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

Publication ,  Journal Article
Wray, NR; Ripke, S; Mattheisen, M; Trzaskowski, M; Byrne, EM; Abdellaoui, A; Adams, MJ; Agerbo, E; Air, TM; Andlauer, TMF; Bacanu, S-A; Cai, N ...
Published in: Nat Genet
May 2018

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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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

May 2018

Volume

50

Issue

5

Start / End Page

668 / 681

Location

United States

Related Subject Headings

  • Schizophrenia
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Multifactorial Inheritance
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
 

Citation

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Chicago
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Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., … 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. Nat Genet, 50(5), 668–681. https://doi.org/10.1038/s41588-018-0090-3
Wray, Naomi R., Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M. Byrne, Abdel Abdellaoui, Mark J. Adams, et al. “Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.Nat Genet 50, no. 5 (May 2018): 668–81. https://doi.org/10.1038/s41588-018-0090-3.
Wray NR, Ripke S, Mattheisen M, Trzaskowski M, Byrne EM, Abdellaoui A, et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet. 2018 May;50(5):668–81.
Wray, Naomi R., et al. “Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.Nat Genet, vol. 50, no. 5, May 2018, pp. 668–81. Pubmed, doi: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, Gaspar HA, Gill M, Giusti-Rodríguez P, Goes FS, Gordon SD, Grove J, Hall LS, Hannon E, Hansen CS, Hansen TF, Herms S, Hickie IB, Hoffmann P, Homuth G, Horn C, Hottenga J-J, Hougaard DM, Hu M, Hyde CL, Ising M, Jansen R, Jin F, Jorgenson E, Knowles JA, Kohane IS, Kraft J, Kretzschmar WW, Krogh J, Kutalik Z, Lane JM, Li Y, Lind PA, Liu X, Lu L, MacIntyre DJ, MacKinnon DF, Maier RM, Maier W, Marchini J, Mbarek H, McGrath P, McGuffin P, Medland SE, Mehta D, Middeldorp CM, Mihailov E, Milaneschi Y, Milani L, Mill J, Mondimore FM, Montgomery GW, Mostafavi S, Mullins N, Nauck M, Ng B, Nivard MG, Nyholt DR, O’Reilly PF, Oskarsson H, Owen MJ, Painter JN, Pedersen CB, Pedersen MG, Peterson RE, Pettersson E, Peyrot WJ, Pistis G, Posthuma D, Purcell SM, Quiroz JA, Qvist P, Rice JP, Riley BP, Rivera M, Saeed Mirza S, Saxena R, Schoevers R, Schulte EC, Shen L, Shi J, Shyn SI, Sigurdsson E, Sinnamon GBC, Smit JH, Smith DJ, Stefansson H, Steinberg S, Stockmeier CA, Streit F, Strohmaier J, Tansey KE, Teismann H, Teumer A, Thompson W, Thomson PA, Thorgeirsson TE, Tian C, Traylor M, Treutlein J, Trubetskoy V, Uitterlinden AG, Umbricht D, Van der Auwera S, van Hemert AM, Viktorin A, Visscher PM, Wang Y, Webb BT, Weinsheimer SM, Wellmann J, Willemsen G, Witt SH, Wu Y, Xi HS, Yang J, Zhang F, eQTLGen, 23andMe, Arolt V, Baune BT, Berger K, Boomsma DI, Cichon S, Dannlowski U, de Geus ECJ, DePaulo JR, Domenici E, Domschke K, Esko T, Grabe HJ, Hamilton SP, Hayward C, Heath AC, Hinds DA, Kendler KS, Kloiber S, Lewis G, Li QS, Lucae S, Madden PFA, Magnusson PK, Martin NG, McIntosh AM, Metspalu A, Mors O, Mortensen PB, Müller-Myhsok B, Nordentoft M, Nöthen MM, O’Donovan MC, Paciga SA, Pedersen NL, Penninx BWJH, Perlis RH, Porteous DJ, Potash JB, Preisig M, Rietschel M, Schaefer C, Schulze TG, Smoller JW, Stefansson K, Tiemeier H, Uher R, Völzke H, Weissman MM, Werge T, Winslow AR, Lewis CM, Levinson DF, Breen G, Børglum AD, Sullivan PF, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet. 2018 May;50(5):668–681.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

May 2018

Volume

50

Issue

5

Start / End Page

668 / 681

Location

United States

Related Subject Headings

  • Schizophrenia
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Multifactorial Inheritance
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female