Genome-wide association analysis reveals insights into the genetic architecture of right ventricular structure and function

Nay Aung; Jose D Vargas; Chaojie Yang; Kenneth Fung; Mihir M Sanghvi; Stefan K Piechnik; Stefan Neubauer; Ani Manichaikul; Jerome I Rotter; Kent D Taylor; Joao A C Lima; David A Bluemke; Steven M Kawut; Steffen E Petersen; Patricia B Munroe

doi:10.1038/s41588-022-01083-2

Genome-wide association analysis reveals insights into the genetic architecture of right ventricular structure and function

Nat Genet. 2022 Jun;54(6):783-791. doi: 10.1038/s41588-022-01083-2. Epub 2022 Jun 13.

Authors

Nay Aung^{1

2

3}, Jose D Vargas^{4

5}, Chaojie Yang⁶, Kenneth Fung^{1

2

3}, Mihir M Sanghvi^{1

2

3}, Stefan K Piechnik⁷, Stefan Neubauer⁷, Ani Manichaikul⁶, Jerome I Rotter⁸, Kent D Taylor⁸, Joao A C Lima⁹, David A Bluemke¹⁰, Steven M Kawut¹¹, Steffen E Petersen^{12

13

14}, Patricia B Munroe^{15

16}

Affiliations

¹ William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
² National Institute for Health Research, Barts Cardiovascular Biomedical Research Centre, Queen Mary University of London, London, UK.
³ Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London, UK.
⁴ Veterans Affairs Medical Center, Washington, DC, USA.
⁵ Georgetown University, Washington, DC, USA.
⁶ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
⁷ Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
⁸ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
⁹ Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.
¹⁰ Department of Radiology, University of Wisconsin, Madison, WI, USA.
¹¹ Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
¹² William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. s.e.petersen@qmul.ac.uk.
¹³ National Institute for Health Research, Barts Cardiovascular Biomedical Research Centre, Queen Mary University of London, London, UK. s.e.petersen@qmul.ac.uk.
¹⁴ Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London, UK. s.e.petersen@qmul.ac.uk.
¹⁵ William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. p.b.munroe@qmul.ac.uk.
¹⁶ National Institute for Health Research, Barts Cardiovascular Biomedical Research Centre, Queen Mary University of London, London, UK. p.b.munroe@qmul.ac.uk.

PMID: 35697868
DOI: 10.1038/s41588-022-01083-2

Abstract

Right ventricular (RV) structure and function influence the morbidity and mortality from coronary artery disease (CAD), dilated cardiomyopathy (DCM), pulmonary hypertension and heart failure. Little is known about the genetic basis of RV measurements. Here we perform genome-wide association analyses of four clinically relevant RV phenotypes (RV end-diastolic volume, RV end-systolic volume, RV stroke volume, RV ejection fraction) from cardiovascular magnetic resonance images, using a state-of-the-art deep learning algorithm in 29,506 UK Biobank participants. We identify 25 unique loci associated with at least one RV phenotype at P < 2.27 ×10^-8, 17 of which are validated in a combined meta-analysis (n = 41,830). Several candidate genes overlap with Mendelian cardiomyopathy genes and are involved in cardiac muscle contraction and cellular adhesion. The RV polygenic risk scores (PRSs) are associated with DCM and CAD. The findings substantially advance our understanding of the genetic underpinning of RV measurements.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cardiomyopathy, Dilated*
Genome-Wide Association Study
Heart Ventricles
Humans
Stroke Volume / physiology
Ventricular Dysfunction, Right* / complications

Abstract

Publication types

MeSH terms

Grants and funding