TY - JOUR
T1 - Genetic association of recovery from eating disorders
T2 - The role of GABA receptor SNPs
AU - Bloss, Cinnamon S.
AU - Berrettini, Wade
AU - Bergen, Andrew W.
AU - Magistretti, Pierre
AU - Duvvuri, Vikas
AU - Strober, Michael
AU - Brandt, Harry
AU - Crawford, Steve
AU - Crow, Scott
AU - Fichter, Manfred M.
AU - Halmi, Katherine A.
AU - Johnson, Craig
AU - Kaplan, Allan S.
AU - Keel, Pamela
AU - Klump, Kelly L.
AU - Mitchell, James
AU - Treasure, Janet
AU - Woodside, D. Blake
AU - Marzola, Enrica
AU - Schork, Nicholas J.
AU - Kaye, Walter H.
PY - 2011/10/1
Y1 - 2011/10/1
N2 -
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.
AB -
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.
KW - GABA
KW - anorexia nervosa
KW - eating/metabolic disorders
KW - genetic association
KW - recovery from eating disorders
KW - single nucleotide polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=80052733666&partnerID=8YFLogxK
U2 - 10.1038/npp.2011.108
DO - 10.1038/npp.2011.108
M3 - Article
C2 - 21750581
AN - SCOPUS:80052733666
VL - 36
SP - 2222
EP - 2232
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
IS - 11
ER -