Abstract
Genome-wide association studies (GWAS) 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 (m h/week), 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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Acknowledgments
This work was funded by Vanderbilt Clinical and Translational Research Scholar award (5KL2RR024975) to TLE. We would also like to acknowledge the Women’s Health Initiative Presentations and Publications committee for helpful comments during the preparation of this manuscript. Additional funds were provided by the Building Interdisciplinary Research Careers in Women’s Health career development program (K12HD4383) to DRVE.
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The authors have no conflicts of interest to disclose.
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Velez Edwards, D.R., Naj, A.C., Monda, K. et al. Gene-environment interactions and obesity traits among postmenopausal African-American and Hispanic women in the Women’s Health Initiative SHARe Study. Hum Genet 132, 323–336 (2013). https://doi.org/10.1007/s00439-012-1246-3
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DOI: https://doi.org/10.1007/s00439-012-1246-3