Genetic association of recovery from eating disorders: the role of GABA receptor SNPs

Neuropsychopharmacology. 2011 Oct;36(11):2222-32. doi: 10.1038/npp.2011.108. Epub 2011 Jul 13.

Abstract

Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a strictly defined discovery cohort of women who were over age 25 years, carried a lifetime diagnosis of an ED, and for whom data were available regarding the presence (n=361 ongoing symptoms in the past year, ie, 'ill') or absence (n=115 no symptoms in the past year, ie, 'recovered') of ED symptoms. An intronic SNP (rs17536211) in GABRG1 showed the strongest statistical evidence of association (p=4.63 × 10(-6), false discovery rate (FDR)=0.021, odds ratio (OR)=0.46). We replicated these findings in a more liberally defined cohort of women age 25 years or younger (n=464 ill, n=107 recovered; p=0.0336, OR=0.68; combined sample p=4.57 × 10(-6), FDR=0.0049, OR=0.55). Enrichment analyses revealed that GABA (γ-aminobutyric acid) SNPs were over-represented among SNPs associated at p<0.05 in both the discovery (Z=3.64, p=0.0003) and combined cohorts (Z=2.07, p=0.0388). In follow-up phenomic association analyses with a third independent cohort (n=154 ED cases, n=677 controls), rs17536211 was associated with trait anxiety (p=0.049), suggesting a possible mechanism through which this variant may influence ED outcome. These findings could provide new insights into the development of more effective interventions for the most treatment-resistant patients.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Feeding and Eating Disorders / diagnosis
  • Feeding and Eating Disorders / genetics*
  • Female
  • Follow-Up Studies
  • Genetic Association Studies / methods*
  • Humans
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, GABA / genetics*
  • Receptors, GABA-A / genetics*
  • Recovery of Function / genetics*
  • Young Adult

Substances

  • GABRG1 protein, human
  • Receptors, GABA
  • Receptors, GABA-A