Genome-wide association study of major depressive disorder: New results, meta-analysis, and lessons learned

Wray, N. R., Pergadia, M. L., Blackwood, D. H. R., Penninx, B. W. J. H., Gordon, S. D., Nyholt, D. R., Ripke, S., MacIntyre, D. J., McGhee, K. A., MacLean, A. W., Smit, J. H., Hottenga, J. J., Willemsen, G., Middeldorp, C. M., De Geus, E. J. C., Lewis, C. M., McGuffin, P., Hickie, I. B., Van Den Oord, E. J. C. G., Liu, J. Z., MacGregor, S., McEvoy, B. P., Byrne, E. M., Medland, S. E., Statham, D. J., Henders, A. K., Heath, A. C., Montgomery, G. W., Martin, N. G., Boomsma, D. I., Madden, P. A. F. and Sullivan, P. F. (2012) Genome-wide association study of major depressive disorder: New results, meta-analysis, and lessons learned. Molecular Psychiatry, 17 1: 36-48. doi:10.1038/mp.2010.109

Author Wray, N. R.
Pergadia, M. L.
Blackwood, D. H. R.
Penninx, B. W. J. H.
Gordon, S. D.
Nyholt, D. R.
Ripke, S.
MacIntyre, D. J.
McGhee, K. A.
MacLean, A. W.
Smit, J. H.
Hottenga, J. J.
Willemsen, G.
Middeldorp, C. M.
De Geus, E. J. C.
Lewis, C. M.
McGuffin, P.
Hickie, I. B.
Van Den Oord, E. J. C. G.
Liu, J. Z.
MacGregor, S.
McEvoy, B. P.
Byrne, E. M.
Medland, S. E.
Statham, D. J.
Henders, A. K.
Heath, A. C.
Montgomery, G. W.
Martin, N. G.
Boomsma, D. I.
Madden, P. A. F.
Sullivan, P. F.
Title Genome-wide association study of major depressive disorder: New results, meta-analysis, and lessons learned
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1359-4184
Publication date 2012-01-01
Year available 2012
Sub-type Article (original research)
DOI 10.1038/mp.2010.109
Open Access Status Not yet assessed
Volume 17
Issue 1
Start page 36
End page 48
Total pages 464
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1312 Molecular Biology
2738 Psychiatry and Mental health
2804 Cellular and Molecular Neuroscience
Abstract Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000 sample (2431 cases, 3673 screened controls and 1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000 study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P0.020, odds ratio1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P0.51). We estimate that sample sizes 1.8-to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.
Keyword Depression
Genome wide association study
Major Depressive Disorder
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 241944
RO1 MH059160
NWO-SPI 56-464-1419
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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