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MDPI, International Journal of Molecular Sciences, 18(21), p. 6724, 2020

DOI: 10.3390/ijms21186724

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HisCoM-G×E: Hierarchical Structural Component Analysis of Gene-Based Gene–Environment Interactions

Journal article published in 2020 by Sungkyoung Choi ORCID, Sungyoung Lee, Iksoo Huh, Heungsun Hwang, Taesung Park
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Gene–environment interaction (G×E) studies are one of the most important solutions for understanding the “missing heritability” problem in genome-wide association studies (GWAS). Although many statistical methods have been proposed for detecting and identifying G×E, most employ single nucleotide polymorphism (SNP)-level analysis. In this study, we propose a new statistical method, Hierarchical structural CoMponent analysis of gene-based Gene–Environment interactions (HisCoM-G×E). HisCoM-G×E is based on the hierarchical structural relationship among all SNPs within a gene, and can accommodate all possible SNP-level effects into a single latent variable, by imposing a ridge penalty, and thus more efficiently takes into account the latent interaction term of G×E. The performance of the proposed method was evaluated in simulation studies, and we applied the proposed method to investigate gene–alcohol intake interactions affecting systolic blood pressure (SBP), using samples from the Korea Associated REsource (KARE) consortium data.