Genetic variation in the hypothalamic-pituitary-adrenocortical axis regulatory factor, T-box 19, and the angry/hostility personality trait.

Neurotic personality traits are important factors in several psychiatric disorders and suicidal behavior. Here, we have investigated the existence of potential relationships between neurotic personality traits and genetic variation. Non-suicidal parents derived from trios (suicide attempter and both parents) and non-suicidal volunteers, examined by the Neuroticism, Extraversion and Openness (NEO) Personality Inventory - Revised (NEO PI-R), were divided into screening and replication samples. The screening sample (n= 127) was used to select potential relationships between neurotic personality traits and genetic variation among 130 single nucleotide polymorphisms (SNPs). Screening (analysis of variance) with regard to the personality dimension neuroticism indicated potential relationships at three different loci. More detailed analysis of these three SNPs at NEO PI-R facet level indicated four potential relationships. T-test analysis in the replication sample (n= 617) was used to retest the relationships indicated during screening. One of those relationships was confirmed in the replication sample (P= 0.0052; Bonferroni correction), indicating that genetic variation at the human T-box 19 (TBX19) locus is related to the personality trait angry/hostility. Furthermore, using analysis of haplotypes among trios by transmission disequilibrium test and its extension, the family-based association test, overtransmission of a haplotype GAC at the TBX19 locus was associated with increased angry/hostility scores among suicide attempters (P= 0.009; Bonferroni correction). This is to our knowledge the first report on the association of the angry hostility personality trait with genetic variation at the TBX19 locus, an important regulator of the hypothalamic-pituitary-adrenocortical axis.