Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Abstract

Personality is influenced by genetic and environmental factors and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132-260,861). Of these genome-wide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422-18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit-hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion-introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety).

Figure 1. Manhattan plots for personality traits in the combined sample of 23andMe and GPC data (discovery/stage1 sample)

Sample size: Agreeableness: N=76,551; conscientiousness: N=76,551; extraversion: N=122,886; neuroticism: N=122,867; openness: N=76,581. Number of SNPs: Agreeableness: N=2,165,398; conscientiousness: N=2,166,809; extraversion: N=6,343,667; neuroticism: N=6,337,541; openness: N=2,167,320.

Figure 2. Regional association plot

The figure shows the distribution of -log₁₀(p-value) of SNPs on chromosome 8p of the significant SNPs for neuroticism (a) and extraversion (b) in the combined discovery analysis. These two SNPs (LD r²=0.5 in LDlink) have opposite signs of β's in GWAS results of neuroticism and extraversion. The opposite signals might be attributable to negative phenotypic association between neuroticism and extraversion. Regional plots with detailed annotation information for significant SNPs are also shown in Supplementary Fig. 4.

Figure 3. Genetic correlations between personality traits (23andMe sample) and psychiatric disorders

(a) The heat map illustrates genetic correlations between phenotypes. The values in the color squares correspond to genetic correlations. Asterisks denote genetic correlations significantly different from zero: * P<0.05; ** P<0.00091 (Bonferroni correction threshold). (b) The loading plot shows loadings of the personality traits and psychiatric disorders on the first two principal components derived from the genetic correlation matrix on the left. A small angle between arrows indicates a high correlation between variables and arrows pointing to opposite directions indicate a negative correlation in the space of the two principal components.