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

Nat Genet
Authors
Naomi Wray
Stephan Ripke
Manuel Mattheisen
Maciej Trzaskowski
Enda Byrne
Abdel Abdellaoui
Mark Adams
Esben Agerbo
Tracy Air
Till Andlauer
Silviu-Alin Bacanu
Marie Bækvad-Hansen
Aartjan Beekman
Tim Bigdeli
Elisabeth Binder
Douglas Blackwood
Julien Bryois
Henriette Buttenschøn
Jonas Bybjerg-Grauholm
Na Cai
Enrique Castelao
Jane Christensen
Toni-Kim Clarke
Jonathan Coleman
Lucía Colodro-Conde
Baptiste Couvy-Duchesne
Nick Craddock
Gregory Crawford
Cheynna Crowley
Hassan Dashti
Gail Davies
Ian Deary
Franziska Degenhardt
Eske Derks
Nese Direk
Conor Dolan
Erin Dunn
Thalia Eley
Nicholas Eriksson
Valentina Escott-Price
Farnush Kiadeh
Hilary Finucane
Andreas Forstner
Josef Frank
Héléna Gaspar
Michael Gill
Paola Giusti-Rodríguez
Fernando Goes
Scott Gordon
Jakob Grove
Lynsey Hall
Eilis Hannon
Christine Hansen
Thomas Hansen
Stefan Herms
Ian Hickie
Per Hoffmann
Georg Homuth
Carsten Horn
Jouke-Jan Hottenga
David Hougaard
Ming Hu
Craig Hyde
Marcus Ising
Rick Jansen
Fulai Jin
Eric Jorgenson
James Knowles
Isaac Kohane
Julia Kraft
Warren Kretzschmar
Jesper Krogh
Zoltán Kutalik
Jacqueline Lane
Yihan Li
Yun Li
Penelope Lind
Xiaoxiao Liu
Leina Lu
Donald MacIntyre
Dean MacKinnon
Robert Maier
Wolfgang Maier
Jonathan Marchini
Hamdi Mbarek
Patrick McGrath
Peter McGuffin
Sarah Medland
Divya Mehta
Christel Middeldorp
Evelin Mihailov
Yuri Milaneschi
Lili Milani
Jonathan Mill
Francis Mondimore
Grant Montgomery
Sara Mostafavi
Niamh Mullins
Matthias Nauck
Bernard Ng
Michel Nivard
Dale Nyholt
Paul O'Reilly
Hogni Oskarsson
Michael Owen
Jodie Painter
Carsten Pedersen
Marianne Pedersen
Roseann Peterson
Erik Pettersson
Wouter Peyrot
Giorgio Pistis
Danielle Posthuma
Shaun Purcell
Jorge Quiroz
Per Qvist
John Rice
Brien Riley
Margarita Rivera
Saira Mirza
Richa Saxena
Robert Schoevers
Eva Schulte
Ling Shen
Jianxin Shi
Stanley Shyn
Engilbert Sigurdsson
Grant Sinnamon
Johannes Smit
Daniel Smith
Hreinn Stefansson
Stacy Steinberg
Craig Stockmeier
Fabian Streit
Jana Strohmaier
Katherine Tansey
Henning Teismann
Alexander Teumer
Wesley Thompson
Pippa Thomson
Thorgeir Thorgeirsson
Chao Tian
Matthew Traylor
Jens Treutlein
Vassily Trubetskoy
André Uitterlinden
Daniel Umbricht
Sandra Van der Auwera
Albert van Hemert
Alexander Viktorin
Peter Visscher
Yunpeng Wang
Bradley Webb
Shantel Weinsheimer
Jürgen Wellmann
Gonneke Willemsen
Stephanie Witt
Yang Wu
Hualin Xi
Jian Yang
Futao Zhang
eQTLGen
23andMe
Volker Arolt
Bernhard Baune
Klaus Berger
Dorret Boomsma
Sven Cichon
Udo Dannlowski
E de Geus
J Raymond DePaulo
Enrico Domenici
Katharina Domschke
Tõnu Esko
Hans Grabe
Steven Hamilton
Caroline Hayward
Andrew Heath
David Hinds
Kenneth Kendler
Stefan Kloiber
Glyn Lewis
Qingqin Li
Susanne Lucae
Pamela Madden
Patrik Magnusson
Nicholas Martin
Andrew McIntosh
Andres Metspalu
Ole Mors
Preben Mortensen
Bertram Müller-Myhsok
Merete Nordentoft
Markus Nöthen
Michael O'Donovan
Sara Paciga
Nancy Pedersen
Brenda Penninx
Roy Perlis
David Porteous
James Potash
Martin Preisig
Marcella Rietschel
Catherine Schaefer
Thomas Schulze
Jordan Smoller
Kari Stefansson
Henning Tiemeier
Rudolf Uher
Henry Völzke
Myrna Weissman
Thomas Werge
Ashley Winslow
Cathryn Lewis
Douglas Levinson
Gerome Breen
Anders Børglum
Patrick Sullivan
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Keywords
Female
Humans
Male
Genetic Predisposition to Disease
Phenotype
Risk Factors
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Case-Control Studies
Multifactorial Inheritance
Schizophrenia
Depressive Disorder, Major
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.
Year of Publication
2018
Journal
Nat Genet
Volume
50
Issue
5
Pages
668-681
Date Published
2018 05
ISSN
1546-1718
DOI
10.1038/s41588-018-0090-3
PubMed ID
29700475
PubMed Central ID
PMC5934326
Links
Grant list
U01 MH085520 / MH / NIMH NIH HHS / United States
P50 CA097007 / CA / NCI NIH HHS / United States
U01 MH046276 / MH / NIMH NIH HHS / United States
MC_QA137853 / MRC_ / Medical Research Council / United Kingdom
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom
R01 MH067257 / MH / NIMH NIH HHS / United States
R01 MH059587 / MH / NIMH NIH HHS / United States
MC_PC_U127561128 / MRC_ / Medical Research Council / United Kingdom
R01 MH059586 / MH / NIMH NIH HHS / United States
P50 CA093459 / CA / NCI NIH HHS / United States
U01 MH109528 / MH / NIMH NIH HHS / United States
R01 MH060879 / MH / NIMH NIH HHS / United States
R01 MH061675 / MH / NIMH NIH HHS / United States
MC_UU_00007/10 / MRC_ / Medical Research Council / United Kingdom
MR/N015746/1 / MRC_ / Medical Research Council / United Kingdom
R01 CA133996 / CA / NCI NIH HHS / United States
T32 HL007901 / HL / NHLBI NIH HHS / United States
R01 ES011740 / ES / NIEHS NIH HHS / United States
U01 MH079469 / MH / NIMH NIH HHS / United States
R01 MH060870 / MH / NIMH NIH HHS / United States
R01 MH081800 / MH / NIMH NIH HHS / United States
R01 DA034076 / DA / NIDA NIH HHS / United States
R01 MH059571 / MH / NIMH NIH HHS / United States
G0200243 / MRC_ / Medical Research Council / United Kingdom
R01 MH059565 / MH / NIMH NIH HHS / United States
U01 MH109536 / MH / NIMH NIH HHS / United States
U01 MH079470 / MH / NIMH NIH HHS / United States
R01 HG009658 / HG / NHGRI NIH HHS / United States
U01 MH109532 / MH / NIMH NIH HHS / United States
R01 MH059566 / MH / NIMH NIH HHS / United States
K01 MH109772 / MH / NIMH NIH HHS / United States
U01 MH094421 / MH / NIMH NIH HHS / United States
P30 GM103328 / GM / NIGMS NIH HHS / United States
MC_PC_17228 / MRC_ / Medical Research Council / United Kingdom
S10 OD018164 / OD / NIH HHS / United States
R01 MH059588 / MH / NIMH NIH HHS / United States
U01 MH046318 / MH / NIMH NIH HHS / United States
MR/L023784/2 / MRC_ / Medical Research Council / United Kingdom
MR/L010305/1 / MRC_ / Medical Research Council / United Kingdom

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