Statistical Approaches to Gene x Environment Interactions for Complex Phenotypes

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