Genetic study uncovers exploitable variation af

image: Jithesh Puthen Veettil
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Credit: Qatar Foundation

Doha, Qatar, February 15, 2022: A group of Qatar Foundation researchers has reported the first comprehensive study of the distribution of actionable genetic variation affecting drugs in any Middle Eastern population, with potential implications for preventive pharmacogenomics implementation in the region. The study was published online in npj genomic medicine – a leading peer-reviewed open access scientific journal published by Nature Research.

The study entitled “A population-based study of clinically actionable genetic variation affecting drug response from the Middle Easthighlights a diverse distribution of actionable pharmacogenomic variants in the Qatari population compared to other global populations, including a higher frequency in the Qatari population of multiple gene variants SLCO1B1, known to increase the risk of muscle toxicity after taking certain lipid-lowering drugs such as simvastatin. In contrast, an actionable variation in another gene, CYP3A5known to affect dose adjustments to achieve immunosuppression when using the drug tacrolimus, was lower in Qataris compared to other populations.

Pharmacogenomics uses genomic data to predict whether or not an individual will respond to a specific drug. Thus, it is helpful to move away from a “trial and error” way of prescribing drugs to be more accurate, avoiding drugs that are not safe for the patient, but choosing those that are most effective based on their genetic makeup.

The study led by Dr. Puthen Veettil Jithesh from the College of Health and Life Sciences (CHLS) at Hamad Bin Khalifa University (HBKU) of the Qatar Foundation (QF), along with other scientists from the Qatar Genome Program Research Consortium, includes whole genome sequence data from over 6,000 Qataris.

These data were analyzed using bioinformatics pipelines to identify the frequency distribution of over 1000 pharmacogenes. Additionally, detailed and focused analysis was undertaken on 15 genes affecting 46 drugs, which have guidelines for clinical implementation, to understand the clinical impact of actionable genetic variability in the population.

Dr. Jithesh says: “Our results indicate that 99.5% of the individuals studied have at least one clinically actionable genetic variability with potential effect on drug safety and efficacy. Several of these drugs are widely prescribed in Qatar and other parts of the world, and our findings therefore have important implications for the clinical implementation of pharmacogenomics in the country and beyond. Once validated, patients can receive the right drug at the right dose based on their genetic makeup, without any trial and error process. Pharmacogenomics is often seen as the poster child for precision medicine, with its direct clinical applications.

Sir Munir Pirmohamed, David Weatherall Professor of Medicine at the University of Liverpool, and also author of the paper, said: “This study fills a gap in our understanding of clinically actionable genetic variation affecting drugs in populations of the Middle East and assisting in our planning for the implementation of precision medicine in the country.

Georges Nemer, Professor and Acting Dean of the CHLS, says: “This publication demonstrates our commitment to strong applied research in the field of precision medicine and elevates our graduate programs in genomics and precision medicine to higher levels of excellence.

Said Ismail, director of the Qatar Genome Program, which is part of QF Research, Development, and Innovation, said, “Based on these research results, we have initiated three pilot pharmacogenomics studies with our partners in clinics across the Hamad Medical Corporation hospital. Such projects are the cornerstone of implementing precision medicine into the practice of clinical care. We at the Qatar Genome Program are proud to expand these efforts and will continue this effort with greater population representation in the near future.

**ENDS**

Review abstract accepted:

The clinical implementation of pharmacogenomics will help to personalize drug prescriptions and alleviate the personal and financial burden of drug ineffectiveness and adverse effects. However, such implementation is lagging in many parts of the world, including the Middle East, primarily due to the lack of data on the distribution of exploitable pharmacogenomic variation in these ethnicities. We analyzed 6045 whole genomes from the Qatari population for the allele frequency distribution of 2629 variants in 1026 genes known to affect 559 drugs or drug classes. We also performed a targeted analysis of the genotypes or diplotypes of 15 genes affecting 46 drugs, which have guidelines for clinical implementation and predict their phenotypic impact. The allele frequencies of 1,320 variants in 703 genes affecting 299 drugs or drug classes were significantly different between the Qatari population and other global populations. On average, Qataris carry 3.6 actionable genotypes/diplotypes, affecting 13 drugs with guidelines for clinical implementation, and 99.5% of individuals had at least one clinically actionable genotype/diplotype. An increased risk of simvastatin-induced myopathy could be predicted in approximately 32% of Qataris from SLCO1B1 diplotypes, which is higher compared to many other populations, while fewer Qataris may require adjustments of tacrolimus dosing to achieve immunosuppression based on CYP3A5 diplotypes compared to other global populations. A distinct distribution of exploitable pharmacogenomic variation was also observed among Qatari subpopulations. Our in-depth study of the distribution of drug-affecting actionable genetic variation in a Middle Eastern population has potential implications for preventive pharmacogenomics implementation in the region and beyond.

Reference:

Jithesh PV, Abuhaliqa M, Syed N, Ahmed I, El Anbari M, Bastaki K, Sherif S, Umlai UK, Jan Z, Gandhi G, Manickam C, Selvaraj S, George C, Bangarusamy D, Abdel-latif R, Al- Shafai M, Tatari-Calderone Z, Estivill X, Pirmohamed M, QGP Research Consortium (2022) A population-based study of clinically exploitable genetic variation affecting drug response from the Middle East. NPJ Genomic Medicine https://doi.org/10.1038/s41525-022-00281-5

About the Qatar Genome Program

The Qatar Genome Program (QGP) is the largest genome project in the Middle East with a mission to promote genomic research and clinical implementation at the national level. The QGP is designed around a comprehensive strategy involving large-scale genome sequencing and multi-omics data, building local and international research partnerships, building local human capacity, facilitating integration into the health system, the development of guidelines and policies, public awareness as well as the empowerment and education of the sick.

About Hamad Bin Khalifa University

Innovate today, shape tomorrow

Hamad Bin Khalifa University (HBKU), a member of the Qatar Foundation for Education, Science and Community Development (QF), was founded in 2010 as a research-intensive university that acts as a catalyst of transformative change in Qatar and the region while having global impact. Located in Education City, HBKU is committed to strengthening and cultivating human capabilities through an enriching academic experience, an innovative ecosystem, and unique partnerships. HBKU offers multidisciplinary undergraduate and graduate programs in its colleges and offers research and scholarship opportunities in its institutes and centers. For more information about HBKU, visit www.hbku.edu.qa.

Qatar Foundation – Unlocking Human Potential

The Qatar Foundation for Education, Science and Community Development (QF) is a non-profit organization that supports Qatar on its journey towards a diverse and sustainable economy. QF strives to serve the people of Qatar and beyond by providing specialized programs in its innovation-driven ecosystem of education, research and development, and community development.

QF was founded in 1995 by His Highness Sheikh Hamad bin Khalifa Al Thani, Father Amir, and Her Highness Sheikha Moza bint Nasser, who shared the vision of providing Qatar with quality education. Today, QF’s world-class education system provides lifelong learning opportunities for community members from the age of six months through to doctoral level, enabling graduates to thrive. in a global environment and to contribute to the development of the nation.

QF is also creating a multidisciplinary innovation center in Qatar, where local researchers work to address local and global challenges. By promoting a culture of lifelong learning and fostering social engagement through programs that embody Qatari culture, QF is committed to empowering the local community and contributing to a better world for all.

For a complete list of QF initiatives and projects, please visit: www.qf.org.qa

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