Association of Kallikrein Related Peptidase 3 (KLK3) gene with dermatophytosis in the UK biobank cohort

Abstract

Background: In a previous genome wide association study (GWAS) of UK Biobank (UKB) data, we identified one susceptibility locus, tubulointerstitial nephritis antigen (TINAG), with genome wide significance for dermatophytosis. We used genotype calls from file UKB22418. These data are derived directly from Affymetrix DNA microarrays but are missing many genotype calls. Using computationally efficient approaches, UKB has entered imputed genotypes into a second dataset, UKB22828, increasing the number of testable variants by over 100-fold to 96 million variants.

Methods: In the current study, we used UKB imputed genotypes in UKB22828 to identify dermatophytosis susceptibility loci. To identify cases of dermatophytosis, we used ICD10 code B35, which covers tinea barbae, tinea capitis, tinea unguium, tinea manuum, tinea pedis, tinea corporis, tinea imbricata, tinea cruris, other dermatophytoses and dermatophytosis, unspecified. We used PLINK, a whole-genome association analysis toolset, to analyse the UKB22828 chromosome files.

Results: GWAS summary (Manhattan) plot of the meta-analysis association statistics highlighted two susceptibility loci, TINAG and Kallikrein Related Peptidase 3 (KLK3), with genome wide significance for dermatophytosis. KLK3, also known as prostate specific antigen (PSA), belongs to a subclass of serine proteases with a variety of physiological functions.

Conclusion: KLK3 may be a dermatophytosis susceptibility gene. KLK3 could affect risk of dermatophytosis, since kallikreins are necessary for normal homeostasis of the skin.

Keywords: GWAS; dermatophytosis; genes; mycoses; polygenic.