Abstract

Human personality (i.e., temperament and character) is a complex trait related to mental health, influenced by genetic and environmental factors. Despite the efforts performed during the past decades, its genetic background is only just beginning to be identified. With the aim of dissecting the genetic basis of temperament, we performed a Genome-Wide Association Study (GWAS) on Cloninger’s Temperament and Character Inventory in 587 individuals belonging to different Italian genetic isolates. Data analysis led to the identification of four new genes associated with different temperament scales, such as Novelty Seeking (NS), Harm Avoidance (HA), and Reward Dependence (RD). In detail, we identified suggestive and significant associations between: MAGI2 (highest p-value = 9.14 × 10−8), a gene already associated with schizophrenia and depressive disorder, and the NS–Extravagance scale; CALCB (highest p-value = 4.34 × 10−6), a gene likely involved in the behavioral evolution from wild wolf to domestic dog, and the NS–Disorderliness scale; BTBD3 (highest p-value = 2.152 × 10−8), a gene already linked to obsessive–compulsive disorder, and the HA–Fatigability scale; PRKN (highest p-value = 8.27 × 10−9), a gene described for early onset Parkinson’s disease, and the RD scale. Our work provides new relevant insights into the genetics of temperament, helping to elucidate the molecular basis of psychiatric disorders.

Highlights

  • Human personality is a complex trait resulting from the innate predisposition to respond to external stimuli and interaction with environmental factors [1]

  • Regarding GTEx analysis, we found an association between the top SNP rs10832317 and the expression level of CALCB gene in brain–cerebellum

  • MAGI2 has been associated with Alzheimer0 s Disease (AD) [23] and it has been proposed as a candidate transcriptomic biomarker of AD [24]

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Summary

Introduction

Human personality is a complex trait resulting from the innate predisposition to respond to external stimuli and interaction with environmental factors [1]. Twins, and adopted children demonstrated that personality is strongly biologically determined, showing that its heritability ranges between 30% and 60% [2,3]. To date, genome-wide association studies (GWAS) allowed only a limited portion of the heritable component to be highlighted, suggesting that the understanding of the link between genetic variants and personality remains challenging [4]

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