Statistical Approaches to Gene X Environment Interactions for Complex Phenotypes
Statistical Approaches to Gene X Environment Interactions for Complex Phenotypes
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Abstract
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
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Front Matter
- 1 Introduction and Overview of Statistical Approaches to Gene × Environment Interactions for Complex Phenotypes
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2
Two-Stage Procedures for the Identification of Gene × Environment and Gene × Gene Interactions in Genome-Wide Association Studies
Charles Kooperberg and others
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3
Marker-Set Approaches for Assessing Gene × Environment Interactions at Gene Level
Jung-Ying Tzeng andArnab Maity
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4
Set-Based Gene × Environment Interaction Tests for Complex Diseases with Application to Genome-Wide Association and Sequencing Studies
Shuo Jiao
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5
A Gene-Based Approach for Testing Gene × Gene and Gene × Environment Interactions
Tao Wang
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6
An Overview of the RELIEF Algorithm and Advancements
Alexandre Todorov
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7
Gene × Environment Interaction in Obesity: The Contribution of Randomized Clinical Trials
Jeanne M. McCaffery andCaroline Y. Doyle
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8
Statistical Strategies for Modeling Gene × Environment Interactions in Longitudinal Cohort Studies
Bhramar Mukherjee and others
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9
Cumulative Gene × Environment Influences on Neurobehavioral Development in Humans and Nonhuman Primates
Fatima Umber Ahmed andErin Loraine Kinnally
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10
Complex Phenotypes and the Use of Polygenic Scores to Investigate Gene × Environment Interactions for Substance Use
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11
A Statistical Framework for Mediation in Environmental Epigenetics
Duncan C. Thomas
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End Matter
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