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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 | Farnush Hassan Farhadi Kiadeh | Hilary K Finucane | Andreas J Forstner | Josef Frank | Héléna A Gaspar | Michael Gill | Paola Giusti-Rodríguez | Fernando S Goes | Scott D Gordon | Jakob Grove | Lynsey S Hall | Eilis Hannon | Christine Søholm Hansen | Thomas F Hansen | Stefan Herms | Ian B Hickie | Per Hoffmann | Georg Homuth | Carsten Horn | Jouke-Jan Hottenga | David M Hougaard | Ming Hu | Craig L Hyde | Marcus Ising | Rick Jansen | Fulai Jin | Eric Jorgenson | James A Knowles | Isaac S Kohane | Julia Kraft | Warren W Kretzschmar | Jesper Krogh | Zoltán Kutalik | Jacqueline M Lane | Yihan Li | Yun Li | Penelope A Lind | Xiaoxiao Liu | Leina Lu | Donald J MacIntyre | Dean F MacKinnon | Robert M Maier | Wolfgang Maier | Jonathan Marchini | Hamdi Mbarek | Patrick McGrath | Peter McGuffin | Sarah E Medland | Divya Mehta | Christel M Middeldorp | Evelin Mihailov | Yuri Milaneschi | Lili Milani | Jonathan Mill | Francis M Mondimore | Grant W Montgomery | Sara Mostafavi | Niamh Mullins | Matthias Nauck | Bernard Ng | Michel G Nivard | Dale R Nyholt | Paul F O'Reilly | Hogni Oskarsson | Michael J Owen | Jodie N Painter | Carsten Bøcker Pedersen | Marianne Giørtz Pedersen | Roseann E Peterson | Erik Pettersson | Wouter J Peyrot | Giorgio Pistis | Danielle Posthuma | Shaun M Purcell | Jorge A Quiroz | Per Qvist | John P Rice | Brien P Riley | Margarita Rivera | Saira Saeed Mirza | Richa Saxena | Robert Schoevers | Eva C Schulte | Ling Shen | Jianxin Shi | Stanley I Shyn | Engilbert Sigurdsson | Grant B C Sinnamon | Johannes H Smit | Daniel J Smith | Hreinn Stefansson | Stacy Steinberg | Craig A Stockmeier | Fabian Streit | Jana Strohmaier | Katherine E Tansey | Henning Teismann | Alexander Teumer | Wesley Thompson | Pippa A Thomson | Thorgeir E Thorgeirsson | Chao Tian | Matthew Traylor | Jens Treutlein | Vassily Trubetskoy | André G Uitterlinden | Daniel Umbricht | Sandra Van der Auwera | Albert M van Hemert | Alexander Viktorin | Peter M Visscher | Yunpeng Wang | Bradley T Webb | Shantel Marie Weinsheimer | Jürgen Wellmann | Gonneke Willemsen | Stephanie H Witt | Yang Wu | Hualin S Xi | Jian Yang | Futao Zhang | eQTLGen | 23andMe | Volker Arolt | Bernhard T Baune | Klaus Berger | Dorret I Boomsma | Sven Cichon | Udo Dannlowski | E C J de Geus | J Raymond DePaulo | Enrico Domenici | Katharina Domschke | Tõnu Esko | Hans J Grabe | Steven P Hamilton | Caroline Hayward | Andrew C Heath | David A Hinds | Kenneth S Kendler | Stefan Kloiber | Glyn Lewis | Qingqin S Li | Susanne Lucae | Pamela F A Madden | Patrik K Magnusson | Nicholas G Martin | Andrew M McIntosh | Andres Metspalu | Ole Mors | Preben Bo Mortensen | Bertram Müller-Myhsok | Merete Nordentoft | Markus M Nöthen | Michael C O'Donovan | Sara A Paciga | Nancy L Pedersen | Brenda W J H Penninx | Roy H Perlis | David J Porteous | James B Potash | Martin Preisig | Marcella Rietschel | Catherine Schaefer | Thomas G Schulze | Jordan W Smoller | Kari Stefansson | Henning Tiemeier | Rudolf Uher | Henry Völzke | Myrna M Weissman | Thomas Werge | Ashley R Winslow | Cathryn M Lewis | Douglas F Levinson | Gerome Breen | Anders D Børglum | Patrick F Sullivan | Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Nature genetics | 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.

Pubmed ID: 29700475 RIS Download

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Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: R01 MH061675
  • Agency: NCI NIH HHS, United States
    Id: R01 CA133996
  • Agency: NCI NIH HHS, United States
    Id: P50 CA097007
  • Agency: NIMH NIH HHS, United States
    Id: U01 MH046276
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH067257
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH059587
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH059586
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_00007/10
  • Agency: Medical Research Council, United Kingdom
    Id: MR/L023784/2
  • Agency: NCI NIH HHS, United States
    Id: P50 CA093459
  • Agency: NIMH NIH HHS, United States
    Id: U01 MH109528
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH060879
  • Agency: Medical Research Council, United Kingdom
    Id: MC_PC_17228
  • Agency: NIMH NIH HHS, United States
    Id: U01 MH085520
  • Agency: Medical Research Council, United Kingdom
    Id: G0200243
  • Agency: Medical Research Council, United Kingdom
    Id: MR/L010305/1
  • Agency: NHLBI NIH HHS, United States
    Id: T32 HL007901
  • Agency: NIEHS NIH HHS, United States
    Id: R01 ES011740
  • Agency: NIMH NIH HHS, United States
    Id: U01 MH079469
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH060870
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH081800
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA034076
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH059571
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH059565
  • Agency: Medical Research Council, United Kingdom
    Id: MR/N015746/1
  • Agency: NIMH NIH HHS, United States
    Id: U01 MH109536
  • Agency: NIMH NIH HHS, United States
    Id: U01 MH079470
  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG009658
  • Agency: NIMH NIH HHS, United States
    Id: U01 MH109532
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH059566
  • Agency: NIMH NIH HHS, United States
    Id: K01 MH109772
  • Agency: NIMH NIH HHS, United States
    Id: U01 MH094421
  • Agency: NIGMS NIH HHS, United States
    Id: P30 GM103328
  • Agency: NIH HHS, United States
    Id: S10 OD018164
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH059588
  • Agency: NIMH NIH HHS, United States
    Id: U01 MH046318
  • Agency: Medical Research Council, United Kingdom
    Id: MC_QA137853
  • Agency: Medical Research Council, United Kingdom
    Id: MR/K026992/1

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