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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Veröffentlicht in:Nature communications Jg. 13; H. 1; S. 4505 - 18
Hauptverfasser: 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
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 03.08.2022
Nature Publishing Group
Nature Portfolio
Schlagworte:
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-Zugang:Volltext
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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: Matthias E.
  surname: Futschik
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  givenname: Jian
  surname: Huang
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  organization: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
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  surname: Bai
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  organization: Department of Brain Sciences, Imperial College London, Department of Computing, Imperial College London
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  givenname: Muralidharan
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  fullname: Sargurupremraj, Muralidharan
  organization: Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases, University of Texas Health Sciences Center, University of Bordeaux, Inserm, Bordeaux Population Health Research Center
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  givenname: Alexander
  orcidid: 0000-0002-8309-094X
  surname: Teumer
  fullname: Teumer, Alexander
  organization: Institute for Community Medicine, University Medicine Greifswald, DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Department of Population Medicine and Lifestyle Diseases Prevention, Medical University of Bialystok
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  givenname: Monique M. B.
  orcidid: 0000-0002-0626-9305
  surname: Breteler
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  organization: Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), Faculty of Medicine, University of Bonn
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  surname: Petretto
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  organization: Programme in Cardiovascular & Metabolic Disorders and Centre for Computational Biology, Duke-NUS Medical School, Institute of Big Data and Artificial Intelligence, China Pharmaceutical University (CPU), Computational Biology Programme, Faculty of Science, National University of Singapore
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  surname: Ho
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  organization: Computational Biology Programme, Faculty of Science, National University of Singapore
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  orcidid: 0000-0001-9088-234X
  surname: Amouyel
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  givenname: Stefan T.
  surname: Engelter
  fullname: Engelter, Stefan T.
  organization: Department of Neurology and Stroke Center, University Hospital and University of Basel, Department of Clinical Neurology and Neurorehabilitation, University Department of Geriatric Medicine FELIX PLATTER, University of Basel
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  organization: Department of Radiology and Neuroradiology, University Medicine Greifswald
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  surname: Völker
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  organization: DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald
– sequence: 14
  givenname: Henry
  surname: Völzke
  fullname: Völzke, Henry
  organization: Institute for Community Medicine, University Medicine Greifswald, DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald
– sequence: 15
  givenname: Marcus
  orcidid: 0000-0001-7471-475X
  surname: Dörr
  fullname: Dörr, Marcus
  organization: DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Department of Internal Medicine B, University Medicine Greifswald
– sequence: 16
  givenname: Mohammed-Aslam
  surname: Imtiaz
  fullname: Imtiaz, Mohammed-Aslam
  organization: Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE)
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  givenname: N. Ahmad
  orcidid: 0000-0001-6184-458X
  surname: Aziz
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  givenname: Valerie
  orcidid: 0000-0001-5589-9701
  surname: Lohner
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  organization: Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE)
– sequence: 19
  givenname: James S.
  orcidid: 0000-0002-6110-5880
  surname: Ware
  fullname: Ware, James S.
  organization: National Heart and Lung Institute, Imperial College London, Programme in Cardiovascular Genetics and Genomics, Royal Brompton & Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust, MRC London Institute of Medical Sciences (LMS), Imperial College London
– sequence: 20
  givenname: Stephanie
  orcidid: 0000-0001-8675-7968
  surname: Debette
  fullname: Debette, Stephanie
  organization: University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Department of Neurology, Institute for Neurodegenerative Diseases, Bordeaux University Hospital – CHU Bordeaux
– sequence: 21
  givenname: Paul
  orcidid: 0000-0002-7511-5684
  surname: Elliott
  fullname: Elliott, Paul
  organization: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, UK Dementia Research Institute at Imperial College London, Health Data Research (HDR) UK London at Imperial College London, Britsh Heart Foundation Centre of Research Excellence at Imperial College London, National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London, MRC Centre for Environment and Health, School of Public Health, Imperial College London
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  orcidid: 0000-0001-6403-016X
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  givenname: Paul M.
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  surname: Matthews
  fullname: Matthews, Paul M.
  email: p.matthews@imperial.ac.uk
  organization: Department of Brain Sciences, Imperial College London, UK Dementia Research Institute at Imperial College London, National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London
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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
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multidisciplinary
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Phenomics
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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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