involve a combination of fluid flow and molecular dynamics. Rather than velocimetry in turbulence, MTV techniques offer a unique view on basic dispersion processes at the smallest scales of turbulence. In this way we have measured the spreading of clouds whose size is a few times the Kolmogorov length and the Batchelor dispersion of objects whose size is inside the inertial range.

  18. A candidate's experience doing research during training.

    PubMed

    Hadge, Luke

    2012-10-01

    A psychoanalytic candidate explores his experience of participating in a research project at his institute during his training. The candidate has been a member of Sabrina Cherry's prospective study of psychoanalytic practice and professional development conducted at the Columbia University Center for Psychoanalytic Training and Research. While much as been written about candidacy from numerous perspectives, there is little in the literature about how being engaged in research affects a candidate's overall training experience. In particular, attention is paid to understanding the benefits, synergies, conflicts, and tensions in combining research with such aspects of analytic training as the training analysis, control cases, supervision, classes, and institute life. A parallel is drawn between the listening and interpretive skills learned in order to practice analysis and the method of textual analysis employed in the research project. The author believes that his research training and the impact of the specific research topic have enriched and deepened his analytic training, while at the same time revealing certain anxieties in integrating research with the development of his analytic skills and identity.

  19. UNCOVERING THE NUCLEUS CANDIDATE FOR NGC 253

    SciTech Connect

    Günthardt, G. I.; Camperi, J. A.; Agüero, M. P.; Díaz, R. J.; Gomez, P. L.; Schirmer, M.; Bosch, G. E-mail: camperi@oac.uncor.edu E-mail: rdiaz@gemini.edu E-mail: mschirmer@gemini.edu

    2015-11-15

    NGC 253 is the nearest spiral galaxy with a nuclear starburst that becomes the best candidate for studying the relationship between starburst and active galactic nucleus activity. However, this central region is veiled by large amounts of dust, and it has been so far unclear which is the true dynamical nucleus to the point that there is no strong evidence that the galaxy harbors a supermassive black hole co-evolving with the starburst as was supposed earlier. Near-infrared (NIR) spectroscopy, especially NIR emission line analysis, could be advantageous in shedding light on the true nucleus identity. Using Flamingos-2 at Gemini South we have taken deep K-band spectra along the major axis of the central structure and through the brightest infrared source. In this work, we present evidence showing that the brightest NIR and mid-infrared source in the central region, already known as radio source TH7 and so far considered just a large stellar supercluster, in fact presents various symptoms of a genuine galactic nucleus. Therefore, it should be considered a valid nucleus candidate. Mentioning some distinctive aspects, it is the most massive compact infrared object in the central region, located at 2.″0 of the symmetry center of the galactic bar, as measured in the K-band emission. Moreover, our data indicate that this object is surrounded by a large circumnuclear stellar disk and it is also located at the rotation center of the large molecular gas disk of NGC 253. Furthermore, a kinematic residual appears in the H{sub 2} rotation curve with a sinusoidal shape consistent with an outflow centered in the candidate nucleus position. The maximum outflow velocity is located about 14 pc from TH7, which is consistent with the radius of a shell detected around the nucleus candidate, observed at 18.3 μm (Qa) and 12.8 μm ([Ne ii]) with T-ReCS. Also, the Brγ emission line profile shows a pronounced blueshift and this emission line also has the highest equivalent width at this

  20. Uncovering the Nucleus Candidate for NGC 253

    NASA Astrophysics Data System (ADS)

    Günthardt, G. I.; Agüero, M. P.; Camperi, J. A.; Díaz, R. J.; Gomez, P. L.; Bosch, G.; Schirmer, M.

    2015-11-01

    NGC 253 is the nearest spiral galaxy with a nuclear starburst that becomes the best candidate for studying the relationship between starburst and active galactic nucleus activity. However, this central region is veiled by large amounts of dust, and it has been so far unclear which is the true dynamical nucleus to the point that there is no strong evidence that the galaxy harbors a supermassive black hole co-evolving with the starburst as was supposed earlier. Near-infrared (NIR) spectroscopy, especially NIR emission line analysis, could be advantageous in shedding light on the true nucleus identity. Using Flamingos-2 at Gemini South we have taken deep K-band spectra along the major axis of the central structure and through the brightest infrared source. In this work, we present evidence showing that the brightest NIR and mid-infrared source in the central region, already known as radio source TH7 and so far considered just a large stellar supercluster, in fact presents various symptoms of a genuine galactic nucleus. Therefore, it should be considered a valid nucleus candidate. Mentioning some distinctive aspects, it is the most massive compact infrared object in the central region, located at 2.″0 of the symmetry center of the galactic bar, as measured in the K-band emission. Moreover, our data indicate that this object is surrounded by a large circumnuclear stellar disk and it is also located at the rotation center of the large molecular gas disk of NGC 253. Furthermore, a kinematic residual appears in the H2 rotation curve with a sinusoidal shape consistent with an outflow centered in the candidate nucleus position. The maximum outflow velocity is located about 14 pc from TH7, which is consistent with the radius of a shell detected around the nucleus candidate, observed at 18.3 μm (Qa) and 12.8 μm ([Ne ii]) with T-ReCS. Also, the Brγ emission line profile shows a pronounced blueshift and this emission line also has the highest equivalent width at this