Journal
HUMAN HEREDITY
Volume 75, Issue 2-4, Pages 160-174Publisher
KARGER
DOI: 10.1159/000353181
Keywords
Type 2 diabetes; Obesity; Weight loss; Diet; Genetics
Categories
Funding
- Department of Health and Human Services through National Institutes of Health [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]
- Johns Hopkins Medical Institutions Bayview General Clinical Research Center [M01RR02719]
- Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center [M01RR01066]
- University of Colorado Health Sciences Center General Clinical Research Center [M01RR00051]
- Clinical Nutrition Research Unit [P30 DK48520]
- University of Tennessee at Memphis General Clinical Research Center [M01RR0021140]
- University of Pittsburgh General Clinical Research Center (GCRC) [M01RR000056]
- Clinical Translational Research Center (CTRC)
- Clinical and Translational Science Award [UL1 RR 024153]
- NIH [DK 046204]
- VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs
- Frederic C. Bartter General Clinical Research Center [M01RR01346]
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR001346, M01RR000051, M01RR001066, M01RR002719, UL1RR024153, M01RR000056] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [U01DK057171, P30DK017047, ZIADK075077, U01DK057002, U01DK057008, U01DK057136, U01DK057154, P30DK079637, P30DK046204, U01DK057135, U01DK057182, U01DK057177, U01DK057151, P30DK048520, U01DK057149, U01DK056990, U01DK057178, U01DK057219, U01DK057078, U01DK056992, U01DK057131] Funding Source: NIH RePORTER
- National Institute on Minority Health and Health Disparities [P20MD006899] Funding Source: NIH RePORTER
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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 Illumina CARe 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 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. (C) 2013 S. Karger AG, Basel
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