Deciphering the Impact of EPHA1-AS1 Gene Polymorphism on Social Cognition Deficits in Parkinson's Disease

Ephrin type-A receptor 1 (EPHA1) has been identified as a potential contributor to the pathogenesis of Parkinson's disease (PD). The complex interactions between PD symptoms and the EPHA1 protein warrant further exploration.

A cohort of 509 participants, including 362 normal controls (NCs) and 147 PD patients, was included and genotyped for the ephrin type-A receptor 1-antisense 1 (EPHA1-AS1) gene. Overall and emotion-specific social cognition were assessed using the Reading the Mind in the Eyes Test. The relationship between the EPHA1-AS1 gene, PD, and social cognition was analyzed using the Mann-Whitney U test, the Quade test, and moderation analysis.

Compared to NCs, PD patients showed markedly poorer social cognition, especially in overall and negative emotions, regardless of genotype. The rs2966700 variant significantly affects the positive subscore among all participants (p = 0.006), with TT carriers performing better. Furthermore, PD was a significant moderator of the association between rs2966700 and the positive subscore (p = 0.001), with PD patients carrying the C allele performing worse.

This study offers new insights into the interaction between the EPHA1-AS1 gene and PD, thereby enhancing our understanding of its impact on social cognition, particularly in recognizing positive emotions in individuals with PD.