Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials

Publication Description
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.

Primary Author
Papandonatos,George D.
Pan,Qing
Pajewski,Nicholas M.
Delahanty,Linda M.
Peter,Inga
Erar,Bahar
Ahmad,Shafqat
Harden,Maegan
Chen,Ling
Fontanillas,Pierre
Wagenknecht,Lynne E.
Kahn,Steven E.
Wing,Rena R.
Jablonski,Kathleen A.
Huggins,Gordon S.
Knowler,William C.
Florez,Jose C.
McCaffery,Jeanne M.
Franks,Paul W.

Volume
64

Issue
12

Start Page
4312

Other Pages
4321

Publisher
American Diabetes Association

URL
https://www.ncbi.nlm.nih.gov/pubmed/26253612

PMID
26253612

PMCID
PMC4657576



Reference Type
Journal Article

Periodical Full
Diabetes

Publication Year
2015

Publication Date
Dec

Place of Publication
United States

ISSN/ISBN
0012-1797

Document Object Index
10.2337/db15-0441