If you are a member of PGRN.org you can apply to feature your PGx related research project on this site.
On January 18th-19th 2017, the PGRN-RIKEN Meeting was held in Yokohama, Japan. The meeting brought together researchers from the US, and Japan, as well as other countries, to discuss PGRN-RIKEN collaboration research results. Before the PGRN-RIKEN meeting, PGRN members were invited to submit proposals for RIKEN to perform either targeted sequencing or genome wide genotyping on their DNA samples from pharmacogenomics studies of well-phenotypes patients. The proposals were rigorously peer-reviewed by Principal Investigators of the PGRN-RIKEN collaboration. Only top scored projects were selected for genomewide genotyping or targeted sequencing. At the meeting, three new proposals were considered for genotyping. In addition four investigators presented research in progress of PGRN-RIKEN collaborative research studies. Finally, invited speakers included: Dr. Kazuhiko Yamamoto, from RIKEN Institute, who gave an overview of functional genetics of autoimmune diseases; Dr. Henk-Jan Guchelaar, from Leiden University Medical Center, who gave an overview on the design and implementation strategy of the Ubiquitous Pharmacogenomics Consortium; and Dr. Mark Ratain<>, co-Leader of the PGRN-RIKEN collaboration, who presented the University of Chicago's experience with preemptive pharmacogenomics, the “1200 Patients Project." The PGRN-RIKEN group meets twice a year, alternating between San Francisco and Tokyo. We will keep you posted here about submitting proposals for the next meeting in San Francisco.
Four Genes Reached Genomewide Association Study Significance Level on Intolerance of Angiotensin-Converting Enzyme Inhibitors
The PREDICTION-ADR Consortium conducted a meta-analysis GWAS to identify genetic determinants for Angiotensin-Converting Enzyme (ACE) Inhibitors intolerance in European populations (972 cases and 4189 controls) (PMID: 28030426). ACE inhibitors are commonly used to treat high blood pressure, heart failure and kidney disease. The main reasons for intolerance to the drug are persistent dry cough and life-threatening angio-oedema of the lips, tongue and upper airway. The group identified four genes with eight SNPs reaching genomewide significance (p<5x10-8). These genes are RBFOX3, GABRG2, SH2B1 and MBOAT1. GABRG2 is a member of the GABA-A receptor gene family, and play a major role in the benzodiazepine pathway. The group speculates that GABRG2 could be an interesting target due to the supporting evidence of its role in susceptibility to cough. Unfortunately, the group did not investigate the role of significantly associated genes nor exploring the functional roles of the SNPs within the genes.
Launched in 2014, the NIH Common Fund’s Illuminating the Druggable Genome (IDG) Program enables researchers to explore understudied proteins with the potential to be modified by medicines. In November, a request for grant applications moved IDG into its implementation phase. The program plans to allocate $54 million to advance research through the development, broad dissemination, and use of community scientific resources to study human proteins for which publicly available information or active research is lacking. IDG aims to catalyze the discovery of novel biology, with a particular focus on understudied members of the protein kinase, ion channel, and non-olfactory G-protein-coupled receptor (GPCR) families. The program is administered by NIDDK, the National Center for Advancing Translational Sciences and the National Cancer Institute: https://commonfund.nih.gov/idg/index
This one-day symposium is organized by the Clinical Pharmacogenetics Implementation Consortium (CPIC ® ) as part of the Pharmacogenomics Research Network (PGRN) Symposium. Talks by world-class speakers from high profile academic, hospital and health service organizations will highlight how the USA and other countries are leading the way in strategizing the implementation of pharmacogenetics. This event will provide a great opportunity to meet with speakers from all sectors involved in pharmacogenetic implementation who will share their strategies and perspectives and provide tough examples for implementation. Further details and the registration link will soon be available here.
Location: Washington Marriott Wardman Park, Washington, DC, USA
Three main sessions and two panel discussions (see full agenda here):
Session I: Strategies for Implementing Pharmacogenetics
The Pharmacogenomics iPSC (induced Pluripotent Stem Cell) Library and Service (PiLS) is the latest resource that was funded by NIGMS Enabling Resources for Pharmacogenomics (R24) mechanism. Together with the other PGRN Centers and Resources, PiLS is the first resource that provides PGRN members with the iPSC Library and Service to enable pharmacogenomics studies.
PiLS is planning to roll out a pilot service to generate gene targeted iPSC clones for up to three selected projects. Projects will be recruited through announcement in NIGMS website as well as pgrn.org (join PGRN member to get e-mail about all PGRN announcements). PiLS iPSC library will be generated from genotyped healthy control samples of a cell bank established at the University of Florida. This original cell bank was established from salvaged samples from the Type 1 Diabetes Genetics Consortium (T1DGC), an international consortium established to identify the genes and alleles that contribute to risk for Type 1 Diabetes (T1D). The biosamples to be used were recruited with informed consent as part of the NIDDK/NIAID/NHGRI/NICHD supported Type 1 Diabetes Genetics Consortium (T1DGC). The iPSC library has integrated SNP database that could provide PGRN researcher practical and accessible methods to study potential impact of SNPs on drug response. The proposed resources are found at the PiLS webpage.
If you plan to use iPSC for your research anytime soon or are using iPSC for your research, please help to take this on-line survey or to include your feedback or comment about the PiLS resource. Based on your comments and research feasibility, PiLS could roll out the pilot service to tailor general needs. If you prefer to send in your comments and feedback or questions by e-mail, please send to Dr. Katherine E. Santostefano, firstname.lastname@example.org and email@example.com.
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
The Hub team