Abstract P157: Does Physical Activity Modify the Association of 15 Well-established Obesity Loci with BMI: The ARIC Study
This study investigates gene-by-physical activity interaction with 15 well-replicated body mass index (BMI) loci in the Atherosclerosis Risk in Communities (ARIC) Study, a prospective, multi-center, bi-racial population-based cohort of adults (N=15,792 at baseline (1987-1989), aged 45-64). Our analyses were restricted to subjects of self-reported European descent with complete genotype and phenotype data (n=8059, 53% female, mean age 54.3 (SD 5.7)). BMI was computed from measured height and weight. Physical activity (PA) was measured using a modified validated Baecke questionnaire, resulting in an ordinal score ranging from 1.00-10.00 for sport and leisure-time activity. Physical activity was dichotomized at the sex-specific median for high/low PA, with high PA as the referent. BMI was regressed on single nucleotide polymorphism (SNP), PA level, SNP*PA level, and study-specific covariates assuming an additive genetic model. To account for multiple testing, interaction p-values less than 0.006 (0.10/15) were considered statistically significant. Mean BMI was 27.0 (SD 4.8) kg/m2, and sports and leisure time physical activity was 5.00 (SD 1.13, range 1.75-9.25) units. We replicated the main effects of SNP on BMI for FTO (rs9939609, p=8.52E-11) and SEC16B/RASAL2 (rs10913469, p=0.001), and NEGR1 was borderline significant (rs2815752, p=0.006). MAF was the only SNP that displayed a directionally inconsistent effect estimate with earlier findings (Beta: -0.02, SE -0.16, 0.13). Four of the interactions had a p-value <0.1, including SEC16B, PTER, NEGR1, and SH2B1. The largest magnitude effect estimates among the nominally significant interactions were observed for SNPs rs10913469 (locus SEC16B/RASAL2, frequency: 0.2024) and rs10508503 (locus PTER, frequency: 0.0871). For rs10913469, each additional copy of the risk allele resulted in an increased BMI of 0.58 kg/m2 for those in the low PA category, but an increase of only 0.07 kg/m2 for those in the high PA category (p-interaction=0.007). For rs10508503, each additional copy of the risk allele resulted in an increased BMI of 0.51 kg/m2 for those in the low PA category, and a decreased BMI of 0.14 kg/m2 for those in the high PA category (p-interaction=0.013). Mean BMIs for those in the low physical activity category increase with additional copies of the C (risk) allele (mean BMI for TT=25.6, TC=27.2, CC=27.6 kg/m2, p=0.04), while mean BMIs of those with high PA do not differ between genotypes (mean BMI for TT=26.7, TC=26.8, CC=26.6 kg/m2, p=0.51). While we found a significant main effect of the SEC16B/RASAL2 SNP on BMI (p=0.001), for the PTER SNP we did not (p=0.229). These novel findings demonstrate the importance of context specific genetic effects and contribute to the growing literature highlighting the possible importance of physical activity in the attenuation of underlying genetic risk.
- © 2013 by American Heart Association, Inc.