A population study of clinically actionable genetic variation affecting drug response from the Middle East
<p dir="ltr">Clinical 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 M...
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2022
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| author | Puthen Veettil Jithesh (12040358) |
| author2 | Mohammed Abuhaliqa (18434091) Najeeb Syed (12561967) Ikhlak Ahmed (150200) Mohammed El Anbari (767963) Kholoud Bastaki (18434094) Shimaa Sherif (12862990) Umm-Kulthum Umlai (4991660) Zainab Jan (17306614) Geethanjali Gandhi (18434097) Chidambaram Manickam (18434100) Senthil Selvaraj (314873) Chinnu George (18434103) Dhinoth Bangarusamy (14894490) Rania Abdel-latif (18295396) Mashael Al-Shafai (3466301) Zohreh Tatari-Calderone (9194307) Xavier Estivill (23803) Munir Pirmohamed (40546) Tariq Abu Saqri (14778580) Tariq Abu Zaid (14778589) Nahla Afifi (193245) Rashid Al-Ali (846229) Souhaila Al-Khodor (247417) Wadha Al-Muftah (14152551) Yasser Al-Sarraj (11721425) Omar Albagha (8977856) Eiman Alkhayat (14778574) Fatima Alkuwari (14778562) Hakeem Almabrazi (6561371) Mashael Alshafai (14778607) Asmaa Althani (499903) Muhammad Alvi (4831311) Ramin Badii (491543) Radja Badji (14152548) Lotfi Chouchane (61840) Dima Darwish (14152545) Ahmed El Khouly (14778592) Maryem Ennaifar (14778556) Tasnim Fadl (14152533) Khalid Fakhro (3441305) Eleni Fethnou (14778568) Mehshad Hamza (14778586) Said I. Ismail (11721428) Puthen V. Jithesh (7639115) Mohammedhusen Khatib (14778583) Wei Liu (20030) Stephan Lorenz (466378) Hamdi Mbarek (134997) Younes Mokrab (6367) Tushar Pathare (14778595) Shafeeq Poolat (14778598) Fatima Qafoud (14778571) Fazulur Rehaman Vempalli (14778577) Chadi Saad (5369351) Karsten Suhre (67967) Zohreh Tatari (14778613) Ramzi Temanni (671528) Sara Tomei (3441323) Heba Yasin (14152542) The Qatar Genome Program Research Consortium (14778616) |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| author_facet | Puthen Veettil Jithesh (12040358) Mohammed Abuhaliqa (18434091) Najeeb Syed (12561967) Ikhlak Ahmed (150200) Mohammed El Anbari (767963) Kholoud Bastaki (18434094) Shimaa Sherif (12862990) Umm-Kulthum Umlai (4991660) Zainab Jan (17306614) Geethanjali Gandhi (18434097) Chidambaram Manickam (18434100) Senthil Selvaraj (314873) Chinnu George (18434103) Dhinoth Bangarusamy (14894490) Rania Abdel-latif (18295396) Mashael Al-Shafai (3466301) Zohreh Tatari-Calderone (9194307) Xavier Estivill (23803) Munir Pirmohamed (40546) Tariq Abu Saqri (14778580) Tariq Abu Zaid (14778589) Nahla Afifi (193245) Rashid Al-Ali (846229) Souhaila Al-Khodor (247417) Wadha Al-Muftah (14152551) Yasser Al-Sarraj (11721425) Omar Albagha (8977856) Eiman Alkhayat (14778574) Fatima Alkuwari (14778562) Hakeem Almabrazi (6561371) Mashael Alshafai (14778607) Asmaa Althani (499903) Muhammad Alvi (4831311) Ramin Badii (491543) Radja Badji (14152548) Lotfi Chouchane (61840) Dima Darwish (14152545) Ahmed El Khouly (14778592) Maryem Ennaifar (14778556) Tasnim Fadl (14152533) Khalid Fakhro (3441305) Eleni Fethnou (14778568) Mehshad Hamza (14778586) Said I. Ismail (11721428) Puthen V. Jithesh (7639115) Mohammedhusen Khatib (14778583) Wei Liu (20030) Stephan Lorenz (466378) Hamdi Mbarek (134997) Younes Mokrab (6367) Tushar Pathare (14778595) Shafeeq Poolat (14778598) Fatima Qafoud (14778571) Fazulur Rehaman Vempalli (14778577) Chadi Saad (5369351) Karsten Suhre (67967) Zohreh Tatari (14778613) Ramzi Temanni (671528) Sara Tomei (3441323) Heba Yasin (14152542) The Qatar Genome Program Research Consortium (14778616) |
| author_role | author |
| dc.creator.none.fl_str_mv | Puthen Veettil Jithesh (12040358) Mohammed Abuhaliqa (18434091) Najeeb Syed (12561967) Ikhlak Ahmed (150200) Mohammed El Anbari (767963) Kholoud Bastaki (18434094) Shimaa Sherif (12862990) Umm-Kulthum Umlai (4991660) Zainab Jan (17306614) Geethanjali Gandhi (18434097) Chidambaram Manickam (18434100) Senthil Selvaraj (314873) Chinnu George (18434103) Dhinoth Bangarusamy (14894490) Rania Abdel-latif (18295396) Mashael Al-Shafai (3466301) Zohreh Tatari-Calderone (9194307) Xavier Estivill (23803) Munir Pirmohamed (40546) Tariq Abu Saqri (14778580) Tariq Abu Zaid (14778589) Nahla Afifi (193245) Rashid Al-Ali (846229) Souhaila Al-Khodor (247417) Wadha Al-Muftah (14152551) Yasser Al-Sarraj (11721425) Omar Albagha (8977856) Eiman Alkhayat (14778574) Fatima Alkuwari (14778562) Hakeem Almabrazi (6561371) Mashael Alshafai (14778607) Asmaa Althani (499903) Muhammad Alvi (4831311) Ramin Badii (491543) Radja Badji (14152548) Lotfi Chouchane (61840) Dima Darwish (14152545) Ahmed El Khouly (14778592) Maryem Ennaifar (14778556) Tasnim Fadl (14152533) Khalid Fakhro (3441305) Eleni Fethnou (14778568) Mehshad Hamza (14778586) Said I. Ismail (11721428) Puthen V. Jithesh (7639115) Mohammedhusen Khatib (14778583) Wei Liu (20030) Stephan Lorenz (466378) Hamdi Mbarek (134997) Younes Mokrab (6367) Tushar Pathare (14778595) Shafeeq Poolat (14778598) Fatima Qafoud (14778571) Fazulur Rehaman Vempalli (14778577) Chadi Saad (5369351) Karsten Suhre (67967) Zohreh Tatari (14778613) Ramzi Temanni (671528) Sara Tomei (3441323) Heba Yasin (14152542) The Qatar Genome Program Research Consortium (14778616) |
| dc.date.none.fl_str_mv | 2022-02-15T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/s41525-022-00281-5 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/A_population_study_of_clinically_actionable_genetic_variation_affecting_drug_response_from_the_Middle_East/25679874 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Pharmacology and pharmaceutical sciences Pharmacogenomics Personalized medicine Drug prescriptions Adverse drug reactions Allele frequencies Whole genomes Qatari population Genotypes Diplotypes |
| dc.title.none.fl_str_mv | A population study of clinically actionable genetic variation affecting drug response from the Middle East |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Clinical 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.</p><h2>Other Information</h2><p dir="ltr">Published in: npj Genomic Medicine<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41525-022-00281-5" target="_blank">https://dx.doi.org/10.1038/s41525-022-00281-5</a></p><p dir="ltr">Additional institutions affiliated with: Qatar University Health - QU</p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_d0affcc24776668853b8880f2a3d4b20 |
| identifier_str_mv | 10.1038/s41525-022-00281-5 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25679874 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | A population study of clinically actionable genetic variation affecting drug response from the Middle EastPuthen Veettil Jithesh (12040358)Mohammed Abuhaliqa (18434091)Najeeb Syed (12561967)Ikhlak Ahmed (150200)Mohammed El Anbari (767963)Kholoud Bastaki (18434094)Shimaa Sherif (12862990)Umm-Kulthum Umlai (4991660)Zainab Jan (17306614)Geethanjali Gandhi (18434097)Chidambaram Manickam (18434100)Senthil Selvaraj (314873)Chinnu George (18434103)Dhinoth Bangarusamy (14894490)Rania Abdel-latif (18295396)Mashael Al-Shafai (3466301)Zohreh Tatari-Calderone (9194307)Xavier Estivill (23803)Munir Pirmohamed (40546)Tariq Abu Saqri (14778580)Tariq Abu Zaid (14778589)Nahla Afifi (193245)Rashid Al-Ali (846229)Souhaila Al-Khodor (247417)Wadha Al-Muftah (14152551)Yasser Al-Sarraj (11721425)Omar Albagha (8977856)Eiman Alkhayat (14778574)Fatima Alkuwari (14778562)Hakeem Almabrazi (6561371)Mashael Alshafai (14778607)Asmaa Althani (499903)Muhammad Alvi (4831311)Ramin Badii (491543)Radja Badji (14152548)Lotfi Chouchane (61840)Dima Darwish (14152545)Ahmed El Khouly (14778592)Maryem Ennaifar (14778556)Tasnim Fadl (14152533)Khalid Fakhro (3441305)Eleni Fethnou (14778568)Mehshad Hamza (14778586)Said I. Ismail (11721428)Puthen V. Jithesh (7639115)Mohammedhusen Khatib (14778583)Wei Liu (20030)Stephan Lorenz (466378)Hamdi Mbarek (134997)Younes Mokrab (6367)Tushar Pathare (14778595)Shafeeq Poolat (14778598)Fatima Qafoud (14778571)Fazulur Rehaman Vempalli (14778577)Chadi Saad (5369351)Karsten Suhre (67967)Zohreh Tatari (14778613)Ramzi Temanni (671528)Sara Tomei (3441323)Heba Yasin (14152542)The Qatar Genome Program Research Consortium (14778616)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesPharmacology and pharmaceutical sciencesPharmacogenomicsPersonalized medicineDrug prescriptionsAdverse drug reactionsAllele frequenciesWhole genomesQatari populationGenotypesDiplotypes<p dir="ltr">Clinical 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.</p><h2>Other Information</h2><p dir="ltr">Published in: npj Genomic Medicine<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41525-022-00281-5" target="_blank">https://dx.doi.org/10.1038/s41525-022-00281-5</a></p><p dir="ltr">Additional institutions affiliated with: Qatar University Health - QU</p>2022-02-15T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41525-022-00281-5https://figshare.com/articles/journal_contribution/A_population_study_of_clinically_actionable_genetic_variation_affecting_drug_response_from_the_Middle_East/25679874CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/256798742022-02-15T03:00:00Z |
| spellingShingle | A population study of clinically actionable genetic variation affecting drug response from the Middle East Puthen Veettil Jithesh (12040358) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Pharmacology and pharmaceutical sciences Pharmacogenomics Personalized medicine Drug prescriptions Adverse drug reactions Allele frequencies Whole genomes Qatari population Genotypes Diplotypes |
| status_str | publishedVersion |
| title | A population study of clinically actionable genetic variation affecting drug response from the Middle East |
| title_full | A population study of clinically actionable genetic variation affecting drug response from the Middle East |
| title_fullStr | A population study of clinically actionable genetic variation affecting drug response from the Middle East |
| title_full_unstemmed | A population study of clinically actionable genetic variation affecting drug response from the Middle East |
| title_short | A population study of clinically actionable genetic variation affecting drug response from the Middle East |
| title_sort | A population study of clinically actionable genetic variation affecting drug response from the Middle East |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Pharmacology and pharmaceutical sciences Pharmacogenomics Personalized medicine Drug prescriptions Adverse drug reactions Allele frequencies Whole genomes Qatari population Genotypes Diplotypes |