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

the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

doi:10.1038/s41588-018-0090-3

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

the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Department of Clinical Medicine

777 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
Journal	Nature Genetics
Volume	50
Issue number	5
Pages (from-to)	668-681
Number of pages	14
ISSN	1061-4036
DOIs	https://doi.org/10.1038/s41588-018-0090-3
Publication status	Published - 2018

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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.",

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 Valentina Escott-Price and Kiadeh, {Farnush Hassan Farhadi} and Finucane, {Hilary K.} and Forstner, {Andreas J.} and Hansen, {Christine S{\o}holm} and Hansen, {Thomas F.} and Jesper Krogh and Pedersen, {Carsten B{\o}cker} and Pedersen, {Marianne Gi{\o}rtz} and Merete Nordentoft and Thomas Werge and {the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium}",

year = "2018",

doi = "10.1038/s41588-018-0090-3",

language = "English",

volume = "50",

pages = "668--681",

journal = "Nature Genetics",

issn = "1061-4036",

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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 - Hansen, Christine Søholm

AU - Hansen, Thomas F.

AU - Krogh, Jesper

AU - Pedersen, Carsten Bøcker

AU - Pedersen, Marianne Giørtz

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

PY - 2018

Y1 - 2018

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

AN - SCOPUS:85046022254

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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