Genomic and pleiotropic analyses of resting QT interval identifies novel loci and overlap with atrial electrical disorders
<div><p>The resting QT interval, an electrocardiographic (ECG) measure of ventricular myocardial repolarization, is a heritable risk marker of cardiovascular mortality, but the mechanisms remain incompletely understood. Previously reported candidate genes have provided insights into the...
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2021
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| _version_ | 1864513517668794368 |
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| author | Stefan van Duijvenboden (7116386) |
| author2 | Julia Ramírez (4506787) William J Young (11285093) Michele Orini (3097818) Borbala Mifsud (3907267) Andrew Tinker (477693) Pier D Lambiase (10680720) Patricia B Munroe (7948379) |
| author2_role | author author author author author author author |
| author_facet | Stefan van Duijvenboden (7116386) Julia Ramírez (4506787) William J Young (11285093) Michele Orini (3097818) Borbala Mifsud (3907267) Andrew Tinker (477693) Pier D Lambiase (10680720) Patricia B Munroe (7948379) |
| author_role | author |
| dc.creator.none.fl_str_mv | Stefan van Duijvenboden (7116386) Julia Ramírez (4506787) William J Young (11285093) Michele Orini (3097818) Borbala Mifsud (3907267) Andrew Tinker (477693) Pier D Lambiase (10680720) Patricia B Munroe (7948379) |
| dc.date.none.fl_str_mv | 2021-07-19T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1093/hmg/ddab197 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Genomic_and_pleiotropic_analyses_of_resting_QT_interval_identifies_novel_loci_and_overlap_with_atrial_electrical_disorders/25713804 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Cardiovascular medicine and haematology Resting QT interval Electrocardiographic (ECG) measure Variants European ancestry UK Biobank Loci |
| dc.title.none.fl_str_mv | Genomic and pleiotropic analyses of resting QT interval identifies novel loci and overlap with atrial electrical disorders |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <div><p>The resting QT interval, an electrocardiographic (ECG) measure of ventricular myocardial repolarization, is a heritable risk marker of cardiovascular mortality, but the mechanisms remain incompletely understood. Previously reported candidate genes have provided insights into the regulatory mechanisms of the QT interval. However, there are still important knowledge gaps. We aimed to gain new insights by (i) providing new candidate genes, (ii) identifying pleiotropic associations with other cardiovascular traits, and (iii) scanning for sexually dimorphic genetic effects. We conducted a genome-wide association analysis for resting QT interval with ~9.8 million variants in 52 107 individuals of European ancestry without known cardiovascular disease from the UK Biobank. We identified 40 loci, 13 of which were novel, including 2 potential sex-specific loci, explaining ~11% of the trait variance. Candidate genes at novel loci were involved in myocardial structure and arrhythmogenic cardiomyopathy. Investigation of pleiotropic effects of QT interval variants using phenome-wide association analyses in 302 000 unrelated individuals from the UK Biobank and pairwise genome-wide comparisons with other ECG and cardiac imaging traits revealed genetic overlap with atrial electrical pathology. These findings provide novel insights into how abnormal myocardial repolarization and increased cardiovascular mortality may be linked.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Human Molecular 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/10.1093/hmg/ddab197" target="_blank">https://dx.doi.org/10.1093/hmg/ddab197</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_9543e7c18b6ca03cbdb5b725cc20f198 |
| identifier_str_mv | 10.1093/hmg/ddab197 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25713804 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Genomic and pleiotropic analyses of resting QT interval identifies novel loci and overlap with atrial electrical disordersStefan van Duijvenboden (7116386)Julia Ramírez (4506787)William J Young (11285093)Michele Orini (3097818)Borbala Mifsud (3907267)Andrew Tinker (477693)Pier D Lambiase (10680720)Patricia B Munroe (7948379)Biomedical and clinical sciencesCardiovascular medicine and haematologyResting QT intervalElectrocardiographic (ECG) measureVariantsEuropean ancestryUK BiobankLoci<div><p>The resting QT interval, an electrocardiographic (ECG) measure of ventricular myocardial repolarization, is a heritable risk marker of cardiovascular mortality, but the mechanisms remain incompletely understood. Previously reported candidate genes have provided insights into the regulatory mechanisms of the QT interval. However, there are still important knowledge gaps. We aimed to gain new insights by (i) providing new candidate genes, (ii) identifying pleiotropic associations with other cardiovascular traits, and (iii) scanning for sexually dimorphic genetic effects. We conducted a genome-wide association analysis for resting QT interval with ~9.8 million variants in 52 107 individuals of European ancestry without known cardiovascular disease from the UK Biobank. We identified 40 loci, 13 of which were novel, including 2 potential sex-specific loci, explaining ~11% of the trait variance. Candidate genes at novel loci were involved in myocardial structure and arrhythmogenic cardiomyopathy. Investigation of pleiotropic effects of QT interval variants using phenome-wide association analyses in 302 000 unrelated individuals from the UK Biobank and pairwise genome-wide comparisons with other ECG and cardiac imaging traits revealed genetic overlap with atrial electrical pathology. These findings provide novel insights into how abnormal myocardial repolarization and increased cardiovascular mortality may be linked.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Human Molecular 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/10.1093/hmg/ddab197" target="_blank">https://dx.doi.org/10.1093/hmg/ddab197</a></p>2021-07-19T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1093/hmg/ddab197https://figshare.com/articles/journal_contribution/Genomic_and_pleiotropic_analyses_of_resting_QT_interval_identifies_novel_loci_and_overlap_with_atrial_electrical_disorders/25713804CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/257138042021-07-19T03:00:00Z |
| spellingShingle | Genomic and pleiotropic analyses of resting QT interval identifies novel loci and overlap with atrial electrical disorders Stefan van Duijvenboden (7116386) Biomedical and clinical sciences Cardiovascular medicine and haematology Resting QT interval Electrocardiographic (ECG) measure Variants European ancestry UK Biobank Loci |
| status_str | publishedVersion |
| title | Genomic and pleiotropic analyses of resting QT interval identifies novel loci and overlap with atrial electrical disorders |
| title_full | Genomic and pleiotropic analyses of resting QT interval identifies novel loci and overlap with atrial electrical disorders |
| title_fullStr | Genomic and pleiotropic analyses of resting QT interval identifies novel loci and overlap with atrial electrical disorders |
| title_full_unstemmed | Genomic and pleiotropic analyses of resting QT interval identifies novel loci and overlap with atrial electrical disorders |
| title_short | Genomic and pleiotropic analyses of resting QT interval identifies novel loci and overlap with atrial electrical disorders |
| title_sort | Genomic and pleiotropic analyses of resting QT interval identifies novel loci and overlap with atrial electrical disorders |
| topic | Biomedical and clinical sciences Cardiovascular medicine and haematology Resting QT interval Electrocardiographic (ECG) measure Variants European ancestry UK Biobank Loci |