CIDR: GENOTYPING SERVICES USING GWAS ILLUMINA H3AFRICA ARRAY FOR NINDS (OWOLABI)

CIDR：使用 GWAS ILLUMINA H3AFRICA 阵列为 NINDS (OWOLABI) 提供基因分型服务

• 批准号: 10948250
• 负责人: Kimberly F Doheny
• 金额: $ 50.4万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-13 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10948250
• 关键词: CIDR; GENOTYPING; SERVICES; USING; GWAS

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 challenging. A substantial amount of genetic risk for stroke remains 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, replicate 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 the 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 several 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.

中风是全球第二大死亡原因。缺血性卒中占美国卒中的90%，是由多种复杂和相互作用的生物学过程引起的临床高潮， 各种遗传和环境因素，从而使其潜在机制的分析具有挑战性。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研究不能转化为临床应用，因为它们尚未得到验证和功能注释。更好地了解这些独特的 要成功地采取有针对性的干预措施，减轻这一巨大负担，就必须考虑各种因素。由于其较高的中风遗传率和精细定位的分辨率，非洲大陆人群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。SIBS-Genomics的总体目标是发现、复制和功能性表征与非洲血统人群缺血性卒中相关的新型遗传变异。SIBS基因组学将利用美国和非洲的几个NIH资助的计划，这些计划由SIBS基因组学研究人员领导，包括中风调查研究和 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卒中新基因位点的努力，从而促进对缺血性卒中相应分子机制的理解，原因如下：a）使用具有全面协变量数据集的准确表型受试者 （SIREN开发的专利的特殊中风表型软件），B）使用NIH资助的新型最有效芯片进行非洲血统的密集全基因组关联研究，c）未探索的人群， 显著更高的遗传率和中风的种族偏好;以及由于其低连锁不平衡而用于精细定位的更高分辨率。