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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 10
Ng, MY2
Butler, AW2 6
Uher, R2 22
Cohen-Woods, S2
Ising, M11
Craddock, N13
Owen, MJ13
Korszun, A10
Jones, L14
Jones, I13
Gill, M19
Rice, JP4
Hauser, J16
Henigsberg, N7
Maier, W3
Zobel, A3
Mors, O20
Placentino, AS15
Rietschel, M12
Souery, D9
Kozel, D1
Preisig, M21
Lucae, S11
Binder, EB11
Aitchison, KJ2
Tozzi, F8
Muglia, P8 17 18
Breen, G2 5
Craig, IW2
Farmer, AE2
Müller-Myhsok, B11
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
2013 Impact Factor: 3.271
 
DOIhttp://dx.doi.org/10.1002/ajmg.b.32093
 
ISI Accession Number IDWOS:000308879900013
 
DC FieldValue
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.isiWOS:000308879900013
 
dc.identifier.issn1552-4841
2013 Impact Factor: 3.271
 
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
 
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<description.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&lt;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. &#169; 2012 Wiley Periodicals, Inc.</description.abstract>
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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