TY - JOUR
T1 - Genetic predisposition to weight loss and regain with lifestyle intervention
T2 - Analyses from the diabetes prevention program and the look AHEAD randomized controlled trials
AU - GIANT Consortium
AU - Diabetes Prevention Program and the Look AHEAD Research Groups
AU - Papandonatos, George D.
AU - Pan, Qing
AU - Pajewski, Nicholas M.
AU - Delahanty, Linda M.
AU - Peter, Inga
AU - Erar, Bahar
AU - Ahmad, Shafqat
AU - Harden, Maegan
AU - Chen, Ling
AU - Fontanillas, Pierre
AU - Wagenknecht, Lynne E.
AU - Kahn, Steven E.
AU - Wing, Rena R.
AU - Jablonski, Kathleen A.
AU - Huggins, Gordon S.
AU - Knowler, William C.
AU - Florez, Jose C.
AU - McCaffery, Jeanne M.
AU - Franks, Paul W.
N1 - Publisher Copyright:
© 2015 by the American Diabetes Association.
PY - 2015/12
Y1 - 2015/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84962159225&partnerID=8YFLogxK
U2 - 10.2337/db15-0441
DO - 10.2337/db15-0441
M3 - Article
C2 - 26253612
AN - SCOPUS:84962159225
SN - 0012-1797
VL - 64
SP - 4312
EP - 4321
JO - Diabetes
JF - Diabetes
IS - 12
ER -