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AuthorJithesh, Puthen Veettil
AuthorAbuhaliqa, Mohammed
AuthorSyed, Najeeb
AuthorAhmed, Ikhlak
AuthorEl Anbari, Mohammed
AuthorBastaki, Kholoud
AuthorSherif, Shimaa
AuthorUmlai, Umm-Kulthum
AuthorJan, Zainab
AuthorGandhi, Geethanjali
AuthorManickam, Chidambaram
AuthorSelvaraj, Senthil
AuthorGeorge, Chinnu
AuthorBangarusamy, Dhinoth
AuthorAbdel-latif, Rania
AuthorAl-Shafai, Mashael
AuthorTatari-Calderone, Zohreh
AuthorEstivill, Xavier
AuthorPirmohamed, Munir
AuthorAbdel-latif, Rania
AuthorSaqri, Tariq Abu
AuthorZaid, Tariq Abu
AuthorAfifi, Nahla
AuthorAl-Ali, Rashid
AuthorAl-Khodor, Souhaila
AuthorAl-Muftah, Wadha
AuthorAl-Sarraj, Yasser
AuthorAlbagha, Omar
AuthorAlkhayat, Eiman
AuthorAlkuwari, Fatima
AuthorAlmabrazi, Hakeem
AuthorAlshafai, Mashael
AuthorAlthani, Asmaa
AuthorAlvi, Muhammad
AuthorBadii, Ramin
AuthorBadji, Radja
AuthorChouchane, Lotfi
AuthorDarwish, Dima
AuthorEl Khouly, Ahmed
AuthorEnnaifar, Maryem
AuthorEstivill, Xavier
AuthorFadl, Tasnim
AuthorFakhro, Khalid
AuthorFethnou, Eleni
AuthorHamza, Mehshad
AuthorIsmail, Said I.
AuthorJithesh, Puthen V.
AuthorKhatib, Mohammedhusen
AuthorLiu, Wei
AuthorLorenz, Stephan
AuthorMbarek, Hamdi
AuthorMokrab, Younes
AuthorPathare, Tushar
AuthorPoolat, Shafeeq
AuthorQafoud, Fatima
AuthorVempalli, Fazulur Rehaman
AuthorSaad, Chadi
AuthorSuhre, Karsten
AuthorSyed, Najeeb
AuthorTatari, Zohreh
AuthorTemanni, Ramzi
AuthorTomei, Sara
AuthorYasin, Heba
Available date2023-08-28T09:09:49Z
Publication Date2022
Publication Namenpj Genomic Medicine
ResourceScopus
ISSN20567944
URIhttp://dx.doi.org/10.1038/s41525-022-00281-5
URIhttp://hdl.handle.net/10576/46830
AbstractClinical implementation of pharmacogenomics will help in personalizing drug prescriptions and alleviate the personal and financial burden due to inefficacy and adverse reactions to drugs. However, such implementation is lagging in many parts of the world, including the Middle East, mainly due to the lack of data on the distribution of actionable pharmacogenomic variation in these ethnicities. We analyzed 6,045 whole genomes from the Qatari population for the distribution of allele frequencies of 2,629 variants in 1,026 genes known to affect 559 drugs or classes of drugs. We also performed a focused analysis of genotypes or diplotypes of 15 genes affecting 46 drugs, which have guidelines for clinical implementation and predicted their phenotypic impact. The allele frequencies of 1,320 variants in 703 genes affecting 299 drugs or class of drugs were significantly different between the Qatari population and other world populations. On average, Qataris carry 3.6 actionable genotypes/diplotypes, affecting 13 drugs with guidelines for clinical implementation, and 99.5% of the individuals had at least one clinically actionable genotype/diplotype. Increased risk of simvastatin-induced myopathy could be predicted in ~32% of Qataris from the diplotypes of SLCO1B1, which is higher compared to many other populations, while fewer Qataris may need tacrolimus dosage adjustments for achieving immunosuppression based on the CYP3A5 diplotypes compared to other world populations. Distinct distribution of actionable pharmacogenomic variation was also observed among the Qatari subpopulations. Our comprehensive study of the distribution of actionable genetic variation affecting drugs in a Middle Eastern population has potential implications for preemptive pharmacogenomic implementation in the region and beyond. 2022, The Author(s).
SponsorPVJ is supported by faculty funding from the College of Health & Life Sciences, HBKU. Qatar Biobank and Qatar Genome Program are Research, Development & Innovation's entities within Qatar Foundation for Education, Science and Community Development. Funders had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Languageen
PublisherNature Research
SubjectPersonalized medicine
Pharmacogenomics
TitleA population study of clinically actionable genetic variation affecting drug response from the Middle East
TypeArticle
Issue Number1
Volume Number7
dc.accessType Open Access


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