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

Catherine M. Francis, Matthias E. Futschik, Jian Huang, Wenjia Bai, Muralidharan Sargurupremraj, Alexander Teumer, Monique M. B. Breteler, Enrico Petretto, Amanda S. R. Ho, Philippe Amouyel, Stefan T. Engelter, Robin Bülow, Uwe Völker, Henry Völzke, Marcus Dörr, Mohammed-Aslam Imtiaz, N. Ahmad Aziz, Valerie Lohner, James S. Ware, Stephanie Debette, Paul Elliott, Abbas Dehghan () and Paul M. Matthews ()
Additional contact information
Catherine M. Francis: National Heart and Lung Institute, Imperial College London, Programme in Cardiovascular Genetics and Genomics
Matthias E. Futschik: Imperial College London
Jian Huang: Imperial College London
Wenjia Bai: Imperial College London
Muralidharan Sargurupremraj: University of Texas Health Sciences Center
Alexander Teumer: University Medicine Greifswald
Monique M. B. Breteler: German Center for Neurodegenerative Diseases (DZNE)
Enrico Petretto: Duke-NUS Medical School
Amanda S. R. Ho: National University of Singapore
Philippe Amouyel: University of Lille
Stefan T. Engelter: University Hospital and University of Basel
Robin Bülow: University Medicine Greifswald
Uwe Völker: DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald
Henry Völzke: University Medicine Greifswald
Marcus Dörr: DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald
Mohammed-Aslam Imtiaz: German Center for Neurodegenerative Diseases (DZNE)
N. Ahmad Aziz: German Center for Neurodegenerative Diseases (DZNE)
Valerie Lohner: German Center for Neurodegenerative Diseases (DZNE)
James S. Ware: National Heart and Lung Institute, Imperial College London, Programme in Cardiovascular Genetics and Genomics
Stephanie Debette: University of Bordeaux, Inserm, Bordeaux Population Health Research Center
Paul Elliott: Imperial College London
Abbas Dehghan: Imperial College London
Paul M. Matthews: Imperial College London

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32219-x

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DOI: 10.1038/s41467-022-32219-x

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