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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Published in:Nature communications Vol. 13; no. 1; pp. 4505 - 18
Main Authors: 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.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 03.08.2022
Nature Publishing Group
Nature Portfolio
Subjects:
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
Online Access:Get full text
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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. 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.
AbstractList 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.
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.
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-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 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 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 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.
ArticleNumber 4505
Author Ho, Amanda S. R.
Debette, Stephanie
Huang, Jian
Völzke, Henry
Sargurupremraj, Muralidharan
Aziz, N. Ahmad
Elliott, Paul
Dörr, Marcus
Ware, James S.
Breteler, Monique M. B.
Bai, Wenjia
Francis, Catherine M.
Matthews, Paul M.
Teumer, Alexander
Lohner, Valerie
Dehghan, Abbas
Futschik, Matthias E.
Imtiaz, Mohammed-Aslam
Amouyel, Philippe
Bülow, Robin
Petretto, Enrico
Engelter, Stefan T.
Völker, Uwe
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  givenname: James S.
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  surname: Ware
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  givenname: Stephanie
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  surname: Debette
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  surname: Elliott
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Snippet Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular...
Aortic distensibility is a risk factor for multiple cardiovascular events, but the genetic etiology is not well understood. Here, the authors identify genetic...
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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
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Genetic variance
Genetics
Genome-Wide Association Study
Genomes
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Humanities and Social Sciences
Humans
Insulin-like growth factors
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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
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Title Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities
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