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

Naomi R. Wray, Stephan Ripke, Manuel Mattheisen, MacIej Trzaskowski, Enda M. Byrne, Abdel Abdellaoui, Mark J. Adams, Esben Agerbo, Tracy M. Air, Till M.F. Andlauer, Silviu Alin Bacanu, Marie Bækvad-Hansen, Aartjan F.T. Beekman, Tim B. Bigdeli, Elisabeth B. Binder, Douglas R.H. Blackwood, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai & 196 others Enrique Castelao, Jane Hvarregaard Christensen, Toni Kim Clarke, Jonathan I.R. Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Cheynna A. Crowley, Hassan S. Dashti, Gail Davies, Ian J. Deary, Franziska Degenhardt, Eske M. Derks, Nese DIrek, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Nicholas Eriksson, Valentina Escott-Price, Farnush Hassan Farhadi Kiadeh, Hilary K. Finucane, Andreas J. Forstner, Josef Frank, Héléna A. Gaspar, Michael Gill, Paola Giusti-Rodríguez, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Eilis Hannon, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke Jan Hottenga, David M. Hougaard, Ming Hu, Craig L. Hyde, Marcus Ising, Rick Jansen, Fulai Jin, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Jesper Krogh, Zoltán Kutalik, Jacqueline M. Lane, Yihan Li, Yun Li, Penelope A. Lind, Xiaoxiao Liu, Leina Lu, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E. Medland, DIvya Mehta, Christel M. Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Jonathan Mill, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O'Reilly, Hogni Oskarsson, Michael J. Owen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Erik Pettersson, Wouter J. Peyrot, Giorgio Pistis, Danielle Posthuma, Shaun M. Purcell, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Margarita Rivera, Saira Saeed Mirza, Richa Saxena, Robert Schoevers, Eva C. Schulte, Ling Shen, Jianxin Shi, Stanley I. Shyn, Engilbert Sigurdsson, Grant B.C. Sinnamon, Johannes H. Smit, Daniel J. Smith, Hreinn Stefansson, Stacy Steinberg, Craig A. Stockmeier, Fabian Streit, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Chao Tian, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Sandra Van Der Auwera, Albert M. Van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H. Witt, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Bernhard T. Baune, Klaus Berger, Dorret I. Boomsma, Sven Cichon, Udo Dannlowski, E. C.J. De Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Tõnu Esko, Hans J. Grabe, Steven P. Hamilton, Caroline Hayward, Andrew C. Heath, David A. Hinds, Kenneth S. Kendler, Stefan Kloiber, Glyn Lewis, Qingqin S. Li, Susanne Lucae, Pamela F.A. Madden, Patrik K. Magnusson, Nicholas G. Martin, Andrew M. McIntosh, Andres Metspalu, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M. Nöthen, Michael C. O'Donovan, Sara A. Paciga, Nancy L. Pedersen, Brenda W.J.H. Penninx, Roy H. Perlis, David J. Porteous, James B. Potash, Martin Preisig, Marcella Rietschel, Catherine Schaefer, Thomas G. Schulze, Jordan W. Smoller, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Henry Völzke, Myrna M. Weissman, Thomas Werge, Ashley R. Winslow, Cathryn M. Lewis, Douglas F. Levinson, Gerome Breen, Anders D. Børglum, Patrick F. Sullivan

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)668-681
Number of pages14
JournalNature Genetics
Volume50
Issue number5
DOIs
Publication statusPublished - 1 May 2018

Cite this

Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., ... Sullivan, P. F. (2018). Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nature Genetics, 50(5), 668-681. https://doi.org/10.1038/s41588-018-0090-3
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 ; 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. / Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. In: Nature Genetics. 2018 ; Vol. 50, No. 5. pp. 668-681.
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title = "Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression",
abstract = "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.",
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journal = "Nature Genetics",
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Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TMF, Bacanu, SA, Bækvad-Hansen, M, Beekman, AFT, Bigdeli, TB, Binder, EB, Blackwood, DRH, Bryois, J, Buttenschøn, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, TK, Coleman, JIR, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Crowley, CA, Dashti, HS, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, DIrek, N, Dolan, CV, Dunn, EC, Eley, TC, Eriksson, N, Escott-Price, V, Kiadeh, FHF, Finucane, HK, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Giusti-Rodríguez, P, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hannon, E, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, JJ, Hougaard, DM, Hu, M, Hyde, CL, Ising, M, Jansen, R, Jin, F, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Lane, JM, Li, Y, Li, Y, Lind, PA, Liu, X, Lu, L, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, DI, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mill, J, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Purcell, SM, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Saeed Mirza, S, Saxena, R, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, SI, Sigurdsson, E, Sinnamon, GBC, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Stockmeier, CA, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Tian, C, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van Der Auwera, S, Van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, DI, Cichon, S, Dannlowski, U, De Geus, ECJ, Depaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Hinds, DA, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PFA, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Müller-Myhsok, B, Nordentoft, M, Nöthen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Völzke, H, Weissman, MM, Werge, T, Winslow, AR, Lewis, CM, Levinson, DF, Breen, G, Børglum, AD & Sullivan, PF 2018, 'Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression' Nature Genetics, vol. 50, no. 5, pp. 668-681. https://doi.org/10.1038/s41588-018-0090-3

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; 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.

In: Nature Genetics, Vol. 50, No. 5, 01.05.2018, p. 668-681.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression

AU - Wray, Naomi R.

AU - Ripke, Stephan

AU - Mattheisen, Manuel

AU - Trzaskowski, MacIej

AU - Byrne, Enda M.

AU - Abdellaoui, Abdel

AU - Adams, Mark J.

AU - Agerbo, Esben

AU - Air, Tracy M.

AU - Andlauer, Till M.F.

AU - Bacanu, Silviu Alin

AU - Bækvad-Hansen, Marie

AU - Beekman, Aartjan F.T.

AU - Bigdeli, Tim B.

AU - Binder, Elisabeth B.

AU - Blackwood, Douglas R.H.

AU - Bryois, Julien

AU - Buttenschøn, Henriette N.

AU - Bybjerg-Grauholm, Jonas

AU - Cai, Na

AU - Castelao, Enrique

AU - Christensen, Jane Hvarregaard

AU - Clarke, Toni Kim

AU - Coleman, Jonathan I.R.

AU - Colodro-Conde, Lucía

AU - Couvy-Duchesne, Baptiste

AU - Craddock, Nick

AU - Crawford, Gregory E.

AU - Crowley, Cheynna A.

AU - Dashti, Hassan S.

AU - Davies, Gail

AU - Deary, Ian J.

AU - Degenhardt, Franziska

AU - Derks, Eske M.

AU - DIrek, Nese

AU - Dolan, Conor V.

AU - Dunn, Erin C.

AU - Eley, Thalia C.

AU - Eriksson, Nicholas

AU - Escott-Price, Valentina

AU - Kiadeh, Farnush Hassan Farhadi

AU - Finucane, Hilary K.

AU - Forstner, Andreas J.

AU - Frank, Josef

AU - Gaspar, Héléna A.

AU - Gill, Michael

AU - Giusti-Rodríguez, Paola

AU - Goes, Fernando S.

AU - Gordon, Scott D.

AU - Grove, Jakob

AU - Hall, Lynsey S.

AU - Hannon, Eilis

AU - Hansen, Christine Søholm

AU - Hansen, Thomas F.

AU - Herms, Stefan

AU - Hickie, Ian B.

AU - Hoffmann, Per

AU - Homuth, Georg

AU - Horn, Carsten

AU - Hottenga, Jouke Jan

AU - Hougaard, David M.

AU - Hu, Ming

AU - Hyde, Craig L.

AU - Ising, Marcus

AU - Jansen, Rick

AU - Jin, Fulai

AU - Jorgenson, Eric

AU - Knowles, James A.

AU - Kohane, Isaac S.

AU - Kraft, Julia

AU - Kretzschmar, Warren W.

AU - Krogh, Jesper

AU - Kutalik, Zoltán

AU - Lane, Jacqueline M.

AU - Li, Yihan

AU - Li, Yun

AU - Lind, Penelope A.

AU - Liu, Xiaoxiao

AU - Lu, Leina

AU - MacIntyre, Donald J.

AU - MacKinnon, Dean F.

AU - Maier, Robert M.

AU - Maier, Wolfgang

AU - Marchini, Jonathan

AU - Mbarek, Hamdi

AU - McGrath, Patrick

AU - McGuffin, Peter

AU - Medland, Sarah E.

AU - Mehta, DIvya

AU - Middeldorp, Christel M.

AU - Mihailov, Evelin

AU - Milaneschi, Yuri

AU - Milani, Lili

AU - Mill, Jonathan

AU - Mondimore, Francis M.

AU - Montgomery, Grant W.

AU - Mostafavi, Sara

AU - Mullins, Niamh

AU - Nauck, Matthias

AU - Ng, Bernard

AU - Nivard, Michel G.

AU - Nyholt, Dale R.

AU - O'Reilly, Paul F.

AU - Oskarsson, Hogni

AU - Owen, Michael J.

AU - Painter, Jodie N.

AU - Pedersen, Carsten Bøcker

AU - Pedersen, Marianne Giørtz

AU - Peterson, Roseann E.

AU - Pettersson, Erik

AU - Peyrot, Wouter J.

AU - Pistis, Giorgio

AU - Posthuma, Danielle

AU - Purcell, Shaun M.

AU - Quiroz, Jorge A.

AU - Qvist, Per

AU - Rice, John P.

AU - Riley, Brien P.

AU - Rivera, Margarita

AU - Saeed Mirza, Saira

AU - Saxena, Richa

AU - Schoevers, Robert

AU - Schulte, Eva C.

AU - Shen, Ling

AU - Shi, Jianxin

AU - Shyn, Stanley I.

AU - Sigurdsson, Engilbert

AU - Sinnamon, Grant B.C.

AU - Smit, Johannes H.

AU - Smith, Daniel J.

AU - Stefansson, Hreinn

AU - Steinberg, Stacy

AU - Stockmeier, Craig A.

AU - Streit, Fabian

AU - Strohmaier, Jana

AU - Tansey, Katherine E.

AU - Teismann, Henning

AU - Teumer, Alexander

AU - Thompson, Wesley

AU - Thomson, Pippa A.

AU - Thorgeirsson, Thorgeir E.

AU - Tian, Chao

AU - Traylor, Matthew

AU - Treutlein, Jens

AU - Trubetskoy, Vassily

AU - Uitterlinden, André G.

AU - Umbricht, Daniel

AU - Van Der Auwera, Sandra

AU - Van Hemert, Albert M.

AU - Viktorin, Alexander

AU - Visscher, Peter M.

AU - Wang, Yunpeng

AU - Webb, Bradley T.

AU - Weinsheimer, Shantel Marie

AU - Wellmann, Jürgen

AU - Willemsen, Gonneke

AU - Witt, Stephanie H.

AU - Wu, Yang

AU - Xi, Hualin S.

AU - Yang, Jian

AU - Zhang, Futao

AU - Arolt, Volker

AU - Baune, Bernhard T.

AU - Berger, Klaus

AU - Boomsma, Dorret I.

AU - Cichon, Sven

AU - Dannlowski, Udo

AU - De Geus, E. C.J.

AU - Depaulo, J. Raymond

AU - Domenici, Enrico

AU - Domschke, Katharina

AU - Esko, Tõnu

AU - Grabe, Hans J.

AU - Hamilton, Steven P.

AU - Hayward, Caroline

AU - Heath, Andrew C.

AU - Hinds, David A.

AU - Kendler, Kenneth S.

AU - Kloiber, Stefan

AU - Lewis, Glyn

AU - Li, Qingqin S.

AU - Lucae, Susanne

AU - Madden, Pamela F.A.

AU - Magnusson, Patrik K.

AU - Martin, Nicholas G.

AU - McIntosh, Andrew M.

AU - Metspalu, Andres

AU - Mors, Ole

AU - Mortensen, Preben Bo

AU - Müller-Myhsok, Bertram

AU - Nordentoft, Merete

AU - Nöthen, Markus M.

AU - O'Donovan, Michael C.

AU - Paciga, Sara A.

AU - Pedersen, Nancy L.

AU - Penninx, Brenda W.J.H.

AU - Perlis, Roy H.

AU - Porteous, David J.

AU - Potash, James B.

AU - Preisig, Martin

AU - Rietschel, Marcella

AU - Schaefer, Catherine

AU - Schulze, Thomas G.

AU - Smoller, Jordan W.

AU - Stefansson, Kari

AU - Tiemeier, Henning

AU - Uher, Rudolf

AU - Völzke, Henry

AU - Weissman, Myrna M.

AU - Werge, Thomas

AU - Winslow, Ashley R.

AU - Lewis, Cathryn M.

AU - Levinson, Douglas F.

AU - Breen, Gerome

AU - Børglum, Anders D.

AU - Sullivan, Patrick F.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85046022254&partnerID=8YFLogxK

U2 - 10.1038/s41588-018-0090-3

DO - 10.1038/s41588-018-0090-3

M3 - Article

VL - 50

SP - 668

EP - 681

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 5

ER -