A Meta-Analysis of Cognitive Empathy: Heritability and Correlates of the ‘Reading the Mind in the Eyes’ Test with Psychiatric Conditions, Psychological Traits and Subcortical Volumes

Background Cognitive empathy is the ability to recognize or imagine another person’s mental states, such as their thoughts, intentions, desires, goals, and feelings. Cognitive empathy (also known as ‘theory of mind’ or ‘mentalizing’) is distinct from affective empathy, which is the drive to respond to another’s mental state with an appropriate emotion. Cognitive empathy has been linked to several psychiatric conditions, but little is known about its genetic architecture. Methods We conducted genome-wide association studies of cognitive empathy using the ‘Reading the Mind in the Eyes’ Test (Eyes test) in 88,056 research participants with European ancestry (44,574 females and 43,482 males) from 23andMe Inc., and an additional 1,581 participants with European ancestry (939 females and 642 males) from the Australian Twin Registry. In addition, we quantified the heritability explained by all variants, and calculated genetic correlations between scores on the Eyes test and various traits. Results We confirmed a female advantage on the Eyes Test (Cohen’s d = 0.21, P Discussion Our study highlights the genetic contributions of social cognition and its relation to psychological traits and subcortical brain volumes. In particular, we show that variants that contribute to Eyes test also contribute to volumes of the striatum, implicating these regions in cognitive empathy. We also show that some of the phenotypic sex differences can be attributed to differences in genetic architecture between males and females for the Eyes test. Delineating how these different genetic architectures interact with sex-specific biological pathways will help elucidate the mechanisms that underlie biological sex-difference for the Eyes test.