Genome-wide association scan for five major dimensions of personality

Personality traits are summarized by five broad dimensions with pervasive influences on major life outcomes, strong links to psychiatric disorders and clear heritable components. To identify genetic variants associated with each of the five dimensions of personality we performed a genome-wide association (GWA) scan of 3972 individuals from a genetically isolated population within Sardinia, Italy. On the basis of the analyses of 362 129 single-nucleotide polymorphisms we found several strong signals within or near genes previously implicated in psychiatric disorders. They include the association of neuroticism with SNAP25 (rs362584, P= 5 x 10(-5)), extraversion with BDNF and two cadherin genes (CDH13 and CDH23; Ps<5 x 10(-5)), openness with CNTNAP2 (rs10251794, P= 3 x 10(-5)), agreeableness with CLOCK (rs6832769, P= 9 x 10(-6)) and conscientiousness with DYRK1A (rs2835731, P= 3 x 10(-5)). Effect sizes were small (less than 1% of variance), and most failed to replicate in the follow-up independent samples (N up to 3903), though the association between agreeableness and CLOCK was supported in two of three replication samples (overall P= 2 x 10(-5)). We infer that a large number of loci may influence personality traits and disorders, requiring larger sample sizes for the GWA approach to confidently identify associated genetic variants. Molecular Psychiatry (2010) 15, 647-656; doi: 10.1038/mp.2008.113; published online 28 October 2008