Neuroticism is a relatively stable personality trait –– characterized by negative emotionality (for example, worry and guilt). Clearly the trait of neuroticism would be regarded as multifactorial, i.e. contributions of hundreds if not thousands of genes, plus epigenetic factors, plus environmental effects. Heritability estimated from twin studies ranges from 30% to 50% “heritable”, and DNA-variant-based heritability ranges from 6% to 15%. Increased neuroticism is also associated with poor mental and physical health, translating to a high economic burden.
The strong genetic correlation between neuroticism and mental health, especially anxiety and major depressive disorder (MDD), means that exploring genetic contribution to differences in neuroticism is one way to understand more about these common and burdensome illnesses. In the largest genome-wide association study (GWAS) of MDD –– 130,664 cases versus 330,470 controls –– 44 independent associated genetic loci were identified, and as many as 11 genetic loci have been associated with neuroticism.
Authors [see attached] report 116 significant independent loci from a GWAS of neuroticism in 329,821 UK Biobank participants; 15 of these loci were replicated at P <0.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and brain-differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (rg = 0.82), MDD (rg = 0.69), and subjective well-being (rg = –0.68) together with other mental health traits. These data should help advance our understanding of neuroticism and its association with MDD. Nat Genet Jan 2o18; 50: 6–10