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Nat Genet DOI:10.1038/s41588-022-01090-3

Genetic analysis of right heart structure and function in 40,000 people.

Publication TypeJournal Article
Year of Publication2022
AuthorsPirruccello, JP, Di Achille, P, Nauffal, V, Nekoui, M, Friedman, SF, Klarqvist, MDR, Chaffin, MD, Weng, L-C, Cunningham, JW, Khurshid, S, Roselli, C, Lin, H, Koyama, S, Ito, K, Kamatani, Y, Komuro, I, Jurgens, SJ, Benjamin, EJ, Batra, P, Natarajan, P, Ng, K, Hoffmann, U, Lubitz, SA, Ho, JE, Lindsay, ME, Philippakis, AA, Ellinor, PT
Corporate AuthorsBioBank Japan Project
JournalNat Genet
Volume54
Issue6
Pages792-803
Date Published2022 Jun
ISSN1546-1718
KeywordsCardiomyopathy, Dilated, Genome-Wide Association Study, Heart, Heart Defects, Congenital, Humans, Stroke Volume, Ventricular Function, Right
Abstract

Congenital heart diseases often involve maldevelopment of the evolutionarily recent right heart chamber. To gain insight into right heart structure and function, we fine-tuned deep learning models to recognize the right atrium, right ventricle and pulmonary artery, measuring right heart structures in 40,000 individuals from the UK Biobank with magnetic resonance imaging. Genome-wide association studies identified 130 distinct loci associated with at least one right heart measurement, of which 72 were not associated with left heart structures. Loci were found near genes previously linked with congenital heart disease, including NKX2-5, TBX5/TBX3, WNT9B and GATA4. A genome-wide polygenic predictor of right ventricular ejection fraction was associated with incident dilated cardiomyopathy (hazard ratio, 1.33 per standard deviation; P = 7.1 × 10) and remained significant after accounting for a left ventricular polygenic score. Harnessing deep learning to perform large-scale cardiac phenotyping, our results yield insights into the genetic determinants of right heart structure and function.

DOI10.1038/s41588-022-01090-3
Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/35697867?dopt=Abstract

Alternate JournalNat Genet
PubMed ID35697867
Grant List14CVD01 / / Fondation Leducq /
1RO1HL092577 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
R01HL128914 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
K24HL105780 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
K08HL159346 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
5T32HL007604 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
T32HL007208 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
1R01HL139731 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
R01HL134893 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
R01HL140224 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
2R01HL092577 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
1R01HL141434 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
JP20km0405209 / / Japan Agency for Medical Research and Development (AMED) /
JP20ek0109487 / / Japan Agency for Medical Research and Development (AMED) /
18SFRN34110082 / / American Heart Association (American Heart Association, Inc.) /