Gene-environment interactions and obesity traits among postmenopausal African-American and Hispanic women in the Women’s Health Initiative SHARe Study

Abstract

Genome-wide association studies of obesity measures have identified associations with single nucleotide polymorphisms (SNPs). However, no large-scale evaluation of gene-environment interactions has been performed. We conducted a search of gene-environment (G×E) interactions in post-menopausal African-American and Hispanic women from the Women’s Health Initiative SNP Health Association Resource GWAS study. Single SNP linear regression on body mass index (BMI) and waist-to-hip circumference ratio (WHR) adjusted for multidimensional-scaling-derived axes of ancestry and age was run in race-stratified data with 871,512 SNPs available from African-Americans (N=8,203) and 786,776 SNPs from Hispanics (N=3,484). Tests of G×E interaction at all SNPs for recreational physical activity (met-hrs/wk), dietary energy intake (kcal/day), alcohol intake (categorical), cigarette smoking years, and cigarette smoking (ever vs. never) were run in African-Americans and Hispanics adjusted for ancestry and age at interview, followed by meta-analysis of G×E interaction terms. The strongest evidence for concordant G×E interactions in African-Americans and Hispanics was for smoking and marker rs10133840 (Q statistic P=0.70, beta=−0.01, P=3.81×10−7) with BMI as the outcome. The strongest evidence for G×E interaction within a cohort was in African-Americans with WHR as outcome for dietary energy intake and rs9557704 (SNP×kcal =−0.04, P=2.17×10−7). No results exceeded the Bonferroni–corrected statistical significance threshold

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