title: A genome-wide meta-analysis of association studies of Cloninger's Temperament Scales.
abstract: Temperament has a strongly heritable component, yet multiple independent genome-wide studies have failed to identify significant genetic associations. We have assembled the largest sample to date of persons with genome-wide genotype data, who have been assessed with Cloninger's Temperament and Character Inventory. Sum scores for novelty seeking, harm avoidance, reward dependence and persistence have been measured in over 11,000 persons collected in four different cohorts. Our study had >80% power to identify genome-wide significant loci (P<1.25 × 10(-8), with correction for testing four scales) accounting for ≥0.4% of the phenotypic variance in temperament scales. Using meta-analysis techniques, gene-based tests and pathway analysis we have tested over 1.2 million single-nucleotide polymorphisms (SNPs) for association to each of the four temperament dimensions. We did not discover any SNPs, genes, or pathways to be significantly related to the four temperament dimensions, after correcting for multiple testing. Less than 1% of the variability in any temperament dimension appears to be accounted for by a risk score derived from the SNPs showing strongest association to the temperament dimensions. Elucidation of genetic loci significantly influencing temperament and personality will require potentially very large samples, and/or a more refined phenotype. Item response theory methodology may be a way to incorporate data from cohorts assessed with multiple personality instruments, and might be a method by which a large sample of a more refined phenotype could be acquired.
authors: Center for Neurobehavioral Genetics, University of California, Los Angeles, CA, USA.
authors: S K
authors: SK
authors: Service
authors: K J H
authors: KJ
authors: Verweij
authors: J
authors: J
authors: Lahti
authors: E
authors: E
authors: Congdon
authors: J
authors: J
authors: Ekelund
authors: M
authors: M
authors: Hintsanen
authors: K
authors: K
authors: Räikkönen
authors: T
authors: T
authors: Lehtimäki
authors: M
authors: M
authors: Kähönen
authors: E
authors: E
authors: Widen
authors: A
authors: A
authors: Taanila
authors: J
authors: J
authors: Veijola
authors: A C
authors: AC
authors: Heath
authors: P A F
authors: PA
authors: Madden
authors: G W
authors: GW
authors: Montgomery
authors: C
authors: C
authors: Sabatti
authors: M-R
authors: MR
authors: Järvelin
authors: A
authors: A
authors: Palotie
authors: O
authors: O
authors: Raitakari
authors: J
authors: J
authors: Viikari
authors: N G
authors: NG
authors: Martin
authors: J G
authors: JG
authors: Eriksson
authors: L
authors: L
authors: Keltikangas-Järvinen
authors: N R
authors: NR
authors: Wray
authors: N B
authors: NB
authors: Freimer
mesh_terms: D000328:Adult; D001315:Australia; D015331:Cohort Studies; D005260:Female; D005387:Finland; D018740:Genetic Heterogeneity; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010551:Personality / Q000235:genetics*; D010555:Personality Inventory / Q000706:statistics & numerical data*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011594:Psychometrics / Q000706:statistics & numerical data; D015203:Reproducibility of Results; D013694:Temperament; D014427:Twins / Q000235:genetics / Q000523:psychology