From the Mayo Clinic Jacksonville, FL (J.F.M.); University of Alabama at Birmingham (D.K.A., L.A.M.); Mayo Clinic Rochester, MN (R.D.B.); Massachusetts General Hospital, Boston, MA (H.A., J.R., O.W.); University of British Columbia, Vancouver, British Columbia, Canada (O.R.B.); University of Maryland School of Medicine and Veterans Administration Medical Center, Baltimore, MD (J.W.C., P.F.M., B.D.M., A.R.S., S.J.K.); University Medical Center Utrecht, Utrecht, The Netherlands (P.I.W.d.B.); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (P.I.W.d.B.); Broad Institute of Harvard, MIT, Cambridge, MA (P.I.W.d.B.); Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D.); Johns Hopkins University, Baltimore, MD (K.F.D.); University of Texas Health Science Center at Houston (M.F.); Saint Francis Medical Center, Lynwood, CA (R.P.G.); NINDS Neurogenetics Cluster, Bethesda, MD (K.G.); IMIM-Hospital Universitari del Mar, Barcelona, Spain (J.J.C.); University of Florida, College of Pharmacy, Gainesville, FL (J.A.J.); Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Sweden (K.J., C.J.); University of Washington, Seattle, WA (C.C.L.); Washington University School of Medicine, St. Louis, MO (J.-M.L.); Lund University, Lund, Sweden (A.L.); St. George's University of London, London, United Kingdom (H.S.M.); Medical University Graz, Graz, Austria (R.S.); Brigham and Women's Hospital, Boston, MA (K.M.R.); University of Virginia, Charlottesville, VA (S.S.R., B.B.W.); Radcliffe Infirmary, Oxford, England (P.M.R.); University of Miami, Coral Gables, FL (T.R., R.L.S.); Imperial College London, London, United Kingdom (P.S.); Jagiellonian University, Krakow, Poland (A.S.); Albert Einstein College of Medicine, Bronx, NY (S.W.-S.); University of Edinburgh, Edinburgh, United Kingdom (C.S.); Universitaire Ziekenhuizen Leuven, Leuven, Belgium (V.N.S.T.); and University of Cincinnati, Cincinnati, OH (
Stroke. 2013 Oct;44(10):2694-702. doi: 10.1161/STROKEAHA.113.001857. Epub 2013 Sep 10.
Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The National Institute of Neurological Disorders and Stroke SiGN (Stroke Genetics Network) contributes substantially to meta-analyses that focus on specific subtypes of stroke.
The National Institute of Neurological Disorders and Stroke SiGN includes ischemic stroke cases from 24 genetic research centers: 13 from the United States and 11 from Europe. Investigators harmonize ischemic stroke phenotyping using the Web-based causative classification of stroke system, with data entered by trained and certified adjudicators at participating genetic research centers. Through the Center for Inherited Diseases Research, the Network plans to genotype 10,296 carefully phenotyped stroke cases using genome-wide single nucleotide polymorphism arrays and adds to these another 4253 previously genotyped cases, for a total of 14,549 cases. To maximize power for subtype analyses, the study allocates genotyping resources almost exclusively to cases. Publicly available studies provide most of the control genotypes. Center for Inherited Diseases Research-generated genotypes and corresponding phenotypes will be shared with the scientific community through the US National Center for Biotechnology Information database of Genotypes and Phenotypes, and brain MRI studies will be centrally archived.
The Stroke Genetics Network, with its emphasis on careful and standardized phenotyping of ischemic stroke and stroke subtypes, provides an unprecedented opportunity to uncover genetic determinants of ischemic stroke.
对现有全基因组数据的荟萃分析表明，有必要针对缺血性脑卒中的亚型进行基因发现研究。国家神经疾病与卒中研究所 SiGN（卒中遗传学网络）为专注于特定类型卒中的荟萃分析做出了重要贡献。
国家神经疾病与卒中研究所 SiGN 包含来自 24 个遗传研究中心的缺血性脑卒中病例：美国 13 个，欧洲 11 个。研究人员使用基于网络的卒中因果分类系统对缺血性卒中表型进行协调，数据由参与遗传研究中心的经过培训和认证的裁判输入。通过遗传性疾病研究中心，该网络计划使用全基因组单核苷酸多态性芯片对 10296 例精心表型的卒中病例进行基因分型，并增加另外 4253 例之前已基因分型的病例，总共 14549 例病例。为了最大限度地提高亚型分析的功效，该研究几乎完全将基因分型资源分配给病例。公共可用的研究提供了大部分对照基因型。遗传性疾病研究中心生成的基因型和相应的表型将通过美国国家生物技术信息中心的基因型和表型数据库与科学界共享，脑 MRI 研究将集中存档。
卒中遗传学网络专注于缺血性卒中和卒中亚型的精心和标准化表型，为发现缺血性卒中的遗传决定因素提供了前所未有的机会。
