Genetic and functional insights into the fractal structure of the heart
| Autor: | Daniel Rueckert, Paul M. Matthews, James S. Ware, Ewan Birney, Wenjia Bai, Albert Henry, Sanjay K Prasad, Jakob Gierten, Thomas Thumberger, Maria Laura Costantino, Stuart A. Cook, Marta Serrani, Pawel Tokarczuk, Declan P. O'Regan, Hannah Meyer, Joachim Wittbrodt, Timothy J W Dawes, Antonio de Marvao, R. Thomas Lumbers, Jiashen Cai |
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| Přispěvatelé: | British Heart Foundation, Imperial College Healthcare NHS Trust- BRC Funding, Wellcome Trust, Medical Research Council (MRC) |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult General Science & Technology Oryzias Genome-wide association study 030204 cardiovascular system & hematology Biology BUILDING PLAN Article 03 medical and health sciences Gene Knockout Techniques 0302 clinical medicine Mendelian randomization medicine Animals Humans Genetic Predisposition to Disease TRABECULATIONS Cytoskeleton Genetic association Aged Multidisciplinary Science & Technology Heart development Myocardium Hemodynamics Heart Middle Aged medicine.disease Phenotype Genetic architecture Cardiovascular physiology Multidisciplinary Sciences 030104 developmental biology Fractals Evolutionary biology Cardiovascular Diseases Genetic Loci Heart failure MORPHOGENESIS Science & Technology - Other Topics GROWTH Genome-Wide Association Study |
| Zdroj: | Nature |
| Popis: | The inner surfaces of the human heart are covered by a complex network of muscular strands that is thought to be a remnant of embryonic development1,2. The function of these trabeculae in adults and their genetic architecture are unknown. Here we performed a genome-wide association study to investigate image-derived phenotypes of trabeculae using the fractal analysis of trabecular morphology in 18,096 participants of the UK Biobank. We identified 16 significant loci that contain genes associated with haemodynamic phenotypes and regulation of cytoskeletal arborization3,4. Using biomechanical simulations and observational data from human participants, we demonstrate that trabecular morphology is an important determinant of cardiac performance. Through genetic association studies with cardiac disease phenotypes and Mendelian randomization, we find a causal relationship between trabecular morphology and risk of cardiovascular disease. These findings suggest a previously unknown role for myocardial trabeculae in the function of the adult heart, identify conserved pathways that regulate structural complexity and reveal the influence of the myocardial trabeculae on susceptibility to cardiovascular disease. A genome-wide association study shows that myocardial trabeculae are an important determinant of cardiac performance in the adult heart, identifies conserved pathways that regulate structural complexity and reveals the influence of trabeculae on the susceptibility to cardiovascular disease. |
| Databáze: | OpenAIRE |
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