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

Wray, N.R.; Ripke, S.; Mattheisen, M.; Trzaskowski, M.; Byrne, E.M.; Abdellaoui, A.; Adams, M.J.; Agerbo, E.; Air, T.M.; Andlauer, TMF; Bacanu, S.A.; Bækvad-Hansen, M.; Beekman, AFT; Bigdeli, T.B.; Binder, E.B.; Blackwood, DRH; Bryois, J.; Buttenschøn, H.N.; Bybjerg-Grauholm, J.; Cai, N.; Castelao, E.; Christensen, J.H.; Clarke, T.K.; Coleman, JIR; Colodro-Conde, L.; Couvy-Duchesne, B.; Craddock, N.; Crawford, G.E.; Crowley, C.A.; Dashti, H.S.; Davies, G.; Deary, I.J.; Degenhardt, F.; Derks, E.M.; Direk, N.; Dolan, C.V.; Dunn, E.C.; Eley, T.C.; Eriksson, N.; Escott-Price, V.; Kiadeh, FHF; Finucane, H.K.; Forstner, A.J.; Frank, J.; Gaspar, H.A.; Gill, M.; Giusti-Rodríguez, P.; Goes, F.S.; Gordon, S.D.; Grove, J.; Hall, L.S.; Hannon, E.; Hansen, C.S.; Hansen, T.F.; Herms, S.; Hickie, I.B.; Hoffmann, P.; Homuth, G.; Horn, C.; Hottenga, J.J.; Hougaard, D.M.; Hu, M.; Hyde, C.L.; Ising, M.; Jansen, R.; Jin, F.; Jorgenson, E.; Knowles, J.A.; Kohane, I.S.; Kraft, J.; Kretzschmar, W.W.; Krogh, J.; Kutalik, Z.; Lane, J.M.; Li, Y.; Li, Y.; Lind, P.A.; Liu, X.; Lu, L.; MacIntyre, D.J.; MacKinnon, D.F.; Maier, R.M.; Maier, W.; Marchini, J.; Mbarek, H.; McGrath, P.; McGuffin, P.; Medland, S.E.; Mehta, D.; Middeldorp, C.M.; Mihailov, E.; Milaneschi, Y.; Milani, L.; Mill, J.; Mondimore, F.M.; Montgomery, G.W.; Mostafavi, S.; Mullins, N.; Nauck, M.; Ng, B.; Nivard, M.G.; Nyholt, D.R.; O'Reilly, P.F.; Oskarsson, H.; Owen, M.J.; Painter, J.N.; Pedersen, C.B.; Pedersen, M.G.; Peterson, R.E.; Pettersson, E.; Peyrot, W.J.; Pistis, G.; Posthuma, D.; Purcell, S.M.; Quiroz, J.A.; Qvist, P.; Rice, J.P.; Riley, B.P.; Rivera, M.; Saeed Mirza, S.; Saxena, R.; Schoevers, R.; Schulte, E.C.; Shen, L.; Shi, J.; Shyn, S.I.; Sigurdsson, E.; Sinnamon, GBC; Smit, J.H.; Smith, D.J.; Stefansson, H.; Steinberg, S.; Stockmeier, C.A.; Streit, F.; Strohmaier, J.; Tansey, K.E.; Teismann, H.; Teumer, A.; Thompson, W.; Thomson, P.A.; Thorgeirsson, T.E.; Tian, C.; Traylor, M.; Treutlein, J.; Trubetskoy, V.; Uitterlinden, A.G.; Umbricht, D.; Van der Auwera, S.; van Hemert, A.M.; Viktorin, A.; Visscher, P.M.; Wang, Y.; Webb, B.T.; Weinsheimer, S.M.; Wellmann, J.; Willemsen, G.; Witt, S.H.; Wu, Y.; Xi, H.S.; Yang, J.; Zhang, F.; Arolt, V.; Baune, B.T.; Berger, K.; Boomsma, D.I.; Cichon, S.; Dannlowski, U.; de Geus, ECJ; DePaulo, J.R.; Domenici, E.; Domschke, K.; Esko, T.; Grabe, H.J.; Hamilton, S.P.; Hayward, C.; Heath, A.C.; Hinds, D.A.; Kendler, K.S.; Kloiber, S.; Lewis, G.; Li, Q.S.; Lucae, S.; Madden, PFA; Magnusson, P.K.; Martin, N.G.; McIntosh, A.M.; Metspalu, A.; Mors, O.; Mortensen, P.B.; Müller-Myhsok, B.; Nordentoft, M.; Nöthen, M.M.; O'Donovan, M.C.; Paciga, S.A.; Pedersen, N.L.; Penninx, BWJH; Perlis, R.H.; Porteous, D.J.; Potash, J.B.; Preisig, M.; Rietschel, M.; Schaefer, C.; Schulze, T.G.; Smoller, J.W.; Stefansson, K.; Tiemeier, H.; Uher, R.; Völzke, H.; Weissman, M.M.; Werge, T.; Winslow, A.R.; Lewis, C.M.; Levinson, D.F.; Breen, G.; Børglum, A.D.; Sullivan, P.F.

doi:10.1038/s41588-018-0090-3

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

Details

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Version: Author's accepted manuscript
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Serval ID

serval:BIB_BCBAFC9AB2BB

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature genetics

Author(s)

Wray N.R., Ripke S., Mattheisen M., Trzaskowski M., Byrne E.M., Abdellaoui A., Adams M.J., Agerbo E., Air T.M., Andlauer TMF, Bacanu S.A., Bækvad-Hansen M., Beekman AFT, Bigdeli T.B., Binder E.B., Blackwood DRH, Bryois J., Buttenschøn H.N., Bybjerg-Grauholm J., Cai N., Castelao E., Christensen J.H., Clarke T.K., Coleman JIR, Colodro-Conde L., Couvy-Duchesne B., Craddock N., Crawford G.E., Crowley C.A., Dashti H.S., Davies G., Deary I.J., Degenhardt F., Derks E.M., Direk N., Dolan C.V., Dunn E.C., Eley T.C., Eriksson N., Escott-Price V., Kiadeh FHF, Finucane H.K., Forstner A.J., Frank J., Gaspar H.A., Gill M., Giusti-Rodríguez P., Goes F.S., Gordon S.D., Grove J., Hall L.S., Hannon E., Hansen C.S., Hansen T.F., Herms S., Hickie I.B., Hoffmann P., Homuth G., Horn C., Hottenga J.J., Hougaard D.M., Hu M., Hyde C.L., Ising M., Jansen R., Jin F., Jorgenson E., Knowles J.A., Kohane I.S., Kraft J., Kretzschmar W.W., Krogh J., Kutalik Z., Lane J.M., Li Y., Li Y., Lind P.A., Liu X., Lu L., MacIntyre D.J., MacKinnon D.F., Maier R.M., Maier W., Marchini J., Mbarek H., McGrath P., McGuffin P., Medland S.E., Mehta D., Middeldorp C.M., Mihailov E., Milaneschi Y., Milani L., Mill J., Mondimore F.M., Montgomery G.W., Mostafavi S., Mullins N., Nauck M., Ng B., Nivard M.G., Nyholt D.R., O'Reilly P.F., Oskarsson H., Owen M.J., Painter J.N., Pedersen C.B., Pedersen M.G., Peterson R.E., Pettersson E., Peyrot W.J., Pistis G., Posthuma D., Purcell S.M., Quiroz J.A., Qvist P., Rice J.P., Riley B.P., Rivera M., Saeed Mirza S., Saxena R., Schoevers R., Schulte E.C., Shen L., Shi J., Shyn S.I., Sigurdsson E., Sinnamon GBC, Smit J.H., Smith D.J., Stefansson H., Steinberg S., Stockmeier C.A., Streit F., Strohmaier J., Tansey K.E., Teismann H., Teumer A., Thompson W., Thomson P.A., Thorgeirsson T.E., Tian C., Traylor M., Treutlein J., Trubetskoy V., Uitterlinden A.G., Umbricht D., Van der Auwera S., van Hemert A.M., Viktorin A., Visscher P.M., Wang Y., Webb B.T., Weinsheimer S.M., Wellmann J., Willemsen G., Witt S.H., Wu Y., Xi H.S., Yang J., Zhang F., Arolt V., Baune B.T., Berger K., Boomsma D.I., Cichon S., Dannlowski U., de Geus ECJ, DePaulo J.R., Domenici E., Domschke K., Esko T., Grabe H.J., Hamilton S.P., Hayward C., Heath A.C., Hinds D.A., Kendler K.S., Kloiber S., Lewis G., Li Q.S., Lucae S., Madden PFA, Magnusson P.K., Martin N.G., McIntosh A.M., Metspalu A., Mors O., Mortensen P.B., Müller-Myhsok B., Nordentoft M., Nöthen M.M., O'Donovan M.C., Paciga S.A., Pedersen N.L., Penninx BWJH, Perlis R.H., Porteous D.J., Potash J.B., Preisig M., Rietschel M., Schaefer C., Schulze T.G., Smoller J.W., Stefansson K., Tiemeier H., Uher R., Völzke H., Weissman M.M., Werge T., Winslow A.R., Lewis C.M., Levinson D.F., Breen G., Børglum A.D., Sullivan P.F.

Working group(s)

eQTLGen, 23andMe, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

ISSN

1546-1718 (Electronic)

ISSN-L

1061-4036

Publication state

Published

Issued date

05/2018

Peer-reviewed

Oui

Volume

Number

Pages

668-681

Language

english

Notes

Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish

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.

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

URN

urn:nbn:ch:serval-BIB_BCBAFC9AB2BB7

OAI-PMH

oai:serval.unil.ch:BIB_BCBAFC9AB2BB

DOI

10.1038/s41588-018-0090-3

Pubmed

29700475

Web of science

000431394900010

Create date

01/05/2018 13:06