Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.
Wray Naomi R, Ripke Stephan, Mattheisen Manuel, Trzaskowski Maciej, Byrne Enda M, Abdellaoui Abdel, Adams Mark J, Agerbo Esben, Air Tracy M, Andlauer Till M F, Bacanu Silviu-Alin, Bækvad-Hansen Marie, Beekman Aartjan F T, Bigdeli Tim B, Binder Elisabeth B, Blackwood Douglas R H, Bryois Julien, Buttenschøn Henriette N, Bybjerg-Grauholm Jonas, Cai Na, Castelao Enrique, Christensen Jane Hvarregaard, Clarke Toni-Kim, Coleman Jonathan I R, Colodro-Conde Lucía, Couvy-Duchesne Baptiste, Craddock Nick, Crawford Gregory E, Crowley Cheynna A, Dashti Hassan S, Davies Gail, Deary Ian J, Degenhardt Franziska, Derks Eske M, Direk Nese, Dolan Conor V, Dunn Erin C, Eley Thalia C, Eriksson Nicholas, Escott-Price Valentina, Kiadeh Farnush Hassan Farhadi, Finucane Hilary K, Forstner Andreas J, Frank Josef, Gaspar Héléna A, Gill Michael, Giusti-Rodríguez Paola, Goes Fernando S, Gordon Scott D, Grove Jakob, Hall Lynsey S, Hannon Eilis, Hansen Christine Søholm, Hansen Thomas F, Herms Stefan, Hickie Ian B, Hoffmann Per, Homuth Georg, Horn Carsten, Hottenga Jouke-Jan, Hougaard David M, Hu Ming, Hyde Craig L, Ising Marcus, Jansen Rick, Jin Fulai, Jorgenson Eric, Knowles James A, Kohane Isaac S, Kraft Julia, Kretzschmar Warren W, Krogh Jesper, Kutalik Zoltán, Lane Jacqueline M, Li Yihan, Li Yun, Lind Penelope A, Liu Xiaoxiao, Lu Leina, MacIntyre Donald J, MacKinnon Dean F, Maier Robert M, Maier Wolfgang, Marchini Jonathan, Mbarek Hamdi, McGrath Patrick, McGuffin Peter, Medland Sarah E, Mehta Divya, Middeldorp Christel M, Mihailov Evelin, Milaneschi Yuri, Milani Lili, Mill Jonathan, Mondimore Francis M, Montgomery Grant W, Mostafavi Sara, Mullins Niamh, Nauck Matthias, Ng Bernard, Nivard Michel G, Nyholt Dale R, O'Reilly Paul F, Oskarsson Hogni, Owen Michael J, Painter Jodie N, Pedersen Carsten Bøcker, Pedersen Marianne Giørtz, Peterson Roseann E, Pettersson Erik, Peyrot Wouter J, Pistis Giorgio, Posthuma Danielle, Purcell Shaun M, Quiroz Jorge A, Qvist Per, Rice John P, Riley Brien P, Rivera Margarita, Saeed Mirza Saira, Saxena Richa, Schoevers Robert, Schulte Eva C, Shen Ling, Shi Jianxin, Shyn Stanley I, Sigurdsson Engilbert, Sinnamon Grant B C, Smit Johannes H, Smith Daniel J, Stefansson Hreinn, Steinberg Stacy, Stockmeier Craig A, Streit Fabian, Strohmaier Jana, Tansey Katherine E, Teismann Henning, Teumer Alexander, Thompson Wesley, Thomson Pippa A, Thorgeirsson Thorgeir E, Tian Chao, Traylor Matthew, Treutlein Jens, Trubetskoy Vassily, Uitterlinden André G, Umbricht Daniel, Van der Auwera Sandra, van Hemert Albert M, Viktorin Alexander, Visscher Peter M, Wang Yunpeng, Webb Bradley T, Weinsheimer Shantel Marie, Wellmann Jürgen, Willemsen Gonneke, Witt Stephanie H, Wu Yang, Xi Hualin S, Yang Jian, Zhang Futao, eQTLGen, 23andMe, Arolt Volker, Baune Bernhard T, Berger Klaus, Boomsma Dorret I, Cichon Sven, Dannlowski Udo, de Geus E C J, DePaulo J Raymond, Domenici Enrico, Domschke Katharina, Esko Tõnu, Grabe Hans J, Hamilton Steven P, Hayward Caroline, Heath Andrew C, Hinds David A, Kendler Kenneth S, Kloiber Stefan, Lewis Glyn, Li Qingqin S, Lucae Susanne, Madden Pamela F A, Magnusson Patrik K, Martin Nicholas G, McIntosh Andrew M, Metspalu Andres, Mors Ole, Mortensen Preben Bo, Müller-Myhsok Bertram, Nordentoft Merete, Nöthen Markus M, O'Donovan Michael C, Paciga Sara A, Pedersen Nancy L, Penninx Brenda W J H, Perlis Roy H, Porteous David J, Potash James B, Preisig Martin, Rietschel Marcella, Schaefer Catherine, Schulze Thomas G, Smoller Jordan W, Stefansson Kari, Tiemeier Henning, Uher Rudolf, Völzke Henry, Weissman Myrna M, Werge Thomas, Winslow Ashley R, Lewis Cathryn M, Levinson Douglas F, Breen Gerome, Børglum Anders D, Sullivan Patrick F, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
СтатьяМетаанализПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод в очереди
Аннотация
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.
Для цитирования: Wray Naomi R, Ripke Stephan, Mattheisen Manuel, Trzaskowski Maciej, Byrne Enda M, Abdellaoui Abdel, Adams Mark J, Agerbo Esben, Air Tracy M, Andlauer Till M F, Bacanu Silviu-Alin, Bækvad-Hansen Marie, Beekman Aartjan F T, Bigdeli Tim B, Binder Elisabeth B, Blackwood Douglas R H, Bryois Julien, Buttenschøn Henriette N, Bybjerg-Grauholm Jonas, Cai Na, Castelao Enrique, Christensen Jane Hvarregaard, Clarke Toni-Kim, Coleman Jonathan I R, Colodro-Conde Lucía, Couvy-Duchesne Baptiste, Craddock Nick, Crawford Gregory E, Crowley Cheynna A, Dashti Hassan S, Davies Gail, Deary Ian J, Degenhardt Franziska, Derks Eske M, Direk Nese, Dolan Conor V, Dunn Erin C, Eley Thalia C, Eriksson Nicholas, Escott-Price Valentina, Kiadeh Farnush Hassan Farhadi, Finucane Hilary K, Forstner Andreas J, Frank Josef, Gaspar Héléna A, Gill Michael, Giusti-Rodríguez Paola, Goes Fernando S, Gordon Scott D, Grove Jakob, Hall Lynsey S, Hannon Eilis, Hansen Christine Søholm, Hansen Thomas F, Herms Stefan, Hickie Ian B, Hoffmann Per, Homuth Georg, Horn Carsten, Hottenga Jouke-Jan, Hougaard David M, Hu Ming, Hyde Craig L, Ising Marcus, Jansen Rick, Jin Fulai, Jorgenson Eric, Knowles James A, Kohane Isaac S, Kraft Julia, Kretzschmar Warren W, Krogh Jesper, Kutalik Zoltán, Lane Jacqueline M, Li Yihan, Li Yun, Lind Penelope A, Liu Xiaoxiao, Lu Leina, MacIntyre Donald J, MacKinnon Dean F, Maier Robert M, Maier Wolfgang, Marchini Jonathan, Mbarek Hamdi, McGrath Patrick, McGuffin Peter, Medland Sarah E, Mehta Divya, Middeldorp Christel M, Mihailov Evelin, Milaneschi Yuri, Milani Lili, Mill Jonathan, Mondimore Francis M, Montgomery Grant W, Mostafavi Sara, Mullins Niamh, Nauck Matthias, Ng Bernard, Nivard Michel G, Nyholt Dale R, O'Reilly Paul F, Oskarsson Hogni, Owen Michael J, Painter Jodie N, Pedersen Carsten Bøcker, Pedersen Marianne Giørtz, Peterson Roseann E, Pettersson Erik, Peyrot Wouter J, Pistis Giorgio, Posthuma Danielle, Purcell Shaun M, Quiroz Jorge A, Qvist Per, Rice John P, Riley Brien P, Rivera Margarita, Saeed Mirza Saira, Saxena Richa, Schoevers Robert, Schulte Eva C, Shen Ling, Shi Jianxin, Shyn Stanley I, Sigurdsson Engilbert, Sinnamon Grant B C, Smit Johannes H, Smith Daniel J, Stefansson Hreinn, Steinberg Stacy, Stockmeier Craig A, Streit Fabian, Strohmaier Jana, Tansey Katherine E, Teismann Henning, Teumer Alexander, Thompson Wesley, Thomson Pippa A, Thorgeirsson Thorgeir E, Tian Chao, Traylor Matthew, Treutlein Jens, Trubetskoy Vassily, Uitterlinden André G, Umbricht Daniel, Van der Auwera Sandra, van Hemert Albert M, Viktorin Alexander, Visscher Peter M, Wang Yunpeng, Webb Bradley T, Weinsheimer Shantel Marie, Wellmann Jürgen, Willemsen Gonneke, Witt Stephanie H, Wu Yang, Xi Hualin S, Yang Jian, Zhang Futao, eQTLGen, 23andMe, Arolt Volker, Baune Bernhard T, Berger Klaus, Boomsma Dorret I, Cichon Sven, Dannlowski Udo, de Geus E C J, DePaulo J Raymond, Domenici Enrico, Domschke Katharina, Esko Tõnu, Grabe Hans J, Hamilton Steven P, Hayward Caroline, Heath Andrew C, Hinds David A, Kendler Kenneth S, Kloiber Stefan, Lewis Glyn, Li Qingqin S, Lucae Susanne, Madden Pamela F A, Magnusson Patrik K, Martin Nicholas G, McIntosh Andrew M, Metspalu Andres, Mors Ole, Mortensen Preben Bo, Müller-Myhsok Bertram, Nordentoft Merete, Nöthen Markus M, O'Donovan Michael C, Paciga Sara A, Pedersen Nancy L, Penninx Brenda W J H, Perlis Roy H, Porteous David J, Potash James B, Preisig Martin, Rietschel Marcella, Schaefer Catherine, Schulze Thomas G, Smoller Jordan W, Stefansson Kari, Tiemeier Henning, Uher Rudolf, Völzke Henry, Weissman Myrna M, Werge Thomas, Winslow Ashley R, Lewis Cathryn M, Levinson Douglas F, Breen Gerome, Børglum Anders D, Sullivan Patrick F, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.. Nature genetics. 2018. DOI: 10.1038/s41588-018-0090-3.
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