Methods

The allele frequency table was made by searching the PubMed® database (1995 to 2016). Allele frequencies reported in and gnomD browser and phase 3 1000 Genomes were also included (https://gnomad.broadinstitute.org/, http://browser.1000genomes.org/index.html) for alleles that contain single unique variant.

Caveats to estimated allele, diplotype and phenotype frequencies:

Sampling. Allele frequencies collected by CPIC for the supplemental tables are based on published literature reports which typically study small groups of people based on a geographic location (e.g. Malaysia, Berlin, Cairo). Almost no studies use genetic markers to estimate ancestry. Manuscripts are often focused on a specific phenotype (e.g. disease) or study only individuals taking a particular drug. Such samples would not be considered a random sample of the general population. Another consideration is that sample size is important, and PGx studies are typically not large. The frequencies collected from these studies are then used to estimate general estimates of entire ethnic population allele frequencies. Therefore, frequencies from larger groups of subjects and frequencies averaged from many sample populations probably result in better estimates.

Estimation of *1 frequency. In general, there are no population studies that test for all known variant alleles. Because *1 is not genotyped directly in many studies, all alleles that are negative for a sequence variation are defaulted to a *1 assignment. Because CYP4F2*1 is not genotyped directly, all alleles that are negative for a sequence variation are defaulted to a CYP4F2*1 assignment. Likewise, sequence variations of alleles that are not tested may default to a CYP4F2*1 assignment and hence contribute to the frequencies reported for this allele. Therefore, the inferred frequency for CYP4F2*1 was calculated as an average from studies describing allele frequencies for the most common alleles found in a particular biogeographical group.

Biogeographical groups. Biogeographical groups are derived from PMID 30506572. Further details can be found at https://www.pharmgkb.org/page/biogeographicalGroups. These tables group individuals from particular geographic locations into larger biogeographical groups. It is difficult to group populations with certainty, because some populations are often admixed, or at the least, a combination of different ethnicities. Therefore, the margin of error is increased when different subpopulations are grouped together.