Common NOTCH3 Variants and Cerebral Small-Vessel Disease

Loes C A Rutten-Jacobs, Matthew Traylor, Poneh Adib-Samii, Vincent Thijs, Cathie Sudlow, Peter M. Rothwell, Giorgio Boncoraglio, Martin Dichgans, Steve Bevan, James Meschia, Christopher Levi, Natalia S. Rost, Jonathan Rosand, Ahamad Hassan, Hugh S. Markus

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Purpose-The most common monogenic cause of cerebral small-vessel disease is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, caused by NOTCH3 gene mutations. It has been hypothesized that more common variants in NOTCH3 may also contribute to the risk of sporadic small-vessel disease. Previously, 4 common variants (rs10404382, rs1043994, rs10423702, and rs1043997) were found to be associated with the presence of white matter hyperintensity in hypertensive community-dwelling elderly. Methods-We investigated the association of common single nucleotide polymorphisms (SNPs) in NOTCH3 in 1350 patients with MRI-confirmed lacunar stroke and 7397 controls, by meta-analysis of genome-wide association study data sets. In addition, we investigated the association of common SNPs in NOTCH3 with MRI white matter hyperintensity volumes in 3670 white patients with ischemic stroke. In each analysis, we considered all SNPs within the NOTCH3 gene, and within 50-kb upstream and downstream of the coding region. A total of 381 SNPs from the 1000 genome population with a mean allele frequency >0.01 were included in the analysis. A significance level of P

Original languageEnglish
Pages (from-to)1482-1487
Number of pages6
JournalStroke
Volume46
Issue number6
DOIs
Publication statusPublished - Jun 4 2015

Keywords

  • CADASIL
  • cerebral small vessel diseases
  • genetic association studies
  • stroke, lacunar

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialised Nursing

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