Genetic basis of right and left ventricular heart shape

Richard Burns, William J. Young, Nay Aung, Luis R. Lopes, Perry M. Elliott, Petros Syrris, Roberto Barriales-Villa, Catrin Sohrabi, Steffen E. Petersen, Julia Ramírez, Alistair Young () and Patricia B. Munroe ()
Additional contact information
Richard Burns: King’s College London
William J. Young: Charterhouse Square
Nay Aung: Charterhouse Square
Luis R. Lopes: St Bartholomew’s Hospital, Barts Health NHS Trust, West Smithfield
Perry M. Elliott: St Bartholomew’s Hospital, Barts Health NHS Trust, West Smithfield
Petros Syrris: University College London
Roberto Barriales-Villa: INIBIC
Catrin Sohrabi: Charterhouse Square
Steffen E. Petersen: Charterhouse Square
Julia Ramírez: Charterhouse Square
Alistair Young: King’s College London
Patricia B. Munroe: Charterhouse Square

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Heart shape captures variation in cardiac structure beyond traditional phenotypes of mass and volume. Although observational studies have demonstrated associations with cardiometabolic risk factors and diseases, its genetic basis is less understood. We utilised cardiovascular magnetic resonance images from 45,683 UK Biobank participants to construct a heart shape atlas from bi-ventricular end-diastolic surface mesh models through principal component (PC) analysis. Genome-wide association studies were performed on the first 11 PCs that captured 83.6% of shape variance. We identified 43 significant loci, 14 were previously unreported for cardiac traits. Genetically predicted PCs were associated with cardiometabolic diseases. In particular two PCs (2 and 3) linked with more spherical ventricles being associated with increased risk of atrial fibrillation. Our study explores the genetic basis of multidimensional bi-ventricular heart shape using PCA, reporting new loci and biology, as well as polygenic risk scores for exploring genetic relationships of heart shape with cardiometabolic diseases.

Date: 2024
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DOI: 10.1038/s41467-024-53594-7

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