Genome-wide association study of medication-use and associated disease in the UK Biobank.
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ABSTRACT:
SUBMITTER: Wu Y
PROVIDER: S-EPMC6478889 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
Publications
Genome-wide association study of medication-use and associated disease in the UK Biobank.
Wu Yeda Y Byrne Enda M EM Zheng Zhili Z Kemper Kathryn E KE Yengo Loic L Mallett Andrew J AJ Yang Jian J Visscher Peter M PM Wray Naomi R NR
Nature communications 20190423 1
Genome-wide association studies (GWASs) of medication use may contribute to understanding of disease etiology, could generate new leads relevant for drug discovery and can be used to quantify future risk of medication taking. Here, we conduct GWASs of self-reported medication use from 23 medication categories in approximately 320,000 individuals from the UK Biobank. A total of 505 independent genetic loci that meet stringent criteria (P < 10<sup>-8</sup>/23) for statistical significance are iden ...[more]
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Project description:BackgroundAnalyses of the hereditary propensity to dermatophytosis have revealed several proven genetic relationships. They include CARD9 deficiency, HLA-DR4 and HLA-DR8 type and genes encoding interleukin-22, defensin 2 and 4, and genetic defects in dectin-1, which increased the prevalence of dermatophytosis in families and were involved in the inheritance of susceptibility in their members.MethodsTo further investigate the genetic basis of dermatophytosis, we performed a genome-wide association study (GWAS) of the UK Biobank cohort. 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. Data processing was performed on Minerva, a Linux mainframe with Centos 7.6, at the Icahn School of Medicine at Mount Sinai. We used PLINK, a whole-genome association analysis toolset, to analyse the UKB chromosome files and the UK Biobank Data Parser (ukbb parser), a python-based package that allows easy interfacing with the large UK Biobank dataset. We used LocusZoom for the Manhattan and q-q plots. Other statistical analyses were done with R and SPSS 25.ResultsGenome-wide association study (GWAS) and meta-analysis association statistics highlighted one susceptibility locus, Tubulointerstitial Nephritis Antigen (TINAG), with genome-wide significance for dermatophytosis. The top SNP was rs16885197, a missense variant within TINAG, position chr6:54308557, alleles A > G, minor allele frequency (MAF) 0.014. Multivariate logistic regression indicated that the minor G allele increased odds ratio of dermatophytosis by 7.8. Carrying two G alleles raised dermatophytosis odds ratio by a factor of 14.ConclusionMore research into genetic and other predisposing factors for dermatophytosis is critical because of the implications for prophylaxis and therapy. It might be possible to prevent infection and recurrence by identifying people who are vulnerable to chronic dermatophytosis. Identifying high-risk families would enable their members to be educated about the dangers of fungal diseases. New therapeutic techniques to target altered hormonal and immune response pathways might be created. TINAG is a prospective target that should be investigated, based on the findings of this article.
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