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.

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