Genome-wide Study Identifies Association between HLA-B55:01 and Self-Reported Penicillin Allergy.

Am J Hum Genet 2020 10 3;107(4):612-621. Epub 2020 Sep 3.

Department of Epidemiology Research, Statens Serum Institut, Copenhagen 2300, Denmark; Department of Clinical Sciences, Lund University Diabetes Centre, 214 28 Malmö, Sweden; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland.

Hypersensitivity reactions to drugs are often unpredictable and can be life threatening, underscoring a need for understanding their underlying mechanisms and risk factors. The extent to which germline genetic variation influences the risk of commonly reported drug allergies such as penicillin allergy remains largely unknown. We extracted data from the electronic health records of more than 600,000 participants from the UK, Estonian, and Vanderbilt University Medical Center's BioVU biobanks to study the role of genetic variation in the occurrence of self-reported penicillin hypersensitivity reactions. We used imputed SNP to HLA typing data from these cohorts to further fine map the human leukocyte antigen (HLA) association and replicated our results in 23andMe's research cohort involving a total of 1.12 million individuals. Genome-wide meta-analysis of penicillin allergy revealed two loci, including one located in the HLA region on chromosome 6. This signal was further fine-mapped to the HLA-B55:01 allele (OR 1.41 95% CI 1.33-1.49, p value 2.04 × 10) and confirmed by independent replication in 23andMe's research cohort (OR 1.30 95% CI 1.25-1.34, p value 1.00 × 10). The lead SNP was also associated with lower lymphocyte counts and in silico follow-up suggests a potential effect on T-lymphocytes at HLA-B55:01. We also observed a significant hit in PTPN22 and the GWAS results correlated with the genetics of rheumatoid arthritis and psoriasis. We present robust evidence for the role of an allele of the major histocompatibility complex (MHC) I gene HLA-B in the occurrence of penicillin allergy.

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Source
http://dx.doi.org/10.1016/j.ajhg.2020.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536643PMC
October 2020

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