TY - JOUR
T1 - COL4A2 is associated with lacunar ischemic stroke and deep ICH
T2 - Meta-analyses among 21,500 cases and 40,600 controls
AU - Rannikme, Kristiina
AU - Sivakumaran, Vhinoth
AU - Millar, Henry
AU - Malik, Rainer
AU - Anderson, Christopher D.
AU - Chong, Mike
AU - Dave, Tushar
AU - Falcone, Guido J.
AU - Fernandez-Cadenas, Israel
AU - Jimenez-Conde, Jordi
AU - Lindgren, Arne
AU - Montaner, Joan
AU - O'Donnell, Martin
AU - Paré, Guillaume
AU - Radmanesh, Farid
AU - Rost, Natalia S.
AU - Slowik, Agnieszka
AU - Söderholm, Martin
AU - Traylor, Matthew
AU - Pulit, Sara L.
AU - Seshadri, Sudha
AU - Worrall, Brad B.
AU - Woo, Daniel
AU - Markus, Hugh S.
AU - Mitchell, Braxton D.
AU - Dichgans, Martin
AU - Rosand, Jonathan
AU - Sudlow, Cathie L.M.
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/10/24
Y1 - 2017/10/24
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85031410982
UR - https://www.scopus.com/pages/publications/85031410982#tab=citedBy
U2 - 10.1212/WNL.0000000000004560
DO - 10.1212/WNL.0000000000004560
M3 - Article
C2 - 28954878
AN - SCOPUS:85031410982
SN - 0028-3878
VL - 89
SP - 1829
EP - 1839
JO - Neurology
JF - Neurology
IS - 17
ER -