Genetic Association of Recovery from Eating Disorders: The Role of GABA Receptor SNPs

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 x 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 x 10(-6), FDR = 0.0049, OR = 0.55). Enrichment analyses revealed that GABA (gamma-aminobutyric acid) SNPs were over-represented among SNPs associated at po0.05 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. Neuropsychopharmacology (2011) 36, 2222-2232; doi: 10.1038/npp. 2011.108; published online 13 July 2011