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Article: Dissecting the genetic heterogeneity of depression through age at onset

TitleDissecting the genetic heterogeneity of depression through age at onset
Authors
KeywordsAge at onset
Depression
Heterogeneity
Genetic association
Genetic heterogeneity
Issue Date2012
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0148-7299:1/
Citation
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2012, v. 159B n. 7, p. 859-868 How to Cite?
Abstract
Genome-wide studies in major depression have identified few replicated associations, potentially due to heterogeneity within the disorder. Several studies have suggested that age at onset (AAO) can distinguish sub-types of depression with specific heritable components. This paper investigates the role of AAO in the genetic susceptibility for depression using genome-wide association data on 2,746 cases and 1,594 screened controls from the RADIANT studies, with replication performed in 1,471 cases and 1,403 controls from two Munich studies. Three methods were used to analyze AAO: First a time-to-event analysis with controls censored, secondly comparing controls to case-subsets defined using AAO cut-offs, and lastly analyzing AAO as a quantitative trait. In the time-to-event analysis three SNPs reached suggestive significance (P<5E-06), overlapping with the original case-control analysis of this study. In a case-control analysis using AAO thresholds, SNPs in 10 genomic regions showed suggestive association though again none reached genome-wide significance. Lastly, case-only analysis of AAO as a quantitative trait resulted in 5 SNPs reaching suggestive significance. Sex specific analysis was performed as a secondary analysis, yielding one SNP reaching genome-wide significance in early-onset males. No SNPs achieved significance in the replication study after correction for multiple testing. Analysis of AAO as a quantitative trait did suggest that, across all SNPs, common genetic variants explained a large proportion of the variance (51%, P=0.04). This study provides the first focussed analysis of the genetic contribution to AAO in depression, and establishes a statistical framework that can be applied to a quantitative trait underlying any disorder. © 2012 Wiley Periodicals, Inc.
DescriptionResearch article
Persistent Identifierhttp://hdl.handle.net/10722/164566
ISSN
2013 Impact Factor: 3.271
ISI Accession Number ID

 

Author Affiliations
  1. Institute of Public Health Ljubljana
  2. King's College London
  3. Universität Bonn
  4. Washington University in St. Louis
  5. South London and Maudsley NHS Foundation Trust
  6. The University of Hong Kong
  7. University of Zagreb School of Medicine
  8. GlaxoSmithKline
  9. Université Libre de Bruxelles
  10. null
  11. Max-Planck-Institut für Psychiatrie
  12. Zentralinstitut für Seelische Gesundheit
  13. Cardiff University
  14. University of Birmingham
  15. Spedali Civili Di Brescia
  16. Poznan University of Medical Sciences
  17. Neurosearch AS
  18. University of Toronto
  19. Trinity Centre for Health Science
  20. Ârhus Universitetshospital
  21. Universität Lausanne Schweiz
  22. Dalhousie University
DC FieldValueLanguage
dc.contributor.authorPower, RAen_US
dc.contributor.authorKeers, Ren_US
dc.contributor.authorNg, MYen_US
dc.contributor.authorButler, AWen_US
dc.contributor.authorUher, Ren_US
dc.contributor.authorCohen-Woods, Sen_US
dc.contributor.authorIsing, M-
dc.contributor.authorCraddock, N-
dc.contributor.authorOwen, MJ-
dc.contributor.authorKorszun, A-
dc.contributor.authorJones, L-
dc.contributor.authorJones, I-
dc.contributor.authorGill, M-
dc.contributor.authorRice, JP-
dc.contributor.authorHauser, J-
dc.contributor.authorHenigsberg, N-
dc.contributor.authorMaier, W-
dc.contributor.authorZobel, A-
dc.contributor.authorMors, O-
dc.contributor.authorPlacentino, AS-
dc.contributor.authorRietschel, M-
dc.contributor.authorSouery, D-
dc.contributor.authorKozel, D-
dc.contributor.authorPreisig, M-
dc.contributor.authorLucae, S-
dc.contributor.authorBinder, EB-
dc.contributor.authorAitchison, KJ-
dc.contributor.authorTozzi, F-
dc.contributor.authorMuglia, P-
dc.contributor.authorBreen, G-
dc.contributor.authorCraig, IW-
dc.contributor.authorFarmer, AE-
dc.contributor.authorMüller-Myhsok, B-
dc.contributor.authorMcGuffin, P-
dc.contributor.authorLewis, CM-
dc.date.accessioned2012-09-20T08:06:04Z-
dc.date.available2012-09-20T08:06:04Z-
dc.date.issued2012en_US
dc.identifier.citationAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2012, v. 159B n. 7, p. 859-868en_US
dc.identifier.issn1552-4841-
dc.identifier.urihttp://hdl.handle.net/10722/164566-
dc.descriptionResearch article-
dc.description.abstractGenome-wide studies in major depression have identified few replicated associations, potentially due to heterogeneity within the disorder. Several studies have suggested that age at onset (AAO) can distinguish sub-types of depression with specific heritable components. This paper investigates the role of AAO in the genetic susceptibility for depression using genome-wide association data on 2,746 cases and 1,594 screened controls from the RADIANT studies, with replication performed in 1,471 cases and 1,403 controls from two Munich studies. Three methods were used to analyze AAO: First a time-to-event analysis with controls censored, secondly comparing controls to case-subsets defined using AAO cut-offs, and lastly analyzing AAO as a quantitative trait. In the time-to-event analysis three SNPs reached suggestive significance (P<5E-06), overlapping with the original case-control analysis of this study. In a case-control analysis using AAO thresholds, SNPs in 10 genomic regions showed suggestive association though again none reached genome-wide significance. Lastly, case-only analysis of AAO as a quantitative trait resulted in 5 SNPs reaching suggestive significance. Sex specific analysis was performed as a secondary analysis, yielding one SNP reaching genome-wide significance in early-onset males. No SNPs achieved significance in the replication study after correction for multiple testing. Analysis of AAO as a quantitative trait did suggest that, across all SNPs, common genetic variants explained a large proportion of the variance (51%, P=0.04). This study provides the first focussed analysis of the genetic contribution to AAO in depression, and establishes a statistical framework that can be applied to a quantitative trait underlying any disorder. © 2012 Wiley Periodicals, Inc.-
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0148-7299:1/-
dc.relation.ispartofAmerican Journal of Medical Genetics Part B: Neuropsychiatric Geneticsen_US
dc.rightsAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics. Copyright © John Wiley & Sons, Inc.-
dc.subjectAge at onset-
dc.subjectDepression-
dc.subjectHeterogeneity-
dc.subjectGenetic association-
dc.subjectGenetic heterogeneity-
dc.titleDissecting the genetic heterogeneity of depression through age at onseten_US
dc.typeArticleen_US
dc.identifier.emailPower, RA: robert.r.power@kcl.ac.uken_US
dc.identifier.emailButler, AW: wbutler@hku.hk-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ajmg.b.32093-
dc.identifier.pmid22915352-
dc.identifier.scopuseid_2-s2.0-84866330592-
dc.identifier.hkuros210458en_US
dc.identifier.volume159B-
dc.identifier.issue7-
dc.identifier.spage859-
dc.identifier.epage868-
dc.identifier.isiWOS:000308879900013-
dc.publisher.placeUnited States-
dc.identifier.citeulike11148525-

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