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. Schork; Walter H. Kaye

doi:10.1038/npp.2011.108

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 journal › Article › peer-review

34 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 language	English (US)
Pages (from-to)	2222-2232
Number of pages	11
Journal	Neuropsychopharmacology
Volume	36
Issue number	11
DOIs	https://doi.org/10.1038/npp.2011.108
State	Published - Oct 2011
Externally published	Yes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/npp.2011.108

Cite this

Bloss, C. S., Berrettini, W., Bergen, A. W., Magistretti, P., Duvvuri, V., Strober, M., Brandt, H., Crawford, S., Crow, S., Fichter, M. M., Halmi, K. A., Johnson, C., Kaplan, A. S., Keel, P., Klump, K. L., Mitchell, J., Treasure, J., Woodside, D. B., Marzola, E., ... Kaye, W. H. (2011). Genetic association of recovery from eating disorders: The role of GABA receptor SNPs. Neuropsychopharmacology, 36(11), 2222-2232. https://doi.org/10.1038/npp.2011.108

@article{bbf3941b8a364937aff3b43edb83bd2d,

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.",

keywords = "GABA, anorexia nervosa, eating/metabolic disorders, genetic association, recovery from eating disorders, single nucleotide polymorphisms",

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

note = "Funding Information: Dr Kaye has received salary support from the University of Pittsburgh and the University of California, San Diego; research funding/support from the NIMH; research funding for an investigator-initiated treatment study from Astra-Zeneca and consulting fees from Lundbeck, Merck, and the Eating Disorder Center of Denver. In addition, there are honoraria for presentations from academic institutions and meetings, and compensation for grant review activities from the National Institutes of Health. Dr Crow has received support in the past 3 years from Eli Lilly, Pfizer, l\Jovartis, and GSK. Dr Bergen has received compensation from the Center for Scientific Review, National Institutes of Health, and from the National Coalition for Health Professional Education in Genetics. The remaining authors, CS Bloss, C Johnson, DB Woodside, S Crawford, H Brandt, A Kaplan, M Strober, P Magistretti, K Halmi, E Marzola, K Klump, J Treasure, M Fichter, J Mitchell, P Keep, W Berrettini, V Duvvuri, and NJ Schork declare that, except for income received from our primary employers and the above-mentioned funding, no further financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest. Funding Information: We thank the Price Foundation for the support of clinical data and biospecimen collection, genotyping, and data analysis. We further acknowledge the participating families and patients without whom this work would not have been possible. This work was supported by the Price Foundation of Geneva, Switzerland. Drs Bloss and Schork are additionally supported, in part, by an NIH/NCRR flagship Clinical and Translational Science Award Grant (1U54RR025204-01).",

year = "2011",

month = oct,

doi = "10.1038/npp.2011.108",

language = "English (US)",

volume = "36",

pages = "2222--2232",

journal = "Neuropsychopharmacology",

issn = "0893-133X",

publisher = "Springer Nature",

number = "11",

}

Bloss, CS, Berrettini, W, Bergen, AW, Magistretti, P, Duvvuri, V, Strober, M, Brandt, H, Crawford, S, Crow, S, Fichter, MM, Halmi, KA, Johnson, C, Kaplan, AS, Keel, P, Klump, KL, Mitchell, J, Treasure, J, Woodside, DB, Marzola, E, Schork, NJ & Kaye, WH 2011, 'Genetic association of recovery from eating disorders: The role of GABA receptor SNPs', Neuropsychopharmacology, vol. 36, no. 11, pp. 2222-2232. https://doi.org/10.1038/npp.2011.108

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.

N1 - Funding Information: Dr Kaye has received salary support from the University of Pittsburgh and the University of California, San Diego; research funding/support from the NIMH; research funding for an investigator-initiated treatment study from Astra-Zeneca and consulting fees from Lundbeck, Merck, and the Eating Disorder Center of Denver. In addition, there are honoraria for presentations from academic institutions and meetings, and compensation for grant review activities from the National Institutes of Health. Dr Crow has received support in the past 3 years from Eli Lilly, Pfizer, l\Jovartis, and GSK. Dr Bergen has received compensation from the Center for Scientific Review, National Institutes of Health, and from the National Coalition for Health Professional Education in Genetics. The remaining authors, CS Bloss, C Johnson, DB Woodside, S Crawford, H Brandt, A Kaplan, M Strober, P Magistretti, K Halmi, E Marzola, K Klump, J Treasure, M Fichter, J Mitchell, P Keep, W Berrettini, V Duvvuri, and NJ Schork declare that, except for income received from our primary employers and the above-mentioned funding, no further financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest. Funding Information: We thank the Price Foundation for the support of clinical data and biospecimen collection, genotyping, and data analysis. We further acknowledge the participating families and patients without whom this work would not have been possible. This work was supported by the Price Foundation of Geneva, Switzerland. Drs Bloss and Schork are additionally supported, in part, by an NIH/NCRR flagship Clinical and Translational Science Award Grant (1U54RR025204-01).

PY - 2011/10

Y1 - 2011/10

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

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DO - 10.1038/npp.2011.108

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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