Characterization of primary Sjögren's syndrome in the Taiwan Han population through a genome-wide association study and polygenic risk score analysis

Abstract

Background: Sjögren's syndrome (SS) is an autoimmune disorder that primarily affects the exocrine glands, leading to dryness of mucous membranes and systemic manifestations. This study aimed to identify genetic markers associated with primary SS (pSS) in the Taiwan Han population through a hospital-based genome-wide association study (GWAS) and polygenic risk score (PRS) analysis, addressing the lack of genetic research.

Results: This study included 11,390 patients diagnosed with pSS and 113,900 controls. GWAS identified one known locus and eight novel loci. Known HLA alleles, including HLA-DRB1*15:01 and HLA-DQA1*03:01, were successfully replicated in a consistent effect direction. PRS analysis revealed that several autoimmune diseases share similar genetic backgrounds with pSS, including rheumatoid arthritis and systemic lupus erythematosus.

Conclusion: This study represents the largest cohort to date on the genetics of pSS in the Taiwan Han population. Our findings provide valuable insights into the pathogenesis of pSS and emphasize the comorbidities associated with it as an autoimmune disease.

Keywords: Gene polymorphism; Genome-wide association study (GWAS); Human leukocyte antigen (HLA); Phenome-wide association study (PheWAS); Polygenic risk score (PRS); Sjögren's syndrome.