By analyzing the available 1000 Genomes Project Phase 3 data, Wright G. et al. reported findings for 120 pharmacogenes variations in 26 world populations in this recent published paper. Some of the highlights from the analyses include the following.
Number of missense variants per coding sequence length ranges from 0.001 (YEATS4) to 0.058 (IFNL3).
The most conserved pharmacogenes include those genes where somatic mutations are biomarker for selecting cancer treatment for patients (e.g. BRAF, KRAS) or genes associated for disease or drug targets (e.g. HMGCR, ADRB1).
There are 23 pharmacogenes that contained highly differentiated pharmacogenomics variants across the different ethnic populations (e.g. ABCG2, ADH1B, IFNL3) and 17 pharmacogenes, which have rare variant (MAF <0.5%) that was common in one population (e.g. ACE, CYP2C19, CYP2B6, CYP2C8, GSTT1).
97% of the individual in the 1000 Genomes Project carried a high evidence clinical variant. The European populations had the highest mean number of clinical variants (4.1) whereas the African populations had the lowest number of such variants (2.3).
90% of the variation was made up of the rare variants and singletons and the relative frequency of loss-of-function variants is inversely correlated with allele frequency.
It is worth reading what other variations were described in this paper that could be relevant to your pharmacogenomics research. Notably, the code that was used to perform the various analyses is available. Feel free to provide your comment below if there are highlights that are worth mentioning from this papers.
The Hub team