Human cardiovascular disease IBC chip-wide association with weight loss and weight regain in the look AHEAD trial

Hum Hered. 2013;75(2-4):160-74. doi: 10.1159/000353181. Epub 2013 Sep 27.

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 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 ≥ 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.

Trial registration: ClinicalTrials.gov NCT00017953 NCT01270763.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters / genetics
  • Aged
  • Cardiovascular Diseases / genetics*
  • Cohort Studies
  • Female
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis*
  • Polymorphism, Single Nucleotide / genetics
  • Receptor Activator of Nuclear Factor-kappa B / genetics
  • Weight Gain / genetics*
  • Weight Loss / genetics*

Substances

  • ABCB11 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters
  • Receptor Activator of Nuclear Factor-kappa B
  • TNFRSF11A protein, human

Associated data

  • ClinicalTrials.gov/NCT00017953
  • ClinicalTrials.gov/NCT01270763

Grant support