1. Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials
- Author
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Papandonatos, G.D., Pan, Q., Pajewski, N.M., Delahanty, L.M., Peter, I., Erar, B., Ahmad, S., Harden, M., Chen, L., Fontanillas, P., GIANT Consortium (Albrecht, E., Gieger, C., Grallert, H., Heid, I.M., Illig, T., Müller-Nurasyid, M., Peters, A., Thorand, B., Wichmann, H.-E.), Wagenknecht, L.E., Kahn, S.E., Wing, R.R., Jablonski, K.A., Huggins, G.S., Knowler, W.C., Florez, J.C, McCaffery, J.M., Franks, P.W., Diabetes Prevention Program (), and Look AHEAD Research Group ()
- Subjects
Male ,Risk ,medicine.medical_specialty ,Diet, Reducing ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,Motor Activity ,Overweight ,Weight Gain ,Polymorphism, Single Nucleotide ,Body Mass Index ,law.invention ,Mitochondrial Proteins ,Prediabetic State ,Randomized controlled trial ,Recurrence ,Weight loss ,law ,Internal medicine ,Diabetes mellitus ,Weight Loss ,Internal Medicine ,Humans ,Medicine ,Genetic Predisposition to Disease ,Longitudinal Studies ,Obesity ,Eukaryotic Initiation Factors ,Life Style ,Genetic Association Studies ,business.industry ,Genetics/Genomes/Proteomics/Metabolomics ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,3. Good health ,Endocrinology ,Diabetes Mellitus, Type 2 ,Female ,medicine.symptom ,business ,Weight gain ,Body mass index - 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.
- Published
- 2015