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 & 30 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, Jouke Jan Hottenga, Rick Jansen, Hamdi Mbarek, Christel M. Middeldorp, Yuri Milaneschi, Michel G. Nivard, Danielle Posthuma, Johannes H. Smit, Gonneke Willemsen, Dorret I. Boomsma, Brenda W.J.H. Penninx

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
Early online date26 Apr 2018
DOIs
Publication statusPublished - May 2018

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Genome-Wide Association Study
Depression
Schizophrenia
Major Depressive Disorder
Suicide
Antidepressive Agents
Genes
Meta-Analysis
Morbidity
Phenotype
Costs and Cost Analysis
Mortality
Brain

Keywords

  • Journal Article

Cite this

Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., ... Penninx, B. W. J. H. (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 ; Hottenga, Jouke Jan ; Jansen, Rick ; Mbarek, Hamdi ; Middeldorp, Christel M. ; Milaneschi, Yuri ; Nivard, Michel G. ; Posthuma, Danielle ; Smit, Johannes H. ; Willemsen, Gonneke ; Boomsma, Dorret I. ; Penninx, Brenda W.J.H. / 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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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, Jansen, R, Mbarek, H, Middeldorp, CM, Milaneschi, Y, Nivard, MG, Posthuma, D, Smit, JH, Willemsen, G, Boomsma, DI & Penninx, BWJH 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; Hottenga, Jouke Jan; Jansen, Rick; Mbarek, Hamdi; Middeldorp, Christel M.; Milaneschi, Yuri; Nivard, Michel G.; Posthuma, Danielle; Smit, Johannes H.; Willemsen, Gonneke; Boomsma, Dorret I.; Penninx, Brenda W.J.H.

In: Nature Genetics, Vol. 50, No. 5, 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 - Hottenga, Jouke Jan

AU - Jansen, Rick

AU - Mbarek, Hamdi

AU - Middeldorp, Christel M.

AU - Milaneschi, Yuri

AU - Nivard, Michel G.

AU - Posthuma, Danielle

AU - Smit, Johannes H.

AU - Willemsen, Gonneke

AU - Boomsma, Dorret I.

AU - Penninx, Brenda W.J.H.

PY - 2018/5

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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.

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