Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities

Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance ima...

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Vydané v:	Nature communications Ročník 13; číslo 1; s. 4505 - 18
Hlavní autori:	Francis, Catherine M., Futschik, Matthias E., Huang, Jian, Bai, Wenjia, Sargurupremraj, Muralidharan, Teumer, Alexander, Breteler, Monique M. B., Petretto, Enrico, Ho, Amanda S. R., Amouyel, Philippe, Engelter, Stefan T., Bülow, Robin, Völker, Uwe, Völzke, Henry, Dörr, Marcus, Imtiaz, Mohammed-Aslam, Aziz, N. Ahmad, Lohner, Valerie, Ware, James S., Debette, Stephanie, Elliott, Paul, Dehghan, Abbas, Matthews, Paul M.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 03.08.2022 Nature Publishing Group Nature Portfolio
Predmet:	45/43 59/57 631/208/205/2138 631/208/480 631/443/1338/1287 692/4019/592/2727 692/617/375/1370 Aorta Aorta - diagnostic imaging Aortic Aneurysm - diagnostic imaging Aortic Aneurysm - genetics Aortic aneurysms Blood vessels Brain Cardiology and cardiovascular system Cardiovascular diseases Cerebrovascular diseases Etiology Extracellular matrix Female Genetic diversity Genetic variance Genetics Genome-Wide Association Study Genomes Human genetics Human health and pathology Humanities and Social Sciences Humans Insulin-like growth factors Life Sciences Magnetic resonance imaging Male multidisciplinary Muscle contraction Muscles Neuroimaging Neurons and Cognition Phenomics Platelet-derived growth factor Risk analysis Risk factors Science Science (multidisciplinary) Signal transduction Smooth muscle Substantia alba Vascular diseases Vascular endothelial growth factor White Matter - diagnostic imaging
ISSN:	2041-1723, 2041-1723
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Shrnutí:	Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-β, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease. Aortic distensibility is a risk factor for multiple cardiovascular events, but the genetic etiology is not well understood. Here, the authors identify genetic variants linked to aortic distensibility, highlighting mechanistic pathways and causal relationships between distensibility and both aortic aneurysms and brain small vessel disease.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 PMCID: PMC9349177
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-022-32219-x