Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

Details

Ressource 1Download: BIB_DE0B9B35F893.P001.pdf (765.86 [Ko])
State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_DE0B9B35F893
Type
Article: article from journal or magazin.
Collection
Publications
Title
Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.
Journal
Biological psychiatry
Author(s)
Power R.A., Tansey K.E., Buttenschøn H.N., Cohen-Woods S., Bigdeli T., Hall L.S., Kutalik Z., Lee S.H., Ripke S., Steinberg S., Teumer A., Viktorin A., Wray N.R., Arolt V., Baune B.T., Boomsma D.I., Børglum A.D., Byrne E.M., Castelao E., Craddock N., Craig I.W., Dannlowski U., Deary I.J., Degenhardt F., Forstner A.J., Gordon S.D., Grabe H.J., Grove J., Hamilton S.P., Hayward C., Heath A.C., Hocking L.J., Homuth G., Hottenga J.J., Kloiber S., Krogh J., Landén M., Lang M., Levinson D.F., Lichtenstein P., Lucae S., MacIntyre D.J., Madden P., Magnusson P.K., Martin N.G., McIntosh A.M., Middeldorp C.M., Milaneschi Y., Montgomery G.W., Mors O., Müller-Myhsok B., Nyholt D.R., Oskarsson H., Owen M.J., Padmanabhan S., Penninx B.W., Pergadia M.L., Porteous D.J., Potash J.B., Preisig M., Rivera M., Shi J., Shyn S.I., Sigurdsson E., Smit J.H., Smith B.H., Stefansson H., Stefansson K., Strohmaier J., Sullivan P.F., Thomson P., Thorgeirsson T.E., Van der Auwera S., Weissman M.M., Breen G., Lewis C.M.
Working group(s)
CONVERGE Consortium, CARDIoGRAM Consortium, GERAD1 Consortium
ISSN
1873-2402 (Electronic)
ISSN-L
0006-3223
Publication state
Published
Issued date
15/02/2017
Peer-reviewed
Oui
Volume
81
Number
4
Pages
325-335
Language
english
Notes
Open Access funded by Medical Research Council
Publication types: Journal Article
Publication Status: ppublish
Abstract
Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset.
Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer's disease, and coronary artery disease.
We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11-1.21, p = 5.2 × 10(-11)). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD.
We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder.

Pubmed
Web of science
Open Access
Yes
Create date
30/08/2016 14:17
Last modification date
20/08/2019 17:02
Usage data