Genetic Basis and Prognostic Value of Exercise QT Dynamics
<h3>Background</h3><p dir="ltr">Abnormal QT interval responses to heart rate (QT dynamics) is an independent risk predictor for cardiovascular disease in patients, but its genetic basis and prognostic value in a population-based cohort have not been investigated.</p>...
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| مؤلفون آخرون: | , , , , , , |
| منشور في: |
2020
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| _version_ | 1864513516107464704 |
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| author | Stefan van Duijvenboden (7116386) |
| author2 | Julia Ramírez (4506787) William J. Young (18426897) Borbala Mifsud (3907267) Michele Orini (3097818) Andrew Tinker (477693) Patricia B. Munroe (7588601) Pier D. Lambiase (10163594) |
| author2_role | author author author author author author author |
| author_facet | Stefan van Duijvenboden (7116386) Julia Ramírez (4506787) William J. Young (18426897) Borbala Mifsud (3907267) Michele Orini (3097818) Andrew Tinker (477693) Patricia B. Munroe (7588601) Pier D. Lambiase (10163594) |
| author_role | author |
| dc.creator.none.fl_str_mv | Stefan van Duijvenboden (7116386) Julia Ramírez (4506787) William J. Young (18426897) Borbala Mifsud (3907267) Michele Orini (3097818) Andrew Tinker (477693) Patricia B. Munroe (7588601) Pier D. Lambiase (10163594) |
| dc.date.none.fl_str_mv | 2020-08-01T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1161/circgen.119.002774 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Genetic_Basis_and_Prognostic_Value_of_Exercise_QT_Dynamics/25815943 |
| 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 Neurosciences cardiovascular disease exercise genome-wide association study mortality risk factors |
| dc.title.none.fl_str_mv | Genetic Basis and Prognostic Value of Exercise QT Dynamics |
| 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">Abnormal QT interval responses to heart rate (QT dynamics) is an independent risk predictor for cardiovascular disease in patients, but its genetic basis and prognostic value in a population-based cohort have not been investigated.</p><h3>Methods</h3><p dir="ltr">QT dynamics during exercise and recovery were derived in 56 643 individuals from UK Biobank without a history of cardiovascular events. Genome-wide association studies were conducted to identify genetic variants and bioinformatics analyses were performed to prioritize candidate genes. The prognostic value of QT dynamics was evaluated for cardiovascular events (death or hospitalization) and all-cause mortality.</p><h3>Results</h3><p dir="ltr">Heritability of QT dynamics during exercise and recovery were 10.7% and 5.4%, respectively. Genome-wide association studies identified 20 loci, of which 4 loci included genes implicated in mendelian long-QT syndrome. Five loci did not overlap with previously reported resting QT interval loci; candidate genes included KCNQ4 and KIAA1755 . Genetic risk scores were not associated with cardiovascular events in 357 882 unrelated individuals from UK Biobank. We also did not observe associations of QT dynamics during exercise and recovery with cardiovascular events. Increased QT dynamics during recovery was significantly associated with all-cause mortality in the univariate Cox regression analysis (hazard ratio, 1.09 [95% CI, 1.05–1.13], P =2.28×10 -5 ), but the association was not significant after adjusting for clinical risk factors.</p><h3>Conclusions</h3><p dir="ltr">QT interval dynamics during exercise and recovery are heritable markers but do not carry independent prognostic information for clinical outcomes in the UK Biobank, a population-based cohort. Their prognostic importance may relate to cardiovascular disease cohorts where structural heart disease or ischemia may influence repolarization dynamics. The strong overlap between QT dynamics and resting QT interval loci suggests common biological pathways; however, nonoverlapping loci suggests alternative mechanisms may exist that underlie QT interval dynamics.</p><h2>Other Information</h2><p dir="ltr">Published in: Circulation: Genomic and Precision 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/10.1161/circgen.119.002774" target="_blank">https://dx.doi.org/10.1161/circgen.119.002774</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_840b8790aaa6aec092cc7a482d67b037 |
| identifier_str_mv | 10.1161/circgen.119.002774 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25815943 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Genetic Basis and Prognostic Value of Exercise QT DynamicsStefan van Duijvenboden (7116386)Julia Ramírez (4506787)William J. Young (18426897)Borbala Mifsud (3907267)Michele Orini (3097818)Andrew Tinker (477693)Patricia B. Munroe (7588601)Pier D. Lambiase (10163594)Biological sciencesGeneticsBiomedical and clinical sciencesCardiovascular medicine and haematologyNeurosciencescardiovascular diseaseexercisegenome-wide association studymortalityrisk factors<h3>Background</h3><p dir="ltr">Abnormal QT interval responses to heart rate (QT dynamics) is an independent risk predictor for cardiovascular disease in patients, but its genetic basis and prognostic value in a population-based cohort have not been investigated.</p><h3>Methods</h3><p dir="ltr">QT dynamics during exercise and recovery were derived in 56 643 individuals from UK Biobank without a history of cardiovascular events. Genome-wide association studies were conducted to identify genetic variants and bioinformatics analyses were performed to prioritize candidate genes. The prognostic value of QT dynamics was evaluated for cardiovascular events (death or hospitalization) and all-cause mortality.</p><h3>Results</h3><p dir="ltr">Heritability of QT dynamics during exercise and recovery were 10.7% and 5.4%, respectively. Genome-wide association studies identified 20 loci, of which 4 loci included genes implicated in mendelian long-QT syndrome. Five loci did not overlap with previously reported resting QT interval loci; candidate genes included KCNQ4 and KIAA1755 . Genetic risk scores were not associated with cardiovascular events in 357 882 unrelated individuals from UK Biobank. We also did not observe associations of QT dynamics during exercise and recovery with cardiovascular events. Increased QT dynamics during recovery was significantly associated with all-cause mortality in the univariate Cox regression analysis (hazard ratio, 1.09 [95% CI, 1.05–1.13], P =2.28×10 -5 ), but the association was not significant after adjusting for clinical risk factors.</p><h3>Conclusions</h3><p dir="ltr">QT interval dynamics during exercise and recovery are heritable markers but do not carry independent prognostic information for clinical outcomes in the UK Biobank, a population-based cohort. Their prognostic importance may relate to cardiovascular disease cohorts where structural heart disease or ischemia may influence repolarization dynamics. The strong overlap between QT dynamics and resting QT interval loci suggests common biological pathways; however, nonoverlapping loci suggests alternative mechanisms may exist that underlie QT interval dynamics.</p><h2>Other Information</h2><p dir="ltr">Published in: Circulation: Genomic and Precision 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/10.1161/circgen.119.002774" target="_blank">https://dx.doi.org/10.1161/circgen.119.002774</a></p>2020-08-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1161/circgen.119.002774https://figshare.com/articles/journal_contribution/Genetic_Basis_and_Prognostic_Value_of_Exercise_QT_Dynamics/25815943CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/258159432020-08-01T00:00:00Z |
| spellingShingle | Genetic Basis and Prognostic Value of Exercise QT Dynamics Stefan van Duijvenboden (7116386) Biological sciences Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology Neurosciences cardiovascular disease exercise genome-wide association study mortality risk factors |
| status_str | publishedVersion |
| title | Genetic Basis and Prognostic Value of Exercise QT Dynamics |
| title_full | Genetic Basis and Prognostic Value of Exercise QT Dynamics |
| title_fullStr | Genetic Basis and Prognostic Value of Exercise QT Dynamics |
| title_full_unstemmed | Genetic Basis and Prognostic Value of Exercise QT Dynamics |
| title_short | Genetic Basis and Prognostic Value of Exercise QT Dynamics |
| title_sort | Genetic Basis and Prognostic Value of Exercise QT Dynamics |
| topic | Biological sciences Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology Neurosciences cardiovascular disease exercise genome-wide association study mortality risk factors |