34
IRUS Total
Downloads

Genetic and functional insights into the fractal structure of the heart

File Description SizeFormat 
Meyer_accepted_version.pdfAccepted version6.29 MBAdobe PDFView/Open
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