Department of Biology; Brody School of Medicine Center for Health Disparities, East Carolina University, Greenville, NC (K.L.K.).
Aflac Cancer and Blood Disorder Center of Emory University and Children's Healthcare of Atlanta University, GA (H.I.H.).
Stroke. 2020 Aug;51(8):2454-2463. doi: 10.1161/STROKEAHA.120.029123. Epub 2020 Jul 22.
Stroke is a complex disease with multiple genetic and environmental risk factors. Blacks endure a nearly 2-fold greater risk of stroke and are 2× to 3× more likely to die from stroke than European Americans.
The COMPASS (Consortium of Minority Population Genome-Wide Association Studies of Stroke) has conducted a genome-wide association meta-analysis of stroke in >22 000 individuals of African ancestry (3734 cases, 18 317 controls) from 13 cohorts.
In meta-analyses, we identified one single nucleotide polymorphism (rs55931441) near the gene that reached genome-wide significance (=4.62×10) and an additional 29 variants with suggestive evidence of association (<1×10), representing 24 unique loci. For validation, a look-up analysis for a 100 kb region flanking the COMPASS single nucleotide polymorphism was performed in SiGN (Stroke Genetics Network) Europeans, SiGN Hispanics, and METASTROKE (Europeans). Using a stringent Bonferroni correction value of 2.08×10 (0.05/24 unique loci), we were able to validate associations at the locus in both SiGN (=8.18×10) and METASTROKE (=1.72×10) European populations. Overall, 16 of 24 loci showed evidence for validation across multiple populations. Previous studies have reported associations between variants in the gene and lipids, C-reactive protein, and risk of coronary artery disease and stroke. Suggestive associations with variants in the and genes represent potential novel ischemic stroke loci.
These findings represent the most thorough investigation of genetic determinants of stroke in individuals of African descent, to date.
中风是一种复杂的疾病，具有多种遗传和环境风险因素。黑人患中风的风险几乎高出两倍，死于中风的风险比欧洲裔美国人高出 2 到 3 倍。
COMPASS（中风少数人群全基因组关联研究联盟）对 13 个队列中超过 22000 名非洲裔个体（3734 例病例，18317 例对照）进行了中风全基因组关联元分析。
在元分析中，我们在基因附近鉴定出一个单核苷酸多态性（rs55931441），达到了全基因组显著水平（=4.62×10），并发现了另外 29 个具有关联提示证据的变体（<1×10），代表 24 个独特的基因座。为了验证，在 SiGN（中风遗传学网络）欧洲人、SiGN 西班牙裔和 METASTROKE（欧洲人）中进行了 COMPASS 单核苷酸多态性侧翼 100kb 区域的查找分析。使用严格的 Bonferroni 校正值 2.08×10（0.05/24 个独特基因座），我们能够在 SiGN（=8.18×10）和 METASTROKE（=1.72×10）欧洲人群中验证 基因座的关联。总体而言，24 个基因座中有 16 个在多个人群中显示出验证的证据。先前的研究已经报道了基因中的变体与脂质、C 反应蛋白和冠心病和中风风险之间的关联。基因和 基因中的变体与提示性关联代表潜在的新的缺血性中风基因座。
这些发现代表了迄今为止对非洲裔个体中风遗传决定因素最彻底的调查。
