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

Autor:	de Moor 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; Department of Research Methodology, Measurement, and Data Analysis, University of Twente, Enschede, the Netherlands., Verweij 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; Department of Psychology, University of Minnesota, Minneapolis., Luciano M; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland9Department of Psychology, University of Edinburgh, Edinburgh, Scotland., Arias Vasquez 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; Department of Psychology, University of Minnesota, Minneapolis., Derringer J; Department of Psychology, University of Illinois at Urbana-Champaign, Champaign., Esko T; Estonian Genome Center, University of Tartu, Tartu, Estonia., Amin N; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands., Gordon SD; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia., Hansell NK; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia., Hart AB; Department of Human Genetics, University of Chicago, Chicago, Illinois., Seppälä I; Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland., Huffman JE; Medical Research Council Human Genetics, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland., Konte B; Department of Psychiatry, University of Halle, Halle, Germany., Lahti J; Folkhälsan Research Center, Helsinki, Finland22Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland., Lee M; Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond., Miller M; Department of Psychology, University of Minnesota, Minneapolis., Nutile T; Institute of Genetics and Biophysics 'A. Buzzati-Traverso,' National Research Council of Italy, Naples, Italy., Tanaka T; National Institute on Aging, National Institutes of Health, Baltimore, Maryland., Teumer A; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany., Viktorin A; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Wedenoja J; Department of Public Health, University of Helsinki, Helsinki, Finland., Abecasis GR; Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor., Adkins DE; Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond., Agrawal A; Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri., Allik J; Department of Psychology, University of Tartu, Tartu, Estonia33Estonian Academy of Sciences, Tallinn, Estonia., Appel K; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany., Bigdeli TB; Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond., Busonero F; Istituto di Ricerca Genetica e Biomedica, National Research Council of Italy, Monserrato, Italy., Campbell H; Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland., Costa PT; Behavioral Medicine Research Center, Duke University School of Medicine, Durham, North Carolina., Davey Smith G; Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, England., Davies G; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland9Department of Psychology, University of Edinburgh, Edinburgh, Scotland., de Wit H; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois., Ding J; National Institute on Aging, National Institutes of Health, Baltimore, Maryland., Engelhardt BE; Department of Computer Science, Princeton University, Princeton, New Jersey., Eriksson 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; Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands., Ferrucci L; National Institute on Aging, National Institutes of Health, Baltimore, Maryland., Franke 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; Department of Psychiatry, University of Halle, Halle, Germany., Grucza R; Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri., Hartmann AM; Department of Psychiatry, University of Halle, Halle, Germany., Heath AC; Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri., Heinonen K; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland., Henders AK; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia., Homuth G; Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany., Hottenga JJ; Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands., Iacono WG; Department of Psychology, University of Minnesota, Minneapolis., Janzing J; Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands., Jokela M; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland., Karlsson R; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Kemp 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; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois., Latvala A; Department of Public Health, University of Helsinki, Helsinki, Finland43National Institute for Health and Welfare, Helsinki, Finland., Lehtimäki T; Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland., Liewald DC; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland9Department of Psychology, University of Edinburgh, Edinburgh, Scotland., Madden PA; Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri., Magri C; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Magnusson PK; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Marten J; Medical Research Council Human Genetics, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland., Maschio A; Istituto di Ricerca Genetica e Biomedica, National Research Council of Italy, Monserrato, Italy., Medland SE; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia., Mihailov E; Estonian Genome Center, University of Tartu, Tartu, Estonia47Department of Biotechnology, University of Tartu, Tartu, Estonia., Milaneschi Y; Department of Psychiatry, EMGO+ Institute, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands., Montgomery GW; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia., Nauck M; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany., Ouwens KG; Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands., Palotie A; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, England51Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland., Pettersson E; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Polasek O; Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia., Qian Y; National Institute on Aging, National Institutes of Health, Baltimore, Maryland., Pulkki-Råback L; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland., Raitakari 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; Department of Psychology, University of Tartu, Tartu, Estonia., Rose RJ; Department of Psychological and Brain Sciences, Indiana University, Bloomington., Ruggiero D; Institute of Genetics and Biophysics 'A. Buzzati-Traverso,' National Research Council of Italy, Naples, Italy., Schmidt CO; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany., Slutske WS; Department of Psychological Sciences and Missouri Alcoholism Research Center, University of Missouri, Columbia., Sorice R; Institute of Genetics and Biophysics 'A. Buzzati-Traverso,' National Research Council of Italy, Naples, Italy., Starr 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; 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; National Institute on Aging, National Institutes of Health, Baltimore, Maryland60College of Medicine, Florida State University, Tallahassee., Timpson NJ; Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, England., Trochet H; Medical Research Council Human Genetics, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland., Vermeulen 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; Department of Public Health, University of Helsinki, Helsinki, Finland., Widen E; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland., Wouda 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; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia., Zgaga 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; 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; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Palmer AA; Department of Human Genetics, University of Chicago, Chicago, Illinois39Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois., Rujescu D; Department of Psychiatry, University of Halle, Halle, Germany., Ciullo M; Institute of Genetics and Biophysics 'A. Buzzati-Traverso,' National Research Council of Italy, Naples, Italy., Hayward 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; Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland., Metspalu A; Estonian Genome Center, University of Tartu, Tartu, Estonia33Estonian Academy of Sciences, Tallinn, Estonia., Kaprio 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; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland9Department of Psychology, University of Edinburgh, Edinburgh, Scotland., Räikkönen K; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland., Wilson JF; Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland., Keltikangas-Järvinen L; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland., Bierut LJ; Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri., Hettema JM; Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond., Grabe HJ; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany65Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund, Stralsund, Germany., van Duijn CM; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands., Evans 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; National Institute on Aging, National Institutes of Health, Baltimore, Maryland., Pedersen NL; Institute of Genetics and Biophysics 'A. Buzzati-Traverso,' National Research Council of Italy, Naples, Italy., Terracciano A; Folkhälsan Research Center, Helsinki, Finland60College of Medicine, Florida State University, Tallahassee., McGue M; Department of Psychology, University of Minnesota, Minneapolis66Institute of Public Health, University of Southern Denmark, Odense, Denmark., Penninx BW; Department of Psychiatry, EMGO+ Institute, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands., Martin NG; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia., Boomsma DI; Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
Jazyk:	angličtina
Zdroj:	JAMA psychiatry [JAMA Psychiatry] 2015 Jul; Vol. 72 (7), pp. 642-50.
DOI:	10.1001/jamapsychiatry.2015.0554
Abstrakt:	Importance: 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: 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: 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: 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: 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: 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.
Databáze:	MEDLINE
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