Assessing Genetic Factors Influencing the Variability in Psoriatic Arthritis Onset Among Patients with Psoriasis

Objectives Epidemiological studies show that psoriatic arthritis (PsA) develops after psoriasis in 70% of patients, appears simultaneously in 15%, and precedes psoriasis in the remaining 15%. This study aimed to investigate whether genetic factors influence the time between the onset of psoriasis and PsA, and to identify any genetic differences among these 3 subgroups. Methods A total of 703 patients from the Gladman Krembil PsA program were analyzed, with ages at psoriasis and PsA onset recorded. All samples underwent a genome-wide association scan that included over one million single-nucleotide polymorphisms (SNPs). Quality control excluded SNPs with more than 1% missing data and those that did not meet Hardy-Weinberg equilibrium criteria. We treated the age difference between PsA and psoriasis onset as a quantitative trait by subtracting the age at PsA onset from the age at psoriasis onset for each patient. We then performed a quantitative trait locus (QTL) analysis. PsA patients were categorized into 4 groups and compared for genetic differences: (A) PsA occurring at least one year before psoriasis; (B) psoriasis and PsA occurring within one year of each other; (C) PsA occurring one to 10 years after psoriasis; and (D) PsA starting 10 or more years after psoriasis onset. Results The QTL analysis identified over 50 SNPs significantly affected the onset of inflammatory arthritis (p < 1 x 10^-5). Most identified loci were associated with a delay in PsA onset in individuals with the mutant allele compared with those with the wild-type allele. Genes associated with delayed PsA included PSORS1C1, CDSN, TXB5, and OSBLV. Conversely, loci on chromosome 15 (in linkage disequilibrium with MYO1E) and chromosome 17 (in LD with CCDC43 and MEIOC) were associated with an earlier onset of PsA. Comparisons among the PsA onset subsets noted above revealed notable differences, particularly between groups A and D (59 SNPs) and between groups A and C (30 SNPs) at a significance level of p < 1 × 10^-5. Development of polygenic risk scores to identify early- and late-onset PsA is ongoing. Conclusion This study underscores the significant role of genetic mutations in influencing the variability in the onset of PsA among patients with psoriasis. By identifying over 50 SNPs that significantly impact the timing of PsA onset, our findings highlight the complex genetic landscape that contributes to progression from psoriasis to PsA. Best Abstract On Basic Science Research By A Trainee Award