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，中风是几个复杂的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，从而使其潜在的机制， 挑战.中风的大量遗传风险仍然无法解释。此外，遗传变异 以前与非洲和欧洲美国人中风相关的药物不能转化为临床应用 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 为成功地制定量身定制的干预措施，以减轻这一巨大负担，这是必不可少的。 由于其较高的中风遗传率和精细绘图的分辨率， 掌握着推进中风基因组学的王牌，但从未被纳入中风GWAS研究。整体 SIBS-Genomics的目标是发现，验证和功能性表征相关的新遗传变异 有非洲血统的人患缺血性中风SIBS Genomics将利用NIH资助的几项计划， 美国和非洲由SIBS Genomics研究人员领导，包括REGARDS，SiGN，COMPASS，MEPI，THRIVES （U 01 NS 079179），PINGS（NS 094033）和NINDS资助的中风调查研究和教育 网络（SIREN U 54 HG 007479），非洲血统人群中最大的中风研究。事实上，SIBS基因组学 有望大大推进全球发现缺血性中风新基因位点的努力， 促进了对缺血性中风的相应分子机制的理解， 原因：a）使用具有全面协变量数据集的准确表型受试者（特殊卒中 SIREN开发的具有专利的表型分型软件），B）使用NIH资助的新型最有效的芯片进行密集的 非洲血统的全基因组关联研究，c）具有高得多的未探索人群 中风的遗传性和种族偏好;由于其低连锁性，精细定位的分辨率更高 不平衡d）和处理用于未来全基因组测序和transomics分析的样品。 SIBS基因组学的目标将在一个简洁的网络中使用一种新颖的多阶段方法来实现 全球领先的内容专家。验证和功能注释的遗传变异先前报道的 美国人将使用来自非洲大陆的数据进行测试。此外，发现新的变体将是 在非洲大陆寻求并在非洲裔美国人中验证（其中71%来自西非）; 不同血统的美国人将被纳入跨血统荟萃分析。总的来说，新的线索 中风的分子机制将开辟新的靶向生物标志物阵列（用于预测、诊断、预后）， 和干预（神经保护、治疗、预防）。这项独特的transomics研究将转化为 控制美国人群中风负担的有效解决方案，特别是非洲裔美国人， 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.