Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression

作者：N. Wray, S. Ripke, M. Mattheisen, M. Trzaskowski, E. Byrne, A. Abdellaoui, Mark J. Adams, E. Agerbo, Tracy M. Air, Till F M Andlauer, S. Bacanu, Marie Bækvad-Hansen, A. Beekman, T. Bigdeli, E. Binder, D. Blackwood, J. Bryois, H. Buttenschøn, J. Bybjerg-Grauholm, Na Cai, E. Castelao, J. Christensen, Toni‐Kim Clarke, J. Coleman, L. Colodro-Conde, Baptiste Couvy-duchesne, N. Craddock, Gregory E. Crawford, Cheynna A. Crowley, Hassan S. Dashti, G. Davies, Ian J. Deary, F. Degenhardt, E. Derks, N. Direk, C. V. Dolan, Erin C. Dunn, Thalia Eley, N. Eriksson, V. Escott-Price, Farnush Farhadi Hassan Kiadeh, H. Finucane, A. Forstner, J. Frank, Héléna A. Gaspar, Michael Gill, P. Giusti-Rodríguez, F. Goes, S. Gordon, J. Grove, L. Hall, E. Hannon, C. Hansen, T. Hansen, S. Herms, I. Hickie, P. Hoffmann, G. Homuth, Carsten Horn, J. Hottenga, D. Hougaard, Ming Hu, C. Hyde, M. Ising, R. Jansen, Fulai Jin, E. Jorgenson, J. A. Knowles, I. S. Kohane, J. Kraft, Warren W. Kretzschmar, J. Krogh, Z. Kutalik, J. Lane, Yihan Li, Yun Li, P. Lind, Xiaoxiao Liu, Leina Lu, D. Macintyre, D. MacKinnon, Robert M. Maier, Wolfgang Maier, J. Marchini, H. Mbarek, Patrick McGrath, P. Mcguffin, S. Medland, Divya Mehta, C. Middeldorp, E. Mihailov, Y. Milaneschi, L. Milani, Jonathan Mill, Francis M. Mondimore, Grant W. Montgomery, S. Mostafavi, N. Mullins, Matthias Nauck, Bernard Ng, M. Nivard, D. Nyholt, P. O’Reilly, H. Oskarsson, M. Owen, J. Painter, C. B. Pedersen, M. Pedersen, Roseann E. Peterson, E. Pettersson, W. Peyrot, Giorgio Pistis, D. Posthuma, Shaun M Purcell, Jorge A. Quiroz, Per Qvist, J. P. Rice, B. Riley, M. Rivera, S. Mirza, Richa Saxena, Robert Schoevers, E. Schulte, Li Shen, Jianxin Shi, S. Shyn, E. Sigurdsson, Grant C. B. Sinnamon, Johannes H. Smit, Daniel J. Smith, H. Stefánsson, S. Steinberg, C. Stockmeier, Fabian Streit, J. Strohmaier, K. Tansey, H. Teismann, A. Teumer, W. Thompson, P. Thomson, T. Thorgeirsson, C. Tian, M. Traylor, J. Treutlein, V. Trubetskoy, A. Uitterlinden, Daniel Umbricht, S. Van der Auwera, A. V. van Hemert, A. Viktorin, P. M. Visscher, Yunpeng Wang, B. T. Webb, S.M. Weinsheimer, J. Wellmann, G. Willemsen, S. Witt, Yang Wu, H. Xi, Jian Yang, Futao Zhang, V. Arolt, B. T. Baune, K. Berger, D. Boomsma, S. Cichon, U. Dannlowski, E. D. de Geus, J. DePaulo, E. Domenici, K. Domschke, T. Esko, H. Grabe, S. Hamilton, C. Hayward, A. Heath, David A. Hinds, Kenneth S. Kendler, S. Kloiber, Glyn Lewis, Qingqin S. Li, S. Lucae, P. Madden, Patrik Magnusson, N. G. Martin, A. M. McIntosh, A. Metspalu, O. Mors, P. Mortensen, B. Müller-Myhsok, M. Nordentoft, M. Nöthen, M. O’Donovan, S. Paciga, Nancy L. Pedersen, B. Penninx, Roy H. Perlis, David J. Porteous, James B. Potash, M. Preisig, M. Rietschel, Catherine Schaefer, Thomas G Schulze, Jordan W. Smoller, K. Stefánsson, Henning Tiemeier, Rudolf Uher, H. Völzke, Myrna M Weissman, T. Werge, A. Winslow, Cathryn M. Lewis, Doug Levinson, G. Breen, A. Børglum, P. Sullivan · 发表于：Nature Genetics · 年份：2017 · DOI：10.1038/s41588-018-0090-3 · 被引用次数：2751 · 研究领域：Biology、Medicine

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype. A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent risk loci. Comparisons with other psychiatric disorders and candidate gene analyses provide new insights into major depressive disorder.