Genetic architecture of the personality meta-traits - stability and plasticity - and their overlap with psychopathology

Abstract

The Five-Factor model (FFM) personality traits (agreeableness, conscientiousness, extraversion, neuroticism and openness) capture stable individual differences in thinking, feeling and behaviour. It has been shown that the FFM traits share variance through two-higher order "meta-traits", stability and plasticity. It remains unknown, however, whether these meta-traits can capture the shared genetic architecture of the FFM personality traits. Here we combined recent genome-wide association study (GWAS) summary statistics with data from the 23andMe Research Institute (European ancestry; total N = 279,240-682,707) and applied Genomic Structural Equation Modelling, identifying two latent genetic factors consistent with stability and plasticity. We then performed a multivariate GWAS on these factors to capture genetic loci with shared effects across the FFM traits, identifying 81 and 13 independent genome-wide significant loci for stability and plasticity respectively. Transcriptome-wide and cell-type enrichment analyses prioritised candidate effector genes and indicated broad brain involvement for personality traits. Finally, genetic correlation and pleiotropy-aware Mendelian randomisation analyses provided genetic evidence suggesting bi-directional links between stability and psychopathology: higher genetic propensity for stability was protective against psychopathology, whereas greater genetic liability to psychopathology was associated with reduced stability. These results enhance our understanding of the shared genetic architecture underlying personality traits and their overlap with psychopathology.