Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; German Center for Neurodegenerative Diseases, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Department of Genetics, Centre for Molecular Medicine, University Medical Centre Utrecht, Utrecht, Netherlands; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Oxford University, Oxford, UK; Program in Medical Population and Genetics, Broad Institute, Cambridge, MA, USA.
Lancet Neurol. 2019 Jun;18(6):587-599. doi: 10.1016/S1474-4422(19)30043-2. Epub 2019 Apr 8.
Stroke, a leading cause of long-term disability and death worldwide, has a heritable component. Recent gene discovery efforts have expanded the number of known single-gene disorders associated with stroke and have linked common variants at approximately 35 genetic loci to stroke risk. These discoveries have highlighted novel mechanisms and pathways implicated in stroke related to large artery atherosclerosis, cardioembolism, and small vessel disease, and defined shared genetic influences with related vascular traits. Genetics has also successfully established causal relationships with risk factors and holds promise for prioritising targets for exploration in clinical trials. Genome-wide polygenic scores enable the identification of high-risk individuals before the emergence of vascular risk factors. Challenges ahead include a better understanding of rare variants and ancestral differences for integration of genetics into precision medicine, integration with other omics data, uncovering the genetic factors that govern stroke recurrence and stroke outcome, and the conversion of genetic discoveries to novel therapies.
中风是全球导致长期残疾和死亡的主要原因，具有遗传成分。最近的基因发现工作增加了已知与中风相关的单基因疾病的数量，并将大约 35 个遗传基因座的常见变异与中风风险联系起来。这些发现突出了与大动脉粥样硬化、心源性栓塞和小血管疾病相关的中风的新机制和途径，并确定了与相关血管特征的共同遗传影响。遗传学还成功地与危险因素建立了因果关系，并为临床试验中探索目标的优先级提供了希望。全基因组多基因评分可在血管危险因素出现之前识别出高危个体。未来的挑战包括更好地了解罕见变异和祖先差异，以将遗传学纳入精准医学，与其他组学数据整合，揭示控制中风复发和中风结果的遗传因素，以及将遗传发现转化为新疗法。
