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

Cinnamon S. Bloss, Wade Berrettini, Andrew W. Bergen, Pierre Magistretti, Vikas Duvvuri, Michael Strober, Harry Brandt, Steve Crawford, Scott Crow, Manfred M. Fichter, Katherine A. Halmi, Craig Johnson, Allan S. Kaplan, Pamela Keel, Kelly L. Klump, James Mitchell, Janet Treasure, D. Blake Woodside, Enrica Marzola, Nicholas J. SchorkWalter H. Kaye*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2222-2232
Number of pages11
JournalNeuropsychopharmacology
Volume36
Issue number11
DOIs
StatePublished - Oct 1 2011

Keywords

  • GABA
  • anorexia nervosa
  • eating/metabolic disorders
  • genetic association
  • recovery from eating disorders
  • single nucleotide polymorphisms

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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