@article{9491f54174e044d3b2c99115fcc5bf39,
title = "Environmental and genetic predictors of human cardiovascular ageing",
abstract = "Cardiovascular ageing is a process that begins early in life and leads to a progressive change in structure and decline in function due to accumulated damage across diverse cell types, tissues and organs contributing to multi-morbidity. Damaging biophysical, metabolic and immunological factors exceed endogenous repair mechanisms resulting in a pro-fibrotic state, cellular senescence and end-organ damage, however the genetic architecture of cardiovascular ageing is not known. Here we use machine learning approaches to quantify cardiovascular age from image-derived traits of vascular function, cardiac motion and myocardial fibrosis, as well as conduction traits from electrocardiograms, in 39,559 participants of UK Biobank. Cardiovascular ageing is found to be significantly associated with common or rare variants in genes regulating sarcomere homeostasis, myocardial immunomodulation, and tissue responses to biophysical stress. Ageing is accelerated by cardiometabolic risk factors and we also identify prescribed medications that are potential modifiers of ageing. Through large-scale modelling of ageing across multiple traits our results reveal insights into the mechanisms driving premature cardiovascular ageing and reveal potential molecular targets to attenuate age-related processes.",
author = "Mit Shah and Marco, {Marco H.} and Chang Lu and Schiratti, {Pierre Rapha{\"e}l} and Zheng, {Sean L.} and Adam Clement and {de Marvao}, Antonio and Wenjia Bai and King, {Andrew P.} and Ware, {James S.} and Wilkins, {Martin R.} and Johanna Mielke and Eren Elci and Ivan Kryukov and McGurk, {Kathryn A.} and Christian Bender and Freitag, {Daniel F.} and O{\textquoteright}Regan, {Declan P.}",
note = "Funding Information: D.P.O{\textquoteright}R. acknowledges support from Bayer AG, the Medical Research Council (MC_UP_1605/13); National Institute for Health Research (NIHR) Imperial College Biomedical Research Centre; and the British Heart Foundation (RG/19/6/34387, RE/18/4/34215); J.S.W. acknowledges support from the Sir Jules Thorn Charitable Trust [21JTA]. This research has been conducted using the UK Biobank Resource under Application Numbers 28807 and 40616. The genetic association analyses were conducted on the UK Biobank Research Analysis Platform ( https://ukbiobank.dnanexus.com ). We thank James Cole (UCL) and Tobias Kaufmann (University of T{\"u}bingen) for advice on age-delta modelling. We also thank Tim Dawes, Ghalib Bello, and Carlo Biffi (Imperial College London) for developing the three-dimensional cardiac modelling used in this study. We also acknowledge Esther Puy{\'o}l-Anton, Bram Ruijsink and Reza Razavi for the T1 mapping data. Funding Information: D.P.O{\textquoteright}R. acknowledges support from Bayer AG, the Medical Research Council (MC_UP_1605/13); National Institute for Health Research (NIHR) Imperial College Biomedical Research Centre; and the British Heart Foundation (RG/19/6/34387, RE/18/4/34215); J.S.W. acknowledges support from the Sir Jules Thorn Charitable Trust [21JTA]. This research has been conducted using the UK Biobank Resource under Application Numbers 28807 and 40616. The genetic association analyses were conducted on the UK Biobank Research Analysis Platform (https://ukbiobank.dnanexus.com). We thank James Cole (UCL) and Tobias Kaufmann (University of T{\"u}bingen) for advice on age-delta modelling. We also thank Tim Dawes, Ghalib Bello, and Carlo Biffi (Imperial College London) for developing the three-dimensional cardiac modelling used in this study. We also acknowledge Esther Puy{\'o}l-Anton, Bram Ruijsink and Reza Razavi for the T1 mapping data. For the purpose of open access, the authors have applied a creative commons attribution (CC BY) licence to any author-accepted manuscript version arising. Publisher Copyright: {\textcopyright} 2023, Springer Nature Limited.",
year = "2023",
month = dec,
doi = "10.1038/s41467-023-40566-6",
language = "English",
volume = "14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}