Please use this identifier to cite or link to this item:
Title: COL4A2 is associated with lacunar ischemic stroke and deep ICH: Meta-analyses among 21,500 cases and 40,600 controls
Author: Rannikmäe, Kristiina
Sivakumaran, Vhinoth
Millar, Henry
Malik, Rainer
Anderson, Christopher D.
Chong, Mike
Dave, Tushar
Falcone, Guido J.
Fernandez-Cadenas, Israel
Jimenez-Conde, Jordi
Lindgren, Arne
Montaner, Joan
O'Donnell, Martin
Paré, Guillaume
Radmanesh, Farid
Rost, Natalia S.
Slowik, Agnieszka
Söderholm, Martin
Traylor, Matthew
Pulit, Sara L.
Seshadri, Sudha
Worrall, Bradford B.
Woo, Daniel
Markus, Hugh Stephen
Mitchell, Braxton D.
Dichgans, Martin
Rosand, Jonathan
Sudlow, Cathie L.M.
Rabionet Janssen, Raquel
International Stroke Genetics Consortium (ISGC) McArdle PF
Wong, Q.
Gwinn, K
Achterberg, S.
Algra, A.
Amouyel, P.
Arnett, Donna K.
Arsava, E.M.
Attia, J.
Ay, H.
Keywords: Malalties cerebrals
Brain diseases
Issue Date: 27-Sep-2017
Publisher: Lippincott, Williams & Wilkins. Wolters Kluwer Health
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 × 10-4) with both lacunar IS (lead SNP rs9515201: odds ratio [OR] 1.17, 95% confidence interval [CI] 1.11-1.24, p = 6.62 × 10-8) and deep ICH (lead SNP rs4771674: OR 1.28, 95% CI 1.13-1.44, p = 5.76 × 10-5). A SNP in HTRA1 was associated (significance threshold p < 5.5 × 10-4) with lacunar IS (rs79043147: OR 1.23, 95% CI 1.10-1.37, p = 1.90 × 10-4) 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. CONCLUSIONS: These results provide evidence of shared genetic determinants and suggest common pathophysiologic mechanisms of distinct ischemic and hemorrhagic cerebral SVD stroke phenotypes, offering new insights into the causal mechanisms of cerebral SVD.
Note: Reproducció del document publicat a:
It is part of: Neurology, 2017, vol. 89, num. 17
Related resource:
ISSN: 0028-3878
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)

Files in This Item:
File Description SizeFormat 
673627.pdf671.48 kBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.