Clinical and genetic associations of deep learning-derived cardiac magnetic resonance-based left ventricular mass
Open Access
- 21 March 2023
- journal article
- research article
- Published by Springer Nature in Nature Communications
- Vol. 14 (1) , 1-11
Abstract
Left ventricular mass is a risk marker for cardiovascular events, and may indicate an underlying cardiomyopathy. Cardiac magnetic resonance is the gold-standard for left ventricular mass estimation, but is challenging to obtain at scale. Here, we use deep learning to enable genome-wide association study of cardiac magnetic resonance-derived left ventricular mass indexed to body surface area within 43,230 UK Biobank participants. We identify 12 genome-wide associations (1 known at TTN and 11 novel for left ventricular mass), implicating genes previously associated with cardiac contractility and cardiomyopathy. Cardiac magnetic resonance-derived indexed left ventricular mass is associated with incident dilated and hypertrophic cardiomyopathies, and implantable cardioverter-defibrillator implant. An indexed left ventricular mass polygenic risk score ≥90th percentile is also associated with incident implantable cardioverter-defibrillator implant in separate UK Biobank (hazard ratio 1.22, 95% CI 1.05-1.44) and Mass General Brigham (hazard ratio 1.75, 95% CI 1.12-2.74) samples. Here, we perform a genome-wide association study of cardiac magnetic resonance-derived indexed left ventricular mass to identify 11 novel variants and demonstrate that cardiac magnetic resonance-derived and genetically predicted indexed left ventricular mass are associated with incident cardiomyopathy.Keywords
Funding Information
- John S. LaDue Memorial Fellowship
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (1R01HL139731, T32HL007604, R01HL134893, R01HL140224, 1R01HL092577, R01HL128914, K24HL105780, 1R01HL139731)
- American Heart Association (18SFRN34110082, 18SFRN34110082, 18SFRN34250007)
- NIH NHLBI BioData Catalyst Fellows Program
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
This publication has 72 references indexed in Scilit:
- Truncations of Titin Causing Dilated CardiomyopathyNew England Journal of Medicine, 2012
- Improving cardiovascular risk stratification in essential hypertensive patients by indexing left ventricular mass to height2.7Journal Of Hypertension, 2009
- The Relationship of Left Ventricular Mass and Geometry to Incident Cardiovascular EventsJACC, 2008
- Calsarcin-2 deficiency increases exercise capacity in mice through calcineurin/NFAT activationJournal of Clinical Investigation, 2008
- Evaluation of left ventricular mass measured by 3D echocardiography using magnetic resonance imaging as gold standardScandinavian Journal of Clinical and Laboratory Investigation, 2006
- Calcineurin/NFAT Coupling Participates in Pathological, but not Physiological, Cardiac HypertrophyCirculation Research, 2004
- Effect of Type 2 Diabetes Mellitus on Left Ventricular Geometry and Systolic Function in Hypertensive SubjectsCirculation, 2001
- Cardiac fibrosis in mice lacking brain natriuretic peptideProceedings of the National Academy of Sciences, 2000
- Mutations in the cardiac myosin binding protein–C gene on chromosome 11 cause familial hypertrophic cardiomyopathyNature Genetics, 1995
- Proportional hazards tests and diagnostics based on weighted residualsBiometrika, 1994