Vitamin D polygenic score is associated with neuroticism and the general psychopathology factor

Abstract Vitamin D, used here to refer to both 25-hydroxyvitamin D, the main circulating form of the vitamin, and 1,25-hydroxyvitamin D, the biologically active form, has been shown to influence brain development and function. Consistent with these findings, low levels of vitamin D have been implicated in various mental disorders, including depression, schizophrenia, and autism. Recently, a shared variance across multiple categories of mental health disorders has been identified and shown to be genetically influenced. This shared variance, thought to represent a general risk for psychopathology, has been termed the p factor. Individuals with high p factor scores are characterized by high neuroticism and low agreeableness and conscientiousness. Here, we investigated the links between vitamin D polygenic scores — derived from the latest genome-wide association study of circulating vitamin D (25-hydroxyvitamin D) levels — the Big Five personality traits (neuroticism, agreeableness, conscientiousness, openness-to-experience, and extraversion), and the p factor, in a sample of 522 (278 women, mean age 20 ± 1 years) non-Hispanic Caucasians. Vitamin D polygenic scores were significantly and negatively associated with neuroticism and the p factor, even after correcting for multiple comparisons, and controlling for sex, age, ancestry, socioeconomic status, and body mass index. Based on previous research implicating neuroticism as a risk factor for psychopathology, mediation was tested. Results showed a significant indirect effect from the vitamin D polygenic score to the p factor via neuroticism. Our findings support a genetic link between vitamin D levels, neuroticism, and the p factor, but due to the cross-sectional nature of our data, future studies are needed to clarify the causal associations between these phenotypes.