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
27067015
TITLE
Genome-wide analysis of over 106?000 individuals identifies 9 neuroticism-associated loci.
ABSTRACT
Neuroticism is a personality trait of fundamental importance for psychological well-being and public health. It is strongly associated with major depressive disorder (MDD) and several other psychiatric conditions. Although neuroticism is heritable, attempts to identify the alleles involved in previous studies have been limited by relatively small sample sizes. Here we report a combined meta-analysis of genome-wide association study (GWAS) of neuroticism that includes 91 370 participants from the UK Biobank cohort, 6659 participants from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and 8687 participants from a QIMR (Queensland Institute of Medical Research) Berghofer Medical Research Institute (QIMR) cohort. All participants were assessed using the same neuroticism instrument, the Eysenck Personality Questionnaire-Revised (EPQ-R-S) Short Form's Neuroticism scale. We found a single-nucleotide polymorphism-based heritability estimate for neuroticism of ∼15% (s.e.=0.7%). Meta-analysis identified nine novel loci associated with neuroticism. The strongest evidence for association was at a locus on chromosome 8 (P=1.5 × 10(-15)) spanning 4 Mb and containing at least 36 genes. Other associated loci included interesting candidate genes on chromosome 1 (GRIK3 (glutamate receptor ionotropic kainate 3)), chromosome 4 (KLHL2 (Kelch-like protein 2)), chromosome 17 (CRHR1 (corticotropin-releasing hormone receptor 1) and MAPT (microtubule-associated protein Tau)) and on chromosome 18 (CELF4 (CUGBP elav-like family member 4)). We found no evidence for genetic differences in the common allelic architecture of neuroticism by sex. By comparing our findings with those of the Psychiatric Genetics Consortia, we identified a strong genetic correlation between neuroticism and MDD and a less strong but significant genetic correlation with schizophrenia, although not with bipolar disorder. Polygenic risk scores derived from the primary UK Biobank sample captured ∼1% of the variance in neuroticism in the GS:SFHS and QIMR samples, although most of the genome-wide significant alleles identified within a UK Biobank-only GWAS of neuroticism were not independently replicated within these cohorts. The identification of nine novel neuroticism-associated loci will drive forward future work on the neurobiology of neuroticism and related phenotypes.
DATE PUBLISHED
2016 Jun
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2015/11/20
revised 2016/02/19
accepted 2016/03/02
aheadofprint 2016/04/12
entrez 2016/04/13 06:00
pubmed 2016/04/14 06:00
medline 2016/04/14 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Smith DJ Smith D J DJ Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Escott-Price V Escott-Price V V MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Davies G Davies G G Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
Bailey ME Bailey M E S ME School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Colodro-Conde L Colodro-Conde L L QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
Ward J Ward J J Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Vedernikov A Vedernikov A A MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Marioni R Marioni R R Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Cullen B Cullen B B Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Lyall D Lyall D D Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Hagenaars SP Hagenaars S P SP Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
Liewald DC Liewald D C M DC Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
Luciano M Luciano M M Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
Gale CR Gale C R CR MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.
Ritchie SJ Ritchie S J SJ Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
Hayward C Hayward C C Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Nicholl B Nicholl B B Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Bulik-Sullivan B Bulik-Sullivan B B Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Adams M Adams M M Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Couvy-Duchesne B Couvy-Duchesne B B QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
Graham N Graham N N Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Mackay D Mackay D D Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Evans J Evans J J Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Smith BH Smith B H BH Division of Population Health Sciences, University of Dundee, Dundee, UK.
Porteous DJ Porteous D J DJ Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Medland SE Medland S E SE QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
Martin NG Martin N G NG QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
Holmans P Holmans P P MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
McIntosh AM McIntosh A M AM Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Pell JP Pell J P JP Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Deary IJ Deary I J IJ Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
O'Donovan MC O'Donovan M C MC MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
INVESTIGATORS
JOURNAL
VOLUME: 21
ISSUE: 6
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2016
MONTH: Jun
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
104036 Wellcome Trust United Kingdom
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OTHERID SOURCE
PMC4879189 NLM