多队列分析揭示克隆性造血的遗传易感性是中风的特定突变风险因素。
Multi-Cohort Analysis Reveals Genetic Predispositions to Clonal Hematopoiesis as Mutation-Specific Risk Factors for Stroke.
作者信息
Lin Shuyang, Li Yang E, Wang Yan
机构信息
Department of Hematology Washington University School of Medicine in St Louis St. Louis MO 63110 USA.
Department of Genetics Washington University School of Medicine in St Louis St. Louis MO 63110 USA.
出版信息
Adv Genet (Hoboken). 2025 Feb 8;6(1):2400047. doi: 10.1002/ggn2.202400047. eCollection 2025 Mar.
Recent observational studies have found an association between Clonal Hematopoesis (CH) and strokes but with incomplete results. This study aims to comprehensively characterize mutation-specific effects of CH on ischemic and hemorrhagic stroke subtypes and 90-day functional outcomes through publicly available genome-wide association study (GWAS) cohorts and Mendelian Randomization. TET2 is associated with an increased risk of overall stroke (OR = 1.06, = 0.02), ischemic stroke (OR = 1.05, = 0.03), transient ischemic attack (OR = 1.07, = 0.01) and small vessel stroke (OR = 1.29, = 0.01), as well as adverse 90-day modified Rankin scale (mRS ≥ 3) before (OR = 1.34, = 0.005) and after adjusted for age, sex, and stroke severity (OR = 1.30, = 0.02). While the presence of any CH mutation is associated with intracerebral hemorrhage (ICH) (OR = 1.21, = 0.02), specific mutations, SRSF2 and ASXL1 are protective against ICH (OR = 0.9, = 0.04) and nontraumatic subarachnoid hemorrhage (OR = 0.92, = 0.03), respectively. In conclusion, the study provided genetic evidence that TET2 is strongly associated with an increased risk of ischemic stroke and poor functional recovery. Future studies clarifying the relationship between CH and hemorrhagic stroke subtypes are needed.
近期的观察性研究发现克隆性造血(CH)与中风之间存在关联,但结果并不完整。本研究旨在通过公开可用的全基因组关联研究(GWAS)队列和孟德尔随机化,全面描述CH对缺血性和出血性中风亚型以及90天功能结局的突变特异性影响。TET2与总体中风风险增加相关(比值比[OR]=1.06,P=0.02)、缺血性中风(OR=1.05,P=0.03)、短暂性脑缺血发作(OR=1.07,P=0.01)和小血管中风(OR=1.29,P=0.01),以及在调整年龄、性别和中风严重程度之前(OR=1.34,P=0.005)和之后(OR=1.30,P=0.02)的不良90天改良Rankin量表(mRS≥3)相关。虽然任何CH突变的存在都与脑出血(ICH)相关(OR=1.21,P=0.02),但特定突变SRSF2和ASXL1分别对ICH(OR=0.9,P=0.04)和非创伤性蛛网膜下腔出血(OR=0.92,P=0.03)具有保护作用。总之,该研究提供了遗传证据,表明TET2与缺血性中风风险增加和功能恢复不良密切相关。未来需要进一步研究以阐明CH与出血性中风亚型之间的关系。