Systematic Investigation of Blacks with Stroke - Genomics (SIBS-Genomics) Study

中风是全球第二大死亡原因。缺血性中风占高达90%的 在美国，中风是几个复杂和相互作用的生物过程的临床高潮，由 各种遗传和环境因素，从而使对其潜在机制的分析变得容易 挑战。中风的大量遗传风险仍未得到解释。此外，遗传变异 以前在非洲和欧洲美国人中与中风有关的疾病无法转化为临床应用 因为它们还没有经过验证和功能注释。更好地理解这些独特的因素 要形成成功的量身定做的干预措施，以减轻这一巨大负担，就必须做到这一点。 由于其较高的中风遗传率和精细绘图的分辨率，非洲大陆人口 拥有推动卒中基因组学发展的王牌，但从未被纳入卒中GWA研究。整体而言 SIBS基因组学的目标是发现、验证和鉴定相关的新的遗传变异 非洲血统的人患有缺血性中风。SIBS基因组公司将利用美国国立卫生研究院资助的几项计划 由SIBS基因组研究人员领导的美国和非洲，包括问候、符号、指南针、MEPI，蓬勃发展 (U01NS079179)，PINGS(NS094033)和NINDS资助的中风调查研究和教育 网络(SIREN U54HG007479)，这是对非洲血统人群中风的最大研究。的确，SIBS基因组学 承诺大大推进全球努力，从而发现缺血性中风的新基因位点 促进对众多缺血性卒中相应分子机制的了解 原因：a)使用具有全面协变量数据集的准确表型的受试者(特殊中风 SIREN开发了专利的表型软件)，b)使用NIH资助的最有效的新芯片 非洲血统的全基因组关联研究，c)具有显著更高的 中风的遗传性和种族倾向性；由于其低连锁，精细定位的分辨率更高 不平衡。D)以及为未来的全基因组测序和转组学分析处理样本。 SIBS基因组学的目标将在一个简洁的网络中使用新的多阶段方法来实现 全球领先的内容专家。先前报道的遗传变异的验证和功能注释 美国人将使用来自非洲大陆的数据进行测试。此外，新变种的发现将是 在非洲大陆人中寻求，在非裔美国人中得到验证(其中71%是从西非移民的)； 具有不同祖先的美国人将被纳入跨祖先荟萃分析。总体而言，关于 中风的分子机制将开启一系列新的靶向生物标志物(用于预测、诊断、预后)， 以及对中风的干预(神经保护、治疗、预防)。这项独特的跨基因组学研究将转化为 控制美国人群，特别是非洲裔美国人中风负担的有效解决方案 他们的负担仍然不成比例地高。

Stroke is the second leading cause of death globally. Ischemic stroke which accounts for up to 90% of strokes in the USA, is the clinical culmination of several complex and interacting biological processes, initiated by various genetic and environmental factors, thereby making ready analyses of its underlying mechanisms a challenge. Substantial amount of genetic risk for stroke remain unexplained. Moreover, genetic variants previously associated with stroke in African and European Americans could not be translated into clinical use because they have not been validated and functionally annotated. A better understanding of these unique factors is imperative for the formation of successful tailor-made interventions to mitigate this colossal burden. Due to its higher stroke heritability and resolution for fine mapping, the continental African population holds the aces to advancing stroke genomics but has never been included in stroke GWAS studies. The overall goal of SIBS-Genomics, is to discover, validate and functionally characterize novel genetic variants associated with ischemic stroke in people of African ancestry. SIBS Genomics will leverage several NIH-funded initiatives in the US and Africa led by SIBS Genomics investigators including REGARDS, SiGN, COMPASS, MEPI, THRIVES (U01NS079179), PINGS (NS094033) and the NINDS-funded Stroke Investigative Research and Educational Network (SIREN U54HG007479), the largest study of stroke in people of African ancestry. Indeed SIBS Genomics promises to substantially advance the global effort to discover the novel genetic loci for ischemic stroke thereby facilitating the understanding of the corresponding molecular mechanisms of ischemic stroke for numerous reasons: a) use of accurately phenotyped subjects with comprehensive covariate dataset (special stroke phenotyping software with patent developed in SIREN), b) use of a novel NIH-funded most effective chip for dense genome-wide association study in African ancestry, c) an unexplored population with substantially higher heritability and racial predilection of stroke; and higher resolution for fine-mapping due to its low linkage disequilibrium. d) and processing of samples for future whole genome sequencing and transomics analyses. The goal of SIBS Genomics will be accomplished using a novel multi-stage approach in a concise network of leading global content experts. Validation and functional annotation of genetic variants previously reported in Americans will be performed using data from continental Africans. Furthermore, discovery of novel variants will be sought in continental Africans and validated in African Americans (71% of whom migrated from West Africa); while Americans of diverse ancestries will be included in trans-ancestry meta-analyses. Overall, new clues on the molecular mechanisms of stroke will open new array of targeted biomarkers (for prediction, diagnosis, prognosis), and interventions (neuroprotective, treatment, prevention) for stroke. This unique transomics study will translate to efficient solutions for controlling the burden of stroke in American populations, especially African Americans in whom the burden remains disproportionately high.