Assessing Gene Environment Interactions In Genome Wide Association Studies

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Assessing Gene-Environment Interactions in Genome-Wide Association Studies: Statistical Approaches

Author : Philip C. Cooley
Publisher : RTI Press
ISBN 13 :
Total Pages : 24 pages
Book Rating : 4./5 ( download)

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Book Synopsis Assessing Gene-Environment Interactions in Genome-Wide Association Studies: Statistical Approaches by : Philip C. Cooley

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

Assessing Gene-environment Interactions in Genome-wide Association Studies

Author : Philip Chester Cooley
Publisher :
ISBN 13 :
Total Pages : 20 pages
Book Rating : 4.:/5 (18 download)

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Book Synopsis Assessing Gene-environment Interactions in Genome-wide Association Studies by : Philip Chester Cooley

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.

Statistical Approaches to Gene x Environment Interactions for Complex Phenotypes

Author : Michael Windle
Publisher : MIT Press
ISBN 13 : 0262335514
Total Pages : 306 pages
Book Rating : 4.2/5 (623 download)

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Book Synopsis Statistical Approaches to Gene x Environment Interactions for Complex Phenotypes by : Michael Windle

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

Gene-Environment Interaction Analysis

Author : Sumiko Anno
Publisher : CRC Press
ISBN 13 : 9814669644
Total Pages : 208 pages
Book Rating : 4.8/5 (146 download)

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Book Synopsis Gene-Environment Interaction Analysis by : Sumiko Anno

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

Multi-omics strategies for detecting gene-environment interactions

Author : Patrick Deelen
Publisher : Patrick Deelen
ISBN 13 : 9403415991
Total Pages : 196 pages
Book Rating : 4.4/5 (34 download)

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Book Synopsis Multi-omics strategies for detecting gene-environment interactions by : Patrick Deelen

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.

Beyond Genome-wide Association Studies (GWAS)

Author : Molly Hall
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (943 download)

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Book Synopsis Beyond Genome-wide Association Studies (GWAS) by : Molly Hall

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.

Gene-Environment Interactions

Author : Lucio G. Costa
Publisher : John Wiley & Sons
ISBN 13 : 0471758035
Total Pages : 577 pages
Book Rating : 4.4/5 (717 download)

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Book Synopsis Gene-Environment Interactions by : Lucio G. Costa

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.

Gene-gene and Gene-environment Interaction in Complex Trait Genome-wide Association

Author : S. Karger AG
Publisher :
ISBN 13 : 9783805582803
Total Pages : 0 pages
Book Rating : 4.5/5 (828 download)

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Book Synopsis Gene-gene and Gene-environment Interaction in Complex Trait Genome-wide Association by : S. Karger AG

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.

Genes, Behavior, and the Social Environment

Author : Institute of Medicine
Publisher : National Academies Press
ISBN 13 : 0309101964
Total Pages : 385 pages
Book Rating : 4.3/5 (91 download)

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Book Synopsis Genes, Behavior, and the Social Environment by : Institute of Medicine

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.

The Empirical Hierarchical Bayes Approach for Pathway Integration and Gene-environment Interactions in Genome-wide Association Studies

Download The Empirical Hierarchical Bayes Approach for Pathway Integration and Gene-environment Interactions in Genome-wide Association Studies PDF Online Free

Author :
Publisher :
ISBN 13 :
Total Pages : 281 pages
Book Rating : 4.:/5 (931 download)

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Book Synopsis The Empirical Hierarchical Bayes Approach for Pathway Integration and Gene-environment Interactions in Genome-wide Association Studies by :

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...

Genetic Dissection of Complex Traits

Author : D.C. Rao
Publisher : Academic Press
ISBN 13 : 0080569110
Total Pages : 788 pages
Book Rating : 4.0/5 (85 download)

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Book Synopsis Genetic Dissection of Complex Traits by : D.C. Rao

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

Gene Environment Interactions

Author : Moyra Smith
Publisher : Academic Press
ISBN 13 : 0128197978
Total Pages : 438 pages
Book Rating : 4.1/5 (281 download)

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Book Synopsis Gene Environment Interactions by : Moyra Smith

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

Between the Lines of Genetic Code

Author : Leonid Padyukov
Publisher : Academic Press
ISBN 13 : 0123973023
Total Pages : 226 pages
Book Rating : 4.1/5 (239 download)

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Book Synopsis Between the Lines of Genetic Code by : Leonid Padyukov

Download or read book Between the Lines of Genetic Code written by Leonid Padyukov and published by Academic Press. This book was released on 2013-09-28 with total page 226 pages. Available in PDF, EPUB and Kindle. Book excerpt: Between the Lines of Genetic Code lays out methodologies and tools for the measurement and evaluation of gene-gene and gene-environment studies and gives perspective on the future of this discipline. The book begins by defining terms for interaction studies, describing methodologies, and critically assessing the viability of current study designs and the possibilities for integrating designs. It then provides recent applications data with case studies in rheumatoid arthritis, multiple sclerosis, myositis and other complex human diseases. Last, it examines current studies and directions for future applications in patient care. Recent multivariate studies show that gene-gene and gene-environment interactions can explain significant variances in inheritance that have previously been undetectable in univariate analysis. These links among genes and between genes and their environments during the development of diseases may serve as important hints for understanding pathogenic mechanisms and for developing new tools for prognosis, diagnosis, and treatment of various diseases. Systematically integrates methods of defining and detecting gene interactions to provide an overview of the field Critically analyzes current methods and tools to aid researchers in integrating gene interaction studies Includes examples of current biomedical applications and presents current research expected to shape clinical research in the near future

Analysis of Genetic Association Studies

Author : Gang Zheng
Publisher : Springer Science & Business Media
ISBN 13 : 1461422442
Total Pages : 419 pages
Book Rating : 4.4/5 (614 download)

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Book Synopsis Analysis of Genetic Association Studies by : Gang Zheng

Download or read book Analysis of Genetic Association Studies written by Gang Zheng and published by Springer Science & Business Media. This book was released on 2012-01-10 with total page 419 pages. Available in PDF, EPUB and Kindle. Book excerpt: Analysis of Genetic Association Studies is both a graduate level textbook in statistical genetics and genetic epidemiology, and a reference book for the analysis of genetic association studies. Students, researchers, and professionals will find the topics introduced in Analysis of Genetic Association Studies particularly relevant. The book is applicable to the study of statistics, biostatistics, genetics and genetic epidemiology. In addition to providing derivations, the book uses real examples and simulations to illustrate step-by-step applications. Introductory chapters on probability and genetic epidemiology terminology provide the reader with necessary background knowledge. The organization of this work allows for both casual reference and close study.

Detecting Epistasis Effect in Genome-Wide Association Studies Based on Permutation Tests and Ensemble Approaches

Author : Benjamin Philip Horstman
Publisher :
ISBN 13 :
Total Pages : 83 pages
Book Rating : 4.:/5 (63 download)

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Book Synopsis Detecting Epistasis Effect in Genome-Wide Association Studies Based on Permutation Tests and Ensemble Approaches by : Benjamin Philip Horstman

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:

Gene-environmental Interaction Assessment in Genome Wide Association Study

Author : Wei Liu
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (755 download)

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Book Synopsis Gene-environmental Interaction Assessment in Genome Wide Association Study by : Wei Liu

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:

Between the Lines of Genetic Code

Author : Marylyn D. Ritchie
Publisher : Elsevier Inc. Chapters
ISBN 13 : 0128061634
Total Pages : 20 pages
Book Rating : 4.1/5 (28 download)

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Book Synopsis Between the Lines of Genetic Code by : Marylyn D. Ritchie

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.