TY - JOUR

T1 - Genetic Predictors of Change in Waist Circumference and Waist-to-Hip Ratio With Lifestyle Intervention

T2 - The Trans-NIH Consortium for Genetics of Weight Loss Response to Lifestyle Intervention

AU - McCaffery, Jeanne M.

AU - Jablonski, Kathleen A.

AU - Pan, Qing

AU - Astrup, Arne

AU - Revsbech Christiansen, Malene

AU - Corella, Dolores

AU - Corso, Lauren M.L.

AU - Florez, Jose C.

AU - Franks, Paul W.

AU - Gardner, Christopher

AU - Hansen, Torben

AU - Kilpeläinen, Tuomas O.

AU - Knowler, William C.

AU - Lindström, Jaana

AU - Saris, Wim H.M.

AU - Sørensen, Thorkild I. A.

AU - Tuomilehto, Jaakko

AU - Uusitupa, Matti

AU - Wing, Rena R.

AU - Agurs-Collins, Tanya

N1 - Publisher Copyright: © 2022 by the American Diabetes Association.

PY - 2022

Y1 - 2022

N2 - Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with waist circumference (WC) and waist-to-hip ratio (WHR) adjusted for BMI (WCadjBMI and WHRadjBMI), but it remains unclear whether these SNPs relate to change in WCadjBMI or WHRadjBMI with lifestyle intervention for weight loss. 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 8-10 weeks in two lifestyle intervention trials, NUGENOB and DiOGenes, and at 1 year in five lifestyle intervention trials, Look AHEAD, Diabetes Prevention Program, Diabetes Prevention Study, DIETFITS, and PREDIMED-Plus. One-SD higher PS related to a smaller 1-year change in WCadjBMI in the lifestyle intervention arms at year 1 and thus predicted poorer response (β = 0.007; SE = 0.003; P = 0.03) among White participants overall and in White men (β = 0.01; SE = 0.004; P = 0.01). At average weight loss, this amounted to 0.20-0.28 cm per SD. No significant findings emerged in White women or 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 estimated from these 59 SNPs relates to change in WCadjBMI with lifestyle intervention, but the effects are small and not of sufficient magnitude to be clinically significant.

AB - Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with waist circumference (WC) and waist-to-hip ratio (WHR) adjusted for BMI (WCadjBMI and WHRadjBMI), but it remains unclear whether these SNPs relate to change in WCadjBMI or WHRadjBMI with lifestyle intervention for weight loss. 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 8-10 weeks in two lifestyle intervention trials, NUGENOB and DiOGenes, and at 1 year in five lifestyle intervention trials, Look AHEAD, Diabetes Prevention Program, Diabetes Prevention Study, DIETFITS, and PREDIMED-Plus. One-SD higher PS related to a smaller 1-year change in WCadjBMI in the lifestyle intervention arms at year 1 and thus predicted poorer response (β = 0.007; SE = 0.003; P = 0.03) among White participants overall and in White men (β = 0.01; SE = 0.004; P = 0.01). At average weight loss, this amounted to 0.20-0.28 cm per SD. No significant findings emerged in White women or 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 estimated from these 59 SNPs relates to change in WCadjBMI with lifestyle intervention, but the effects are small and not of sufficient magnitude to be clinically significant.

U2 - 10.2337/db21-0741

DO - 10.2337/db21-0741

M3 - Journal article

C2 - 35043141

AN - SCOPUS:85127999986

VL - 71

SP - 669

EP - 676

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 4

ER -