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; 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; Jouke Jan Hottenga; Hamdi Mbarek; Christel M. Middeldorp; Yuri Milaneschi; M. G. Nivard; Danielle Posthuma; Johannes H. Smit; G. Willemsen; Dorret I. Boomsma; Brenda W.J.H. Penninx; Valentina Escott-Price; Farnush Hassan Farhadi Kiadeh; Hilary K. Finucane; Andreas J. Forstner; Josef Frank; H. léna A. Gaspar; Michael Gill; Paola Giusti-Rodríguez; Fernando S. Goes; Scott D. Gordon; Jakob Grove; Lynsey S. Hall; Eilis Hannon; Christine S. holm Hansen; Thomas F. Hansen; Stefan Herms; Ian B. Hickie; Per Hoffmann; Georg Homuth; Carsten Horn; 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; Patrick McGrath; Peter McGuffin; Sarah E. Medland; D. Ivya Mehta; Evelin Mihailov; Lili Milani; Jonathan Mill; Francis M. Mondimore; Grant W. Montgomery; Sara Mostafavi; Niamh Mullins; Matthias Nauck; Bernard Ng; Dale R. Nyholt; Paul F. O'Reilly; Hogni Oskarsson; Michael J. Owen; Jodie N. Painter; Carsten B. cker Pedersen; Marianne Giørtz Pedersen; Roseann E. Peterson; Erik Pettersson; Wouter J. Peyrot; Giorgio Pistis; 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; 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; J. rgen Wellmann; Stephanie H. Witt; Yang Wu; Hualin S. Xi; Jian Yang; Futao Zhang; Volker Arolt; Bernhard T. Baune; Klaus Berger; Sven Cichon; Udo Dannlowski; E. C. J. de Geus; J. Raymond Depaulo; Enrico Domenici; Katharina Domschke; T. nu 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; 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

doi: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

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 CaiEnrique 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, Jouke Jan Hottenga, Hamdi Mbarek, Christel M. Middeldorp, Yuri Milaneschi, M. G. Nivard, Danielle Posthuma, Johannes H. Smit, G. Willemsen, Dorret I. Boomsma, Brenda W.J.H. Penninx, Valentina Escott-Price, Farnush Hassan Farhadi Kiadeh, Hilary K. Finucane, Andreas J. Forstner, Josef Frank, H. léna A. Gaspar, Michael Gill, Paola Giusti-Rodríguez, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Eilis Hannon, Christine S. holm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, 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, Patrick McGrath, Peter McGuffin, Sarah E. Medland, D. Ivya Mehta, Evelin Mihailov, Lili Milani, Jonathan Mill, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Dale R. Nyholt, Paul F. O'Reilly, Hogni Oskarsson, Michael J. Owen, Jodie N. Painter, Carsten B. cker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Erik Pettersson, Wouter J. Peyrot, Giorgio Pistis, 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, 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, J. rgen Wellmann, Stephanie H. Witt, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Bernhard T. Baune, Klaus Berger, Sven Cichon, Udo Dannlowski, E. C. J. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, T. nu 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, 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 journal › Article › Academic › peer-review

1455 Citations (Scopus)

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 language	English
Pages (from-to)	668-681
Number of pages	14
Journal	Nature Genetics
Volume	50
Issue number	5
Early online date	26 Apr 2018
DOIs	https://doi.org/10.1038/s41588-018-0090-3
Publication status	Published - May 2018

Keywords

Journal Article

Access to Document

https://doi.org/10.1038/s41588-018-0090-3

https://research.vu.nl/ws/files/83594942/Genome_wide_association_analyses_identify_44_risk_variants_and_refine_the_genetic_architecture_of_major_depression.pdfLicence: Article 25fa Dutch Copyright Act

Cite this

Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., Adams, M. J., Agerbo, E., Air, T. M., Andlauer, T. M. F., Bacanu, S. A., Bækvad-Hansen, M., Beekman, A. F. T., Bigdeli, T. B., Binder, E. B., Blackwood, D. R. H., Bryois, J., Buttenschøn, H. N., Bybjerg-Grauholm, J., ... 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

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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.",

keywords = "Journal Article",

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

year = "2018",

month = may,

doi = "https://doi.org/10.1038/s41588-018-0090-3",

language = "English",

volume = "50",

pages = "668--681",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "5",

}

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, Hottenga, JJ, Mbarek, H, Middeldorp, CM, Milaneschi, Y, Nivard, MG, Posthuma, D, Smit, JH, Willemsen, G, Boomsma, DI, Penninx, BWJH, Escott-Price, V, Kiadeh, FHF, Finucane, HK, Forstner, AJ, Frank, J, Gaspar, HLA, Gill, M, Giusti-Rodríguez, P, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hannon, E, Hansen, CSH, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, 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, McGrath, P, McGuffin, P, Medland, SE, Mehta, DI, Mihailov, E, Milani, L, Mill, J, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CBC, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, 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, 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, JR, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Cichon, S, Dannlowski, U, de Geus, ECJ, Depaulo, JR, Domenici, E, Domschke, K, Esko, TN, 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, 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

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 - Hottenga, Jouke Jan

AU - Mbarek, Hamdi

AU - Middeldorp, Christel M.

AU - Milaneschi, Yuri

AU - Nivard, M. G.

AU - Posthuma, Danielle

AU - Smit, Johannes H.

AU - Willemsen, G.

AU - Boomsma, Dorret I.

AU - Penninx, Brenda W.J.H.

AU - Escott-Price, Valentina

AU - Kiadeh, Farnush Hassan Farhadi

AU - Finucane, Hilary K.

AU - Forstner, Andreas J.

AU - Frank, Josef

AU - Gaspar, H. léna 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 S. holm

AU - Hansen, Thomas F.

AU - Herms, Stefan

AU - Hickie, Ian B.

AU - Hoffmann, Per

AU - Homuth, Georg

AU - Horn, Carsten

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 - McGrath, Patrick

AU - McGuffin, Peter

AU - Medland, Sarah E.

AU - Mehta, D. Ivya

AU - Mihailov, Evelin

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 - Nyholt, Dale R.

AU - O'Reilly, Paul F.

AU - Oskarsson, Hogni

AU - Owen, Michael J.

AU - Painter, Jodie N.

AU - Pedersen, Carsten B. cker

AU - Pedersen, Marianne Giørtz

AU - Peterson, Roseann E.

AU - Pettersson, Erik

AU - Peyrot, Wouter J.

AU - Pistis, Giorgio

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 - 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, J. rgen

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 - Cichon, Sven

AU - Dannlowski, Udo

AU - de Geus, E. C. J.

AU - Depaulo, J. Raymond

AU - Domenici, Enrico

AU - Domschke, Katharina

AU - Esko, T. nu

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 - 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

Y1 - 2018/5

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.

KW - Journal Article

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

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

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85046022254&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/29700475

U2 - https://doi.org/10.1038/s41588-018-0090-3

DO - https://doi.org/10.1038/s41588-018-0090-3

M3 - Article

C2 - 29700475

SN - 1061-4036

VL - 50

SP - 668

EP - 681

JO - Nature genetics

JF - Nature genetics

IS - 5

ER -

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

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