Single nucleotide polymorphisms (SNPs) associated with waist circumference (WC) and waist-to-hip ratio (WHR) adjusted for BMI (WCadjBMI and WHRadjBMI) have been identified in genome-wide association studies. Still, it was unclear whether these SNPs are related to changes in WCadjBMI or WHRadjBMI with lifestyle intervention for weight loss. For a study, researchers hypothesized that polygenic scores (PS), which are made up of 59 SNPs previously linked to central adiposity, would predict a lower reduction in WCadjBMI or WHRadjBMI at 8–10 weeks in two lifestyle intervention trials, NUGENOB and Diogenes, and 1 year in five lifestyle intervention trials, Look AHEAD, Diabetes Prevention Program, Diabetes Prevention Study, DIETFITS, and PREDIMED-Plus. 

A one-SD increase in PS predicted a lower 1-year improvement in WCadjBMI in the lifestyle intervention arms at year 1 and hence a worse response (β=0.007; SE=0.003; P=0.03) among White participants overall and in White males (β=0.01; SE=0.004; P=0.01). This corresponded to 0.20–0.28 cm per SD of average weight decrease. There were no significant findings in either White women or African American males for the 8–10-week outcomes or WHRadjBMI. In African American women, the results were mixed. The findings suggested that polygenic risk assessed from these 59 SNPs was related to change in WCadjBMI with lifestyle modification, although the effects were minor and not clinically relevant.