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Genetic and functional insights into the fractal structure of the heart
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Title: | Genetic and functional insights into the fractal structure of the heart |
Authors: | Meyer, H Dawes, T Serrani, M Bai, W Tokarczuk, P Cai, J Simoes Monteiro de Marvao, A Henry, A Lumbers, T Gierten, J Thumberger, T Wittbrodt, J Ware, J Rueckert, D Matthews, P Prasad, S Costantino, M Cook, S Birney, E O'Regan, D |
Item Type: | Journal Article |
Abstract: | The inner surfaces of the human heart are covered by a complex network of muscular strands that is thought to be a vestige of embryonic development.1,2 The function of these trabeculae in adults and their genetic architecture are unknown. To investigate this we performed a genome-wide association study using fractal analysis of trabecular morphology as an image-derived phenotype in 18,096 UK Biobank participants. We identified 16 significant loci containing genes associated with haemodynamic phenotypes and regulation of cytoskeletal arborisation.3,4 Using biomechanical simulations and human observational data, we demonstrate that trabecular morphology is an important determinant of cardiac performance. Through genetic association studies with cardiac disease phenotypes and Mendelian randomisation, we find a causal relationship between trabecular morphology and cardiovascular disease risk. These findings suggest an unexpected role for myocardial trabeculae in the function of the adult heart, identify conserved pathways that regulate structural complexity, and reveal their influence on susceptibility to disease |
Issue Date: | 27-Aug-2020 |
Date of Acceptance: | 21-May-2020 |
URI: | http://hdl.handle.net/10044/1/80636 |
DOI: | 10.1038/s41586-020-2635-8 |
ISSN: | 0028-0836 |
Publisher: | Nature Research |
Start Page: | 589 |
End Page: | 594 |
Journal / Book Title: | Nature |
Volume: | 584 |
Issue: | 7822 |
Copyright Statement: | © 2020 Springer Nature Limited. The final publication is available at Springer via https://doi.org/10.1038/s41586-020-2635-8 |
Sponsor/Funder: | British Heart Foundation British Heart Foundation British Heart Foundation Imperial College Healthcare NHS Trust- BRC Funding Imperial College Healthcare NHS Trust- BRC Funding Wellcome Trust Medical Research Council (MRC) British Heart Foundation |
Funder's Grant Number: | NH/17/1/32725 RE/18/4/34215 RG/19/6/34387 RDC04 RDB02 107469/Z/15/Z MR/M003191/1 SP/17/11/32885 |
Keywords: | Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics BUILDING PLAN GROWTH TRABECULATIONS MORPHOGENESIS Adult Aged Animals Cardiovascular Diseases Cytoskeleton Fractals Gene Knockout Techniques Genetic Loci Genetic Predisposition to Disease Genome-Wide Association Study Heart Hemodynamics Humans Middle Aged Myocardium Oryzias Phenotype Myocardium Heart Cytoskeleton Animals Oryzias Humans Cardiovascular Diseases Genetic Predisposition to Disease Phenotype Fractals Adult Aged Middle Aged Hemodynamics Genome-Wide Association Study Gene Knockout Techniques Genetic Loci General Science & Technology |
Publication Status: | Published |
Online Publication Date: | 2020-08-19 |
Appears in Collections: | Computing National Heart and Lung Institute Institute of Clinical Sciences Faculty of Medicine Department of Brain Sciences Faculty of Engineering |