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

By Michelle Luciano, Saskia P Hagenaars, Gail Davies, William David Hill, Toni-Kim Clarke, Masoud Shirali, Riccardo 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

Posted 28 Jul 2017
bioRxiv DOI: 10.1101/168906 (published DOI: 10.1038/s41588-017-0013-8)

Neuroticism is a stable personality trait; twin studies report heritability between 30% and 50%, and SNP-based heritability is about 15%. Higher levels of neuroticism are associated with poorer mental and physical health, and the economic burden of neuroticism for societies is high. To date, genome-wide association (GWA) studies of neuroticism have identified up to 11 genetic loci. 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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