Dissecting the genetic heterogeneity of depression through age at onset.

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State: Public
Version: author
Serval ID
serval:BIB_D5D24EF40F51
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dissecting the genetic heterogeneity of depression through age at onset.
Journal
American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Author(s)
Power R.A., Keers R., Ng M.Y., Butler A.W., Uher R., Cohen-Woods S., Ising M., Craddock N., Owen M.J., Korszun A., Jones L., Jones I., Gill M., Rice J.P., Hauser J., Henigsberg N., Maier W., Zobel A., Mors O., Placentino A.S., Rietschel M., Souery D., Kozel D., Preisig M., Lucae S., Binder E.B., Aitchison K.J., Tozzi F., Muglia P., Breen G., Craig I.W., Farmer A.E., Müller-Myhsok B., McGuffin P., Lewis C.M.
ISSN
1552-485X (Electronic)
ISSN-L
1552-4841
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
159B
Number
7
Pages
859-868
Language
english
Notes
Publication types: Journal Article
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.
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Create date
24/09/2012 16:15
Last modification date
20/08/2019 16:55
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