Phenotypic correlations among neuroticism, anxiety and depression symptoms were substantial; therefore, we expected overlap in the association results. Shared genetic association effects can represent: correlated type 1 error, true genetic pleiotropy, or direct effects of a gene on one trait that indirectly influences the other through a causal pathway. For top neuroticism associations, we observed nominally significant associations with depressive symptoms for SNPs in the POLR3A gene. For extraversion, none of the top hits showed nominal significance for any other trait (but this correlated less strongly with the other measures). The prediction analyses confirmed phenotypic variance in depression/psychological distress attributed to polygenic neuroticism scores. In line with findings that showed pleiotropy was characteristic of 17% of genes and 5% of SNPs associated with diseases/disease traits (Sivakumaran et al. 2011), we interpret our overlapping results across traits as evidence of genetic pleiotropy; alternatively, indirect genetic effects on the correlated trait might be operating. It is also possible that they instead reflect shared type 1 error, although the partly non-overlapping nature of the samples across traits (e.g., the GWAS for depressive symptom scores was a subset of the GWAS sample for neuroticism) should have the effect of reducing correlated error variance.
