Genetic Predictors of Change in Waist Circumference and Waist-to-Hip Ratio With Lifestyle Intervention

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with waist circumference and waist-to-hip ratio adjusted for body mass index (WCadjBMI, WHRadjBMI), but it remains unclear whether these SNPs relate to change in WCadjBMI or WHRadjBMI with lifestyle intervention. We hypothesized that polygenic scores (PS) comprised of 59 SNPs previously associated with central adiposity would predict less of a reduction in WCadjBMI or WHRadjBMI at eight-to-ten weeks in two lifestyle intervention trials, NUGENOB and DiOGenes, and at one year in 5 lifestyle intervention trials, Look AHEAD, Diabetes Prevention Program, Diabetes Prevention Study, DIETFITS, and PREDIMED-Plus. One standard deviation higher PS related to smaller one-year change in WCadjBMI in the lifestyle intervention arms at year 1, and thus predicted poorer response (beta=0.007, SE=0.003, p=0.03) among White participants overall and in White men (beta=0.01, SE=0.004, p=0.01). At average weight loss, this amounted to 0.20-0.28 cm per standard deviation. No significant findings emerged in White women, African American men, for the 8-10 week outcomes or for WHRadjBMI. Findings were heterogeneous in African American women. These results indicate that polygenic risk relates to change in WCadjBMI with lifestyle intervention but the effects are small and not of sufficient magnitude to be clinically significant.