Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials
Year: 2015
Type: article
Abstract: Clinically relevant weight loss is achievable through lifestyle modification, but unintentional weight regain is common. We investigated whether recently discovered genetic variants affect weight loss and/or weight regain during behavioral intervention. Participants at high-risk of type 2 diabetes (Diabetes Prevention Program [DPP]; N = 917/907 intervention/comparison) or with type 2 diabetes (Look AHEAD [Action for Health in Diabetes]; N = 2,014/1,892 intervention/comparison) were from two parallel arm (lifestyle vs. comparison) randomized controlled trials. The associations of 91 established obesity-predisposing loci with weight loss across 4 years and with weight regain across years 2-4 after a minimum of 3% weight loss were tested. Each copy of the minor G allele of MTIF3 rs1885988 was consistently associated with greater weight loss following lifestyle intervention over 4 years across the DPP and Look AHEAD. No such effect was observed across comparison arms, leading to a nominally significant single nucleotide polymorphism×treatment interaction (P = 4.3 × 10(-3)). However, this effect was not significant at a study-wise significance level (Bonferroni threshold P < 5.8 × 10(-4)). Most obesity-predisposing gene variants were not associated with weight loss or regain within the DPP and Look AHEAD trials, directly or via interactions with lifestyle.
Source: Diabetes
DOI: 10.2337/db15-0441
Authors: George D. Papandonatos, Qing Pan, Nicholas M. Pajewski, Linda M. Delahanty, Inga Peter, Bahar Erar, Shafqat Ahmad, Maegan Harden, Ling Chen, Pierre Fontanillas, Lynne E. Wagenknecht, Steven E. Kahn, Rena R. Wing, Kathleen A. Jablonski, Gordon S. Huggins, William C. Knowler, Jose C. Florez, Jeanne M. McCaffery, Paul W. Franks
Institutions: Brown University, George Washington University, Wake Forest University Health Sciences, Wake Forest University, Harvard University, Massachusetts General Hospital, Icahn School of Medicine at Mount Sinai, Lund University, Skåne University Hospital, Broad Institute, Atrium Health Wake Forest Baptist, University of Washington, VA Puget Sound Health Care System, Miriam Hospital, Tufts Medical Center, National Institute of Diabetes and Digestive and Kidney Diseases, Umeå University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G1485640885, G1776253575, G1986296333, G2000805413, G2006034517, A Human-Centered Pharmacogenomic Screen of Metformin Action, 8/22 Limited Competition for the Continuation of the Diabetes Prevention Program Outcomes Study (DPPOS) - Clinical Center, G2491623767, G2702067867, G31446317, G3398210748, G3407579893, G347469348, G3714318003, G410555167, G433373727, G4997665424, G5361611515, G5390604924, 9/22 Limited Competition for Continuation of the Diabetes Prevention Program Outcomes Study (DPPOS) - Clinical Center, G5947254055, G5976813381, G609523450, G6106528919, 7/22 Limited Competition for the Continuation of the Diabetes Prevention Program Outcomes Study (DPPOS) - Clinical Center, G6411832335, G7405737314, G8060355097, 12/16 Action for Health in Diabetes Extension Study Research Project, 16/22 Limited Competition for the Continuation of the Diabetes Prevention Program Outcomes Study (DPPOS) – Clinical Center, New York Obesity Research Center, Diabetes Research Center, G970309226
OpenAlex ID: W2129893651