Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/116527
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Type: Journal article
Title: An analysis of two genome-wide association meta-analyses identifies a new locus for broad depression phenotype
Author: Direk, N.
Williams, S.
Smith, J.
Ripke, S.
Air, T.
Amare, A.
Amin, N.
Baune, B.
Bennett, D.
Blackwood, D.
Boomsma, D.
Breen, G.
Buttenschøn, H.
Byrne, E.
Børglum, A.
Castelao, E.
Cichon, S.
Clarke, T.
Cornelis, M.
Dannlowski, U.
et al.
Citation: Biological Psychiatry, 2017; 82(5):322-329
Publisher: Society of Biological Psychiatry
Issue Date: 2017
ISSN: 0006-3223
1873-2402
Statement of
Responsibility: 
Nese Direk, Stephanie Williams, Jennifer A. Smith ... Tracy M. Air … Azmeraw T. Amare … Bernhard T. Baune ... et al.
Abstract: 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.
Keywords: CHARGE consortium; Depressive symptoms; FHIT gene; Genome-wide association study; Major depressive disorder; Psychiatric Genomics Consortium
Rights: © 2016 Society of Biological Psychiatry
RMID: 0030060837
DOI: 10.1016/j.biopsych.2016.11.013
Appears in Collections:Psychology publications

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