Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
25993607
TITLE
Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder.
ABSTRACT
IMPORTANCE NlmCategory: OBJECTIVE
Neuroticism 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).
OBJECTIVES NlmCategory: OBJECTIVE
To 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 PARTICIPANTS NlmCategory: METHODS
Genome-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 NlmCategory: METHODS
Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts.
RESULTS NlmCategory: RESULTS
A 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 NlmCategory: CONCLUSIONS
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.
DATE PUBLISHED
2015 Jul
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2015/05/21 06:00
pubmed 2015/05/21 06:00
medline 2015/09/15 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Genetics of Personality Consortium
de Moor MH de Moor Marleen H M MH Department 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.
van den Berg SM van den Berg Stéphanie M SM Department of Research Methodology, Measurement, and Data Analysis, University of Twente, Enschede, the Netherlands.
Verweij KJ Verweij Karin J H KJ Department of Developmental Psychology, EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, the Netherlands6QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Krueger RF Krueger Robert F RF Department of Psychology, University of Minnesota, Minneapolis.
Luciano M Luciano Michelle M Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland9Department of Psychology, University of Edinburgh, Edinburgh, Scotland.
Arias Vasquez A Arias Vasquez Alejandro A Department 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.
Matteson LK Matteson Lindsay K LK Department of Psychology, University of Minnesota, Minneapolis.
Derringer J Derringer Jaime J Department of Psychology, University of Illinois at Urbana-Champaign, Champaign.
Esko T Esko Tõnu T Estonian Genome Center, University of Tartu, Tartu, Estonia.
Amin N Amin Najaf N Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Gordon SD Gordon Scott D SD QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Hansell NK Hansell Narelle K NK QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Hart AB Hart Amy B AB Department of Human Genetics, University of Chicago, Chicago, Illinois.
Seppälä I Seppälä Ilkka I Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
Huffman JE Huffman Jennifer E JE Medical Research Council Human Genetics, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland.
Konte B Konte Bettina B Department of Psychiatry, University of Halle, Halle, Germany.
Lahti J Lahti Jari J Folkhälsan Research Center, Helsinki, Finland22Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Lee M Lee Minyoung M Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond.
Miller M Miller Mike M Department of Psychology, University of Minnesota, Minneapolis.
Nutile T Nutile Teresa T Institute of Genetics and Biophysics "A. Buzzati-Traverso," National Research Council of Italy, Naples, Italy.
Tanaka T Tanaka Toshiko T National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Teumer A Teumer Alexander A Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Viktorin A Viktorin Alexander A Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Wedenoja J Wedenoja Juho J Department of Public Health, University of Helsinki, Helsinki, Finland.
Abecasis GR Abecasis Goncalo R GR Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor.
Adkins DE Adkins Daniel E DE Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond.
Agrawal A Agrawal Arpana A Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri.
Allik J Allik Jüri J Department of Psychology, University of Tartu, Tartu, Estonia33Estonian Academy of Sciences, Tallinn, Estonia.
Appel K Appel Katja K Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Bigdeli TB Bigdeli Timothy B TB Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond.
Busonero F Busonero Fabio F Istituto di Ricerca Genetica e Biomedica, National Research Council of Italy, Monserrato, Italy.
Campbell H Campbell Harry H Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
Costa PT Costa Paul T PT Behavioral Medicine Research Center, Duke University School of Medicine, Durham, North Carolina.
Davey Smith G Davey Smith George G Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, England.
Davies G Davies Gail G Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland9Department of Psychology, University of Edinburgh, Edinburgh, Scotland.
de Wit H de Wit Harriet H Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois.
Ding J Ding Jun J National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Engelhardt BE Engelhardt Barbara E BE Department of Computer Science, Princeton University, Princeton, New Jersey.
Eriksson JG Eriksson Johan G JG Folkhälsan 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.
Fedko IO Fedko Iryna O IO Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
Ferrucci L Ferrucci Luigi L National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Franke B Franke Barbara B Donders 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.
Giegling I Giegling Ina I Department of Psychiatry, University of Halle, Halle, Germany.
Grucza R Grucza Richard R Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri.
Hartmann AM Hartmann Annette M AM Department of Psychiatry, University of Halle, Halle, Germany.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri.
Heinonen K Heinonen Kati K Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Henders AK Henders Anjali K AK QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Homuth G Homuth Georg G Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
Hottenga JJ Hottenga Jouke-Jan JJ Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
Iacono WG Iacono William G WG Department of Psychology, University of Minnesota, Minneapolis.
Janzing J Janzing Joost J Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
Jokela M Jokela Markus M Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Karlsson R Karlsson Robert R Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Kemp JP Kemp John P JP Medical 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.
Kirkpatrick MG Kirkpatrick Matthew G MG Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois.
Latvala A Latvala Antti A Department of Public Health, University of Helsinki, Helsinki, Finland43National Institute for Health and Welfare, Helsinki, Finland.
Lehtimäki T Lehtimäki Terho T Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
Liewald DC Liewald David C DC Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland9Department of Psychology, University of Edinburgh, Edinburgh, Scotland.
Madden PA Madden Pamela A F PA Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri.
Magri C Magri Chiara C Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Magnusson PK Magnusson Patrik K E PK Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Marten J Marten Jonathan J Medical Research Council Human Genetics, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland.
Maschio A Maschio Andrea A Istituto di Ricerca Genetica e Biomedica, National Research Council of Italy, Monserrato, Italy.
Medland SE Medland Sarah E SE QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Mihailov E Mihailov Evelin E Estonian Genome Center, University of Tartu, Tartu, Estonia47Department of Biotechnology, University of Tartu, Tartu, Estonia.
Milaneschi Y Milaneschi Yuri Y Department of Psychiatry, EMGO+ Institute, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Nauck M Nauck Matthias M Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
Ouwens KG Ouwens Klaasjan G KG Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
Palotie A Palotie Aarno A Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, England51Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Pettersson E Pettersson Erik E Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Polasek O Polasek Ozren O Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.
Qian Y Qian Yong Y National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Pulkki-Råback L Pulkki-Råback Laura L Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Raitakari OT Raitakari Olli T OT Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland54Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Realo A Realo Anu A Department of Psychology, University of Tartu, Tartu, Estonia.
Rose RJ Rose Richard J RJ Department of Psychological and Brain Sciences, Indiana University, Bloomington.
Ruggiero D Ruggiero Daniela D Institute of Genetics and Biophysics "A. Buzzati-Traverso," National Research Council of Italy, Naples, Italy.
Schmidt CO Schmidt Carsten O CO Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Slutske WS Slutske Wendy S WS Department of Psychological Sciences and Missouri Alcoholism Research Center, University of Missouri, Columbia.
Sorice R Sorice Rossella R Institute of Genetics and Biophysics "A. Buzzati-Traverso," National Research Council of Italy, Naples, Italy.
Starr JM Starr John M JM Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland57Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, Scotland.
St Pourcain B St Pourcain Beate B Medical 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.
Sutin AR Sutin Angelina R AR National Institute on Aging, National Institutes of Health, Baltimore, Maryland60College of Medicine, Florida State University, Tallahassee.
Timpson NJ Timpson Nicholas J NJ Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, England.
Trochet H Trochet Holly H Medical Research Council Human Genetics, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland.
Vermeulen S Vermeulen Sita S Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands61Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands.
Vuoksimaa E Vuoksimaa Eero E Department of Public Health, University of Helsinki, Helsinki, Finland.
Widen E Widen Elisabeth E Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Wouda J Wouda Jasper J Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands4Department of Research Methodology, Measurement, and Data Analysis, University of Twente, Enschede, the Netherlands.
Wright MJ Wright Margaret J MJ QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Zgaga L Zgaga Lina L Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland62Department of Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland.
Porteous D Porteous David D Medical Genetics Section, University of Edinburgh, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland.
Minelli A Minelli Alessandra A Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Palmer AA Palmer Abraham A AA Department of Human Genetics, University of Chicago, Chicago, Illinois39Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois.
Rujescu D Rujescu Dan D Department of Psychiatry, University of Halle, Halle, Germany.
Ciullo M Ciullo Marina M Institute of Genetics and Biophysics "A. Buzzati-Traverso," National Research Council of Italy, Naples, Italy.
Hayward C Hayward Caroline C Medical 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.
Rudan I Rudan Igor I Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
Metspalu A Metspalu Andres A Estonian Genome Center, University of Tartu, Tartu, Estonia33Estonian Academy of Sciences, Tallinn, Estonia.
Kaprio J Kaprio Jaakko J Department of Public Health, University of Helsinki, Helsinki, Finland43National Institute for Health and Welfare, Helsinki, Finland51Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Deary IJ Deary Ian J IJ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland9Department of Psychology, University of Edinburgh, Edinburgh, Scotland.
Räikkönen K Räikkönen Katri K Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Wilson JF Wilson James F JF Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
Keltikangas-Järvinen L Keltikangas-Järvinen Liisa L Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Bierut LJ Bierut Laura J LJ Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri.
Hettema JM Hettema John M JM Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond.
Grabe HJ Grabe Hans J HJ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany65Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund, Stralsund, Germany.
van Duijn CM van Duijn Cornelia M CM Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Evans DM Evans David M DM Medical 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.
Schlessinger D Schlessinger David D National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Pedersen NL Pedersen Nancy L NL Institute of Genetics and Biophysics "A. Buzzati-Traverso," National Research Council of Italy, Naples, Italy.
Terracciano A Terracciano Antonio A Folkhälsan Research Center, Helsinki, Finland60College of Medicine, Florida State University, Tallahassee.
McGue M McGue Matt M Department of Psychology, University of Minnesota, Minneapolis66Institute of Public Health, University of Southern Denmark, Odense, Denmark.
Penninx BW Penninx Brenda W J H BW Department of Psychiatry, EMGO+ Institute, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
INVESTIGATORS
JOURNAL
VOLUME: 72
ISSUE: 7
TITLE: JAMA psychiatry
ISOABBREVIATION: JAMA Psychiatry
YEAR: 2015
MONTH: Jul
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2168-6238
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: JAMA Psychiatry
COUNTRY: United States
ISSNLINKING: 2168-622X
NLMUNIQUEID: 101589550
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
104036 Wellcome Trust United Kingdom
BB/F019394/1 Biotechnology and Biological Sciences Research Council United Kingdom
CZB/4/505 Chief Scientist Office United Kingdom
CZD/16/6/4 Chief Scientist Office United Kingdom
ETM/55 Chief Scientist Office United Kingdom
G0700704 Medical Research Council United Kingdom
MC_PC_15018 Medical Research Council United Kingdom
MC_PC_U127561128 Medical Research Council United Kingdom
MC_UU_12013/3 Medical Research Council United Kingdom
MR/K026992/1 Medical Research Council United Kingdom
R01 DA013240 NIDA NIH HHS United States
R01 DA024417 NIDA NIH HHS United States
R01 DA036216 NIDA NIH HHS United States
R37 DA005147 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Anxiety Disorders psychology
Cell Adhesion Molecules, Neuronal genetics
Depressive Disorder, Major psychology
Genetic Predisposition to Disease psychology
Genome-Wide Association Study psychology
Humans psychology
Multifactorial Inheritance psychology
Personality genetics
Polymorphism, Single Nucleotide genetics
Risk Factors genetics
SUPPLEMENTARY MESH
SUPPLMESHNAME SUPPLMESHTYPE
Neuroticism Disease
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Cell Adhesion Molecules, Neuronal
0 MAGI1 protein, human
OTHER ID's
OTHERID SOURCE
NIHMS738804 NLM
PMC4667957 NLM