Personality traits are the relatively enduring patterns of thoughts, feelings and behaviors that reflect the tendency to respond in certain ways under certain circumstances. Twin and family studies have showed that personality traits are moderately heritable, and can predict various lifetime outcomes, including psychopathology. The Research Domain Criteria characterizes psychiatric diseases as extremes of normal tendencies, including specific personality traits. This implies that heritable variation in personality traits, such as neuroticism, would share a common genetic basis with psychiatric diseases, such as major depressive disorder. Despite considerable efforts over the past several decades, the genetic variants that influence personality are only beginning to be identified. We review these recent and increasingly rapid developments, which focus on the assessment of personality via several commonly used personality questionnaires in healthy human subjects. Study designs covered include twin, linkage, candidate gene association studies, genome‐wide association studies and polygenic analyses. Findings from genetic studies of personality have furthered our understanding about the genetic etiology of personality, which, like neuropsychiatric diseases themselves, is highly polygenic. Polygenic analyses have showed genetic correlations between personality and psychopathology, confirming that genetic studies of personality can help to elucidate the etiology of several neuropsychiatric diseases.
Abraham Palmer and colleagues use genotyping by sequencing to perform genome-wide association studies on CFW mice for behavioral, physiological and gene expression traits. They find many QTLs and incorporate expression QTL analysis to prioritize specific genes at loci of interest that underlie different complex traits. Although mice are the most widely used mammalian model organism, genetic studies have suffered from limited mapping resolution due to extensive linkage disequilibrium (LD) that is characteristic of crosses among inbred strains. Carworth Farms White (CFW) mice are a commercially available outbred mouse population that exhibit rapid LD decay in comparison to other available mouse populations. We performed a genome-wide association study (GWAS) of behavioral, physiological and gene expression phenotypes using 1,200 male CFW mice. We used genotyping by sequencing (GBS) to obtain genotypes at 92,734 SNPs. We also measured gene expression using RNA sequencing in three brain regions. Our study identified numerous behavioral, physiological and expression quantitative trait loci (QTLs). We integrated the behavioral QTL and eQTL results to implicate specific genes, including Azi2 in sensitivity to methamphetamine and Zmynd11 in anxiety-like behavior. The combination of CFW mice, GBS and RNA sequencing constitutes a powerful approach to GWAS in mice.