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An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
4377197
Author(s)
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.; Boomsma, D.; Breen, G.; Buttenschon, H. N.; Byrne, E. M.; Borglum, 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.; 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.; Jr.,; Murabito, J. M.; Muller-Myhsok, B.; Nothen, M. M.; Nyholt, D. R.; O'Donovan, M. C.; Penninx, B. W.; Pergadia, M. L.; Perlis, R.; Potash, J. B.; Preisig, M.; Purcell, S. M.; Quiroz, J. A.; Raikkonen, K.; Rice, J. P.; Rietschel, M.; Rivera, M.; Schulze, T. G.; Shi, J.; Shyn, S.; Sinnamon, G. C.; Smit, J. H.; Smoller, J. W.; Snieder, H.; Tanaka, T.; Tansey, K. E.; Teumer, A.; Uher, R.; Umbricht, D.; Van der Auwera, S.; Ware, E. B.; Weir, D. R.; Weissman, M. M.; Willemsen, G.; Yang, J.; Zhao, W.; Tiemeier, H.; Sullivan, P. F.
An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype
Journal
Biological Psychiatry
Volume
83
Number
5
Pages / Article-Number
322-329
Keywords
CHARGE consortium; Depressive symptoms; FHIT gene; Genome-wide association study; Major depressive disorder; Psychiatric Genomics Consortium
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.
