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116 independent genetic variants influence the neuroticism personality trait in over 329,000 UK Biobank individuals

Michelle Luciano, Saskia P Hagenaars, Gail Davies, W David Hill, Toni-Kim Clarke, Masoud Shirali, Riccardo E Marioni, Sarah E Harris, David C Liewald, Chloe Fawns-Ritchie, Mark J Adams, David M Howard, Cathryn M Lewis, Catharine R. Gale, Andrew M McIntosh, Ian J Deary
doi: https://doi.org/10.1101/168906
Michelle Luciano
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
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  • For correspondence: michelle.luciano@ed.ac.uk
Saskia P Hagenaars
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
2MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK
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Gail Davies
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
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W David Hill
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
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Toni-Kim Clarke
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
3Division of Psychiatry, University of Edinburgh, Edinburgh, UK
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Masoud Shirali
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
3Division of Psychiatry, University of Edinburgh, Edinburgh, UK
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Riccardo E Marioni
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
4Centre for Genomic & Experimental Medicine, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK
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Sarah E Harris
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
4Centre for Genomic & Experimental Medicine, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK
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David C Liewald
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
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Chloe Fawns-Ritchie
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
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Mark J Adams
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
3Division of Psychiatry, University of Edinburgh, Edinburgh, UK
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David M Howard
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
3Division of Psychiatry, University of Edinburgh, Edinburgh, UK
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Cathryn M Lewis
2MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK
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Catharine R. Gale
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
5MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
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Andrew M McIntosh
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
3Division of Psychiatry, University of Edinburgh, Edinburgh, UK
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Ian J Deary
1Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK
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Abstract

Neuroticism is a stable personality trait 1; twin studies report heritability between 30% and 50% 2, and SNP-based heritability is about 15% 3. Higher levels of neuroticism are associated with poorer mental and physical health 4,5, and the economic burden of neuroticism for societies is high 6. To date, genome-wide association (GWA) studies of neuroticism have identified up to 11 genetic loci 3,7. Here we report 116 significant independent genetic loci from a GWA of neuroticism in 329,821 UK Biobank participants, with replication available in a GWA meta-analysis of neuroticism in 122,867 individuals. Genetic signals for neuroticism were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (rg = .82, SE=.03), major depressive disorder (rg = .69, SE=.07) and subjective wellbeing (rg = -.68, SE=.03) alongside other mental health traits. These discoveries significantly advance our understanding of neuroticism and its association with major depressive disorder.

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Posted July 28, 2017.
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116 independent genetic variants influence the neuroticism personality trait in over 329,000 UK Biobank individuals
Michelle Luciano, Saskia P Hagenaars, Gail Davies, W David Hill, Toni-Kim Clarke, Masoud Shirali, Riccardo E Marioni, Sarah E Harris, David C Liewald, Chloe Fawns-Ritchie, Mark J Adams, David M Howard, Cathryn M Lewis, Catharine R. Gale, Andrew M McIntosh, Ian J Deary
bioRxiv 168906; doi: https://doi.org/10.1101/168906
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116 independent genetic variants influence the neuroticism personality trait in over 329,000 UK Biobank individuals
Michelle Luciano, Saskia P Hagenaars, Gail Davies, W David Hill, Toni-Kim Clarke, Masoud Shirali, Riccardo E Marioni, Sarah E Harris, David C Liewald, Chloe Fawns-Ritchie, Mark J Adams, David M Howard, Cathryn M Lewis, Catharine R. Gale, Andrew M McIntosh, Ian J Deary
bioRxiv 168906; doi: https://doi.org/10.1101/168906

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