Genome-wide Study Identifies Association between HLA-B∗55:01 and Self-Reported Penicillin Allergy.

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∗55:01 allele (OR 1.41 95% CI 1.33-1.49, p value 2.04 × 10-31) and confirmed by independent replication in 23andMe's research cohort (OR 1.30 95% CI 1.25-1.34, p value 1.00 × 10-47). 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∗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.

Common clinical blood and urine biomarkers for ischemic stroke: an Estonian Electronic Health Records database study.

BACKGROUND: Ischemic stroke (IS) is a major health risk without generally usable effective measures of primary prevention. Early warning signals that are easy to detect and widely available can save lives. Estonia has one nation-wide Electronic Health Record (EHR) database for the storage of medical information of patients from hospitals and primary care providers. METHODS: We extracted structured and unstructured data from the EHRs of participants of the Estonian Biobank (EstBB) and evaluated different formats of input data to understand how this continuously growing dataset should be prepared for best prediction. The utility of the EHR database for finding blood- and urine-based biomarkers for IS was demonstrated by applying different analytical and machine learning (ML) methods. RESULTS: Several early trends in common clinical laboratory parameter changes (set of red blood indices, lymphocyte/neutrophil ratio, etc.) were established for IS prediction. The developed ML models predicted the future occurrence of IS with very high accuracy and Random Forests was proved as the most applicable method to EHR data. CONCLUSIONS: We conclude that the EHR database and the risk factors uncovered are valuable resources in screening the population for risk of IS as well as constructing disease risk scores and refining prediction models for IS by ML.

Transforming Estonian health data to the Observational Medical Outcomes Partnership (OMOP) Common Data Model: lessons learned.

Objective: To describe the reusable transformation process of electronic health records (EHR), claims, and prescriptions data into Observational Medical Outcome Partnership (OMOP) Common Data Model (CDM), together with challenges faced and solutions implemented. Materials and Methods: We used Estonian national health databases that store almost all residents' claims, prescriptions, and EHR records. To develop and demonstrate the transformation process of Estonian health data to OMOP CDM, we used a 10% random sample of the Estonian population (n = 150 824 patients) from 2012 to 2019 (MAITT dataset). For the sample, complete information from all 3 databases was converted to OMOP CDM version 5.3. The validation was performed using open-source tools. Results: In total, we transformed over 100 million entries to standard concepts using standard OMOP vocabularies with the average mapping rate 95%. For conditions, observations, drugs, and measurements, the mapping rate was over 90%. In most cases, SNOMED Clinical Terms were used as the target vocabulary. Discussion: During the transformation process, we encountered several challenges, which are described in detail with concrete examples and solutions. Conclusion: For a representative 10% random sample, we successfully transferred complete records from 3 national health databases to OMOP CDM and created a reusable transformation process. Our work helps future researchers to transform linked databases into OMOP CDM more efficiently, ultimately leading to better real-world evidence.