Analysis of cardiac magnetic resonance imaging in 36,000 individuals yields genetic insights into dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is an important cause of heart failure and the leading indication for heart transplantation. Many rare genetic variants have been associated with DCM, but common variant studies of the disease have yielded few associated loci. As structural changes in the heart are a def...

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Vydané v:Nature communications Ročník 11; číslo 1; s. 2254 - 10
Hlavní autori: Pirruccello, James P., Bick, Alexander, Wang, Minxian, Chaffin, Mark, Friedman, Samuel, Yao, Jie, Guo, Xiuqing, Venkatesh, Bharath Ambale, Taylor, Kent D., Post, Wendy S., Rich, Stephen, Lima, Joao A. C., Rotter, Jerome I., Philippakis, Anthony, Lubitz, Steven A., Ellinor, Patrick T., Khera, Amit V., Kathiresan, Sekar, Aragam, Krishna G.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London Nature Publishing Group UK 07.05.2020
Nature Publishing Group
Nature Portfolio
Predmet:
45/43
59/57
631/208/205/2138
631/443/592/2727
692/4019/592/75/74
Arteriosclerosis
Atherosclerosis
Cardiomyopathy
Cardiomyopathy, Dilated - diagnostic imaging
Cardiomyopathy, Dilated - genetics
Congestive heart failure
Dilated cardiomyopathy
Genetic diversity
Genetic variance
Genome-wide association studies
Genome-Wide Association Study
Genomes
Heart
Heart - diagnostic imaging
Heart transplantation
Humanities and Social Sciences
Humans
Loci
Magnetic Resonance Imaging
Medical imaging
multidisciplinary
Mutation
Myocardium - metabolism
Pathogenesis
Polymorphism, Single Nucleotide - genetics
Science
Science (multidisciplinary)
Structure-function relationships
Transplantation
Ventricle
ISSN:2041-1723, 2041-1723
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Shrnutí:Dilated cardiomyopathy (DCM) is an important cause of heart failure and the leading indication for heart transplantation. Many rare genetic variants have been associated with DCM, but common variant studies of the disease have yielded few associated loci. As structural changes in the heart are a defining feature of DCM, we report a genome-wide association study of cardiac magnetic resonance imaging (MRI)-derived left ventricular measurements in 36,041 UK Biobank participants, with replication in 2184 participants from the Multi-Ethnic Study of Atherosclerosis. We identify 45 previously unreported loci associated with cardiac structure and function, many near well-established genes for Mendelian cardiomyopathies. A polygenic score of MRI-derived left ventricular end systolic volume strongly associates with incident DCM in the general population. Even among carriers of TTN truncating mutations, this polygenic score influences the size and function of the human heart. These results further implicate common genetic polymorphisms in the pathogenesis of DCM. Structural changes to the left ventricle are characteristic of dilated cardiomyopathy (DCM), a disease for which many rare genetic variants are known. Here, Pirruccello et al. report GWAS of seven cardiac MRI measurements in the left ventricle and describe shared loci and polygenic association with DCM.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-15823-7