Meta-analysis of genome-wide association studies for personality

Abstract

Personality can be thought of as a set of characteristics that influence people's thoughts, feelings and behavior across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in 10 discovery samples (17,375 adults) and five in silico replication samples (3294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data of ≈ 2.4M single-nucleotide polymorphisms (SNPs; directly typed and imputed using HapMap data) were available. In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P=2.8 × 10(-8) and 3.1 × 10(-8)) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P=4.9 × 10(-8)). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.

Figure 1

Regional association plots of the two SNPs genome-wide significant in the discovery set for Openness to Experience and Conscientiousness a. Chromosome 5 locus for Openness to Experience b. Chromosome 18 locus for Conscientiousness Foot note: Physical positions of SNPs and genes are based on build 36 (hg18). The top SNP is shown in blue. SNPs that have an r-squared between 0.8-1 with the top SNP are shown in violet, SNPs with an r-squared between 0.5-0.8 in red, SNPs with an r-squared between 0.2-0.5 in orange, and < 0.2 in yellow.

Figure 1

Regional association plots of the two SNPs genome-wide significant in the discovery set for Openness to Experience and Conscientiousness a. Chromosome 5 locus for Openness to Experience b. Chromosome 18 locus for Conscientiousness Foot note: Physical positions of SNPs and genes are based on build 36 (hg18). The top SNP is shown in blue. SNPs that have an r-squared between 0.8-1 with the top SNP are shown in violet, SNPs with an r-squared between 0.5-0.8 in red, SNPs with an r-squared between 0.2-0.5 in orange, and < 0.2 in yellow.

Figure 2

Association of the two SNPs genome-wide significant in the discovery set with Openness to Experience and Conscientiousness a. Association of rs1477268 with Openness to Experience b. Association of rs2576037 with Conscientiousness Foot note: Effects are reported for the minor allele (see Supplementary Tables 4 and 6).

Figure 2

Association of the two SNPs genome-wide significant in the discovery set with Openness to Experience and Conscientiousness a. Association of rs1477268 with Openness to Experience b. Association of rs2576037 with Conscientiousness Foot note: Effects are reported for the minor allele (see Supplementary Tables 4 and 6).