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; Valentina Escott-Price; Farnush Hassan Farhadi Kiadeh; Hilary K Finucane; Andreas J Forstner; Josef Frank; Thomas F Hansen; Jesper Krogh; Wesley Thompson; Shantel Marie Weinsheimer; Merete Nordentoft; Thomas Werge; eQTLGen

doi: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, Valentina Escott-Price, Farnush Hassan Farhadi Kiadeh, Hilary K Finucane, Andreas J Forstner, Josef Frank, Thomas F Hansen, Jesper Krogh, Wesley Thompson, Shantel Marie Weinsheimer, Merete Nordentoft, Thomas Werge, eQTLGen

2199 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	50
Udgave nummer	5
Sider (fra-til)	668-681
Antal sider	14
ISSN	1061-4036
DOI	https://doi.org/10.1038/s41588-018-0090-3
Status	Udgivet - maj 2018

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10.1038/s41588-018-0090-3

Citationsformater

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., ... eQTLGen (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, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TMF, Bacanu, S-A, 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, T-K, 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, Hansen, TF, Krogh, J, Thompson, W, Weinsheimer, SM, Nordentoft, M , Werge, T & eQTLGen 2018, 'Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression', Nature Genetics, bind 50, nr. 5, s. 668-681. https://doi.org/10.1038/s41588-018-0090-3

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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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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 - Hansen, Thomas F

AU - Krogh, Jesper

AU - Thompson, Wesley

AU - Weinsheimer, Shantel Marie

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - eQTLGen

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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.

U2 - 10.1038/s41588-018-0090-3

DO - 10.1038/s41588-018-0090-3

M3 - Journal 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

Abstract

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