An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

Direk, N. and Williams, S. and Smith, J. A. and Ripke, S. and Air, T. and Amare, A. T. and Amin, N. and Baune, B. T. and Bennett, D. A. and Blackwood, D. H. and Boomsma, D. and Breen, G. and Buttenschon, H. N. and Byrne, E. M. and Borglum, A. D. and Castelao, E. and Cichon, S. and Clarke, T. K. and Cornelis, M. C. and Dannlowski, U. and De Jager, P. L. and Demirkan, A. and Domenici, E. and van Duijn, C. M. and Dunn, E. C. and Eriksson, J. G. and Esko, T. and Faul, J. D. and Ferrucci, L. and Fornage, M. and de Geus, E. and Gill, M. and Gordon, S. D. and Grabe, H. J. and van Grootheest, G. and Hamilton, S. P. and Hartman, C. A. and Heath, A. C. and Hek, K. and Hofman, A. and Homuth, G. and Horn, C. and Jan Hottenga, J. and Kardia, S. L. and Kloiber, S. and Koenen, K. and Kutalik, Z. and Ladwig, K. H. and Lahti, J. and Levinson, D. F. and Lewis, C. M. and Lewis, G. and Li, Q. S. and Llewellyn, D. J. and Lucae, S. and Lunetta, K. L. and MacIntyre, D. J. and Madden, P. and Martin, N. G. and McIntosh, A. M. and Metspalu, A. and Milaneschi, Y. and Montgomery, G. W. and Mors, O. and Mosley, T. H. and Jr., and Murabito, J. M. and Muller-Myhsok, B. and Nothen, M. M. and Nyholt, D. R. and O'Donovan, M. C. and Penninx, B. W. and Pergadia, M. L. and Perlis, R. and Potash, J. B. and Preisig, M. and Purcell, S. M. and Quiroz, J. A. and Raikkonen, K. and Rice, J. P. and Rietschel, M. and Rivera, M. and Schulze, T. G. and Shi, J. and Shyn, S. and Sinnamon, G. C. and Smit, J. H. and Smoller, J. W. and Snieder, H. and Tanaka, T. and Tansey, K. E. and Teumer, A. and Uher, R. and Umbricht, D. and Van der Auwera, S. and Ware, E. B. and Weir, D. R. and Weissman, M. M. and Willemsen, G. and Yang, J. and Zhao, W. and Tiemeier, H. and Sullivan, P. F.. (2016) An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype. Biological Psychiatry, 83 (5). pp. 322-329.

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Official URL: https://edoc.unibas.ch/61540/

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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 x 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 x 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.

Faculties and Departments:	03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Human Genetics (Cichon)
UniBasel Contributors:	Cichon, Sven
Item Type:	Article, refereed
Article Subtype:	Research Article
e-ISSN:	1873-2402
Note:	Publication type according to Uni Basel Research Database: Journal article
Related URLs:	Green Open Access
Identification Number:	doi: 10.1016/j.biopsych.2016.11.013 isi: 000406938900010 pmid: 28049566
Last Modified:	09 Apr 2019 16:09
Deposited On:	09 Apr 2019 16:09

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