Robarts Research Institute and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
Stroke. 2010 Apr;41(4):825-32. doi: 10.1161/STROKEAHA.109.570523. Epub 2010 Feb 18.
As a result of technological advances, the genomic analysis of stroke has shifted from candidate gene association studies to genome-wide association studies (GWAS). Agnostic GWAS evaluate up to 90% of common genetic variation in a single experiment, creating an improved framework for identifying novel genetic leads for biochemical and cellular mechanisms underlying stroke. Given the ubiquity of the GWAS approach, it has become essential for stroke researchers and clinicians to be able to interpret GWAS results. Thus, we review the basic elements of design, methods, presentation, and interpretation of GWAS in the context of stroke research. In 8 recent stroke GWAS reports, no single locus has been identified in 2 GWAS at a genome-wide level of significance. Additionally, no significant association signal between stroke and a locus with previous evidence from candidate gene studies of stroke has been identified yet. Some caveats of the approach and future directions for stroke genomics are discussed, including the use of intermediate phenotypes, Mendelian randomization, phenomics, and deep resequencing. Intelligent, appropriately powered, multidisciplinary studies incorporating knowledge from clinical medicine, epidemiology, genetics, and molecular biology will be required to fully characterize the genomic contributors to stroke.
由于技术的进步，中风的基因组分析已经从候选基因关联研究转向全基因组关联研究（GWAS）。未知的 GWAS 可以在单次实验中评估多达 90%的常见遗传变异，为识别生化和细胞机制中风的新遗传线索创造了一个改进的框架。鉴于 GWAS 方法的普遍性，中风研究人员和临床医生必须能够解释 GWAS 结果。因此，我们在中风研究的背景下，回顾了 GWAS 的基本设计、方法、呈现和解释要素。在最近的 8 项中风 GWAS 报告中，没有一个单一的基因座在全基因组水平上被确定为与中风有关。此外，尚未确定中风与候选基因研究中风有先前证据的基因座之间存在显著关联信号。讨论了该方法的一些注意事项和中风基因组学的未来方向，包括使用中间表型、孟德尔随机化、表型组学和深度重测序。需要智能、适当加权、多学科的研究，将临床医学、流行病学、遗传学和分子生物学的知识结合起来，才能充分描述中风的基因组贡献者。
