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Direk, N.* ; Williams, S.* ; Smith, J.A.* ; Ripke, S.* ; Air, T.* ; Amare, A.T.* ; Amin, N.* ; Baune, B.T.* ; Bennett, D.A.* ; Blackwood, D.H.R.* ; Boomsma, D.* ; Breen, G.* ; Buttenschøn, H.N.* ; Byrne, E.M.* ; Børglum, A.D.* ; Castelao, E.* ; Cichon, S.* ; Clarke, T.K.* ; Cornelis, M.C.* ; Dannlowski, U.* ; de Jager, P.L.* ; Demirkan, A.* ; Domenici, E.* ; van Duijn, C.M.* ; Dunn, E.C.* ; Eriksson, J.G.* ; Esko, T.* ; Faul, J.D.* ; Ferrucci, L.* ; Fornage, M.* ; de Geus, E.* ; Gill, M.* ; Gordon, S.D.* ; Grabe, H.J.* ; van Grootheest, G.* ; Hamilton, S.P.* ; Hartman, C.A.* ; Heath, A.C.* ; Hek, K.* ; Hofman, A.* ; Homuth, G.* ; Horn, C.* ; Jan Hottenga, J.* ; Kardia, S.L.R.* ; Kloiber, S.* ; Koenen, K.* ; Kutalik, Z.* ; Ladwig, K.-H. ; Lahti, J.* ; Levinson, D.F.* ; Lewis, C.M.* ; Lewis, G.* ; Li, Q.S.* ; Llewellyn, D.J.* ; Lucae, S.* ; Lunetta, K.L.* ; MacIntyre, D.J.* ; Madden, P.* ; Martin, N.G.* ; McIntosh, A.M.* ; Metspalu, A.* ; Milaneschi, Y.* ; Montgomery, G.W.* ; Mors, O.* ; Mosley, T.H.* ; Murabito, J.M.* ; Müller-Myhsok, B.* ; Nöthen, M.M.*

An analysis of two genome-wide association meta-analyses identifies a new locus for broad depression phenotype.

Biol. Psychiatry 82, 322-329 (2017)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Background: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. Methods: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a . p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. Results: The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10-9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10-9). Conclusions: This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Charge Consortium ; Depressive Symptoms ; Fhit Gene ; Genome-wide Association Study ; Major Depressive Disorder ; Psychiatric Genomics Consortium; National Comorbidity Survey; Major Depression; Minor Depression; Subthreshold Depression; Symptoms; Risk; Disorder; Stress; Heritability; Population
ISSN (print) / ISBN 0006-3223
e-ISSN 1873-2402
Journal Biological Psychiatry
Quellenangaben Volume: 82, Issue: 5, Pages: 322-329 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)