Direk, N;
Williams, S;
Smith, JA;
Ripke, S;
Air, T;
Amare, AT;
Amin, N;
... Sullivan, PF; + view all
(2017)
An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype.
Biological Psychiatry
, 82
(5)
pp. 322-329.
10.1016/j.biopsych.2016.11.013.
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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.
| Type: | Article |
|---|---|
| Title: | An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.biopsych.2016.11.013 |
| Publisher version: | http://doi.org/10.1016/j.biopsych.2016.11.013 |
| Language: | English |
| Additional information: | © Society of Biological Psychiatry, 2016. This manuscript version is made available under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International license (CC BY-NC-ND 4.0). This license allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licenses are available at https://creativecommons.org/licenses/. Access may be initially restricted by the publisher. |
| Keywords: | CHARGE consortium, Depressive symptoms, FHIT gene, Genome-wide association study, Major depressive disorder, Psychiatric Genomics Consortium |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1536203 |
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