Genetic Predictors of Change in Waist Circumference and Waist-To-Hip Ratio with Lifestyle Intervention: the Trans-NIH consortium for Genetics of Weight Loss Response to Lifestyle Intervention
posted on 2022-01-18, 20:59authored byJeanne M. McCaffery, Kathleen A. Jablonski, Qing Pan, Arne Astrup, Malene Revsbech Christiansen, Dolores Corella, Lauren M.L. Corso, Jose C. Florez, Paul W. Franks, Christopher Gardner, Torben Hansen, Tuomas Kilpeläinen, William C. Knowler, Jaana Lindström, Wim H.M. Saris, Thorkild IA Sørensen, Jaakko Tuomilehto, Matti Uusitupa, Rena R. Wing, Tanya Agurs-Collins
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.