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

eQTLGen Consortium; 23andMe Research Team; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; 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; Lynsey S. Hall; Donald J. MacIntyre; Pippa A. Thomson; Caroline Hayward; Andrew M. McIntosh; David J. Porteous

doi:10.1038/s41588-018-0090-3

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

eQTLGen Consortium, 23andMe Research Team, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 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 BryoisHenriette 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, Lynsey S. Hall, Donald J. MacIntyre, Pippa A. Thomson, Caroline Hayward, Andrew M. McIntosh, David J. Porteous

Research output: Contribution to journal › Article › peer-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 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

Access to Document

10.1038/s41588-018-0090-3

2018-02-14 Wray Nat Gen Accepted ManuscriptAccepted author manuscript, 12.9 MB

3 Finished

Stratifying Resilience and Depression Longitudinally
McIntosh, A., Deary, I., Evans, K., Haley, C. & Porteous, D.
UK-based charities
1/01/15 → 30/06/21
Project: Research
Generation Scotland
Porteous, D.
UK central government bodies/local authorities, health and hospital authorities
1/04/11 → 31/03/14
Project: Research
Genetic Health 21st Century
Porteous, D., Laurie, G. & Tait, J.
UK central government bodies/local authorities, health and hospital authorities
1/10/03 → 31/08/07
Project: Research

1 Review article

Uncovering the genetic architecture of major depression
McIntosh, A., Sullivan, P. F. & Lewis, C. M., 3 Apr 2019, (E-pub ahead of print) In: Neuron.
Research output: Contribution to journal › Review article › peer-review

Open Access
File

2 Invited talk

The genetics of depression
Andrew McIntosh (Invited speaker)
26 Mar 2019
Activity: Academic talk or presentation types › Invited talk
Identifying the mechanisms of distress, depression and resilience
Andrew McIntosh (Assessor)
3 Mar 2018 → 4 Mar 2018
Activity: Academic talk or presentation types › Invited talk

Pippa Thomson
- Pippa.Thomson@ed.ac.uk
- Deanery of Molecular, Genetic and Population Health Sciences - Lecturer
- Centre for Genomic and Experimental Medicine - Lecturer
- Edinburgh Neuroscience
Person: Academic: Research Active

Cite this

eQTLGen Consortium, 23andMe Research Team, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 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., ... Porteous, D. J. (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

eQTLGen Consortium ; 23andMe Research Team ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium ; 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 ; Escott-Price, Valentina ; Kiadeh, Farnush Hassan Farhadi ; Finucane, Hilary K. ; Forstner, Andreas J. ; Frank, Josef ; Hall, Lynsey S. ; MacIntyre, Donald J. ; Thomson, Pippa A. ; Hayward, Caroline ; McIntosh, Andrew M. ; Porteous, David J. / 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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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 = "{eQTLGen Consortium} and {23andMe Research Team} and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and 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 Kiadeh, {Farnush Hassan Farhadi} and Finucane, {Hilary K.} and Forstner, {Andreas J.} and Josef Frank and Hall, {Lynsey S.} and MacIntyre, {Donald J.} and Thomson, {Pippa A.} and Caroline Hayward and McIntosh, {Andrew M.} and Porteous, {David J.}",

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month = may,

doi = "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",

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eQTLGen Consortium, 23andMe Research Team, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 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, Hall, LS, MacIntyre, DJ , Thomson, PA , Hayward, C , McIntosh, AM & Porteous, DJ 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. / eQTLGen Consortium; 23andMe Research Team; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; 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; Escott-Price, Valentina; Kiadeh, Farnush Hassan Farhadi; Finucane, Hilary K.; Forstner, Andreas J.; Frank, Josef; Hall, Lynsey S.; MacIntyre, Donald J.; Thomson, Pippa A.; Hayward, Caroline ; McIntosh, Andrew M.; Porteous, David J.

In: Nature Genetics, Vol. 50, No. 5, 05.2018, p. 668-681.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression

AU - eQTLGen Consortium

AU - 23andMe Research Team

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

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 - Hall, Lynsey S.

AU - MacIntyre, Donald J.

AU - Thomson, Pippa A.

AU - Hayward, Caroline

AU - McIntosh, Andrew M.

AU - Porteous, David J.

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.

U2 - 10.1038/s41588-018-0090-3

DO - 10.1038/s41588-018-0090-3

M3 - Article

VL - 50

SP - 668

EP - 681

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 5

ER -

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

Abstract

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Projects

Stratifying Resilience and Depression Longitudinally

Generation Scotland

Genetic Health 21st Century

Research output

Uncovering the genetic architecture of major depression

Activities

The genetics of depression

Identifying the mechanisms of distress, depression and resilience

Profiles

Pippa Thomson

Cite this