Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals
<h3>Background: </h3><p dir="ltr">The current study explores the genetic underpinnings of cardiac arrhythmia phenotypes within Middle Eastern populations, which are under-represented in genomic medicine research. Methods: Whole-genome sequencing data from 14,259 individua...
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| مؤلفون آخرون: | , , , , , , , |
| منشور في: |
2024
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| _version_ | 1864513509360926720 |
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| author | Fatima Qafoud (14778571) |
| author2 | Mohamed Elshrif (19326013) Khalid Kunji (828224) Asma Althani (193235) Amar Salam (19326016) Jassim Al Suwaidi (284932) Nidal Asaad (284935) Dawood Darbar (181657) Mohamad Saad (214545) |
| author2_role | author author author author author author author author |
| author_facet | Fatima Qafoud (14778571) Mohamed Elshrif (19326013) Khalid Kunji (828224) Asma Althani (193235) Amar Salam (19326016) Jassim Al Suwaidi (284932) Nidal Asaad (284935) Dawood Darbar (181657) Mohamad Saad (214545) |
| author_role | author |
| dc.creator.none.fl_str_mv | Fatima Qafoud (14778571) Mohamed Elshrif (19326013) Khalid Kunji (828224) Asma Althani (193235) Amar Salam (19326016) Jassim Al Suwaidi (284932) Nidal Asaad (284935) Dawood Darbar (181657) Mohamad Saad (214545) |
| dc.date.none.fl_str_mv | 2024-02-15T12:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/jcm13041102 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Genetic_Susceptibility_to_Arrhythmia_Phenotypes_in_a_Middle_Eastern_Cohort_of_14_259_Whole-Genome_Sequenced_Individuals/26491147 |
| 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 Clinical sciences arrythmia atrial fibrillation cardiomyopathy Middle East genomics diversity whole-genome sequencing diverse populations |
| dc.title.none.fl_str_mv | Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Background: </h3><p dir="ltr">The current study explores the genetic underpinnings of cardiac arrhythmia phenotypes within Middle Eastern populations, which are under-represented in genomic medicine research. Methods: Whole-genome sequencing data from 14,259 individuals from the Qatar Biobank were used and contained 47.8% of Arab ancestry, 18.4% of South Asian ancestry, and 4.6% of African ancestry. The frequency of rare functional variants within a set of 410 candidate genes for cardiac arrhythmias was assessed. Polygenic risk score (PRS) performance for atrial fibrillation (AF) prediction was evaluated. Results: This study identified 1196 rare functional variants, including 162 previously linked to arrhythmia phenotypes, with varying frequencies across Arab, South Asian, and African ancestries. Of these, 137 variants met the pathogenic or likely pathogenic (P/LP) criteria according to ACMG guidelines. Of these, 91 were in ACMG actionable genes and were present in 1030 individuals (~7%). Ten P/LP variants showed significant associations with atrial fibrillation <i>p</i> < 2.4 × 10<sup>−10</sup>. Five out of ten existing PRSs were significantly associated with AF (e.g., PGS000727, <i>p</i> = 0.03, OR = 1.43 [1.03, 1.97]). Conclusions: Our study is the largest to study the genetic predisposition to arrhythmia phenotypes in the Middle East using whole-genome sequence data. It underscores the importance of including diverse populations in genomic investigations to elucidate the genetic landscape of cardiac arrhythmias and mitigate health disparities in genomic medicine.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Clinical 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/10.3390/jcm13041102" target="_blank">https://dx.doi.org/10.3390/jcm13041102</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_ee48d3ff04fcb1d3e9c8e703530a3e4b |
| identifier_str_mv | 10.3390/jcm13041102 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26491147 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced IndividualsFatima Qafoud (14778571)Mohamed Elshrif (19326013)Khalid Kunji (828224)Asma Althani (193235)Amar Salam (19326016)Jassim Al Suwaidi (284932)Nidal Asaad (284935)Dawood Darbar (181657)Mohamad Saad (214545)Biological sciencesGeneticsBiomedical and clinical sciencesCardiovascular medicine and haematologyClinical sciencesarrythmiaatrial fibrillationcardiomyopathyMiddle Eastgenomicsdiversitywhole-genome sequencingdiverse populations<h3>Background: </h3><p dir="ltr">The current study explores the genetic underpinnings of cardiac arrhythmia phenotypes within Middle Eastern populations, which are under-represented in genomic medicine research. Methods: Whole-genome sequencing data from 14,259 individuals from the Qatar Biobank were used and contained 47.8% of Arab ancestry, 18.4% of South Asian ancestry, and 4.6% of African ancestry. The frequency of rare functional variants within a set of 410 candidate genes for cardiac arrhythmias was assessed. Polygenic risk score (PRS) performance for atrial fibrillation (AF) prediction was evaluated. Results: This study identified 1196 rare functional variants, including 162 previously linked to arrhythmia phenotypes, with varying frequencies across Arab, South Asian, and African ancestries. Of these, 137 variants met the pathogenic or likely pathogenic (P/LP) criteria according to ACMG guidelines. Of these, 91 were in ACMG actionable genes and were present in 1030 individuals (~7%). Ten P/LP variants showed significant associations with atrial fibrillation <i>p</i> < 2.4 × 10<sup>−10</sup>. Five out of ten existing PRSs were significantly associated with AF (e.g., PGS000727, <i>p</i> = 0.03, OR = 1.43 [1.03, 1.97]). Conclusions: Our study is the largest to study the genetic predisposition to arrhythmia phenotypes in the Middle East using whole-genome sequence data. It underscores the importance of including diverse populations in genomic investigations to elucidate the genetic landscape of cardiac arrhythmias and mitigate health disparities in genomic medicine.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Clinical 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/10.3390/jcm13041102" target="_blank">https://dx.doi.org/10.3390/jcm13041102</a></p>2024-02-15T12:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/jcm13041102https://figshare.com/articles/journal_contribution/Genetic_Susceptibility_to_Arrhythmia_Phenotypes_in_a_Middle_Eastern_Cohort_of_14_259_Whole-Genome_Sequenced_Individuals/26491147CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/264911472024-02-15T12:00:00Z |
| spellingShingle | Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals Fatima Qafoud (14778571) Biological sciences Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology Clinical sciences arrythmia atrial fibrillation cardiomyopathy Middle East genomics diversity whole-genome sequencing diverse populations |
| status_str | publishedVersion |
| title | Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals |
| title_full | Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals |
| title_fullStr | Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals |
| title_full_unstemmed | Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals |
| title_short | Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals |
| title_sort | Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals |
| topic | Biological sciences Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology Clinical sciences arrythmia atrial fibrillation cardiomyopathy Middle East genomics diversity whole-genome sequencing diverse populations |