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

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COL4A2 is associated with lacunar ischemic stroke and deep ICH : Meta-analyses among 21,500 cases and 40,600 controls. / 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, Brad B.; Woo, Daniel; Markus, Hugh S.; Mitchell, Braxton D.; Dichgans, Martin; Rosand, Jonathan; Sudlow, Cathie L M.

In: Neurology, Vol. 89, No. 17, 24.10.2017, p. 1829-1839.

Research output: Contribution to journalArticle

Harvard

Rannikmäe, K, Sivakumaran, V, Millar, H, Malik, R, Anderson, CD, Chong, M, Dave, T, Falcone, GJ, Fernandez-Cadenas, I, Jimenez-Conde, J, Lindgren, A, Montaner, J, O'Donnell, M, Paré, G, Radmanesh, F, Rost, NS, Slowik, A, Söderholm, M, Traylor, M, Pulit, SL, Seshadri, S, Worrall, BB, Woo, D, Markus, HS, Mitchell, BD, Dichgans, M, Rosand, J & Sudlow, CLM 2017, 'COL4A2 is associated with lacunar ischemic stroke and deep ICH: Meta-analyses among 21,500 cases and 40,600 controls', Neurology, vol. 89, no. 17, pp. 1829-1839. https://doi.org/10.1212/WNL.0000000000004560

APA

Rannikmäe, 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., Traylor, M., ... Sudlow, C. L. M. (2017). COL4A2 is associated with lacunar ischemic stroke and deep ICH: Meta-analyses among 21,500 cases and 40,600 controls. Neurology, 89(17), 1829-1839. https://doi.org/10.1212/WNL.0000000000004560

CBE

Rannikmäe K, Sivakumaran V, Millar H, Malik R, Anderson CD, Chong M, Dave T, Falcone GJ, Fernandez-Cadenas I, Jimenez-Conde J, Lindgren A, Montaner J, O'Donnell M, Paré G, Radmanesh F, Rost NS, Slowik A, Söderholm M, Traylor M, Pulit SL, Seshadri S, Worrall BB, Woo D, Markus HS, Mitchell BD, Dichgans M, Rosand J, Sudlow CLM. 2017. COL4A2 is associated with lacunar ischemic stroke and deep ICH: Meta-analyses among 21,500 cases and 40,600 controls. Neurology. 89(17):1829-1839. https://doi.org/10.1212/WNL.0000000000004560

MLA

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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, Brad B. ; Woo, Daniel ; Markus, Hugh S. ; Mitchell, Braxton D. ; Dichgans, Martin ; Rosand, Jonathan ; Sudlow, Cathie L M. / COL4A2 is associated with lacunar ischemic stroke and deep ICH : Meta-analyses among 21,500 cases and 40,600 controls. In: Neurology. 2017 ; Vol. 89, No. 17. pp. 1829-1839.

RIS

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 - Rannikmäe, 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

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.

KW - COL4A2

KW - ischemic stroke

KW - ICH

UR - http://www.scopus.com/inward/record.url?scp=85031410982&partnerID=8YFLogxK

U2 - 10.1212/WNL.0000000000004560

DO - 10.1212/WNL.0000000000004560

M3 - Article

C2 - 28954878

AN - SCOPUS:85031410982

VL - 89

SP - 1829

EP - 1839

JO - Neurology

JF - Neurology

SN - 1526-632X

IS - 17

ER -