AbstractEmpathy is the ability to recognize and respond to the emotional states of other individuals. It is an important psychological process that facilitates navigating social interactions and maintaining relationships, which are important for well-being. Several psychological studies have identified difficulties in both self-report and performance-based measures of empathy in a range of psychiatric conditions. To date, no study has systematically investigated the genetic architecture of empathy using genome-wide association studies (GWAS). Here we report the results of the largest GWAS of empathy to date using a well-validated self-report measure of empathy, the Empathy Quotient (EQ), in 46,861 research participants from 23andMe, Inc. We identify 11 suggestive loci (P < 1 × 10⁻⁶), though none were significant at P < 2.5 × 10⁻⁸ after correcting for multiple testing. The most significant SNP was identified in the non-stratified analysis (rs4882760; P = 4.29 × 10⁻⁸), and is an intronic SNP in TMEM132C. The EQ had a modest but significant narrow-sense heritability (0.11 ± 0.014; P = 1.7 × 10⁻¹⁴). As predicted, based on earlier work, we confirmed a significant female advantage on the EQ (P < 2 × 10⁻¹⁶, Cohen’s d = 0.65). We identified similar SNP heritability and high genetic correlation between the sexes. Also, as predicted, we identified a significant negative genetic correlation between autism and the EQ (r_g = −0.27 ± 0.07, P = 1.63 × 10⁻⁴). We also identified a significant positive genetic correlation between the EQ and risk for schizophrenia (r_g = 0.19 ± 0.04; P = 1.36 × 10⁻⁵), risk for anorexia nervosa (r_g = 0.32 ± 0.09; P = 6 × 10⁻⁴), and extraversion (r_g = 0.45 ± 0.08; 5.7 × 10⁻⁸). This is the first GWAS of self-reported empathy. The results suggest that the genetic variations associated with empathy also play a role in psychiatric conditions and psychological traits.