Polygenic Score: A Tool for Evaluating the Genetic Background of Sporadic Hidradenitis Suppurativa

Abstract

Sporadic hidradenitis suppurativa (spHS) is a multifactorial disease in which genetic predisposition is intertwined with environmental factors. Owing to the still-to-date limited knowledge of spHS genetics, we calculated polygenic scores (PGSs) to study the genetic underpinnings that contribute to spHS within European demographic. A total of 256 patients with spHS and 1686 healthy controls were analyzed across 6 European clinical centers. PGSs were calculated using a clumping and thresholding technique on 70% of the total sample, with the remaining 30% used for testing. The PANTHER tool was used to identify overrepresented genes. We generated a PGS characterized by 923 SNPs with a statistically significant association with spHS (P = 2 × 10^-2). The statistically significant age-, sex-, and ancestry-adjusted association of our developed PGSs in spHS allows us to attribute a genetic contribution to the susceptibility of spHS (pseudo-R2 = 0.0053). Variants enriched for developing PGSs show a statistically significant preference for mapping to genes that encode primarily for cell adhesion proteins. Although this study developed a polygenic model associated with spHS, the low number of patients enrolled is a limitation. However, we believe that with larger experimental datasets, our model has the potential to serve as a valuable tool for predicting spHS states in future studies.

Keywords: Disease association; Genetics; Polygenic score; Sporadic hidradenitis suppurativa; Susceptibility.