A genome-wide association study of anorexia nervosa

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countri...

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Detalhes bibliográficos
Autores: Fernández Aranda, Fernando, Jiménez-Murcia, Susana, Rabionet Janssen, Raquel, Genetic Consortium for Anorexia Nervosa, Wellcome Trust Case Control Consortium 3
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2014
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/165857
Acesso em linha:https://hdl.handle.net/2445/165857
Access Level:acceso abierto
Palavra-chave:Anorèxia nerviosa
Genòmica
Anorexia nervosa
Genomics
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spelling A genome-wide association study of anorexia nervosaFernández Aranda, FernandoJiménez-Murcia, SusanaRabionet Janssen, RaquelGenetic Consortium for Anorexia NervosaWellcome Trust Case Control Consortium 3Anorèxia nerviosaGenòmicaAnorexia nervosaGenomicsAnorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P = 3.01 x 10(-7)) in SOX2OT and rs17030795 (P = 5.84 x 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P = 5.76 x 10(-6)) between CUL3 and FAM124B and rs1886797 (P = 8.05 x 10(-6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P= 4x10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.Nature Publishing Group2014info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/165857Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1038/mp.2013.187Molecular Psychiatry, 2014, vol. 19, num. 10, p. 1085-1094https://doi.org/10.1038/mp.2013.187info:eu-repo/grantAgreement/EC/FP7/201413info:eu-repo/grantAgreement/EC/FP7/262055info:eu-repo/grantAgreement/EC/FP7/254774(c) Fernández Aranda, Fernando et al., 2014info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1658572026-05-27T06:46:51Z
dc.title.none.fl_str_mv A genome-wide association study of anorexia nervosa
title A genome-wide association study of anorexia nervosa
spellingShingle A genome-wide association study of anorexia nervosa
Fernández Aranda, Fernando
Anorèxia nerviosa
Genòmica
Anorexia nervosa
Genomics
title_short A genome-wide association study of anorexia nervosa
title_full A genome-wide association study of anorexia nervosa
title_fullStr A genome-wide association study of anorexia nervosa
title_full_unstemmed A genome-wide association study of anorexia nervosa
title_sort A genome-wide association study of anorexia nervosa
dc.creator.none.fl_str_mv Fernández Aranda, Fernando
Jiménez-Murcia, Susana
Rabionet Janssen, Raquel
Genetic Consortium for Anorexia Nervosa
Wellcome Trust Case Control Consortium 3
author Fernández Aranda, Fernando
author_facet Fernández Aranda, Fernando
Jiménez-Murcia, Susana
Rabionet Janssen, Raquel
Genetic Consortium for Anorexia Nervosa
Wellcome Trust Case Control Consortium 3
author_role author
author2 Jiménez-Murcia, Susana
Rabionet Janssen, Raquel
Genetic Consortium for Anorexia Nervosa
Wellcome Trust Case Control Consortium 3
author2_role author
author
author
author
dc.subject.none.fl_str_mv Anorèxia nerviosa
Genòmica
Anorexia nervosa
Genomics
topic Anorèxia nerviosa
Genòmica
Anorexia nervosa
Genomics
description Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P = 3.01 x 10(-7)) in SOX2OT and rs17030795 (P = 5.84 x 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P = 5.76 x 10(-6)) between CUL3 and FAM124B and rs1886797 (P = 8.05 x 10(-6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P= 4x10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.
publishDate 2014
dc.date.none.fl_str_mv 2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/165857
url https://hdl.handle.net/2445/165857
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1038/mp.2013.187
Molecular Psychiatry, 2014, vol. 19, num. 10, p. 1085-1094
https://doi.org/10.1038/mp.2013.187
info:eu-repo/grantAgreement/EC/FP7/201413
info:eu-repo/grantAgreement/EC/FP7/262055
info:eu-repo/grantAgreement/EC/FP7/254774
dc.rights.none.fl_str_mv (c) Fernández Aranda, Fernando et al., 2014
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Fernández Aranda, Fernando et al., 2014
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Clíniques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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