A genome-wide meta-analysis of association studies of Cloninger's Temperament Scales.
paper
Cited
Public
- Authors
- Service, S K; Verweij, K J H; Lahti, J; Congdon, E; Ekelund, J; Hintsanen, M; Räikkönen, K; Lehtimäki, T; Kähönen, M; Widen, E; Taanila, A; Veijola, J; Heath, A C; Madden, P A F; Montgomery, G W; Sabatti, C; Järvelin, M-R; Palotie, A; Raitakari, O; Viikari, J; Martin, N G; Eriksson, J G; Keltikangas-Järvinen, L; Wray, N R; Freimer, N B
- Year
- 2012
- Journal
- Translational psychiatry
- PMID
- 22832960
- DOI
- 10.1038/tp.2012.37
- PMCID
- PMC3365256
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.
QQ plots of meta-analysis results for each of the four temperament scales. On the x-axis is the distribution of –log10 P-values expected under the null hypothesis of no association of SNPs to the phenotype. On the y-axis is the ordered distribution of observed –log10 P-values. Deviation from the 1:1 line in the bulk of the distribution can suggest inflation of test statistics. The 95% confidence bands (dashed lines) are generated assuming the jth order statistic from a uniform (0.1) sample has a beta (j,n–j+1) distribution, and assuming independence. (a) Harm avoidance; (b) novelty seeking; (c) reward dependence; (d) persistence.
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