Download or read book Assessing Gene Environment Interactions in Genome Wide Association Studies Statistical Approaches written by Philip C. Cooley and published by RTI Press. This book was released on 2014-05-14 with total page 24 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this report, we address a scenario that uses synthetic genotype case-control data that is influenced by environmental factors in a genome-wide association study (GWAS) context. The precise way the environmental influence contributes to a given phenotype is typically unknown. Therefore, our study evaluates how to approach a GWAS that may have an environmental component. Specifically, we assess different statistical models in the context of a GWAS to make association predictions when the form of the environmental influence is questionable. We used a simulation approach to generate synthetic data corresponding to a variety of possible environmental-genetic models, including a “main effects only” model as well as a “main effects with interactions” model. Our method takes into account the strength of the association between phenotype and both genotype and environmental factors, but we focus on low-risk genetic and environmental risks that necessitate using large sample sizes (N = 10,000 and 200,000) to predict associations with high levels of confidence. We also simulated different Mendelian gene models, and we analyzed how the collection of factors influences statistical power in the context of a GWAS. Using simulated data provides a “truth set” of known outcomes such that the association-affecting factors can be unambiguously determined. We also test different statistical methods to determine their performance properties. Our results suggest that the chances of predicting an association in a GWAS is reduced if an environmental effect is present and the statistical model does not adjust for that effect. This is especially true if the environmental effect and genetic marker do not have an interaction effect. The functional form of the statistical model also matters. The more accurately the form of the environmental influence is portrayed by the statistical model, the more accurate the prediction will be. Finally, even with very large samples sizes, association predictions involving recessive markers with low risk can be poor

Download or read book Assessing Gene environment Interactions in Genome wide Association Studies written by Philip Chester Cooley and published by . This book was released on 2014 with total page 20 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this report, we address a scenario that uses synthetic genotype case-control data that is influenced by environmental factors in a genome-wide association study (GWAS) context. The precise way the environmental influence contributes to a given phenotype is typically unknown. Therefore, our study evaluates how to approach a GWAS that may have an environmental component. Specifically, we assess different statistical models in the context of a GWAS to make association predictions when the form of the environmental influence is questionable. We used a simulation approach to generate synthetic data corresponding to a variety of possible environmental-genetic models, including a "main effects only" model as well as a "main effects with interactions" model. Our method takes into account the strength of the association between phenotype and both genotype and environmental factors, but we focus on low-risk genetic and environmental risks that necessitate using large sample sizes (N = 10,000 and 200,000) to predict associations with high levels of confidence. We also simulated different Mendelian gene models, and we analyzed how the collection of factors influences statistical power in the context of a GWAS. Using simulated data provides a "truth set" of known outcomes such that the association-affecting factors can be unambiguously determined. We also test different statistical methods to determine their performance properties. Our results suggest that the chances of predicting an association in a GWAS is reduced if an environmental effect is present and the statistical model does not adjust for that effect. This is especially true if the environmental effect and genetic marker do not have an interaction effect. The functional form of the statistical model also matters. The more accurately the form of the environmental influence is portrayed by the statistical model, the more accurate the prediction will be. Finally, even with very large samples sizes, association predictions involving recessive markers with low risk can be poor.

Download or read book Statistical Approaches to Gene x Environment Interactions for Complex Phenotypes written by Michael Windle and published by MIT Press. This book was released on 2016-07-08 with total page 306 pages. Available in PDF, EPUB and Kindle. Book excerpt: Diverse methodological and statistical approaches for investigating the role of gene-environment interactions in a range of complex diseases and traits. Findings from the Human Genome Project and from Genome-Wide Association (GWA) studies indicate that many diseases and traits manifest a more complex genomic pattern than previously assumed. These findings, and advances in high-throughput sequencing, suggest that there are many sources of influence—genetic, epigenetic, and environmental. This volume investigates the role of the interactions of genes and environment (G × E) in diseases and traits (referred to by the contributors as complex phenotypes) including depression, diabetes, obesity, and substance use. The contributors first present different statistical approaches or strategies to address G × E and G × G interactions with high-throughput sequenced data, including two-stage procedures to identify G × E and G × G interactions, marker-set approaches to assessing interactions at the gene level, and the use of a partial-least square (PLS) approach. The contributors then turn to specific complex phenotypes, research designs, or combined methods that may advance the study of G × E interactions, considering such topics as randomized clinical trials in obesity research, longitudinal research designs and statistical models, and the development of polygenic scores to investigate G × E interactions. Contributors Fatima Umber Ahmed, Yin-Hsiu Chen, James Y. Dai, Caroline Y. Doyle, Zihuai He, Li Hsu, Shuo Jiao, Erin Loraine Kinnally, Yi-An Ko, Charles Kooperberg, Seunggeun Lee, Arnab Maity, Jeanne M. McCaffery, Bhramar Mukherjee, Sung Kyun Park, Duncan C. Thomas, Alexandre Todorov, Jung-Ying Tzeng, Tao Wang, Michael Windle, Min Zhang

Download or read book Gene Environment Interaction Analysis written by Sumiko Anno and published by CRC Press. This book was released on 2016-03-30 with total page 208 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gene-environment (GE) interaction analysis is a statistical method for clarifying GE interactions applicable to a phenotype or a disease that is the result of interactions between genes and the environment. This book is the first to deal with the theme of GE interaction analysis. It compiles and details cutting-edge research in bioinformatics

Download or read book Multi omics strategies for detecting gene environment interactions written by Patrick Deelen and published by Patrick Deelen. This book was released on 2019-05-06 with total page 196 pages. Available in PDF, EPUB and Kindle. Book excerpt: Our DNA, 3 billion letters long, is the blueprint of life. People differ from each other in around 1% of these letters. However, it is largely unknown which of these differences cause disease, nor how exactly changes in DNA ultimately lead to disease. In my PhD research I contributed to the detection of these genetic risk factors and studied how these DNA changes actually disrupt the correct functioning of cells. Using the "Genome of the Netherlands" project results, in which the BBMRI-NL consortium fully mapped the DNA of 250 Dutch families, I was able to improve genetic research in other groups of people and thereby better detect genetic risk factors. I then looked at how these DNA changes disrupt individual cells in a large number of people participating in various Dutch bio-banks such as Lifelines. By looking at DNA, RNA, epigenetics and proteins at the same time, I was able to discover many genetic risk factors, which biological processes they disrupt, and which ones offer starting points for the development of new medicines that can repair these disrupted processes. In addition, through the large-scale re-use of RNA data, I was able to map how many genes relate together and to disease. With these big data analyses, I subsequently developed a new algorithm that is now being used to make a diagnosis more quickly in people with a serious illness. With my PhD research, I contributed to the immediate improvement of patient care and collected new knowledge that could help in the longer term with the development of new medicines.

Download or read book Beyond Genome wide Association Studies GWAS written by Molly Hall and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Genome-wide association studies (GWAS) have identified numerous loci associated with human phenotypes. This approach, however, does not consider the richly diverse and complex environment with which humans interact throughout the life course, nor does it allow for interrelationships among genetic loci and across traits. Methods that embrace pleiotropy (the effect of one locus on more than one trait), gene-environment (GxE) and gene-gene (GxG) interactions will further unveil the impact of alterations in biological pathways and identify genes that are only involved with disease in the context of the environment. This valuable information can be used to assess personal risk and choose the most appropriate medical interventions based on an individual's genotype and environment. Additionally, a richer picture of the genetic and environmental aspects that impact complex disease will inform environmental regulations to protect vulnerable populations. Three key limitations of GWAS lead to an inability to robustly model trait prediction in a manner that reflects biological complexity: 1) GWAS explore traits in isolation, one phenotype at a time, preventing investigators from uncovering relationships that exist among multiple traits; 2) GWAS do not account for the exposome; rather, they simply explore the effect of genetic loci on an outcome; and 3) GWAS do not allow for interactions between genetic loci, despite the complexity that exists in biology. The aims described in this dissertation address these limitations. Methods employed in each aim have the potential to: uncover genetic interactions, unveil complex biology behind phenotype networks, inform public policy decisions concerning environmental exposures, and ultimately assess individual disease-risk.

Download or read book Gene Environment Interactions written by Lucio G. Costa and published by John Wiley & Sons. This book was released on 2005-12-16 with total page 577 pages. Available in PDF, EPUB and Kindle. Book excerpt: Understanding the play between heredity and environment, and relating it to disease causation, is the task of ecogenetics. Gene-Environment Interactions: Fundamentals of Ecogenetics presents the first comprehensive survey of this discipline, reflecting its relationship with toxicology, epidemiology, pharmacology, public health, and other medical and biological fields. Divided into four sections, the text elucidates key basic and advanced topics: * Section 1 covers fundamentals, including the history of the discipline, a discussion of the molecular laboratory tools currently available to assess genotypes, using such measurements in molecular epidemiology studies, and the statistical issues involved in their analysis. * Section 2 focuses on a number of key genetic polymorphisms relevant for ecogenetics, including enzymes of phase I and phase II metabolism, enzymes involved in DNA repair, as well as receptors and ion channels. This highlights characteristics of selected, widely studied genotypic/phenotypic differences, and allows discussion of how given genetic variations can influence responses to exogenous chemicals. * Section 3 examines gene-environment interactions through a disease-based approach, addressing how genetic polymorphisms can influence susceptibility to various diseases. Chapters cover important disease conditions such as various types of cancer, neurodegenerative diseases, cardiovascular disease, chronic pulmonary diseases, infectious diseases, diabetes, and obesity. * The final section discusses the ethical, legal, and social issues that arise when investigating and evaluating genetic polymorphisms in human populations, as well as the impact of ecogenetics on risk assessment, regulatory policies, and medicine and public health. Packed with clear examples illustrating concepts, as well as numerous tables and figures, Gene-Environment Interactions: Fundamentals of Ecogenetics is a unique resource for a wide range of physicians, students, and other specialists.

Download or read book Genetic Dissection of Complex Traits written by D.C. Rao and published by Academic Press. This book was released on 2008-04-23 with total page 788 pages. Available in PDF, EPUB and Kindle. Book excerpt: The field of genetics is rapidly evolving and new medical breakthroughs are occuring as a result of advances in knowledge of genetics. This series continually publishes important reviews of the broadest interest to geneticists and their colleagues in affiliated disciplines. Five sections on the latest advances in complex traits Methods for testing with ethical, legal, and social implications Hot topics include discussions on systems biology approach to drug discovery; using comparative genomics for detecting human disease genes; computationally intensive challenges, and more

Download or read book Genes Behavior and the Social Environment written by Institute of Medicine and published by National Academies Press. This book was released on 2006-12-07 with total page 385 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the past century, we have made great strides in reducing rates of disease and enhancing people's general health. Public health measures such as sanitation, improved hygiene, and vaccines; reduced hazards in the workplace; new drugs and clinical procedures; and, more recently, a growing understanding of the human genome have each played a role in extending the duration and raising the quality of human life. But research conducted over the past few decades shows us that this progress, much of which was based on investigating one causative factor at a time—often, through a single discipline or by a narrow range of practitioners—can only go so far. Genes, Behavior, and the Social Environment examines a number of well-described gene-environment interactions, reviews the state of the science in researching such interactions, and recommends priorities not only for research itself but also for its workforce, resource, and infrastructural needs.

Download or read book Gene gene and Gene environment Interaction in Complex Trait Genome wide Association written by S. Karger AG and published by . This book was released on 2007 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The recent gene-mapping successes have opened up unparalleled opportunities for determining the relationship of genetic variation to health and disease. Thus the focus of genetic research has been shifting towards identifying genes that increase the risk for susceptibility to disease, particularly in the presence of some environmental agent. This special issue highlights and summarizes many of the new and exciting methodological advances in localizing such genes. Several of the world's leaders in the field of human genetics have contributed their expertise to this compilation. Developing these methods is especially important considering the vast amount of genome-wide association data that will be generated in the coming years. Any geneticist interested in identifying the genetic influences on complex disease risks and the environmental factors that will permit us to reduce or eliminate those risks will appreciate this update on novel analytical methods.

Download or read book The Empirical Hierarchical Bayes Approach for Pathway Integration and Gene environment Interactions in Genome wide Association Studies written by and published by . This book was released on 2012 with total page 281 pages. Available in PDF, EPUB and Kindle. Book excerpt: Complex diseases such as cancer result from a complicated interplay of multiple genetic and environmental factors. To unveil their genetic component, the simple analysis of single-nucleotide polymorphisms (SNP) as done in genome-wide association studies (GWAS) is not sufficient. Complementary approaches considering the complexity of diseases, such as the incorporation of biological pathway information or detection of gene-environment interaction, are necessary. In this thesis we focus on an empirical hierarchical Bayes model proposed for the integration of external information into genome-w...

Download or read book Detecting Epistasis Effect in Genome Wide Association Studies Based on Permutation Tests and Ensemble Approaches written by Benjamin Philip Horstman and published by . This book was released on 2010 with total page 83 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Genetic Epidemiology written by Melissa A. Austin and published by CABI. This book was released on 2013 with total page 223 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic epidemiology plays a key role in discovering genetic factors influencing health and disease, and in understanding how genes and environmental risk factors interact. There is growing interest in this field within public health, with the goal of translating the results into promoting health and preventing disease in both families and populations. This textbook provides graduate students with a working knowledge of genetic epidemiology research methods. Following an overview of the field, the book reviews key genetic concepts, provides an update on relevant genomic technology, including genome-wide chips and DNA sequencing, and describes methods for assessing the magnitude of genetic influences on diseases and risk factors. The book focuses on research study designs for discovering disease susceptibility genes, including family-based linkage analysis, candidate gene and genome-side association studies, assessing gene-environment interactions and epistasis, studies of Non-Mendelian inheritance, and statistical analyses of data from these studies. Specific applications of each research method are illustrated using a variety of diseases and risk factors relevant to public health, and useful web-based genetic analysis software, human reference panels, and repositories, that can greatly facilitate this work, are described.

Download or read book Gene environmental Interaction Assessment in Genome Wide Association Study written by Wei Liu and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Gene Environment Interactions written by Moyra Smith and published by Academic Press. This book was released on 2020-01-14 with total page 438 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gene Environment Interactions: Nature and Nurture in the Twenty-first Century offers a rare, synergistic view of ongoing revelations in gene environment interaction studies, drawing together key themes from epigenetics, microbiomics, disease etiology, and toxicology to illuminate pathways for clinical translation and the paradigm shift towards precision medicine. Across eleven chapters, Dr. Smith discusses interactions with the environment, human adaptations to environmental stimuli, pathogen encounters across the centuries, epigenetic modulation of gene expression, transgenerational inheritance, the microbiome’s intrinsic effects on human health, and the gene-environment etiology of cardiovascular, metabolic, psychiatric, behavioral and monogenic disorders. Later chapters illuminate how our new understanding of gene environment interactions are driving advances in precision medicine and novel treatments. In addition, the book's author shares strategies to support clinical translation of these scientific findings to improve heath literacy among the general population. Offers a thorough, interdisciplinary discussion on recent revelations from gene environment interaction studies Illuminates environmental factors affecting disease-gene etiology and treatment Supports the clinical translation of gene environment interaction findings into novel therapeutics and precision medicine

Download or read book Between the Lines of Genetic Code written by Marylyn D. Ritchie and published by Elsevier Inc. Chapters. This book was released on 2013-09-28 with total page 20 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gene–gene interactions are a critical component of the genetic architecture of complex, human traits. Unfortunately, the detection and characterization of interactions is a challenge. This is due to a number of factors including the combinatorial explosion of possible interactions in large-scale genomic data, limited power in small sample sizes, and potential difficulty interpreting or validating the resulting interaction models. A number of data mining methods have been developed to deal with one or more of these challenges. In this chapter, we discuss the importance of looking for gene–gene interactions as well as some of the challenges facing this type of analysis. Additionally, we review the alternative analytic approaches being considered to improve our ability to detect and model gene–gene interactions. Finally, we conclude with the future directions of interaction analysis.

Download or read book Environment wide Associations to Disease and Disease related Phenotypes written by Chirag Jagdish Patel and published by Stanford University. This book was released on 2011 with total page 189 pages. Available in PDF, EPUB and Kindle. Book excerpt: Common diseases arise out of combination of both genetic and environmental influences. Advances in genomic technology have enabled investigators to create hypotheses regarding the contribution of genetic factors at a breathtaking pace. However, the assessment of multiple and specific environmental factors—and their interactions with the genome-- has not. We lack high-throughput analytic methodologies to comprehensively and systematically associate multiple physical and specific environmental factors, or the "envirome", to disease and human health. We claim that the creation of hypotheses regarding the environmental contribution to disease is practicable through high-throughput analytic methods that have been well established in genomics. In the following dissertation, we develop and apply methods to systematically and comprehensively associate specific factors of the envirome with disease states, prioritizing factors for in-depth future study. The current disciplines of studying the environmental determinants of health include toxicology and epidemiology, which operate on molecular and population scales, respectively. This dissertation proposes approaches in both of these disciplines. For example, we have developed a framework to conduct the first "Environment-wide Association Study" (EWAS), systematically associating environmental factors to disease on a population scale. We have applied this framework to investigate type 2 diabetes and heart disease on cohorts that are representative United States population, finding novel and robust associations in diverse and independent cohorts. Given the lack of explained risk resulting from current day genome-wide studies, the time is ripe to usher in a more comprehensive study of the environment, or "enviromics", toward better understanding of multifactorial diseases and their prevention.