Effects of genome-wide neuroticism-associated variants on five-factor model personality traits in schizophrenia

Patients with schizophrenia (SCZ) have characteristic personality traits compared with healthy subjects. Genome-wide significant variants for neuroticism have been reported in healthy subjects. However, the associations of these genome-wide neuroticism-associated variants with five-factor personality traits in patients with SCZ are less clear. We investigated the influences of nine independent genome-wide significant variants for neuroticism on five-factor personality traits (neuroticism, extraversion, openness, agreeableness, and conscientiousness) assessed by the NEO Five-Factor Inventory (NEO-FFI) in 107 patients with SCZ and 119 healthy controls (HCs). As expected, patients with SCZ scored significantly higher for neuroticism and lower for extraversion, openness, agreeableness and conscientiousness than HCs (p < 0.05). Of nine neuroticism-associated variants, the T allele at rs4653663 related to lower neuroticism was only significantly associated with lower neuroticism in patients with SCZ (β = -0.27, p = 3.88 × 10^-3) and in combined subjects (β = -0.15, p = 0.026). Furthermore, of other personality traits, the genetic variant was significantly associated with higher agreeableness in combined subjects (β = 0.17, p = 9.41×10^-3), higher conscientiousness in patients with SCZ (β = 0.21, p = 0.031) and lower conscientiousness in HCs (β = -0.20, p = 0.034), and nominally associated with higher extraversion in patients with SCZ (β = 0.18, p = 0.056) and in combined subjects (β = 0.13, p = 0.051). These outcomes were not affected by clinical variables. We suggest that genome-wide neuroticism-associated variant could be associated with neuroticism as well as other personality traits in schizophrenia.