An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

Nese Direk; Stephanie Williams; Jennifer A. Smith; Stephan Ripke; Tracy Air; Azmeraw T. Amare; Najaf Amin; Bernhard T. Baune; David A. Bennett; Douglas H.R. Blackwood; Dorret Boomsma; Gerome Breen; Henriette N. Buttenschøn; Enda M. Byrne; Anders D. Børglum; Enrique Castelao; Sven Cichon; Toni-Kim Clarke; Marilyn C. Cornelis; Udo Dannlowski; Philip L. De Jager; Ayse Demirkan; Enrico Domenici; Cornelia M. van Duijn; Erin C. Dunn; Johan G. Eriksson; Tonu Esko; Jessica D. Faul; Luigi Ferrucci; Myriam Fornage; Eco de Geus; Michael Gill; Scott D. Gordon; Hans Jörgen Grabe; Gerard van Grootheest; Steven P. Hamilton; Catharina A. Hartman; Andrew C. Heath; Karin Hek; Albert Hofman; Georg Homuth; Carsten Horn; Jouke Jan Hottenga; Sharon L.R. Kardia; Stefan Kloiber; Karestan Koenen; Zoltán Kutalik; Karl-Heinz Ladwig; Jari Lahti; Douglas F. Levinson; Cathryn M. Lewis; Glyn Lewis; Qingqin S. Li; David J. Llewellyn; Susanne Lucae; Kathryn L. Lunetta; Donald J. MacIntyre; Pamela Madden; Nicholas G. Martin; Andrew M. McIntosh; Andres Metspalu; Yuri Milaneschi; Grant W. Montgomery; Ole Mors; Thomas H. Mosley; Joanne M. Murabito; Bertram Müller-Myhsok; Markus M. Nöthen; Dale R. Nyholt; Michael C. O’Donovan; Brenda W. Penninx; Michele L. Pergadia; Roy Perlis; James B. Potash; Martin Preisig; Shaun M. Purcell; Jorge A. Quiroz; Katri Räikkönen; John P. Rice; Marcella Rietschel; Margarita Rivera; Thomas G. Schulze; Jianxin Shi; Stanley Shyn; Grant C. Sinnamon; Johannes H. Smit; Jordan W. Smoller; Harold Snieder; Toshiko Tanaka; Katherine E. Tansey; Alexander Teumer; Rudolf Uher; Daniel Umbricht; Sandra Van der Auwera; Erin B. Ware; David R. Weir; Myrna M. Weissman; Gonneke Willemsen; Jingyun Yang; Wei Zhao; Henning Tiemeier; Patrick F. Sullivan

doi:10.1016/j.biopsych.2016.11.013

Back

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

Journal article

Peer reviewed

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

Nese Direk, Stephanie Williams, Jennifer A. Smith, Stephan Ripke, Tracy Air, Azmeraw T. Amare, Najaf Amin, Bernhard T. Baune, David A. Bennett, Douglas H.R. Blackwood, …

Biological psychiatry (1969), Vol.82(5), pp.322-329

01/09/2017

DOI: https://doi.org/10.1016/j.biopsych.2016.11.013

PMID: 28049566

Abstract

CHARGE consortium

Depressive symptoms

FHIT gene

Genome-wide association study

Major depressive disorder

Psychiatric Genomics Consortium

The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10–9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10–9). This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.

Metrics

1 Record Views

50 Times Cited - Web of Science

See more details

Details

Title: An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype
Creators: Nese Direk - Dokuz Eylül University
Stephanie Williams - University of North Carolina at Chapel Hill
Jennifer A. Smith - University of Michigan–Ann Arbor
Stephan Ripke - Massachusetts General Hospital
Tracy Air - University of Adelaide
Azmeraw T. Amare - University Medical Center Groningen
Najaf Amin - Erasmus MC
Bernhard T. Baune - University of Adelaide
David A. Bennett - Rush University Medical Center
Douglas H.R. Blackwood - University of Edinburgh
Dorret Boomsma - University of Amsterdam
Gerome Breen - King's College London
Henriette N. Buttenschøn - Lundbeck Foundation
Enda M. Byrne - University of Queensland
Anders D. Børglum - Aarhus University
Enrique Castelao - University of Lausanne
Sven Cichon - Life & Brain
Toni-Kim Clarke - University of Edinburgh
Marilyn C. Cornelis - Northwestern University
Udo Dannlowski - University of Münster
Philip L. De Jager - Broad Institute
Ayse Demirkan - Erasmus MC
Enrico Domenici - University of Trento
Cornelia M. van Duijn - Erasmus MC
Erin C. Dunn - Broad Institute
Johan G. Eriksson - University of Helsinki
Tonu Esko - University of Tartu
Jessica D. Faul - University of Michigan–Ann Arbor
Luigi Ferrucci - National Institute on Aging
Myriam Fornage - Brown Foundation
Eco de Geus - University of Amsterdam
Michael Gill - Trinity College Dublin
Scott D. Gordon - QIMR Berghofer Medical Research Institute
Hans Jörgen Grabe - Universitätsmedizin Greifswald
Gerard van Grootheest - Amsterdam Neuroscience
Steven P. Hamilton - Kaiser Permanente San Francisco Medical Center
Catharina A. Hartman - University Medical Center Groningen
Andrew C. Heath - Washington University in St. Louis
Karin Hek - Erasmus MC
Albert Hofman - Erasmus MC
Georg Homuth - Universität Greifswald
Carsten Horn - Roche
Jouke Jan Hottenga - University of Amsterdam
Sharon L.R. Kardia - University of Michigan–Ann Arbor
Stefan Kloiber - Max Planck Institute of Psychiatry
Karestan Koenen - Columbia University
Zoltán Kutalik - Institute of Social and Preventive Medicine
Karl-Heinz Ladwig - Center for Environmental Health
Jari Lahti - University of Helsinki
Douglas F. Levinson - Stanford University
Cathryn M. Lewis - King's College London
Glyn Lewis - University College London
Qingqin S. Li - Janssen
David J. Llewellyn - University of Exeter
Susanne Lucae - Max Planck Institute of Psychiatry
Kathryn L. Lunetta - Boston University
Donald J. MacIntyre - University of Edinburgh
Pamela Madden - Washington University in St. Louis
Nicholas G. Martin - QIMR Berghofer Medical Research Institute
Andrew M. McIntosh - University of Edinburgh
Andres Metspalu - University of Tartu
Yuri Milaneschi - EMGO Institute for Health and Care Research
Grant W. Montgomery - QIMR Berghofer Medical Research Institute
Ole Mors - Lundbeck Foundation
Thomas H. Mosley - University of Mississippi Medical Center
Joanne M. Murabito - National Heart Lung and Blood Institute
Bertram Müller-Myhsok - Max Planck Institute of Psychiatry
Markus M. Nöthen - University of Bonn
Dale R. Nyholt - Queensland University of Technology
Michael C. O’Donovan - Cardiff University
Brenda W. Penninx - University of Amsterdam
Michele L. Pergadia - Washington University in St. Louis
Roy Perlis - Massachusetts General Hospital
James B. Potash - University of Iowa
Martin Preisig - University of Lausanne
Shaun M. Purcell - Icahn School of Medicine at Mount Sinai
Jorge A. Quiroz - Roche
Katri Räikkönen - University of Helsinki
John P. Rice - Washington University in St. Louis
Marcella Rietschel - University Hospital Heidelberg
Margarita Rivera - Universidad de Granada
Thomas G. Schulze - University of Göttingen
Jianxin Shi - National Cancer Institute
Stanley Shyn - Group Health Cooperative
Grant C. Sinnamon - James Cook University
Johannes H. Smit - EMGO Institute for Health and Care Research
Jordan W. Smoller - Broad Institute
Harold Snieder - University Medical Center Groningen
Toshiko Tanaka - National Institute on Aging
Katherine E. Tansey - Cardiff University
Alexander Teumer - Universitätsmedizin Greifswald
Rudolf Uher - King's College London
Daniel Umbricht - Roche
Sandra Van der Auwera - Universitätsmedizin Greifswald
Erin B. Ware - University of Michigan–Ann Arbor
David R. Weir - University of Michigan–Ann Arbor
Myrna M. Weissman - Columbia University
Gonneke Willemsen - University of Amsterdam
Jingyun Yang - Rush University Medical Center
Wei Zhao - University of Michigan–Ann Arbor
Henning Tiemeier - Erasmus MC
Patrick F. Sullivan - Karolinska Institutet
Publication Details: Biological psychiatry (1969), Vol.82(5), pp.322-329
Publisher: Elsevier Inc
Number of pages: 8
Date published: 01/09/2017
Identifiers: 99928794502346
Academic Unit: Institute for Sustainability; Surrey Institute for People-Centred AI; School of Biosciences
Language: English
Resource Type: Journal article

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

Abstract

Metrics

Details

Usage Policy