期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-32219-x
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资金
- NHLI
- BHF Imperial Centre of Research Excellence [RE/18/4/34215]
- BHF Clinical Research Fellowship [FS/15/81/31817]
- Edmond J Safra Foundation
- National Institute for Health Research (NIHR)
- UK Dementia Research Institute
- NIHR Biomedical Research Centre at Imperial College London
- Medical Research Council (UK)
- British Heart Foundation [RE/18/4/34215]
- NIHR Imperial College Biomedical Research Centre
- Sir Jules Thorn Charitable Trust [21/JTA]
- MRC [MR/L01341X/1, MR/S019669/1]
- NIHR
- NIHR Imperial Biomedical Research Centre
- Imperial College British Heart Foundation Centre for Research Excellence [RE/18/4/34215]
- UK Dementia Research Institute at Imperial College London [MC_PC_17114]
- Health Data Research UK for London
- French National Research Agency (ANR) [ANR-18-RHUS-002]
- ERC
- EU H2020 [640643, 667375, 754517]
- Inserm
- Lille 2 University
- Institut Pasteur de Lille
- Lille University Hospital
- ERDF (FEDER funds)
- Region Nord-Pas de-Calais [09120030]
- Centre National de Genotypage
- Emil Aaltonen Foundation
- Paavo Ilmari Ahvenainen Foundation
- Helsinki University Central Hospital Research Fund
- Helsinki University Medical Foundation
- Paivikki and Sakari Sohlberg Foundation
- Aarne Koskelo Foundation
- Maire Taponen Foundation
- Aarne and Aili Turunen Foundation
- Lilly Foundation
- Alfred Kordelin Foundation
- Finnish Medical Foundation
- Orion Farmos Research Foundation
- Maud Kuistila Foundation
- Finnish Brain Foundation
- Biomedicum Helsinki Foundation
- Projet Hospitalier de Recherche Clinique Regional
- Fondation de France
- Genopole de Lille
- Adrinord
- Basel Stroke-Funds
- Kathe-Zingg-Schwichtenberg Fonds of the Swiss Academy of Medical Sciences
- Swiss Heart Foundation
- Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03IS2061A]
- Ministry of Cultural Affairs
- Social Ministry of the Federal State of Mecklenburg West Pomerania
- Siemens Healthineers, Erlangen, Germany
- Federal State of Mecklenburg-West Pomerania
- Lily Safra
The study identifies genetic variants associated with aortic distensibility, highlighting the causal relationships between aortic distensibility and aortic aneurysms as well as brain small vessel disease. The findings provide new insights into the mechanisms related to cardiovascular development, extracellular matrix production, and smooth muscle cell contraction.
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. 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.
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