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

  • 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
Publishing year: 2015
Language: English
Pages: 4312-4321
Publication/Series: Diabetes
Volume: 64
Issue: 12
Document type: Journal article
Publisher: American Diabetes Association Inc.

Abstract english

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.


  • Endocrinology and Diabetes


  • Genetic and Molecular Epidemiology
  • ISSN: 1939-327X
E-mail: shafqat [dot] ahmad [at] med [dot] lu [dot] se

Doctoral student

Genetic and Molecular Epidemiology

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