Genome Wide Association Studies of Empathizing and Systemizing

Background: Autism Spectrum Conditions (autism) are neurodevelopmental and are characterized by difficulties in social interaction and communication alongside unusually repetitive and stereotyped behaviours, unusually narrow interests, and resistance to unexpected change. Several lines of evidence suggest that, on average, individuals with autism have preserved systemizing abilities but are impaired in select domains of empathy. The genetic architecture of these traits have not been investigated. We investigated the heritability of these two traits and the genetic correlation between these traits and five psychiatric conditions, including autism.

Objectives: (1) To identify common genetic variants associated with self-report measures of empathing and systemizing; (2) To quantify additive heritabilities explained by the common variants and the differences in heritability of these traits in typical males and females; (3) To identify enrichment in biological pathways; (4) To calculate the genetic correlation between these traits and other psychiatric conditions, including autism. 

Methods: We collaborated with 23andMe Inc., a personal genetics company, to perform a genome wide association study (GWAS) of empathy (measured using the Empathy Quotient (EQ), n = 46,861) and systemizing (measured using the Systemizing Quotient-Revised (SQ-R), n = 51,564). Sex specific analyses were performed to identify sex-specific architecture. Linkage disequalibrium (LD) score regression was used to calculate inflation in p-values due to unaccounted population stratification, heritability, and genetic correlation. We calculated genetic correlation between the psychological traits and five psychiatric conditions (autism, schizophrenia, anorexia nervosa, bipolar disorder, and major depressive disorder) using summary GWAS data from the Psychiatric Genomics Consortium. Pathway analysis was performed to identify enriched biological networks, gene sets, and tissue specific expression. 

Results: We identified two significant loci associated with systemizing, and one with empathy. Additionally, we identified a locus that was significant in the males-only subset with systemizing. Approximately 11% of the variance for both the traits is explained by additive genetic effects of the SNPs examined. There was no statistical difference between male and female heritabilities. As expected, empathy had a negative genetic correlation (i.e SNPs contributed to higher autism risk but lower empathy) with autism, and systemizing had a positive genetic correlation with autism (i.e SNPs contributed to higher autism risk and higher systemizing). Unexpectedly, both systemizing and empathy were positively correlated with other psychiatric conditions, namely schizophrenia, major depressive disorder, anorexia nervosa, and bipolar disorder. 

Conclusions: The study shows that empathy and systemizing are genetically correlated with several psychiatric conditions. Though males and females perform differently on the SQ-R and the EQ, their additive heritabilities are not statistically different.