Analysis of 14,392 whole genomes reveals 3.5% of Qataris carry medically actionable variants
<p dir="ltr">Arabic populations are underrepresented in large genome projects; therefore, the frequency of clinically actionable variants among Arabs is largely unknown. Here, we investigated genetic variation in 14,392 whole genomes from the Qatar Genome Program (QGP) across the lis...
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2024
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| _version_ | 1864513541501878272 |
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| author | Amal Elfatih (14778550) |
| author2 | Chadi Saad (5369351) The Qatar Genome Program Research Consortium (14778616) Qatar Genome Project Management (14778619) Said Ismail (1567891) Wadha Al-Muftah (14152551) Radja Badji (14152548) Dima Darwish (14152545) Tasnim Fadl (14152533) Heba Yasin (14152542) Maryem Ennaifar (14778556) Rania Abdel-latif (18295396) Fatima Alkuwari (14778562) Muhammad Alvi (4831311) Yasser Al Sarraj (14778565) Asmaa Althani (499903) Biobank and Sample Preparation (14778622) Eleni Fthenou (216980) Fatima Qafoud (14778571) Eiman Alkhayat (14778574) Nahla Afifi (193245) Sequencing and Genotyping group (14778625) Sara Tomei (3441323) Wei Liu (20030) Stephan Lorenz (466378) Applied Bioinformatics Core (14778628) Najeeb Syed (12561967) Hakeem Almabrazi (6561371) Fazulur Rehaman Vempalli (14778577) Ramzi Temanni (671528) Data Management and Computing Infrastructure group (14778631) Tariq Abu Saqri (14778580) Mohammed husen Khatib (22046600) Mehshad Hamza (14778586) Tariq Abu Zaid (14778589) Ahmed El Khouly (14778592) Tushar Pathare (14778595) Shafeeq Poolat (14778598) Rashid Al-Ali (846229) Consortium Lead Principal Investigators (14778634) Omar M. E. Albagha (11704871) Souhaila Al-Khodor (247417) Mashael Alshafai (14778607) Ramin Badii (491543) Lotfi Chouchane (61840) Xavier Estivill (23803) Khalid Fakhro (3441305) Hamdi Mbarek (134997) Younes Mokrab (6367) Jithesh V. Puthen (14778610) Karsten Suhre (67967) Zohreh Tatari (14778613) Borbala Mifsud (3907267) |
| 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_facet | Amal Elfatih (14778550) Chadi Saad (5369351) The Qatar Genome Program Research Consortium (14778616) Qatar Genome Project Management (14778619) Said Ismail (1567891) Wadha Al-Muftah (14152551) Radja Badji (14152548) Dima Darwish (14152545) Tasnim Fadl (14152533) Heba Yasin (14152542) Maryem Ennaifar (14778556) Rania Abdel-latif (18295396) Fatima Alkuwari (14778562) Muhammad Alvi (4831311) Yasser Al Sarraj (14778565) Asmaa Althani (499903) Biobank and Sample Preparation (14778622) Eleni Fthenou (216980) Fatima Qafoud (14778571) Eiman Alkhayat (14778574) Nahla Afifi (193245) Sequencing and Genotyping group (14778625) Sara Tomei (3441323) Wei Liu (20030) Stephan Lorenz (466378) Applied Bioinformatics Core (14778628) Najeeb Syed (12561967) Hakeem Almabrazi (6561371) Fazulur Rehaman Vempalli (14778577) Ramzi Temanni (671528) Data Management and Computing Infrastructure group (14778631) Tariq Abu Saqri (14778580) Mohammed husen Khatib (22046600) Mehshad Hamza (14778586) Tariq Abu Zaid (14778589) Ahmed El Khouly (14778592) Tushar Pathare (14778595) Shafeeq Poolat (14778598) Rashid Al-Ali (846229) Consortium Lead Principal Investigators (14778634) Omar M. E. Albagha (11704871) Souhaila Al-Khodor (247417) Mashael Alshafai (14778607) Ramin Badii (491543) Lotfi Chouchane (61840) Xavier Estivill (23803) Khalid Fakhro (3441305) Hamdi Mbarek (134997) Younes Mokrab (6367) Jithesh V. Puthen (14778610) Karsten Suhre (67967) Zohreh Tatari (14778613) Borbala Mifsud (3907267) |
| author_role | author |
| dc.creator.none.fl_str_mv | Amal Elfatih (14778550) Chadi Saad (5369351) The Qatar Genome Program Research Consortium (14778616) Qatar Genome Project Management (14778619) Said Ismail (1567891) Wadha Al-Muftah (14152551) Radja Badji (14152548) Dima Darwish (14152545) Tasnim Fadl (14152533) Heba Yasin (14152542) Maryem Ennaifar (14778556) Rania Abdel-latif (18295396) Fatima Alkuwari (14778562) Muhammad Alvi (4831311) Yasser Al Sarraj (14778565) Asmaa Althani (499903) Biobank and Sample Preparation (14778622) Eleni Fthenou (216980) Fatima Qafoud (14778571) Eiman Alkhayat (14778574) Nahla Afifi (193245) Sequencing and Genotyping group (14778625) Sara Tomei (3441323) Wei Liu (20030) Stephan Lorenz (466378) Applied Bioinformatics Core (14778628) Najeeb Syed (12561967) Hakeem Almabrazi (6561371) Fazulur Rehaman Vempalli (14778577) Ramzi Temanni (671528) Data Management and Computing Infrastructure group (14778631) Tariq Abu Saqri (14778580) Mohammed husen Khatib (22046600) Mehshad Hamza (14778586) Tariq Abu Zaid (14778589) Ahmed El Khouly (14778592) Tushar Pathare (14778595) Shafeeq Poolat (14778598) Rashid Al-Ali (846229) Consortium Lead Principal Investigators (14778634) Omar M. E. Albagha (11704871) Souhaila Al-Khodor (247417) Mashael Alshafai (14778607) Ramin Badii (491543) Lotfi Chouchane (61840) Xavier Estivill (23803) Khalid Fakhro (3441305) Hamdi Mbarek (134997) Younes Mokrab (6367) Jithesh V. Puthen (14778610) Karsten Suhre (67967) Zohreh Tatari (14778613) Borbala Mifsud (3907267) |
| dc.date.none.fl_str_mv | 2024-07-17T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/s41431-024-01656-1 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Analysis_of_14_392_whole_genomes_reveals_3_5_of_Qataris_carry_medically_actionable_variants/29899739 |
| 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 Cardiovascular medicine and haematology Oncology and carcinogenesis Health sciences Epidemiology Whole genome sequencing Qatar Genome Program (QGP) Population-specific genetic risk Cancer genetics Cardiovascular disease genetics |
| dc.title.none.fl_str_mv | Analysis of 14,392 whole genomes reveals 3.5% of Qataris carry medically actionable variants |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Arabic populations are underrepresented in large genome projects; therefore, the frequency of clinically actionable variants among Arabs is largely unknown. Here, we investigated genetic variation in 14,392 whole genomes from the Qatar Genome Program (QGP) across the list of 78 actionable genes (v3.1) determined by the American College of Medical Genetics and Genomics (ACMG). Variants were categorized into one of the following groups: (1) Pathogenic (P), (2) Likely pathogenic (LP), and (3) Rare variants of uncertain significance with evidence of pathogenicity. For the classification, we used variant databases, effect predictors, and the disease-relevant phenotypes available for the cohort. Data on cardiovascular disease, cancer, and hypercholesterolemia allowed us to assess the disease-relevant phenotype association of rare missense variants. We identified 248 distinct variants in 50 ACMG genes that fulfilled our criteria to be included in one of the three groups affecting 1036 genotype-positive participants of the QGP cohort. The most frequent variants were in TTN, followed by RYR1 and ATP7B. The prevalence of reportable secondary findings was 3.5%. A further 46 heterozygous variants in six genes with an autosomal recessive mode of inheritance were detected in 200 individuals, accounting for an additional 1.4%. Altogether, they affect 5% of the population. Due to the high consanguinity rate in the QGP cohort (28% in spouses and 60% in parents), P and LP variants both in genes with dominant and recessive inheritance are important for developing better treatment options and preventive strategies in Qatar and the Arabic population of the Middle East.</p><h2>Other Information</h2><p dir="ltr">Published in: European Journal of Human Genetics<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/s41431-024-01656-1" target="_blank">https://dx.doi.org/10.1038/s41431-024-01656-1</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_65bebde7e87f2d4d1c2e57cab92a1b46 |
| identifier_str_mv | 10.1038/s41431-024-01656-1 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/29899739 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Analysis of 14,392 whole genomes reveals 3.5% of Qataris carry medically actionable variantsAmal Elfatih (14778550)Chadi Saad (5369351)The Qatar Genome Program Research Consortium (14778616)Qatar Genome Project Management (14778619)Said Ismail (1567891)Wadha Al-Muftah (14152551)Radja Badji (14152548)Dima Darwish (14152545)Tasnim Fadl (14152533)Heba Yasin (14152542)Maryem Ennaifar (14778556)Rania Abdel-latif (18295396)Fatima Alkuwari (14778562)Muhammad Alvi (4831311)Yasser Al Sarraj (14778565)Asmaa Althani (499903)Biobank and Sample Preparation (14778622)Eleni Fthenou (216980)Fatima Qafoud (14778571)Eiman Alkhayat (14778574)Nahla Afifi (193245)Sequencing and Genotyping group (14778625)Sara Tomei (3441323)Wei Liu (20030)Stephan Lorenz (466378)Applied Bioinformatics Core (14778628)Najeeb Syed (12561967)Hakeem Almabrazi (6561371)Fazulur Rehaman Vempalli (14778577)Ramzi Temanni (671528)Data Management and Computing Infrastructure group (14778631)Tariq Abu Saqri (14778580)Mohammed husen Khatib (22046600)Mehshad Hamza (14778586)Tariq Abu Zaid (14778589)Ahmed El Khouly (14778592)Tushar Pathare (14778595)Shafeeq Poolat (14778598)Rashid Al-Ali (846229)Consortium Lead Principal Investigators (14778634)Omar M. E. Albagha (11704871)Souhaila Al-Khodor (247417)Mashael Alshafai (14778607)Ramin Badii (491543)Lotfi Chouchane (61840)Xavier Estivill (23803)Khalid Fakhro (3441305)Hamdi Mbarek (134997)Younes Mokrab (6367)Jithesh V. Puthen (14778610)Karsten Suhre (67967)Zohreh Tatari (14778613)Borbala Mifsud (3907267)Biological sciencesGeneticsBiomedical and clinical sciencesCardiovascular medicine and haematologyOncology and carcinogenesisHealth sciencesEpidemiologyWhole genome sequencingQatar Genome Program (QGP)Population-specific genetic riskCancer geneticsCardiovascular disease genetics<p dir="ltr">Arabic populations are underrepresented in large genome projects; therefore, the frequency of clinically actionable variants among Arabs is largely unknown. Here, we investigated genetic variation in 14,392 whole genomes from the Qatar Genome Program (QGP) across the list of 78 actionable genes (v3.1) determined by the American College of Medical Genetics and Genomics (ACMG). Variants were categorized into one of the following groups: (1) Pathogenic (P), (2) Likely pathogenic (LP), and (3) Rare variants of uncertain significance with evidence of pathogenicity. For the classification, we used variant databases, effect predictors, and the disease-relevant phenotypes available for the cohort. Data on cardiovascular disease, cancer, and hypercholesterolemia allowed us to assess the disease-relevant phenotype association of rare missense variants. We identified 248 distinct variants in 50 ACMG genes that fulfilled our criteria to be included in one of the three groups affecting 1036 genotype-positive participants of the QGP cohort. The most frequent variants were in TTN, followed by RYR1 and ATP7B. The prevalence of reportable secondary findings was 3.5%. A further 46 heterozygous variants in six genes with an autosomal recessive mode of inheritance were detected in 200 individuals, accounting for an additional 1.4%. Altogether, they affect 5% of the population. Due to the high consanguinity rate in the QGP cohort (28% in spouses and 60% in parents), P and LP variants both in genes with dominant and recessive inheritance are important for developing better treatment options and preventive strategies in Qatar and the Arabic population of the Middle East.</p><h2>Other Information</h2><p dir="ltr">Published in: European Journal of Human Genetics<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/s41431-024-01656-1" target="_blank">https://dx.doi.org/10.1038/s41431-024-01656-1</a></p>2024-07-17T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41431-024-01656-1https://figshare.com/articles/journal_contribution/Analysis_of_14_392_whole_genomes_reveals_3_5_of_Qataris_carry_medically_actionable_variants/29899739CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/298997392024-07-17T03:00:00Z |
| spellingShingle | Analysis of 14,392 whole genomes reveals 3.5% of Qataris carry medically actionable variants Amal Elfatih (14778550) Biological sciences Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology Oncology and carcinogenesis Health sciences Epidemiology Whole genome sequencing Qatar Genome Program (QGP) Population-specific genetic risk Cancer genetics Cardiovascular disease genetics |
| status_str | publishedVersion |
| title | Analysis of 14,392 whole genomes reveals 3.5% of Qataris carry medically actionable variants |
| title_full | Analysis of 14,392 whole genomes reveals 3.5% of Qataris carry medically actionable variants |
| title_fullStr | Analysis of 14,392 whole genomes reveals 3.5% of Qataris carry medically actionable variants |
| title_full_unstemmed | Analysis of 14,392 whole genomes reveals 3.5% of Qataris carry medically actionable variants |
| title_short | Analysis of 14,392 whole genomes reveals 3.5% of Qataris carry medically actionable variants |
| title_sort | Analysis of 14,392 whole genomes reveals 3.5% of Qataris carry medically actionable variants |
| topic | Biological sciences Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology Oncology and carcinogenesis Health sciences Epidemiology Whole genome sequencing Qatar Genome Program (QGP) Population-specific genetic risk Cancer genetics Cardiovascular disease genetics |