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

描述（由申请人提供）：在美国，卒中是心血管相关死亡率和发病率的主要原因，并且广泛认为该疾病的实质性遗传贡献。我们建议识别在吸烟的情况下影响被改变的基因。我们将重点关注急性发作性卒中（即，56岁之前中风发作），遗传因素和吸烟相关风险可能发挥更大的作用。将采用两阶段方法，首先对马里兰州大学过去20年来基于人群的病例对照研究中积累的929例初发性卒中病例和936例对照进行全基因组关联研究。然后在第2阶段复制集中对1%最强相关的SNP进行基因分型，该复制集将利用来自国际卒中遗传学联盟的9个参与研究中心提供的1，853例新发病例和1，199例对照。除了关注非典型性卒中外，我们的研究还包括女性和男性，以及非洲裔美国人和白人。这项拟议的研究将补充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。 简单总结：中风被定义为急性脑部血管疾病，是第三大死亡原因和主要残疾原因。我们研究的长期目标是描述中风易感性的遗传和环境基础，以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.