Genes for personality traits: implications for psychopathology

Abstract

Although 30–60% of the variance in many personality traits is inherited, until recently, little was known about the genes responsible. Preliminary studies of family history in bipolar disorder and of X-linkage of personality traits in colour-blindness suggested a ‘quantitative trait locus’ (QTL) approach to the genetics of normal personality. In methodically similar but independent studies of 124 Israeli and 315 American normal volunteers, an association was found between the dopamine D4 receptor gene (D4DR) and the personality trait of novelty-seeking. In the Israeli sample there was preliminary evidence for an interaction between the D4DR gene and the serotonin 2C receptor gene (5-HT-2C), with a marked effect on the trait of reward dependence. In addition to receptors, monoamine uptake mechanisms, such as the serotonin transporter (5-HTT), are candidate genes for personality traits. 5-HTT gene transcription is modulated by a frequent polymorphism in its promoter region, with resulting effects on 5-HTT expression and 5-HT uptake. In an extended American sample totalling 505 subjects, the 5-HTT polymorphism was associated with anxiety- and depression-related personality traits. The allelic variation in functional expression of the 5-HTT may also be a susceptibility factor for disorders of the affective spectrum. Further investigation of genes for personality traits may provide additional links between normal personality and psychiatric illness.