P106 Genome-Wide Association Study of a rare papulosquamous disease: pityriasis rubra pilaris

Abstract Pityriasis rubra pilaris (PRP) is a rare chronic skin disorder that causes persistent inflammation, thickening and shedding of the skin. In terms of classification, it is a papulosquamous disease and its clinical features that have the closest overlap with psoriasis. Genetic studies have thus far identified variants in the CARD14 gene that contribute to the susceptibility of PRP, but a genome-wide association study (GWAS) has not yet been conducted. Therefore, it was our aim to perform a GWAS using the genotype data of nearly 200 000 individuals available from the Estonian Biobank database (EstBB). The patients included 100 EstBB participants who had a registered ICD-10 diagnosis code for PRP–L44.0. The control group consisted of 199 647 individuals who did not have the L44.0 diagnosis. An additive GWAS was performed using the SAIGE program adjusting for age, sex, and the first 10 genetic principal components. Since the group of patients was smaller than typically used in GWAS, we lowered the threshold for statistical significance to P < 5 × 10−7. The FUMA platform was used for functional annotation of association signals. Significant associations appeared in genomic regions of chromosome 4 [single nucleotide polymorphism (SNP) rs115367424, P = 2.08 × 10−7], chromosome 6 (lead SNP rs142103230, P = 5.71 × 10−8) and chromosome 14 (lead SNP rs8012648, P = 2.44 × 10−7). The nearest gene to rs115367424 is CCSER1, which has been associated with poor melanoma survival. The candidate SNPs of chromosome 6 are situated within an intron of PRKN gene that functions as a modulator of innate immunity to infectious agents and its genetic variants have been associated with susceptibility to leprosy. Chromosome 14 candidate SNPs are intronic variants of FBLN5 gene that can promote dermal wound healing and attenuate burn injury-induced inflammatory responses. The results presented here require confirmation in future studies, and the identification of possible functional variants in the three discussed genomic regions calls for further investigation. Genetic research on PRP is challenging due to its very rare occurrence, but considering the severity of the disease, this scientific attention is still very much needed.