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© Research
Publication : Genetics

Joint Analysis of Multiple Interaction Parameters in Genetic Association Studies

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Genetics - 21 Dec 2018

Kim J, Ziyatdinov A, Laville V, Hu FB, Rimm E, Kraft P, Aschard H

Link to Pubmed [PMID] – 30578273

Genetics 2019 02;211(2):483-494

With growing human genetic and epidemiologic data, there has been increased interest for the study of gene-by-environment (G-E) interaction effects. Still, major questions remain on how to test jointly a large number of interactions between multiple SNPs and multiple exposures. In this study, we first compared the relative performance of four fixed-effect joint analysis approaches using simulated data, considering up to 10 exposures and 300 SNPs: (1) omnibus test, (2) multi-exposure and genetic risk score (GRS) test, (3) multi-SNP and environmental risk score (ERS) test, and (4) GRS-ERS test. Our simulations explored both linear and logistic regression while considering three statistics: the test, the test, and the (LRT). We further applied the approaches to three large sets of human cohort data ( = 37,664), focusing on type 2 diabetes (T2D), obesity, hypertension, and coronary heart disease with smoking, physical activity, diets, and total energy intake. Overall, GRS-based approaches were the most robust, and had the highest power, especially when the G-E interaction effects were correlated with the marginal genetic and environmental effects. We also observed severe miscalibration of joint statistics in logistic models when the number of events per variable was too low when using either the test or LRT test. Finally, our real data application detected nominally significant interaction effects for three outcomes (T2D, obesity, and hypertension), mainly from the GRS-ERS approach. In conclusion, this study provides guidelines for testing multiple interaction parameters in modern human cohorts including extensive genetic and environmental data.

https://www.ncbi.nlm.nih.gov/pubmed/30578273