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

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TitleDissecting the genetic heterogeneity of depression through age at onset
AuthorsPower, RA2
Keers, R2 12
Ng, MY2
Butler, AW2 7
Uher, R2 22
Cohen-Woods, S2
Ising, M13
Craddock, N17
Owen, MJ17
Korszun, A12
Jones, L15
Jones, I17
Gill, M20
Rice, JP4
Hauser, J16
Henigsberg, N6
Maier, W3
Zobel, A3
Mors, O21
Placentino, AS11
Rietschel, M14
Souery, D9
Kozel, D1
Preisig, M10
Lucae, S13
Binder, EB13
Aitchison, KJ2
Tozzi, F8
Muglia, P8 18 19
Breen, G2 5
Craig, IW2
Farmer, AE2
Müller-Myhsok, B13
McGuffin, P2
Lewis, CM2
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/
CitationAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2012, v. 159B n. 7, p. 859-868 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ajmg.b.32093
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.
DescriptionResearch article
ISSN1552-4841
2011 Impact Factor: 3.705
2011 SCImago Journal Rankings: 0.288
DOIhttp://dx.doi.org/10.1002/ajmg.b.32093
DC Field
Value
dc.contributor.authorPower, RA
dc.contributor.authorKeers, R
dc.contributor.authorNg, MY
dc.contributor.authorButler, AW
dc.contributor.authorUher, R
dc.contributor.authorCohen-Woods, S
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.issued2012
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.description.natureLink_to_subscribed_fulltext
dc.descriptionResearch article
dc.identifier.citationAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2012, v. 159B n. 7, p. 859-868 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ajmg.b.32093
dc.identifier.citeulike11148525
dc.identifier.doihttp://dx.doi.org/10.1002/ajmg.b.32093
dc.identifier.epage868
dc.identifier.hkuros210458
dc.identifier.issn1552-4841
2011 Impact Factor: 3.705
2011 SCImago Journal Rankings: 0.288
dc.identifier.issue7
dc.identifier.pmid22915352
dc.identifier.scopuseid_2-s2.0-84866330592
dc.identifier.spage859
dc.identifier.urihttp://hdl.handle.net/10722/164566
dc.identifier.volume159B
dc.languageeng
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0148-7299:1/
dc.publisher.placeUnited States
dc.relation.ispartofAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
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 onset
dc.typeArticle
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. University of Zagreb School of Medicine
  7. The University of Hong Kong
  8. GlaxoSmithKline
  9. Université Libre de Bruxelles
  10. University Hospital Center
  11. Spedali Civili Di Brescia
  12. null
  13. Max-Planck-Institut für Psychiatrie
  14. Zentralinstitut für Seelische Gesundheit
  15. University of Birmingham
  16. Poznan University of Medical Sciences
  17. Cardiff University
  18. Neurosearch AS
  19. University of Toronto
  20. Trinity Centre for Health Science
  21. Ârhus Universitetshospital
  22. Dalhousie University