Genome-wide association scan for five major dimensions of personality

Abstract

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 singlenucleotide 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 Â 10 À5 ), extraversion with BDNF and two cadherin genes (CDH13 and CDH23; Ps < 5 Â 10 À5 ), openness with CNTNAP2 (rs10251794, P = 3 Â 10 À5 ), agreeableness with CLOCK (rs6832769, P = 9 Â 10 À6 ) and conscientiousness with DYRK1A (rs2835731, P = 3 Â 10 À5 ). 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 Â 10 À5 ). 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.

Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes

“…[46][47][48][49][50][51][52][53][54][55] In addition, some cadherins have been specifically identified in genome-wide association scans of ADHD, addiction and neuroticism personality features. [56][57][58] Of related interest, variants in CDH2 and other cadherins have been widely found to CDH2 variants in OCD and TD PR Moya et al be associated with various cancers 16,59,60 and, specifically, upregulated CDH2 has been associated with transepithelial spreading of melanoma and pancreatic cancer together with rapid recurrence of cancer. [61][62][63] In summary, although CDH2 is an attractive candidate gene based on the CCD study findings, 11 the present results suggest that these CDH2 variants are not disease-causing by themselves.…”

High-Resolution Genetic Mapping of Complex Traits from a Combined Analysis of F2 and Advanced Intercross Mice

“…Some of the genes within these regions had coding SNPs known to be involved in anxiety-like behavior and/or conditioned fear; examples include the nuclear receptor subfamily 6, group A, member 1 gene [Nr6a1 (Heydendael et al 2013)], the phospholipase D1 gene [Pld1 (Sun et al 2013)], the cadherin 23 gene [Cdh23 (Terracciano et al 2010, but see Schwander et al 2009)], the prosaposin gene [Psap (Hovatta et al 2005;Donner et al 2008)], and the SLIT and NTRK-like family, member 5 gene [Slitrk5 (Shmelkov et al 2010)]. However, we are cautious about interpreting the functional relevance of nonsynonymous coding SNPs; we do not currently have expression QTL (eQTL) data that could be used to detect heritable regulatory polymorphisms.…”

Compulsion or Chronobiology? A Case of Severe Obsessive-Compulsive Disorder Treated with Cognitive-Behavioral Therapy Augmented with Chronotherapy

“…Circadian clock genes have also been associated with mood disorders and personality characteristics, and it is possible that some patients have a genetic predisposition to both OCD and circadian phase delay. 5 We acknowledge that the correlational relationship observed herein between timing and duration of compulsions precludes conclusions regarding causality. Endogenous circadian phase was not measured in this patient.…”