Published March 14, 2023 | Version v1
Publication Open

Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease

Creators

  • 1. William Harvey Research Institute
  • 2. Queen Mary University of London
  • 3. Barts Health NHS Trust
  • 4. St Bartholomew's Hospital
  • 5. Fred Hutch Cancer Center
  • 6. Seattle University
  • 7. University Medical Center Groningen
  • 8. University of Groningen
  • 9. Centre for Global Health Research
  • 10. University of Edinburgh
  • 11. UCLA Medical Center
  • 12. Harbor–UCLA Medical Center
  • 13. Maastricht University
  • 14. Wellcome Centre for Human Genetics
  • 15. John Radcliffe Hospital
  • 16. University of Oxford
  • 17. Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine
  • 18. Universidad de Zaragoza
  • 19. University College London
  • 20. Fondation pour l'innovation en Cadiométabolisme et Nutrition
  • 21. Unité de recherche sur les maladies cardiovasculaires et métaboliques
  • 22. Inserm
  • 23. Sorbonne Université
  • 24. University of North Carolina at Chapel Hill
  • 25. IRCCS Materno Infantile Burlo Garofolo
  • 26. Johns Hopkins Medicine
  • 27. Johns Hopkins University
  • 28. Institute for Biomedicine
  • 29. Eurac Research
  • 30. University of Copenhagen
  • 31. University of Mississippi Medical Center
  • 32. Jackson Memorial Hospital
  • 33. Leiden University Medical Center
  • 34. Novo Nordisk Foundation
  • 35. MRC Institute of Genetics and Molecular Medicine
  • 36. Universidad Peruana Cayetano Heredia
  • 37. Universidade Federal de Minas Gerais
  • 38. University of Washington
  • 39. Erasmus MC
  • 40. Population Health Research Institute
  • 41. McMaster University
  • 42. Université Laval
  • 43. University Hospital of Basel
  • 44. University of Basel
  • 45. University Medical Center Utrecht
  • 46. Emory University
  • 47. Western General Hospital
  • 48. Health Data Research UK
  • 49. University of Illinois at Chicago
  • 50. Azienda Sanitaria Universitaria Integrata di Trieste
  • 51. University of Trieste
  • 52. National Center of Human Genomics Research
  • 53. University of Paris-Saclay
  • 54. Atomic Energy and Alternative Energies Commission
  • 55. CEA Saclay
  • 56. Medical Genetics & Functional Genomics
  • 57. Fondation Jean Dausset-CEPH
  • 58. Region Zealand
  • 59. Harvard University
  • 60. Boston Children's Hospital
  • 61. University of Michigan–Ann Arbor
  • 62. University of California, Los Angeles
  • 63. Fundação Oswaldo Cruz
  • 64. Frederiksberg Hospital
  • 65. Center for Clinical Research and Prevention
  • 66. University of Glasgow
  • 67. The University of Texas Health Science Center at Houston
  • 68. University of Lübeck
  • 69. University Hospital of Bern
  • 70. University of Bern
  • 71. University of Liechtenstein
  • 72. Private University in the Principality of Liechtenstein
  • 73. Fudan University
  • 74. Karolinska Institutet
  • 75. Wake Forest University
  • 76. Netherlands Heart Institute
  • 77. Hospital das Clínicas da Universidade Federal de Minas Gerais
  • 78. Beth Israel Deaconess Medical Center
  • 79. Pitié-Salpêtrière Hospital
  • 80. Assistance Publique – Hôpitaux de Paris
  • 81. Hamad bin Khalifa University
  • 82. Cleveland Clinic Lerner College of Medicine

Description

Abstract The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle ( N = 118,780) and 11 for the frontal QRS-T angle ( N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.

⚠️ This is an automatic machine translation with an accuracy of 90-95%

Translated Description (Arabic)

الملخص الزوايا ثلاثية الأبعاد المكانية وثنائية الأبعاد الأمامية QRS - T هي مقاييس مشتقة من مخطط القلب المتجهي. إنها تنبؤات مخاطر مستقلة لعدم انتظام ضربات القلب، لكن البيولوجيا الأساسية غير معروفة. باستخدام دراسات الارتباط على مستوى الجينوم متعدد النسب، نحدد 61 (58 موقعًا لم يتم الإبلاغ عنها سابقًا) لزاوية QRS - T المكانية ( N = 118،780) و 11 لزاوية QRS - T الأمامية ( N = 159،715). لم يتم الإبلاغ عن سبعة من أصل 61 موقع زاوية QRS - T المكانية لقياسات تخطيط القلب الكهربائية الأخرى. ويلاحظ حدوث إثراء في المسارات المتعلقة بتطور القلب والأوعية الدموية، وتقلص العضلات، والتضخم. تحدد دراسات الارتباط على مستوى الجينوم الزوجي مع سمات مخطط كهربية القلب الكلاسيكية التأثيرات الجينية المشتركة مع فاصل PR ومدة QRS. يشير المسح على نطاق الفينوم إلى وجود ارتباطات مع الرجفان الأذيني والإحصار الأذيني البطيني والانصمام الشرياني وترتبط قياسات زاوية QRS - T المحددة وراثيًا بإحصار الفرع الحزمي والحزمة (وأيضًا الإحصار الأذيني البطيني لزاوية QRS - T الأمامية). نحدد البيولوجيا المحتملة التي تنطوي عليها زاوية QRS - T وعلاقاتها الوراثية مع سمات وأمراض القلب والأوعية الدموية، وقد تسترشد بها الأبحاث المستقبلية والتنبؤ بالمخاطر.

Translated Description (French)

Résumé Les angles QRS-T spatiaux tridimensionnels et frontaux bidimensionnels sont des mesures dérivées du cardiogramme vectoriel. Ce sont des prédicteurs indépendants du risque d'arythmie, mais la biologie sous-jacente est inconnue. À l'aide d'études d'association à l'échelle du génome multi-ancestres, nous identifions 61 (58 non rapportés auparavant) loci pour l'angle QRS-T spatial ( N = 118 780) et 11 pour l'angle QRS-T frontal ( N = 159 715). Sept des 61 locus d'angle spatial QRS-T n'ont pas été rapportés pour d'autres mesures électrocardiographiques. Des enrichissements sont observés dans les voies liées au développement cardiaque et vasculaire, à la contraction musculaire et à l'hypertrophie. Des études d'association à l'échelle du génome par paires avec des traits ECG classiques identifient des influences génétiques partagées avec l'intervalle PR et la durée QRS. Le balayage à l'échelle du phénome indique des associations avec la fibrillation auriculaire, le bloc auriculo-ventriculaire et l'embolie artérielle et les mesures d'angle QRS-T déterminées génétiquement sont associées au bloc de branche fasciculaire et au bloc de branche en faisceau (ainsi qu'au bloc auriculo-ventriculaire pour l'angle QRS-T frontal). Nous identifions la biologie potentielle impliquée dans l'angle QRS-T et leurs relations génétiques avec les traits et les maladies cardiovasculaires, ce qui pourrait éclairer les recherches futures et la prédiction des risques.

Translated Description (Spanish)

Resumen Los ángulos QRS-T espaciales tridimensionales y frontales bidimensionales son medidas derivadas del vectorcardiograma. Son predictores de riesgo independientes para la arritmia, pero se desconoce la biología subyacente. Utilizando estudios de asociación de todo el genoma de múltiples ascendencias, identificamos 61 (58 no informados previamente) loci para el ángulo QRS-T espacial ( N = 118,780) y 11 para el ángulo QRS-T frontal ( N = 159,715). Siete de los 61 loci espaciales del ángulo QRS-T no se han informado para otras medidas electrocardiográficas. Se observan enriquecimientos en vías relacionadas con el desarrollo cardíaco y vascular, la contracción muscular y la hipertrofia. Los estudios de asociación de todo el genoma por pares con rasgos de ECG clásicos identifican influencias genéticas compartidas con el intervalo PR y la duración del QRS. La exploración de todo el fenoma indica asociaciones con fibrilación auricular, bloqueo auriculoventricular y embolia arterial y las medidas del ángulo QRS-T determinadas genéticamente están asociadas con el bloqueo fascicular y de rama (y también el bloqueo auriculoventricular para el ángulo QRS-T frontal). Identificamos la biología potencial involucrada en el ángulo QRS-T y sus relaciones genéticas con rasgos y enfermedades cardiovasculares, lo que puede informar la investigación futura y la predicción de riesgos.

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Additional details

Additional titles

Translated title (Arabic)
الهندسة الوراثية للمؤشرات الحيوية الكهربائية المكانية لعدم انتظام ضربات القلب والعلاقة مع أمراض القلب والأوعية الدموية
Translated title (French)
Architecture génétique des biomarqueurs électriques spatiaux pour l'arythmie cardiaque et la relation avec les maladies cardiovasculaires
Translated title (Spanish)
Arquitectura genética de biomarcadores eléctricos espaciales para arritmia cardiaca y relación con enfermedad cardiovascular

Identifiers

Other
https://openalex.org/W4324141222
DOI
10.1038/s41467-023-36997-w

Is supplement to
https://openalex.org/W4294300631 (Other)
https://openalex.org/W3195763484 (Other)
https://openalex.org/W2947486460 (Other)
https://openalex.org/W2511825003 (Other)
https://openalex.org/W2412956493 (Other)
https://openalex.org/W2268467698 (Other)
https://openalex.org/W2154394227 (Other)
https://openalex.org/W2082423905 (Other)
https://openalex.org/W2056109499 (Other)
https://openalex.org/W2031314127 (Other)

GreSIS Basics Section

Is Global South Knowledge
Yes
Country
Peru

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