Evidence map›Paper›PMID 25993607›Full record

SynthesisJAMA psychiatry2015

Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder.

Genetics of Personality Consortium, Marleen H M de Moor, Stéphanie M van den Berg, Karin J H Verweij, Robert F Krueger, Michelle Luciano, Alejandro Arias Vasquez, Lindsay K Matteson, Jaime Derringer, Tõnu Esko and 109 more

Open access · greenAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in JAMA psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed, 11 pooled it
39.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

132 citing papers in PubMed, 11 syntheses or guidelines pooled it, 361 citations in OpenAlex.

  1. Pooled it
  2. Genome-wide association study of shared liability to anxiety disorders in Army STARRS.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2020
    Pooled it
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  7. Genetic risk variants for social anxiety.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2017
    Pooled it
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  12. [Embryonic origin of temperament: notochord and early signaling].Revista medica del Instituto Mexicano del Seguro Social · 2026
    Review
  13. Personality Genomics.Annual review of psychology · 2026
    Review
  14. Article
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72 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

119 authors at 20 institutions in 12 countries.

Genetics of Personality Consortium
Marleen H M de MoorDepartment of Clinical Child and Family Studies, VU University Amsterdam, Amsterdam, the Netherlands2Department of Methods, VU University Amsterdam, Amsterdam, the Netherlands3Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Ne.
Stéphanie M van den BergDepartment of Research Methodology, Measurement, and Data Analysis, University of Twente, Enschede, the Netherlands.
Karin J H VerweijDepartment of Developmental Psychology, EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, the Netherlands6QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Robert F KruegerDepartment of Psychology, University of Minnesota, Minneapolis.
Michelle LucianoCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland9Department of Psychology, University of Edinburgh, Edinburgh, Scotland.
Alejandro Arias VasquezDepartment of Cognitive Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands11Donders Institute for Cognitive Neuroscience, Radboud University Nijmegen, Nijmegen, the Netherlands12Department of Psychiatry, Radboud University.
Lindsay K MattesonDepartment of Psychology, University of Minnesota, Minneapolis.
Jaime DerringerDepartment of Psychology, University of Illinois at Urbana-Champaign, Champaign.
Tõnu EskoEstonian Genome Center, University of Tartu, Tartu, Estonia.
Najaf AminDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Scott D GordonQIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Narelle K HansellQIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Amy B HartDepartment of Human Genetics, University of Chicago, Chicago, Illinois.
Ilkka SeppäläDepartment of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
Jennifer E HuffmanMedical Research Council Human Genetics, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland.
Bettina KonteDepartment of Psychiatry, University of Halle, Halle, Germany.
Jari LahtiFolkhälsan Research Center, Helsinki, Finland22Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Minyoung LeeDepartment of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond.
Mike MillerDepartment of Psychology, University of Minnesota, Minneapolis.
Teresa NutileInstitute of Genetics and Biophysics "A. Buzzati-Traverso," National Research Council of Italy, Naples, Italy.
Toshiko TanakaNational Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Alexander ViktorinDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Juho WedenojaDepartment of Public Health, University of Helsinki, Helsinki, Finland.
Goncalo R AbecasisCenter for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor.
Daniel E AdkinsDepartment of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond.
Arpana AgrawalDepartment of Psychiatry, Washington University School of Medicine, St Louis, Missouri.
Jüri AllikDepartment of Psychology, University of Tartu, Tartu, Estonia33Estonian Academy of Sciences, Tallinn, Estonia.
Katja AppelDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Timothy B BigdeliDepartment of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond.
Fabio BusoneroIstituto di Ricerca Genetica e Biomedica, National Research Council of Italy, Monserrato, Italy.
Harry CampbellInstitute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
Paul T CostaBehavioral Medicine Research Center, Duke University School of Medicine, Durham, North Carolina.
George Davey SmithMedical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, England.
Gail DaviesCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland9Department of Psychology, University of Edinburgh, Edinburgh, Scotland.
Harriet de WitDepartment of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois.
Jun DingNational Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Barbara E EngelhardtDepartment of Computer Science, Princeton University, Princeton, New Jersey.
Johan G ErikssonFolkhälsan Research Center, Helsinki, Finland41Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland42Vasa Central Hospital, Vasa, Finland43National Institute for Health and Welf.
Iryna O FedkoDepartment of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
Luigi FerrucciNational Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Barbara FrankeDonders Institute for Cognitive Neuroscience, Radboud University Nijmegen, Nijmegen, the Netherlands12Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands13Department of Human Genetics, Radboud University Nijmege.
Ina GieglingDepartment of Psychiatry, University of Halle, Halle, Germany.
Richard GruczaDepartment of Psychiatry, Washington University School of Medicine, St Louis, Missouri.
Annette M HartmannDepartment of Psychiatry, University of Halle, Halle, Germany.
Andrew C HeathDepartment of Psychiatry, Washington University School of Medicine, St Louis, Missouri.
Kati HeinonenInstitute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Anjali K HendersQIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Georg HomuthInterfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
Jouke-Jan HottengaDepartment of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
William G IaconoDepartment of Psychology, University of Minnesota, Minneapolis.
Joost JanzingDepartment of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
Markus JokelaInstitute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Robert KarlssonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
John P KempMedical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, England45University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
Matthew G KirkpatrickDepartment of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois.
Antti LatvalaDepartment of Public Health, University of Helsinki, Helsinki, Finland43National Institute for Health and Welfare, Helsinki, Finland.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
David C LiewaldCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland9Department of Psychology, University of Edinburgh, Edinburgh, Scotland.
Pamela A F MaddenDepartment of Psychiatry, Washington University School of Medicine, St Louis, Missouri.
Chiara MagriDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Patrik K E MagnussonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Jonathan MartenMedical Research Council Human Genetics, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland.
Andrea MaschioIstituto di Ricerca Genetica e Biomedica, National Research Council of Italy, Monserrato, Italy.
Sarah E MedlandQIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Evelin MihailovEstonian Genome Center, University of Tartu, Tartu, Estonia47Department of Biotechnology, University of Tartu, Tartu, Estonia.
Yuri MilaneschiDepartment of Psychiatry, EMGO+ Institute, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
Grant W MontgomeryQIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Matthias NauckInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
Klaasjan G OuwensDepartment of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
Aarno PalotieWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, England51Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Erik PetterssonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Ozren PolasekDepartment of Public Health, Faculty of Medicine, University of Split, Split, Croatia.
Yong QianNational Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Laura Pulkki-RåbackInstitute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Olli T RaitakariDepartment of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland54Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Anu RealoDepartment of Psychology, University of Tartu, Tartu, Estonia.
Richard J RoseDepartment of Psychological and Brain Sciences, Indiana University, Bloomington.
Daniela RuggieroInstitute of Genetics and Biophysics "A. Buzzati-Traverso," National Research Council of Italy, Naples, Italy.
Carsten O SchmidtInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Wendy S SlutskeDepartment of Psychological Sciences and Missouri Alcoholism Research Center, University of Missouri, Columbia.
Rossella SoriceInstitute of Genetics and Biophysics "A. Buzzati-Traverso," National Research Council of Italy, Naples, Italy.
John M StarrCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland57Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, Scotland.
Beate St PourcainMedical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, England58School of Oral and Dental Sciences, University of Bristol, Bristol, England59School of Experimental Psychology, Unive.
Angelina R SutinNational Institute on Aging, National Institutes of Health, Baltimore, Maryland60College of Medicine, Florida State University, Tallahassee.
Nicholas J TimpsonMedical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, England.
Holly TrochetMedical Research Council Human Genetics, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland.
Sita VermeulenDepartment of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands61Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands.
Eero VuoksimaaDepartment of Public Health, University of Helsinki, Helsinki, Finland.
Elisabeth WidenInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Jasper WoudaDepartment of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands4Department of Research Methodology, Measurement, and Data Analysis, University of Twente, Enschede, the Netherlands.
Margaret J WrightQIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Lina ZgagaInstitute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland62Department of Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland.
David PorteousMedical Genetics Section, University of Edinburgh, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland.
Alessandra MinelliDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Abraham A PalmerDepartment of Human Genetics, University of Chicago, Chicago, Illinois39Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois.
Dan RujescuDepartment of Psychiatry, University of Halle, Halle, Germany.
Marina CiulloInstitute of Genetics and Biophysics "A. Buzzati-Traverso," National Research Council of Italy, Naples, Italy.
Caroline HaywardMedical Research Council Human Genetics, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland64Generation Scotland, University of Edinburgh, Centre for Genomic and Experimental Medicine.
Igor RudanInstitute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
Andres MetspaluEstonian Genome Center, University of Tartu, Tartu, Estonia33Estonian Academy of Sciences, Tallinn, Estonia.
Jaakko KaprioDepartment of Public Health, University of Helsinki, Helsinki, Finland43National Institute for Health and Welfare, Helsinki, Finland51Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Ian J DearyCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland9Department of Psychology, University of Edinburgh, Edinburgh, Scotland.
Katri RäikkönenInstitute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
James F WilsonInstitute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
Liisa Keltikangas-JärvinenInstitute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Laura J BierutDepartment of Psychiatry, Washington University School of Medicine, St Louis, Missouri.
John M HettemaDepartment of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond.
Hans J GrabeDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany65Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund, Stralsund, Germany.
Cornelia M van DuijnDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
David M EvansMedical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, England45University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
David SchlessingerNational Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Nancy L PedersenInstitute of Genetics and Biophysics "A. Buzzati-Traverso," National Research Council of Italy, Naples, Italy.
Antonio TerraccianoFolkhälsan Research Center, Helsinki, Finland60College of Medicine, Florida State University, Tallahassee.
Matt McGueDepartment of Psychology, University of Minnesota, Minneapolis66Institute of Public Health, University of Southern Denmark, Odense, Denmark.
Brenda W J H PenninxDepartment of Psychiatry, EMGO+ Institute, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
Nicholas G MartinQIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Dorret I BoomsmaDepartment of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
University of Edinburgh · GBUniversity of Helsinki · FIQIMR Berghofer Medical Research Institute · AUVrije Universiteit Amsterdam · NLNational Research Council · ITUniversitätsmedizin Greifswald · DEWashington University in St. Louis · USKarolinska Institutet · SERadboud University Nijmegen · NLUniversity of Chicago · USUniversity of Minnesota · USUniversity of Tartu · EEVirginia Commonwealth University · USNational Institute on Aging · USAmsterdam UMC Location VUmc · NLErasmus MC · NLInstitute for Molecular Medicine Finland · FIMedical Research Council · GBMRC Institute of Genetics and Molecular Medicine · GBNational Institutes of Health · US

Funding

Subject CollectionU10AA008401 · NIAAA · SUNY DOWNSTATE MEDICAL CENTER · PI Jacquelyn Leigh Meyers · 1989 to 2026
$162.7M
JH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2M
The Collaborative Genetic Study of Nicotine DependenceP01CA089392 · NCI · WASHINGTON UNIVERSITY · PI BIERUT, LAURA J. · 2001 to 2012
$17.3M
PILOT--GENETIC EPIDEMIOLOGY OF ALCOHOL AND TOBACCO CONSUMPTION IN CHINESE SAMPLEP50AA011998 · NIAAA · WASHINGTON UNIVERSITY · PI SHER, KENNETH JAMES · 1999 to 2008
$12.6M
Substance Abuse & Behavioral Disinhibition: Integrating Genes & EnvironmentU01DA024417 · NIDA · UNIVERSITY OF MINNESOTA · PI IACONO, WILLIAM G. · 2007 to 2010
$10.8M
Determinants of Drug Preference in Humans--Administrative SupplementR01DA002812 · NIDA · UNIVERSITY OF CHICAGO · PI DE WIT, HARRIET · 1985 to 2024
$10.6M
THE GENETICS OF VULNERABILITY TO NICOTINE ADDICTIONSR01DA012854 · NIDA · WASHINGTON UNIVERSITY · PI MADDEN, PAMELA ANN · 2000 to 2013
$10.4M
TWIN STUDY OF FEMALE ALCOHOLISMS AND OTHER DISORDERSR01AA009367 · NIAAA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MCGUE, MATTHEW K. · 1992 to 2013
$9.0M
MOLECULAR GENETICS OF SCHIZOPHRENIAR01MH059571 · NIMH · UNIVERSITY OF CHICAGO · PI GEJMAN, PABLO V. · 1999 to 2007
$8.0M
The development of alcohol misuse and related problems from adolescence to early midlifeR01AA015416 · NIAAA · WASHINGTON UNIVERSITY · PI DICK, DANIELLE M, SALVATORE, JESSICA E · 2005 to 2024
$7.6M
Genome Wide Association Coordinating CenterU01HG004446 · NHGRI · UNIVERSITY OF WASHINGTON · PI WEIR, BRUCE S. · 2007 to 2011
$6.6M
Integration of Genomics & Transcriptomics in Normal Twins & Major DepressionRC2MH089951 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SULLIVAN, PATRICK F · 2009 to 2010
$6.5M
Biotechnology and Biological Sciences Research Council BB/F019394/1Chief Scientist Office CZB/4/505Chief Scientist Office CZD/16/6/4Chief Scientist Office ETM/55Medical Research Council G0700704Medical Research Council MC_PC_15018Medical Research Council MC_PC_U127561128Medical Research Council MC_UU_12013/1Medical Research Council MC_UU_12013/3Medical Research Council MC_UU_12013/4Medical Research Council MR/K026992/1NCI NIH HHS P01 CA089392NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS K99 HG006265NHGRI NIH HHS R00 HG006265NHGRI NIH HHS U01 HG004422NHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01 HG004446NIAAA NIH HHS K02 AA018755NIAAA NIH HHS K05 AA000145NIAAA NIH HHS P50 AA011998NIAAA NIH HHS R01 AA007728NIAAA NIH HHS R01 AA009203NIAAA NIH HHS R01 AA009367NIAAA NIH HHS R01 AA011886NIAAA NIH HHS R01 AA012502NIAAA NIH HHS R01 AA013320NIAAA NIH HHS R01 AA013321NIAAA NIH HHS R01 AA015416NIAAA NIH HHS R37 AA007728NIAAA NIH HHS R37 AA012502NIAAA NIH HHS T32 AA007580NIAAA NIH HHS U10 AA008401NIDA NIH HHS K08 DA019951NIDA NIH HHS R01 DA002812NIDA NIH HHS R01 DA012854NIDA NIH HHS R01 DA013240NIDA NIH HHS R01 DA021336NIDA NIH HHS R01 DA024417NIDA NIH HHS R01 DA036216NIDA NIH HHS R21 DA024845NIDA NIH HHS R37 DA005147NIDA NIH HHS R56 DA012854NIDA NIH HHS T32 DA007255NIDA NIH HHS U01 DA024417NIMH NIH HHS R01 MH059565NIMH NIH HHS R01 MH059566NIMH NIH HHS R01 MH059571NIMH NIH HHS R01 MH059586NIMH NIH HHS R01 MH059587NIMH NIH HHS R01 MH059588NIMH NIH HHS R01 MH060870NIMH NIH HHS R01 MH060879NIMH NIH HHS R01 MH061675NIMH NIH HHS R01 MH066140NIMH NIH HHS R01 MH066206NIMH NIH HHS R01 MH067257NIMH NIH HHS R01 MH081802NIMH NIH HHS RC2 MH089951NIMH NIH HHS T32 MH016880NIMH NIH HHS U01 MH046276NIMH NIH HHS U01 MH046289NIMH NIH HHS U01 MH046318NIMH NIH HHS U01 MH079469NIMH NIH HHS U01 MH079470Wellcome Trust 102215Wellcome Trust 104036
6 · The paper itself

Abstract

importanceNeuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases).

objectivesTo identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND

participantsGenome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts.

resultsA genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 < P < .05) and MDD (4.02 × 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE: This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism.

Indexed as

Adaptor Proteins, Signal TransducingAnxiety DisordersCell Adhesion MoleculesCell Adhesion Molecules, NeuronalGenetic Predisposition to DiseaseGenome-Wide Association StudyGuanylate KinasesHumansMajor Depressive DisorderMultifactorial InheritanceNeuroticismPersonalityPolymorphism, Single NucleotideRisk FactorsAdaptor Proteins, Signal TransducingCell Adhesion MoleculesCell Adhesion Molecules, NeuronalGuanylate KinasesMAGI1 protein, human

Identifiers

PMID25993607
PMCPMC4667957
OpenAlexW1914301979

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.