IL31 identified as a key genetic risk factor for prurigo nodularis.

Abstract

Although previous studies have suggested that genetic risk factors can contribute to the development of prurigo nodularis (PN), little is known about the specific variants involved. We aimed to test which genetic variants increase predisposition to PN by conducting a large genome-wide association study. Five separate cohorts (4239 case patients with PN and 583,544 controls) were combined through genome-wide association study meta-analysis, and the results were validated by using the Michigan Genomics Initiative. Data from regulatory regions and expression quantitative trait loci were applied to investigate genetic mechanisms. We identified a genome-wide significant genetic signal for PN (P = 7.5 × 10^-13; odds ratio = 1.17) at the IL31 locus, which has also been associated with psoriasis, atopic dermatitis, and 2 suggestive significant signals (P ≤ 1 × 10^-6) in chromosomes 2 and 6. The IL31 signal is located in a regulatory region for T cells and keratinocytes; interestingly, it occurs substantially more frequently in European individuals than in African individuals. Our results reinforce the role of genetics in PN and advance understanding of the mechanisms and their relationship with other pruritic inflammatory skin diseases.