Journal Article

DZNE-2022-01402

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities.

Francis, C. M. ; Futschik, M. E. ; Huang, J. ; Bai, W. ; Sargurupremraj, M. ; Teumer, A. ; Breteler, M.DZNE* ; Petretto, E. ; Ho, A. S. R. ; Amouyel, P. ; Engelter, S. T. ; Bülow, R. ; Völker, U. ; Völzke, H. ; Dörr, M. ; Imtiaz, M.-A.DZNE* ; Aziz, N. A.DZNE* ; Lohner, V.DZNE* ; Ware, J. S. ; Debette, S. ; Elliott, P. ; Dehghan, A. ; Matthews, P. M. (Corresponding author)

2022
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-022-32219-x

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.

Keyword(s): Aorta: diagnostic imaging (MeSH) ; Aortic Aneurysm: diagnostic imaging (MeSH) ; Aortic Aneurysm: genetics (MeSH) ; Female (MeSH) ; Genome-Wide Association Study (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Phenomics (MeSH) ; White Matter: diagnostic imaging (MeSH)

Note: CC BY

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Contributing Institute(s):

1. Population Health Sciences (AG Breteler)
2. Population & Clinical Neuroepidemiology (AG Aziz)
3. Aging, Cognition and Technology (AG Wolbers)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Experiment(s):

1. Rhineland Study / Bonn

Appears in the scientific report 2022

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