Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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-B<sup>∗</sup>55:01 allele (OR 1.41 95% CI 1.33-1.49, p value 2.04 × 10<sup>-31</sup>) and confirmed by independent replication in 23andMe's research cohort (OR 1.30 95% CI 1.25-1.34, p value 1.00 × 10<sup>-47</sup>). The lead SNP was also associated with lower lymphocyte counts and in silico follow-up suggests a potential effect on T-lymphocytes at HLA-B<sup>∗</sup>55:01. 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.

Original publication




Journal article


American journal of human genetics

Publication Date





612 - 621


Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia.


23andMe Research Team, T-Lymphocytes, Chromosomes, Human, Pair 6, Humans, Arthritis, Rheumatoid, Psoriasis, Drug Hypersensitivity, Genetic Predisposition to Disease, Penicillins, HLA-B Antigens, Histocompatibility Testing, Gene Expression, Polymorphism, Single Nucleotide, Alleles, Genome, Human, Adult, United States, Europe, Female, Male, Protein Tyrosine Phosphatase, Non-Receptor Type 22, Genome-Wide Association Study, Genetic Loci, Electronic Health Records, Self Report