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[PMID]: | 28954878 |
[Au] Autor: | 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; Stroke Genetics Network (SiGN), METASTROKE Collaboration, and International Stroke Genetics Consortium (ISGC) |
[Ad] Endereço: | From the Centre for Clinical Brain Sciences (K.R., C.L.M.S.), College of Medicine and Veterinary Medicine (V.S., H.M.), and Institute for Genetics and Molecular Medicine (C.L.M.S.), University of Edinburgh, UK; Institute for Stroke and Dementia Research (R.M., M.D.), Klinikum der Universität München |
[Ti] Título: | is associated with lacunar ischemic stroke and deep ICH: Meta-analyses among 21,500 cases and 40,600 controls. |
[So] Source: | Neurology;89(17):1829-1839, 2017 Oct 24. | [Is] ISSN: | 1526-632X |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | 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 ( , , , , , and ) 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 was associated (significance threshold < 3.5 × 10 ) with both lacunar IS (lead SNP rs9515201: odds ratio [OR] 1.17, 95% confidence interval [CI] 1.11-1.24, = 6.62 × 10 ) and deep ICH (lead SNP rs4771674: OR 1.28, 95% CI 1.13-1.44, = 5.76 × 10 ). A SNP in was associated (significance threshold < 5.5 × 10 ) with lacunar IS (rs79043147: OR 1.23, 95% CI 1.10-1.37, = 1.90 × 10 ) and less robustly with deep ICH. There was no clear evidence for association of common variants in either or 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. |
[Mh] Termos MeSH primário: |
Hemorragia Cerebral/genética Colágeno Tipo IV/genética Polimorfismo de Nucleotídeo Único/genética Acidente Vascular Cerebral Lacunar/genética
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[Mh] Termos MeSH secundário: |
Hemorragia Cerebral/epidemiologia Europa (Continente)/epidemiologia Estudos de Associação Genética Seres Humanos Acidente Vascular Cerebral Lacunar/epidemiologia
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; META-ANALYSIS |
[Nm] Nome de substância:
| 0 (COL4A2 protein, human); 0 (Collagen Type IV) |
[Em] Mês de entrada: | 1711 |
[Cu] Atualização por classe: | 171105 |
[Lr] Data última revisão:
| 171105 |
[Sb] Subgrupo de revista: | AIM; IM |
[Da] Data de entrada para processamento: | 170929 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1212/WNL.0000000000004560 |
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