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.
This is the first joint meeting of the Pharmacogenomics Research Network (PGRN) and the American Society of Human Genetics (ASHG). We were thrilled with the great turn out. The Symposium brought together scientists from different areas of human genetics and pharmacogenomics! Special thanks to our speakers, poster participants and twitters followers. We also thank you for your participation in the Q&As and for sharing your ideas and expertise through out the symposium. We found all the presentations engaging and enlightening, but would like to particularly thank the panelists for a stimulating discussion on the issues relevant to implementation of pharmacogenomic testing. We also thank the organizers and speakers of the final session focused on the evolution of pharmacogenes. To our knowledge this was a first session of its kind and represents a great example of potential interactions between scientists in pharmacogenomics and those in population genetics. Your feedback and comments on all our sessions are our top priorities. Finally, we promise you that the videos of recorded talks will be posted here soon!
The PGRN-Hub Team
The PGRN Hub congratulates 5 Poster Award Winners and the other poster presenters who described their recent work at the 2016 PGRN-ASHG Symposium– The Expanding Universe of Pharmacogenomics.
Trainee Abstract Award Winners
Best Poster Award Winners
In this October issue of Clinical Pharmacology & Therapeutics, Yang et al. highlighted several important variants in pharmacogenes that could be missed if whole exome sequencing or genotyping array was used instead of whole genome sequencing. Among the thirteen CPIC® important genes, missing important variants are found in CYP2D6, CYP3A5, DPYD, G6PD, IFNL3, VKORC1 if whole genome sequencing were not used.
The Hub team