Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke.
Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke.
复制标题
DOI：
10.1212/wnl.0000000000201006
复制
发表时间：
2022-10-17
期刊：
影响因子：
9.9
通讯作者：
中科院分区：
文献类型：
--
作者：
目前缺血性中风的全基因组关联研究主要集中在迟发性疾病。作为这些研究的补充，我们试图确定常见遗传变异对早发性缺血性中风风险的影响。我们使用 48 项不同研究中获得的 16,730 例病例和 599,237 例非中风对照的个体水平数据或汇总统计数据，对 18-59 岁早发性中风 (EOS) 的全基因组关联研究进行了荟萃分析。我们进一步比较了 EOS 和晚发性卒中 (LOS) 之间相关位点的效应大小，并比较了 EOS 和 LOS 之间静脉血栓栓塞 (VTE) 的多基因风险评分 (PRS)。我们观察到 EOS 与 ABO（已知的中风基因座）中的 2 个变异存在全基因组显着关联。这些变异标记了 O1 和 A1 血型，并且与 LOS 相比，这两种变异在 EOS 中的效应大小明显更大。 EOS 中标记 O1 的 rs529565 的比值比 (OR) 为 0.88（95% 置信区间 [CI]：0.85–0.91），LOS 中的比值比 (OR) 为 0.96（95% CI：0.92–1.00），EOS 中标记 A1 的 rs635634 的比值比 (OR) 为 1.16 (1.11–1.21) LOS 为 1.05 (0.99–1.11)；交互作用的 p 值分别 = 0.001 和 0.005。使用 PRS，我们观察到，与 LOS 相比，VTE（另一种血栓前病症）更大的遗传风险与 EOS 的相关性更强（p = 0.008）。 ABO 基因座、基因预测的 A 型血型和较高的静脉血栓形成遗传倾向与 EOS 的相关性比与 LOS 的相关性更强，这支持血栓前因子在 EOS 中的更强作用。
Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18–59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85–0.91) in EOS vs 0.96 (95% CI: 0.92–1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11–1.21) for EOS vs 1.05 (0.99–1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008). The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.
DOI：
10.1016/j.jstrokecerebrovasdis.2011.10.007
发表时间：
2013-05
期刊：
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
影响因子：
--
作者：
Hamedani AG;Cole JW;Cheng Y;Sparks MJ;O'Connell JR;Stine OC;Wozniak MA;Stern BJ;Mitchell BD;Kittner SJ
通讯作者：
Kittner SJ