Unraveling Sex-Specific Genetic Markers in Psoriatic Arthritis: Insights from a Genome-Wide Association Study

Objectives Sex differences can substantially influence clinical features, disease progression, and treatment responses across various medical conditions, including psoriatic arthritis (PsA). Understanding these differences at a genetic level is crucial for developing personalized treatment approaches and improving disease management. This study utilizes data from the UK Biobank to identify sex-specific genetic variants that may contribute to the susceptibility to PsA, thereby enhancing our understanding of the disease’s underlying mechanisms. Methods Data were extracted from the UK Biobank, including 459 female and 497 male PsA patients. To minimize population stratification, only Caucasian participants were included, resulting in 444 female and 423 male patients, along with 226,198 female and 191,928 male Caucasian controls. A genome-wide association study (GWAS) was conducted, comparing 97,013,422 SNPs between males and females among PsA patients and controls, focusing exclusively on autosomes. Only SNPs with allele frequencies greater than 0.005 in affected cases and controls were included, and associations were considered significant at P < 1 × 10^-6. Results In males, 2,596 SNPs were identified across 104 genes, and in females, 4,542 SNPs were associated with 108 genes. Among these genes, 72 were shared between sexes, including PSORS1C1, the strongest genetic associated locus for psoriatic disease. Additionally, 32 unique genes were identified in males, including ERAP-1 and TRAF3IP2, whereas 35 were identified in females, including HLA-DRB1 and HLA-DQA1. Notably, sex-specific genes have been previously documented to exhibit sex-specific differences in immune responses. Ongoing studies are focusing on pathway enrichment analysis of sex-specific genes for both genders. Conclusion The identification of unique genes in each sex, alongside shared genetic markers, highlights the complexity of PsA’s genetic landscape. These findings suggest that sex-specific genetic factors may play a role in the manifestation and progression of the disease. Further research is essential to validate these results and explore their clinical and molecular implications, which could ultimately lead to more tailored therapeutic strategies for PsA patients.