Rare Coding Variation and Risk of Intracerebral Hemorrhage

Radmanesh, Farid; Falcone, Guido J; Anderson, Chris; McWilliams, David R.; Devan, William J.; Brown, W. Mark; Battey, Thomas W.K.; Ayres, Alison; Raffeld, Miriam R.; Schwab, Kristin; Sun, Guoqiang; Deka, Ranjan; Viswanathan, Anand; Goldstein, Joshua N.; Greenberg, Steven M.; Tirschwell, David; Silliman, Scott; Selim, Magdy; Meschia, James F.; Brown, Devin L.; Worrall, Bradford B.; Langefeld, Carl D.; Woo, Daniel; Rosand, Jonathan

doi:10.1161/strokeaha.115.009838

Cited by 10 publications

(4 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both common and rare genetic variants could have a significant influence on the development as well as the functional outcome of ICH. Previous GWAS provide proof of concept that common variants are associated with both lobar as well as non-lobar ICH including Apolipoprotein E genotype (APOE) variants (rs7412 and rs429358), the rs4311 variant of the angiotensin-converting enzyme (ACE) gene and the rs9588151of the collagen type IV alpha 2 (COL4A2) gene [52][53][54][55][56] ICH also require further investigation [27,73].…”

Section: Genetics Of Ichmentioning

confidence: 99%

Intracerebral hemorrhage: an update on diagnosis and treatment

Hostettler

Seiffge

Werring

2019

Expert Review of Neurotherapeutics

215

151

View full text Add to dashboard Cite

Introduction: Spontaneous nontraumatic intracerebral hemorrhage (ICH) is most often caused by small vessel diseases: hypertensive arteriopathy or cerebral amyloid angiopathy (CAA). Although ICH accounts for only 10-15% of all strokes it causes a high proportion of stroke mortality and morbidity, with few proven effective acute or preventive treatments. Areas covered: We conducted a literature search on etiology, diagnosis, treatment, management and current clinical trials in sICH. In this review we describe the causes, diagnosis, (including new brain imaging biomarkers), classification, pathophysiological understanding, treatment (medical and surgical) and secondary prevention of ICH. Expert commentary: In recent years, significant advances have been made in deciphering causes, understanding pathophysiology, and improving acute treatment and prevention of ICH. However, the clinical outcome remains poor and many challenges remain. Acute interventions delivered rapidly (including medical therapies-targeting hematoma expansion, hemoglobin toxicity, inflammation, edema, anticoagulant reversaland minimally-invasive surgery) are likely to improve acute outcomes. Improved classification of the underlying arteriopathy (from neuroimaging and genetic studies) and prognosis should allow tailored prevention strategies (including sustained blood pressure control and optimized antithrombotic therapy) to further improve longer-term outcome in this devastating disease.

show abstract

Section: Genetics Of Ichmentioning

confidence: 99%

Intracerebral hemorrhage: an update on diagnosis and treatment

Hostettler

Seiffge

Werring

2019

Expert Review of Neurotherapeutics

215

151

View full text Add to dashboard Cite

show abstract

“…Indeed, a published study of intracerebral hemorrhage with a similar sample size (n = 1,553) also did not reveal any novel associations. 30 In contrast, larger studies (n > 8,000) of insulin secretion, 10 myocardial infarction and cholesterol levels, 12 and blood pressure 31 reported statistically significant associations of single low-frequency variants.…”

Section: Discussionmentioning

confidence: 97%

Exome-chip association analysis of intracranial aneurysms

et al. 2020

Self Cite

View full text Add to dashboard Cite

ObjectiveTo investigate to what extent low-frequency genetic variants (with minor allele frequencies <5%) affect the risk of intracranial aneurysms (IAs).MethodsOne thousand fifty-six patients with IA and 2,097 population-based controls from the Netherlands were genotyped with the Illumina HumanExome BeadChip. After quality control (QC) of samples and single nucleotide variants (SNVs), we conducted a single variant analysis using the Fisher exact test. We also performed the variable threshold (VT) test and the sequence kernel association test (SKAT) at different minor allele count (MAC) thresholds of >5 and >0 to test the hypothesis that multiple variants within the same gene are associated with IA risk. Significant results were tested in a replication cohort of 425 patients with IA and 311 controls, and results of the 2 cohorts were combined in a meta-analysis.ResultsAfter QC, 995 patients with IA and 2,080 controls remained for further analysis. The single variant analysis comprising 46,534 SNVs did not identify significant loci at the genome-wide level. The gene-based tests showed a statistically significant association for fibulin 2 (FBLN2) (best p = 1 × 10−6 for the VT test, MAC >5). Associations were not statistically significant in the independent but smaller replication cohort (p > 0.57) but became slightly stronger in a meta-analysis of the 2 cohorts (best p = 4.8 × 10−7 for the SKAT, MAC ≥1).ConclusionGene-based tests indicated an association for FBLN2, a gene encoding an extracellular matrix protein implicated in vascular wall remodeling, but independent validation in larger cohorts is warranted. We did not identify any significant associations for single low-frequency genetic variants.

show abstract

“…Given that the two genes associated with ICH in the present study were not related to intermediate phenotypes, the functional relevance of the association of these genes with ICH remains to be elucidated [ 87 ]. A previous study, performed mainly in patients with European ancestry, using exome array, did not identify any rare coding variants for ICH [ 88 ].…”

Section: Exome Wide Association Studies (Ewas)mentioning

confidence: 99%

Genetics and Epigenetics of Spontaneous Intracerebral Hemorrhage

Giralt‐Steinhauer

Jiménez-Baladó

Fernández-Pérez

et al. 2022

IJMS

View full text Add to dashboard Cite

Intracerebral hemorrhage (ICH) is a complex and heterogeneous disease, and there is no effective treatment. Spontaneous ICH represents the final manifestation of different types of cerebral small vessel disease, usually categorized as: lobar (mostly related to cerebral amyloid angiopathy) and nonlobar (hypertension-related vasculopathy) ICH. Accurate phenotyping aims to reflect these biological differences in the underlying mechanisms and has been demonstrated to be crucial to the success of genetic studies in this field. This review summarizes how current knowledge on genetics and epigenetics of this devastating stroke subtype are contributing to improve the understanding of ICH pathophysiology and their potential role in developing therapeutic strategies.

show abstract

Rare Coding Variation and Risk of Intracerebral Hemorrhage

Cited by 10 publications

References 7 publications

Intracerebral hemorrhage: an update on diagnosis and treatment

Intracerebral hemorrhage: an update on diagnosis and treatment

Exome-chip association analysis of intracranial aneurysms

Genetics and Epigenetics of Spontaneous Intracerebral Hemorrhage

Contact Info

Product

Resources

About