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; Patricia B Munroe

doi:10.1038/s41467-024-53594-7

Genetic basis of right and left ventricular heart shape

Nat Commun. 2024 Nov 14;15(1):9437. doi: 10.1038/s41467-024-53594-7.

Authors

Richard Burns¹, William J Young^{2

3}, Nay Aung^{2

3

4}, Luis R Lopes^{3

5}, Perry M Elliott^{3

5}, Petros Syrris⁵, Roberto Barriales-Villa⁶, Catrin Sohrabi², Steffen E Petersen^{2

3

4

7}, Julia Ramírez^#^{2

8

9}, Alistair Young^#¹⁰, Patricia B Munroe^#^{11

12}

Affiliations

¹ School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
² William Harvey Research Institute, Queen Mary University London, Charterhouse Square, London, UK.
³ Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London, UK.
⁴ NIHR Barts Biomedical Research Centre, Queen Mary of University London, Charterhouse Square, London, UK.
⁵ Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, UK.
⁶ Unidad de Cardiopatías Familiares, Cardiology Service, Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain.
⁷ Health Data Research UK, Gibbs Building, 215 Euston Road, London, UK.
⁸ Aragon Institute of Engineering Research, University of Zaragoza, Zaragoza, Spain.
⁹ Centro de Investigación Biomédica en Red - Bioingeniería, Biomateriales y Nanomedicina, Zaragoza, Spain.
¹⁰ School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK. [email protected].
¹¹ William Harvey Research Institute, Queen Mary University London, Charterhouse Square, London, UK. [email protected].
¹² NIHR Barts Biomedical Research Centre, Queen Mary of University London, Charterhouse Square, London, UK. [email protected].

^# Contributed equally.

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.

MeSH terms

Adult
Aged
Atrial Fibrillation / genetics
Female
Genetic Predisposition to Disease
Genome-Wide Association Study*
Heart Ventricles* / diagnostic imaging
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Phenotype
Polymorphism, Single Nucleotide
Principal Component Analysis

Abstract

MeSH terms

Grants and funding