Polygenic scores clarify the relationship between mental health and gender diversity

BACKGROUNDGender diverse individuals are at increased risk for mental health problems, but it is unclear whether this is due to shared environmental or genetic factors. METHODSIn two SPARK samples, we tested for 16 polygenic scores (PGS) effects on quantitative measures of gender diversity and mental health. In Study 1, N = 639 independent adults (59% autistic) reported their mental health with the Adult Self Report and their gender diversity with the Gender Self Report (GSR). The GSR has two dimensions: Binary (degree of identification with the gender opposite that implied by sex designated at birth) and Nonbinary (degree of identification with a gender that is neither male nor female). In Study 2 (N = 5, 165), we used categorical gender identity. RESULTSIn Study 1, neuropsychiatric PGS were positively associated with mental health problems. Externalizing was positively associated with ADHD PGS ({rho} = 0.12, p {+/-}0.11). However, the GSR was positively associated with cognitive performance PGS (Binary{rho} = 0.11, p < 0.001, FDR = 0.23 and Nonbinary{rho} = 0.12, p < 0.001, FDR = 0.13). Binary was also positively associated with PGS for non-heterosexual sexual behavior ({rho} = 0.09, p = 0.03, FDR = 0.69). In Study 2, the cognitive performance PGS effect replicated; transgender and non-binary individuals had higher PGS: t = 4.16, p < 0.001, FDR < 0.001. They also had higher risky behavior and anorexia PGS. CONCLUSIONSWe show that while gender diversity as a trait is positively associated with mental health problems, the strongest PGS associations with gender diversity were with cognitive performance, not neuropsychiatric conditions.