Genome-wide association study of sporadic brain arteriovenous malformations

Weinsheimer, Shantel; Bendjilali, Nasrine; Nelson, Jeffrey; Guo, Diana E.; Zaroff, Jonathan G.; McCulloch, Charles E.; Salman, Rustam Al-Shahi; Berg, Jonathan; Koeleman, Bobby P. C.; Simon, Matthias; Bostroem, Azize; Fontanella, Marco Maria; Sturiale, Carmelo Lucio; Pola, Roberto; Puca, Alfredo; Lawton, Michael T.; Young, William L.; Pawlikowska, Ludmila; Klijn, Catharina J.M.; Kim, Helen

doi:10.1136/jnnp-2015-312272

Cited by 32 publications

(18 citation statements)

References 41 publications

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“…Recently, Weinsheimer et al reported genome-wide association study to investigate the association of common SNPs with risk of sporadic bAVM in Caucasians, and found that no SNPs including ALK1 IVS3 −3A>G were replicated in the large bAVM replication cohort, suggesting that common SNPs do not contribute strongly to bAVM susceptibility. 32) …”

Section: Single-nucleotide Polymorphisms (Snps) In Bavmsmentioning

confidence: 99%

Pathogenesis of Brain Arteriovenous Malformations

Komiyama

2016

Neurol. Med. Chir.(Tokyo)

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Brain arteriovenous malformations (bAVMs) represent a high risk of intracranial hemorrhages, which are substantial causes of morbidity and mortality of bAVMs, especially in children and young adults. Although a variety of factors leading to hemorrhages of bAVMs are investigated extensively, their pathogenesis is still not well elucidated. The author has reviewed the updated data of genetic aspects of bAVMs, especially focusing on clinical and experimental knowledge from hereditary hemorrhagic telangiectasia, which is the representative genetic disease presenting with bAVMs caused by loss-of-function in one of the two genes: endoglin and activin receptor-like kinase 1. This knowledge may allow us to infer the pathogensis of sporadic bAVMs and in the development of new medical therapies for them.

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Section: Single-nucleotide Polymorphisms (Snps) In Bavmsmentioning

confidence: 99%

Pathogenesis of Brain Arteriovenous Malformations

Komiyama

2016

Neurol. Med. Chir.(Tokyo)

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“…There is evidence to suggest that common genetic polymorphisms vary little in their contribution to arteriovenous malformation. 82…”

Section: Resultsmentioning

confidence: 99%

“…There is evidence to suggest that common genetic polymorphisms vary little in their contribution to arteriovenous malformation. 82 Monogenic disorders associated with arteriovenous malformation. Hereditary hemorrhagic telangiectasia, an autosomal dominant disorder caused by variants in ENG, ALK1, and SMAD4, often presents with multiple cerebral arteriovenous malformations.…”

Section: Arteriovenous Malformationmentioning

confidence: 99%

Genetic susceptibility to cerebrovascular disease: A systematic review

Griessenauer

Farrell

Sarkar

et al. 2018

J Cereb Blood Flow Metab

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Investigation of genetic susceptibility to cerebrovascular disease has been of growing interest. A systematic review of human studies assessing neurogenomic aspects of cerebrovascular disease was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Any association study exploring genetic variants located in the exome associated with one of the major cerebrovascular diseases with at least 500 subjects was eligible for inclusion. Of 6874 manuscripts identified, 35 studies met the inclusion criteria. Most studies of interest focused on ischemic stroke and cerebrovascular occlusive disease. Large cohort genetic association studies on hemorrhagic cerebrovascular disease were less common. In addition to rare, well-established monogenic conditions with significant risk for cerebrovascular disease, a number of genetic variants are also relevant to cerebrovascular pathogenesis as part of a multifactorial process. The 45 polymorphisms identified were located in genes involved in processes related to endothelial and vascular health (15 (33.4%) variants), plasma lipid metabolism (10 (22.2%) variants), inflammation (9 (20%) variants), coagulation (3 (6.7%) variants), and blood pressure modulation (2 (4.4%) variants), and other (6 (13.3%) variants). This work represents a comprehensive overview of genetic variants in the exome relevant to ischemic and hemorrhagic stroke pathophysiology.

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“…Pathogenic mutations in TGF-β signaling, such as ENG, ALK1 gene mutations, are associated with type 1 and type 2 hereditary hemorrhagic telangiectasia (HHT), as well as Loeys-dietz syndrome with cerebrovascular events ( McAllister et al, 1994 ; Cunha et al, 2017 ; Laterza et al, 2019 ). Some genome-wide association studies (GWAS) or whole exome trio sequencing have uncovered various pathogenic gene variants in the TGF-β pathway, which are associated with small vessel ischemic strokes, intracerebral hemorrhages and sporadic brain AVMs ( Weinsheimer et al, 2016 ; Yilmaz et al, 2017 ; Wang et al, 2018 ; Chung et al, 2019 ). Increased expression of TGF-β1 has been found in the brain tissue after ischemic stroke, as well as in hereditary cerebral hemorrhage with amyloidosis-Dutch type ( Krupinski et al, 1996 ; Grand Moursel et al, 2018 ), while a recent transcriptome-wide RNA sequencing study revealed that TGF-β signaling was downregulated in patients with brain AVMs ( Hauer et al, 2020 ).…”

Section: Dysregulation Of Tgf-β Signaling In Cerebrovascular Diseasesmentioning

confidence: 99%

The Roles of TGF-β Signaling in Cerebrovascular Diseases

Zhang

Yang

2020

Front. Cell Dev. Biol.

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Cerebrovascular diseases are one of the leading causes of death worldwide, however, little progress has been made in preventing or treating these diseases to date. The transforming growth factor-β (TGF-β) signaling pathway plays crucial and highly complicated roles in cerebrovascular development and homeostasis, and dysregulated TGF-β signaling contributes to cerebrovascular diseases. In this review, we provide an updated overview of the functional role of TGF-β signaling in the cerebrovascular system under physiological and pathological conditions. We discuss the current understanding of TGF-β signaling in cerebral angiogenesis and the maintenance of brain vessel homeostasis. We also review the mechanisms by which disruption of TGF-β signaling triggers or promotes the progression of cerebrovascular diseases. Finally, we briefly discuss the potential of targeting TGF-β signaling to treat cerebrovascular diseases.

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Genome-wide association study of sporadic brain arteriovenous malformations

Cited by 32 publications

References 41 publications

Pathogenesis of Brain Arteriovenous Malformations

Pathogenesis of Brain Arteriovenous Malformations

Genetic susceptibility to cerebrovascular disease: A systematic review

The Roles of TGF-β Signaling in Cerebrovascular Diseases

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