A1 Refereed original research article in a scientific journal
A genome-wide meta-analysis of association studies of Cloninger's Temperament Scales
Authors: Service SK, Verweij KJH, Lahti J, Congdon E, Ekelund J, Hintsanen M, Raikkonen K, Lehtimaki T, Kahonen M, Widen E, Taanila A, Veijola J, Heath AC, Madden PAF, Montgomery GW, Sabatti C, Jarvelin MR, Palotie A, Raitakari O, Viikari J, Martin NG, Eriksson JG, Keltikangas-Jarvinen L, Wray NR, Freimer NB
Publisher: NATURE PUBLISHING GROUP
Publication year: 2012
Journal: Translational Psychiatry
Journal name in source: TRANSLATIONAL PSYCHIATRY
Journal acronym: TRANSL PSYCHIAT
Article number: ARTN e116
Number in series: 2
Volume: 2
Issue: 2
First page : e116
Number of pages: 9
ISSN: 2158-3188
DOI: https://doi.org/10.1038/tp.2012.37
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 x 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. Translational Psychiatry (2012) 2, e116; doi:10.1038/tp.2012.37; published online 15 May 2012
