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.; BULOW, Robin; VOLKER, Uwe; VOLZKE, Henry; DORR, Marcus; IMTIAZ, Mohammed-Aslam; AZIZ, N. Ahmad; LOHNER, Valerie; WARE, James S.; DEBETTE, Stephanie; ELLIOTT, Paul; DEHGHAN, Abbas; MATTHEWS, Paul M.

doi:10.1038/s41467-022-32219-x

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Article de revue

Ce document a été publié dans

Nature Communications. 2022-08-03, vol. 13, n° 1

Résumé en anglais

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-beta, 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.< Réduire

URI

https://oskar-bordeaux.fr/handle/20.500.12278/170121

DOI

http://dx.doi.org/10.1038/s41467-022-32219-x

Projet Européen

Study on Environmental and GenomeWide predictors of early structural brain Alterations in Young students
Common mechanisms and pathways in Stroke and Alzheimer's disease.
PREvention of STroke in Intracerebral haemorrhaGE survivors with Atrial Fibrillation

Project ANR

Stopping cognitive decline and dementia by fighting covert cerebral small vessel disease

Unités de recherche

Bordeaux Population Health Research Center (BPH) - UMR 1219

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