Genetic predisposition to weight loss & regain with lifestyle intervention: analyses from the Diabetes Prevention Program & the Look AHEAD randomized controlled trials.

Research output: Contribution to journalArticle


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 (Diabetes Prevention Program [DPP]; N=917/907 intervention/comparison) or with (Look AHEAD; N=2,014/1,892 intervention/comparison) type 2 diabetes 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 DPP and LA. No such effect was observed across comparison arms, leading to a nominally significant SNP × 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.


  • 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 Franks
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)4312-4321
Issue number12
Publication statusPublished - 2015
Publication categoryResearch