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United States Department of Agriculture

Agricultural Research Service

Research Project: Dietary Guidelines Adherence and Healthy Body Weight Maintenance Title: Human cardiovascular disease IBC chip-wide association with weight loss and weight regain in the look ahead trial

Author
item Raatz, Susan

Submitted to: Human Heredity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 1, 2013
Publication Date: September 27, 2013
Citation: Raatz, S.K. 2013. Human cardiovascular disease IBC chip-wide association with weight loss and weight regain in the look ahead trial. Human Heredity. 75:160-174.

Interpretive Summary: The present study identified genetic predictors of weight change during behavioral weight loss treatment. 3,899 overweight/obese individuals with type 2 diabetes from Look AHEAD, a randomized controlled trial to determine the effects of intensive lifestyle intervention (ILI), including weight loss and physical activity, relative to diabetes support and education on cardiovascular outcomes. Analyses focused on associations of single nucleotide polymorphisms (SNPs) weight change at year 1 and year 4, and weight regain at year 4, among individuals who lost = 3% at year 1. Two novel regions of significant chip-wide association with year-1 weight loss in ILI were identified. These results provide new insights into potential biological mechanisms and may ultimately inform weight loss treatment.

Technical Abstract: Background/Aims: The present study identified genetic predictors of weight change during behavioral weight loss treatment. Methods: Participants were 3,899 overweight/obese individuals with type 2 diabetes from Look AHEAD, a randomized controlled trial to determine the effects of intensive lifestyle intervention (ILI), including weight loss and physical activity, relative to diabetes support and education on cardiovascular outcomes. Analyses focused on associations of single nucleotide polymorphisms (SNPs) on the IlluminaCARe iSelect (IBC) chip (minor allele frequency >5%; n = 31,959) with weight change at year 1 and year 4, and weight regain at year 4, among individuals who lost = 3% at year 1. Results: Two novel regions of significant chip-wide association with year-1 weight loss in ILI were identified (p <2.96E-06). ABCB11 rs484066 was associated with 1.16 kg higher weight per minor allele at year 1, whereas TNFRSF11A, or RANK, rs17069904 was associated with 1.70 kg lower weight per allele at year 1. Conclusions: This study, the largest to date on genetic predictors of weight loss and regain, indicates that SNPs within ABCB11 , related to bile salt transfer, and TNFRSF11A , implicated in adipose tissue physiology, predict the magnitude of weight loss during behavioral intervention. These results provide new insights into potential biological mechanisms and may ultimately inform weight loss treatment.

Last Modified: 10/21/2014
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