Methods

The allele frequency table was made by searching the PubMed® database (1995 to September 2019). The following criteria were used for HLA-A: (HLA-A) AND (allele OR frequency). In addition, reports were also identified from citations by others or review articles. Studies were considered for inclusion in the HLA-A frequency table if: (1) the ethnicity of the population was clearly indicated, (2) either allele frequencies or genotype frequencies were reported, (3) the method by which the genes were genotyped was indicated, (4) the sample population consisted of at least 50 individuals with a few exceptions (e.g., smaller cohorts that were part of larger studies) and (5) the study represented an original publication (no reviews or meta-analyses). Allele frequencies reported in phase 3 1000 Genomes (http://browser.1000genomes.org/index.html) and from allelefrequencies.net (https://www.allelefrequencies.net) were also included .
Caveats to estimated allele 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.

Biogeographical groups. Biogeographical groups are derived from PMID 30506572. Further details, including the definitions of each group, can be found at https://www.pharmgkb.org/page/biogeographicalGroups. We strongly recommend that users use either the publication or the PharmGKB link provided to familiarize themselves with the grouping system before using these allele frequencies. 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.