We are happy to announce the publication of our latest research article in the American Journal of Human Genetics (AJHG), titled “Frequencies of Pharmacogenomic Alleles across Biogeographic Groups in a Large-Scale Biobank.” The paper is now available online on the AJHG website.
Genetic biobanks provide rich data sets to investigate population-specific pharmacogenomic (PGx) allele frequencies and the implications of equitable and inclusive implementation. Using an integrated UK Biobank 200K genetic dataset (N = 200,044), we estimated the pharmacogenomic (PGx) allele frequencies for seventeen (17) pharmacogenes in five (5) biogeographic groups.
- Pharmacogenes included ABCG2, CACNA1S, CYP2B6, CYP2C19, CYP2C9, CYP3A5, CYP4F2, DPYD, G6PD, IFNL3, NUDT15, RYR1, SLCO1B1, TPMT, UGT1A1, and VKORC1. CFTR and the CYP2C cluster variant (rs12777823) were also investigated. CYP2D6 alleles that could be determined from VCF, and therefore not including structural variants, were also predicted.
- The five (5) biogeographic groups are Europeans (n = 187,660), Central/South Asians (n = 3,460), East Asians (n = 637), African Americans/Afro-Caribbeans (n = 1,926), and Sub-Saharan Africans (n = 1,235)
- Frequencies of PGx alleles, diplotypes, phenotypes, and/or activity scores, if applicable, were reported for each gene in each biogeographic group.
We found that 100% of the UK Biobank participants harbored at least one genetic variant found in known PGx haplotypes.
The main takeaways messages are:
1. UK Biobank PGx frequencies complemented the CPIC frequency tables.2. This study reported frequencies for a nontrivial number of PGx alleles that are rare or seldom tested, especially in the non-European group.3. There are uncataloged PGx alleles.
PGx frequencies estimated from this study will be disseminated via PharmGKB. Biobank-derived allele frequencies can provide guidance for future PGx studies and clinical genetic test panel design, and better serve individuals from wider biogeographic backgrounds.