PuSH - Publication Server of Helmholtz Zentrum München: COL4A2 is associated with lacunar ischemic stroke and deep ICH: Meta-analyses among 21,500 cases and 40,600 controls.

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Rannikme, K.* ; Sivakumaran, V.* ; Millar, H.* ; Malik, R.* ; Anderson, C.D.* ; Chong, M.* ; Dave, T.* ; Falcone, G.J.* ; Fernandez-Cadenas, I.* ; Jimenez-Conde, J.* ; Lindgren, A.* ; Montaner, J.* ; O'Donnell, M.* ; Paré, G.* ; Radmanesh, F.* ; Rost, N.S.* ; Slowik, A.* ; Söderholm, M.* ; SIGN study group (Gieger, C.) ; SIGN study group (Meisinger, C.) ; SIGN study group (Müller-Nurasyid, M.) ; SIGN study group (Strauch, K.) ; SIGN study group (Waldenberger, M.) ; METASTROKE Consortium (Liu, J.) ; Mitchell, B.D.* ; Dichgans, M.* ; Rosand, J.* ; Sudlow, C.L.M.* ; SIGN study group (Peters, A.)

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

Neurology 89, 1829-1839 (2017)

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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.

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