Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease
William Young
(1, 2)
,
Jeffrey Haessler
(3)
,
Jan-Walter Benjamins
(4)
,
Linda Repetto
(5)
,
Jie Yao
,
Aaron Isaacs
,
Andrew Harper
,
Julia Ramirez
,
Sophie Garnier
(6, 7)
,
Stefan van Duijvenboden
,
Antoine Baldassari
,
Maria Pina Concas
,
Thuyvy Duong
,
Luisa Foco
,
Jonas Isaksen
,
Hao Mei
,
Raymond Noordam
,
Casia Nursyifa
,
Anne Richmond
,
Meddly Santolalla
,
Colleen Sitlani
,
Negin Soroush
,
Sébastien Thériault
,
Stella Trompet
,
Stefanie Aeschbacher
,
Fariba Ahmadizar
,
Alvaro Alonso
,
Jennifer Brody
,
Archie Campbell
,
Adolfo Correa
,
Dawood Darbar
,
Antonio de Luca
,
Jean-François Deleuze
(8, 9, 10)
,
Christina Ellervik
,
Christian Fuchsberger
,
Anuj Goel
,
Christopher Grace
,
Xiuqing Guo
,
Torben Hansen
,
Susan Heckbert
,
Rebecca Jackson
,
Jan Kors
,
Maria Fernanda Lima-Costa
,
Allan Linneberg
,
Peter Macfarlane
,
Alanna Morrison
,
Pau Navarro
,
David Porteous
,
Peter Pramstaller
,
Alexander Reiner
,
Lorenz Risch
,
Ulrich Schotten
,
Xia Shen
,
Gianfranco Sinagra
,
Elsayed Soliman
,
Monika Stoll
,
Eduardo Tarazona-Santos
,
Andrew Tinker
,
Katerina Trajanoska
,
Eric Villard
(7, 6)
,
Helen Warren
,
Eric Whitsel
,
Kerri Wiggins
,
Dan Arking
,
Christy Avery
,
David Conen
,
Giorgia Girotto
,
Niels Grarup
,
Caroline Hayward
,
J.Wouter Jukema
,
Dennis Mook-Kanamori
,
Morten Salling Olesen
,
Sandosh Padmanabhan
,
Bruce Psaty
,
Cristian Pattaro
,
Antonio Luiz P. Ribeiro
,
Jerome Rotter
,
Bruno Stricker
,
Pim van der Harst
,
Cornelia van Duijn
,
Niek Verweij
,
James Wilson
,
Michele Orini
,
Philippe Charron
(6, 7, 11)
,
Hugh Watkins
,
Charles Kooperberg
,
Henry Lin
,
James Wilson
,
Jørgen Kanters
,
Nona Sotoodehnia
,
Borbala Mifsud
,
Pier Lambiase
,
Larisa Tereshchenko
,
Patricia Munroe
(2)
1
Barts Health NHS Trust [London, UK]
2 QMUL - Queen Mary University of London
3 FHCRC - Fred Hutchinson Cancer Research Center [Seattle]
4 UMCG - University Medical Center Groningen [Groningen]
5 Edin. - University of Edinburgh
6 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
7 IHU ICAN - Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière]
8 CNRGH - Centre National de Recherche en Génomique Humaine
9 GENMED - Laboratoire d'excellence en GENomique MEDicale
10 CEPH - Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris]
11 CHU Pitié-Salpêtrière [AP-HP]
2 QMUL - Queen Mary University of London
3 FHCRC - Fred Hutchinson Cancer Research Center [Seattle]
4 UMCG - University Medical Center Groningen [Groningen]
5 Edin. - University of Edinburgh
6 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
7 IHU ICAN - Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière]
8 CNRGH - Centre National de Recherche en Génomique Humaine
9 GENMED - Laboratoire d'excellence en GENomique MEDicale
10 CEPH - Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris]
11 CHU Pitié-Salpêtrière [AP-HP]
William Young
- Function : Author
- PersonId : 1237059
- ORCID : 0000-0002-9831-6817
Jan-Walter Benjamins
- Function : Author
- PersonId : 1237060
- ORCID : 0000-0002-5701-0539
Jie Yao
- Function : Author
Aaron Isaacs
- Function : Author
- PersonId : 1237061
- ORCID : 0000-0001-5037-4834
Andrew Harper
- Function : Author
- PersonId : 1217526
- ORCID : 0000-0001-5327-0328
Julia Ramirez
- Function : Author
- PersonId : 1237062
- ORCID : 0000-0003-4130-5866
Sophie Garnier
- Function : Author
- PersonId : 934284
- IdHAL : sophie-garnier
- ORCID : 0000-0002-7492-1617
- IdRef : 031812910
Stefan van Duijvenboden
- Function : Author
Antoine Baldassari
- Function : Author
Maria Pina Concas
- Function : Author
- PersonId : 1237063
- ORCID : 0000-0003-3598-2537
Thuyvy Duong
- Function : Author
Luisa Foco
- Function : Author
- PersonId : 1237064
- ORCID : 0000-0002-6694-3322
Jonas Isaksen
- Function : Author
- PersonId : 1237065
- ORCID : 0000-0003-3227-1131
Hao Mei
- Function : Author
Raymond Noordam
- Function : Author
- PersonId : 1237066
- ORCID : 0000-0001-7801-809X
Casia Nursyifa
- Function : Author
Anne Richmond
- Function : Author
Meddly Santolalla
- Function : Author
Colleen Sitlani
- Function : Author
Negin Soroush
- Function : Author
- PersonId : 1237067
- ORCID : 0000-0003-3110-9896
Sébastien Thériault
- Function : Author
Stella Trompet
- Function : Author
- PersonId : 1237068
- ORCID : 0000-0001-5006-0528
Stefanie Aeschbacher
- Function : Author
Fariba Ahmadizar
- Function : Author
Alvaro Alonso
- Function : Author
- PersonId : 1237069
- ORCID : 0000-0002-2225-8323
Jennifer Brody
- Function : Author
- PersonId : 1237070
- ORCID : 0000-0001-8509-148X
Archie Campbell
- Function : Author
- PersonId : 1237071
- ORCID : 0000-0003-0198-5078
Adolfo Correa
- Function : Author
- PersonId : 1237072
- ORCID : 0000-0002-9501-600X
Dawood Darbar
- Function : Author
- PersonId : 1237073
- ORCID : 0000-0002-4103-5977
Antonio de Luca
- Function : Author
Jean-François Deleuze
- Function : Author
- PersonId : 1391484
- IdHAL : jean-francois-deleuze
- ORCID : 0000-0002-5358-4463
Christina Ellervik
- Function : Author
- PersonId : 1237074
- ORCID : 0000-0002-3088-4375
Christian Fuchsberger
- Function : Author
- PersonId : 1237075
- ORCID : 0000-0002-5918-8947
Anuj Goel
- Function : Author
- PersonId : 1237076
- ORCID : 0000-0003-2307-4021
Christopher Grace
- Function : Author
Xiuqing Guo
- Function : Author
- PersonId : 1237077
- ORCID : 0000-0002-5264-5068
Torben Hansen
- Function : Author
- PersonId : 758676
- ORCID : 0000-0001-8748-3831
Susan Heckbert
- Function : Author
- PersonId : 1237078
- ORCID : 0000-0002-7100-512X
Rebecca Jackson
- Function : Author
Jan Kors
- Function : Author
Maria Fernanda Lima-Costa
- Function : Author
Allan Linneberg
- Function : Author
- PersonId : 1237079
- ORCID : 0000-0002-0994-0184
Peter Macfarlane
- Function : Author
- PersonId : 1237080
- ORCID : 0000-0002-5390-1596
Alanna Morrison
- Function : Author
- PersonId : 1237081
- ORCID : 0000-0001-6381-4296
Pau Navarro
- Function : Author
- PersonId : 1237082
- ORCID : 0000-0001-5576-8584
David Porteous
- Function : Author
- PersonId : 1237083
- ORCID : 0000-0003-1249-6106
Peter Pramstaller
- Function : Author
- PersonId : 1237084
- ORCID : 0000-0002-9831-8302
Alexander Reiner
- Function : Author
- PersonId : 1237085
- ORCID : 0000-0002-1427-4470
Lorenz Risch
- Function : Author
- PersonId : 1237086
- ORCID : 0000-0003-2692-6699
Ulrich Schotten
- Function : Author
Xia Shen
- Function : Author
- PersonId : 1237087
- ORCID : 0000-0003-4390-1979
Gianfranco Sinagra
- Function : Author
- PersonId : 1237088
- ORCID : 0000-0003-2700-8478
Elsayed Soliman
- Function : Author
- PersonId : 1237089
- ORCID : 0000-0001-5632-8150
Monika Stoll
- Function : Author
Eduardo Tarazona-Santos
- Function : Author
Andrew Tinker
- Function : Author
- PersonId : 1237090
- ORCID : 0000-0001-7703-4151
Katerina Trajanoska
- Function : Author
Eric Villard
- Function : Author
- PersonId : 1215042
- IdHAL : evillard
- ORCID : 0000-0001-9801-7297
- IdRef : 177061200
Helen Warren
- Function : Author
- PersonId : 1237091
- ORCID : 0000-0003-0511-1386
Eric Whitsel
- Function : Author
- PersonId : 1237092
- ORCID : 0000-0003-4843-3641
Kerri Wiggins
- Function : Author
- PersonId : 1237093
- ORCID : 0000-0003-2749-1279
Dan Arking
- Function : Author
Christy Avery
- Function : Author
- PersonId : 1237094
- ORCID : 0000-0002-1044-8162
David Conen
- Function : Author
Giorgia Girotto
- Function : Author
- PersonId : 1237095
- ORCID : 0000-0003-4507-6589
Niels Grarup
- Function : Author
- PersonId : 1237096
- ORCID : 0000-0001-5526-1070
Caroline Hayward
- Function : Author
- PersonId : 1237097
- ORCID : 0000-0002-9405-9550
J.Wouter Jukema
- Function : Author
- PersonId : 1237098
- ORCID : 0000-0002-3246-8359
Dennis Mook-Kanamori
- Function : Author
Morten Salling Olesen
- Function : Author
- PersonId : 1237099
- ORCID : 0000-0001-9477-5322
Sandosh Padmanabhan
- Function : Author
Bruce Psaty
- Function : Author
- PersonId : 1237100
- ORCID : 0000-0002-7278-2190
Cristian Pattaro
- Function : Author
- PersonId : 1237101
- ORCID : 0000-0002-4119-0109
Antonio Luiz P. Ribeiro
- Function : Author
- PersonId : 1237102
- ORCID : 0000-0002-2740-0042
Jerome Rotter
- Function : Author
Bruno Stricker
- Function : Author
Pim van der Harst
- Function : Author
Cornelia van Duijn
- Function : Author
- PersonId : 1232587
- ORCID : 0000-0002-2374-9204
Niek Verweij
- Function : Author
- PersonId : 1237103
- ORCID : 0000-0002-4303-7685
James Wilson
- Function : Author
Michele Orini
- Function : Author
- PersonId : 1237104
- ORCID : 0000-0001-5773-0344
Philippe Charron
- Function : Author
- PersonId : 766599
- IdHAL : philippe-charron
- ORCID : 0000-0002-1782-1118
- IdRef : 123379458
Hugh Watkins
- Function : Author
- PersonId : 1217543
- ORCID : 0000-0002-5287-9016
Charles Kooperberg
- Function : Author
- PersonId : 1237105
- ORCID : 0000-0002-7986-8560
Henry Lin
- Function : Author
- PersonId : 1237106
- ORCID : 0000-0001-6771-0486
James Wilson
- Function : Author
- PersonId : 1237107
- ORCID : 0000-0001-5751-9178
Jørgen Kanters
- Function : Author
- PersonId : 1237108
- ORCID : 0000-0002-3267-4910
Nona Sotoodehnia
- Function : Author
Borbala Mifsud
- Function : Author
- PersonId : 1237109
- ORCID : 0000-0003-3429-3094
Pier Lambiase
- Function : Author
Larisa Tereshchenko
- Function : Author
- PersonId : 1237110
- ORCID : 0000-0002-6976-1313
Patricia Munroe
- Function : Author
- PersonId : 1237111
- ORCID : 0000-0002-4176-2947
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.
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Life Sciences [q-bio]Origin | Publication funded by an institution |
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