A genome-wide association study of social trust in 33,882 Danish blood donors

Abstract

Social trust is a heritable trait that has been linked with physical health and longevity. In this study, we performed genome-wide association studies of self-reported social trust in n = 33,882 Danish blood donors. We observed genome-wide and local evidence of genetic similarity with other brain-related phenotypes and estimated the single nucleotide polymorphism-based heritability of trust to be 6% (95% confidence interval = (2.1, 9.9)). In our discovery cohort (n = 25,819), we identified one significantly associated locus (lead variant: rs12776883) in an intronic enhancer region of PLPP4, a gene highly expressed in brain, kidneys, and testes. However, we could not replicate the signal in an independent set of donors who were phenotyped a year later (n = 8063). In the subsequent meta-analysis, we found a second significantly associated variant (rs71543507) in an intergenic enhancer region. Overall, our work confirms that social trust is heritable, and provides an initial look into the genetic factors that influence it.

Figure 1

Social trust in the DBDS. (A) Sex and year of birth distributions in the discovery cohort. Solid lines represent the median year of birth (1968 and 1965 for men and women, respectively); dashed lines represent the 25th and 75th quartiles. (B) The three social trust questionnaire items and their responses in the DBDS discovery cohort (gray bars; n = 25,819; median in red) and a random sample of the Danish population (black line; n = 10,369; source: European Social Survey; median in black). (C) Manhattan plot of associations between genetic sequence variants and social trust in the discovery cohort. (D) Manhattan plot of associations between genetic sequence variants and social trust in the meta-analysis. In (C, D), the horizontal dotted line represents the Bonferroni-corrected 5e−08 significance threshold. The genomic loci found to be associated with social trust (see Table 1) are colored in red and the closest protein-coding gene is indicated.

Figure 2

Genetic correlations between the social trust meta-analysis and 18 psychiatric and psychological traits. Correlation coefficients (rg, unbounded) and 95% confidence intervals (CI) are provided. p values shown are uncorrected. Genetic correlations that are significantly different from zero are marked with an asterisk (uncorrected) or two asterisks (Bonferroni-corrected for 18 tests).

Figure 3

Regional patterns of association between genetic variants around the discovered loci, social trust, and a non-exhaustive list of psychological and psychiatric phenotypes. (A) Locus on chromosome 10 with lead variant rs12776883 as discovered in the discovery GWAS. (B) Locus on chromosome 7 with lead variant rs71543507 as discovered in the meta-analysis.