Refining genome-wide linkage intervals using a meta-analysis of genome-wide association studies identifies loci influencing personality dimensions

Abstract

Personality traits are complex phenotypes related to psychosomatic health. Individually, various gene finding methods have not achieved much success in finding genetic variants associated with personality traits. We performed a meta-analysis of four genome-wide linkage scans (N=6149 subjects) of five basic personality traits assessed with the NEO Five-Factor Inventory. We compared the significant regions from the meta-analysis of linkage scans with the results of a meta-analysis of genome-wide association studies (GWAS) (N∼17 000). We found significant evidence of linkage of neuroticism to chromosome 3p14 (rs1490265, LOD=4.67) and to chromosome 19q13 (rs628604, LOD=3.55); of extraversion to 14q32 (ATGG002, LOD=3.3); and of agreeableness to 3p25 (rs709160, LOD=3.67) and to two adjacent regions on chromosome 15, including 15q13 (rs970408, LOD=4.07) and 15q14 (rs1055356, LOD=3.52) in the individual scans. In the meta-analysis, we found strong evidence of linkage of extraversion to 4q34, 9q34, 10q24 and 11q22, openness to 2p25, 3q26, 9p21, 11q24, 15q26 and 19q13 and agreeableness to 4q34 and 19p13. Significant evidence of association in the GWAS was detected between openness and rs677035 at 11q24 (P-value=2.6 × 10(-06), KCNJ1). The findings of our linkage meta-analysis and those of the GWAS suggest that 11q24 is a susceptible locus for openness, with KCNJ1 as the possible candidate gene.

Figure 1

Results of the meta-analysis of the linkage scans. (a) For neuroticism, (b) for extraversion, (c) for openness, (d) for agreeableness and (e) for conscientiousness. Dots represent P_SR and triangles represent P_OR. The X axis shows the whole autosomal genome divided by solid vertical lines into chromosomes, which are further divided into bins by dotted gray lines. The Y axis shows the negative principal log of the P-values. The red horizontal dotted line represents the nominal threshold P-value=0.5, the gray dotted horizontal line represents the suggestive threshold P-value=0.008 and the light blue horizontal dotted line represents the Bonferroni-corrected threshold P-value=0.0004. A bin is considered significant if a circle for that bin surpasses the sky blue line or if both the circle and the triangle for a specific bin are above the dotted red line. The green diamonds represent the P-values of the SNPs from the results of the meta-analysis of the GWAS of the same traits falling in the bins of interest. The green diamonds with the red outline are the P-values significant/borderline significant after correcting for the number of total SNPs in the bin.