Genetic Risk to Stroke in Smokers and Nonsmokers in Two Ethnic Groups

描述(申请人提供)：在美国，中风是心血管相关死亡和发病率的主要原因，而且这种疾病的重大遗传因素被广泛接受。我们建议识别其影响在吸烟存在时发生改变的基因。我们将重点关注年轻发病的中风(即56岁之前发病的中风)，遗传因素和吸烟相关风险可能在其中发挥更大的作用。将使用两个阶段的方法，首先对过去20年来马里兰大学基于人群的病例对照研究中积累的929例年轻中风病例和936例对照进行全基因组关联研究。然后，将在阶段2复制集中对关联最强的1%的SNPs进行基因分型，该复制集将利用来自国际中风遗传学联合会的9个参与站点贡献的1,853例年轻患者和1,199名对照。除了关注年轻发病的中风，我们的研究还包括女性和男性，以及非裔美国人和白人。这项拟议的研究将补充对老年中风患者的研究，并将成为了解中风风险的遗传基础以及吸烟如何改变这种风险的持续资源。摘要：中风是一种急性脑血管疾病，是导致死亡的第三大原因，也是导致重大残疾的首要原因。我们研究的长期目标是确定卒中易感性的遗传和环境基础，以便开发更有效的预防和治疗策略。

DESCRIPTION (provided by applicant): Stroke is a leading cause of cardiovascular-related mortality and morbidity in the United States, and a substantial genetic contribution to this disease is widely accepted. We propose to identify genes whose effects are modified in the presence of smoking. We will focus on young-onset stroke (i.e., stroke onset before age 56), in whom genetic factors and smoking-associated risk may play an even larger role. A two-stage approach will be used, beginning with a genome-wide association study in 929 young-onset stroke cases and 936 controls accrued from population-based case-control studies at the University of Maryland over the past 20 years. The 1% most strongly associated SNPs will then be genotyped in the Stage 2 replication set, which will utilize 1,853 young-onset cases and 1,199 controls contributed by 9 participating sites from the International Stroke Genetics Consortium. In addition to its focus on young-onset stroke, our study has the strength of including both women and men, and African-Americans and Whites. The proposed study will complement studies of older stroke patients and will be a continuing resource for understanding the genetic basis of stroke risk and how this risk is modified by smoking. Lay summary: Stroke, defined as acute vascular disease of the brain, is the third leading cause of death and the leading cause of major disability. The long-range goal of our research is to characterize the genetic and environmental basis for stroke susceptibility in order to develop more effective prevention and treatment strategies.