Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism

作者：Luciano Michelle^*; Hagenaars Saskia P.; Davies Gail; Hill W. David; Clarke Toni-Kim; Shirali Masoud; Harris Sarah E.; Marioni Riccardo E.; Liewald David C.; Fawns-Ritchie Chloe; Adams Mark J.; Howard David M.; Lewis Cathryn M.^*; Gale Catharine R.; McIntosh Andrew M.; Deary Ian J.

来源：Nature Genetics, 2018, 50(1): 6-+.

DOI：10.1038/s41588-017-0013-8

Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt) 1; heritability estimated from twin studies ranges from 30 to 50%(2), and SNP-based heritability ranges from 6 to 15%(3-6). Increased neuroticism is associated with poorer mental and physical health(7,8), translating to high economic burden(9). Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci(3,4). Here we report 116 significant independent loci from a GWAS of neuroticism in 329,821 UK Biobank participants; 15 of these loci replicated at P < 0.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (r(g) = 0.82, standard error (s.e.) = 0.03), major depressive disorder (MDD; r(g) = 0.69, s.e. = 0.07) and subjective well-being (r(g) = -0.68, s.e. = 0.03) alongside other mental health traits. These discoveries significantly advance understanding of neuroticism and its association with MDD.

• 出版日期2018-1