@article{1970afea115b43ee8baa19a2af156da0,
title = "FTO predicts weight regain in the Look AHEAD clinical trial",
abstract = "Background:Genome-wide association studies have provided new insights into the genetic factors that contribute to the development of obesity. We hypothesized that these genetic markers would also predict magnitude of weight loss and weight regain after initial weight loss.Methods:Established obesity risk alleles available on the Illumina CARe iSelect (IBC) chip were characterized in 3899 overweight or obese participants with type 2 diabetes from the Look AHEAD (Action for Health in Diabetes), a randomized trial to determine the effects of intensive lifestyle intervention (ILI) and diabetes support and education (DSE) on cardiovascular morbidity and mortality. Primary analyses examined the interaction between 13 obesity risk polymorphisms in eight genes and randomized treatment arm in predicting weight change at year 1, and weight regain at year 4 among individuals who lost 3% or more of their baseline weight by year 1.Results:No single-nucleotide polymorphisms (SNPs) were significantly associated with magnitude of weight loss or interacted with treatment arm at year 1. However, fat mass and obesity associated gene (FTO) rs3751812 predicted weight regain within DSE (1.56 kg per risk allele, P=0.005), but not ILI (P=0.761), resulting in SNP × treatment arm interaction (P=0.009). In a partial replication of prior research, the obesity risk (G) allele at BDNF rs6265 was associated with greater weight regain across treatment arms (0.773 kg per risk allele), although results were of borderline statistical significance (P=0.051).Conclusions:Variations in the FTO and BDNF loci may contribute risk of weight regain after weight loss.",
keywords = "diet, genetics, type 2 diabetes, weight loss",
author = "McCaffery, {J. M.} and Papandonatos, {G. D.} and Huggins, {G. S.} and I. Peter and Kahn, {S. E.} and Knowler, {W. C.} and Hudnall, {G. E.} and Lipkin, {E. W.} and Kitabchi, {A. E.} and Wagenknecht, {L. E.} and Wing, {R. R.}",
note = "Funding Information: We acknowledge the Look AHEAD sites that participated in this ancillary study. This study is supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135 and DK56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women{\textquoteright}s Health; and the Centers for Disease Control and Prevention. Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center (M01RR01066); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (M01RR000056 44) and NIH grants (DK 046204 and DK072497); and VA Puget Sound Health Care System and Department of Veterans Affairs; Frederic C Bartter General Clinical Research Center (M01RR01346). AKH was supported by the Training Program in Cardiovascular Research (NIH, 5T32HL069770). The following organizations have committed to make major contributions to Look AHEAD: Federal Express; Health Management Resources; Johnson & Johnson, LifeScan Inc.; Optifast-Novartis Nutrition; Roche Pharmaceuticals; Ross Product Division of Abbott Laboratories; Slim-Fast Foods Company; and Unilever.",
year = "2013",
month = dec,
doi = "10.1038/ijo.2013.54",
language = "English",
volume = "37",
pages = "1545--1552",
journal = "International Journal of Obesity",
issn = "0307-0565",
publisher = "Springer Nature",
number = "12",
}