COL4A2 is associated with lacunar ischemic stroke and deep ICH: Meta-analyses among 21,500 cases and 40,600 controls

Research output: Contribution to journalArticle

Abstract

Objective: To determine whether common variants in familial cerebral small vessel disease (SVD) genes confer risk of sporadic cerebral SVD. Methods: We meta-analyzed genotype data from individuals of European ancestry to determine associations of common single nucleotide polymorphisms (SNPs) in 6 familial cerebral SVD genes (COL4A1, COL4A2, NOTCH3, HTRA1, TREX1, and CECR1) with intracerebral hemorrhage (ICH) (deep, lobar, all; 1,878 cases, 2,830 controls) and ischemic stroke (IS) (lacunar, cardioembolic, large vessel disease, all; 19,569 cases, 37,853 controls). We applied data quality filters and set statistical significance thresholds accounting for linkage disequilibrium and multiple testing. Results: A locus in COL4A2 was associated (significance threshold p , 3.5 3 1024) with both lacunar IS (lead SNP rs9515201: odds ratio [OR] 1.17, 95%confidence interval [CI] 1.11-1.24, p 56.62 31028) and deep ICH (lead SNP rs4771674: OR 1.28, 95%CI 1.13-1.44, p 55.76 3 1025). A SNP in HTRA1 was associated (significance threshold p , 5.5 3 1024) with lacunar IS (rs79043147: OR 1.23, 95%CI 1.10-1.37, p 5 1.90 3 1024) and less robustly with deep ICH. There was no clear evidence for association of common variants in either COL4A2 or HTRA1 with non-SVD strokes or in any of the other genes with any stroke phenotype.

Details

Authors
  • Kristiina Rannikmäe
  • Vhinoth Sivakumaran
  • Henry Millar
  • Rainer Malik
  • Christopher D. Anderson
  • Mike Chong
  • Tushar Dave
  • Guido J. Falcone
  • Israel Fernandez-Cadenas
  • Jordi Jimenez-Conde
  • Joan Montaner
  • Martin O'Donnell
  • Guillaume Paré
  • Farid Radmanesh
  • Natalia S. Rost
  • Agnieszka Slowik
  • Matthew Traylor
  • Sara L Pulit
  • Sudha Seshadri
  • Brad B. Worrall
  • Daniel Woo
  • Hugh S. Markus
  • Braxton D. Mitchell
  • Martin Dichgans
  • Jonathan Rosand
  • Cathie L M Sudlow
Organisations
External organisations
  • University of Edinburgh
  • Massachusetts General Hospital
  • Broad Institute
  • Population Health Research Institute, Ontario
  • University of Maryland School of Medicine
  • Yale University
  • Skåne University Hospital
  • National University of Ireland Galway
  • University of Cambridge
  • University Medical Center Utrecht
  • University of Virginia
  • University of Cincinnati College of Medicine
  • Munich Cluster for Systems Neurology
  • Autonomous University of Barcelona
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • COL4A2, ischemic stroke, ICH
Original languageEnglish
Pages (from-to)1829-1839
Number of pages11
JournalNeurology
Volume89
Issue number17
Publication statusPublished - 2017 Oct 24
Publication categoryResearch
Peer-reviewedYes