title: Genetic association of recovery from eating disorders: the role of GABA receptor SNPs.
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.
authors.affiliation: Scripps Genomic Medicine, Scripps Translational Science Institute, and Scripps Health, La Jolla, CA 92037, USA.
authors.forename: Cinnamon S
authors.initials: CS
authors.lastname: Bloss
authors.forename: Wade
authors.initials: W
authors.lastname: Berrettini
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bergen
authors.forename: Pierre
authors.initials: P
authors.lastname: Magistretti
authors.forename: Vikas
authors.initials: V
authors.lastname: Duvvuri
authors.forename: Michael
authors.initials: M
authors.lastname: Strober
authors.forename: Harry
authors.initials: H
authors.lastname: Brandt
authors.forename: Steve
authors.initials: S
authors.lastname: Crawford
authors.forename: Scott
authors.initials: S
authors.lastname: Crow
authors.forename: Manfred M
authors.initials: MM
authors.lastname: Fichter
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Halmi
authors.forename: Craig
authors.initials: C
authors.lastname: Johnson
authors.forename: Allan S
authors.initials: AS
authors.lastname: Kaplan
authors.forename: Pamela
authors.initials: P
authors.lastname: Keel
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Klump
authors.forename: James
authors.initials: J
authors.lastname: Mitchell
authors.forename: Janet
authors.initials: J
authors.lastname: Treasure
authors.forename: D Blake
authors.initials: DB
authors.lastname: Woodside
authors.forename: Enrica
authors.initials: E
authors.lastname: Marzola
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: Walter H
authors.initials: WH
authors.lastname: Kaye
mesh_terms: D000328:Adult; D015331:Cohort Studies; D001068:Feeding and Eating Disorders / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies / Q000379:methods*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018079:Receptors, GABA / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics*; D020127:Recovery of Function / Q000235:genetics*; D055815:Young Adult
chemical_list: C528795:GABRG1 protein, human; D018079:Receptors, GABA; D011963:Receptors, GABA-A