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; Jakob Grove; Christine Søholm Hansen; Thomas F Hansen; Carsten Bøcker Pedersen; Marianne Giørtz Pedersen; Per Qvist; Jian Yang; Ole Mors; Preben Bo Mortensen; Merete Nordentoft; Thomas Werge; Anders D Børglum; 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

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, Jakob Grove, Christine Søholm Hansen, Thomas F Hansen, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Per Qvist, Jian Yang, Ole Mors, Preben Bo Mortensen, Merete Nordentoft, Thomas Werge, Anders D Børglum, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

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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.

Original language	English
Journal	Nature Genetics
Volume	50
Issue	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

Keywords

Case-Control Studies
Depressive Disorder, Major/genetics
Female
Genetic Predisposition to Disease
Genome-Wide Association Study/methods
Humans
Male
Multifactorial Inheritance
Phenotype
Polymorphism, Single Nucleotide
Risk Factors
Schizophrenia/genetics

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10.1038/s41588-018-0090-3

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934326/pdf/nihms943355.pdf

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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., ... Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (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.",

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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 Silviu-Alin Bacanu 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 Toni-Kim Clarke 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 Jakob Grove and Hansen, {Christine S{\o}holm} and Hansen, {Thomas F} and Pedersen, {Carsten B{\o}cker} and Pedersen, {Marianne Gi{\o}rtz} and Per Qvist and Jian Yang and Ole Mors and Mortensen, {Preben Bo} and Merete Nordentoft and Thomas Werge and B{\o}rglum, {Anders D} and {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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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, Grove, J, Hansen, CS, Hansen, TF, Pedersen, CB , Pedersen, MG , Qvist, P, Yang, J, Mors, O , Mortensen, PB, Nordentoft, M, Werge, T, Børglum, AD & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 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 et al.
In: Nature Genetics, Vol. 50, No. 5, 2018, p. 668-681.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-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 - Grove, Jakob

AU - Hansen, Christine Søholm

AU - Hansen, Thomas F

AU - Pedersen, Carsten Bøcker

AU - Pedersen, Marianne Giørtz

AU - Qvist, Per

AU - Yang, Jian

AU - Mors, Ole

AU - Mortensen, Preben Bo

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - Børglum, Anders D

AU - 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.

KW - Case-Control Studies

KW - Depressive Disorder, Major/genetics

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study/methods

KW - Humans

KW - Male

KW - Multifactorial Inheritance

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

KW - Schizophrenia/genetics

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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

Keywords

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