基于家系队列的缺血性脑卒中基因-环境交互作用研究

Stroke is the first cause of death and adult disability in China. Ischemic stroke, the predominant subtype of stroke, is most seriously harmful to our health. Genetic and environmental factors, as well as gene-environment interaction are thought to contribute to the etiology of ischemic stroke. Studying the gene-environment interaction effects could provide new insights into the biology of ischemic stroke, and help to identify high risk groups. However, scientific evidence concerning the gene-environment interaction effects on ischemic stroke in China is limited. In this study, we aime to conduct a family based cohort study with periodically follow-up on the basis of 1072 families with ischemic stroke. We will use a standard questionnaire to collect the demographic information, medical history and behavioral risk factors for all the subjects on-site. Sample specimens will be collected from all the participants and further performed with genetic lab analysis. We will examine the associations between genetic and environmental factors and ischemic stroke and its two main subtypes, large-artery atherosclerosis and small-artery occlusion lacunar stroke. Comprehensive statistical methods, including FBAT, PGMDR and sparse-net model, will be used to investigate the gene-gene and gene-environment (e.g., smoking, alcohol drinking, physical activity, and dietary habits) interaction effects. The susceptible genetic markers are selected from the GWAS study results, candidate genes, as well as the results of next-generation sequencing-based studies. This study will allow us to comprehensively study the effects of genetic and environmental factors on ischemic stroke, and provide solid evidence for the prevention strategy of targeted medicine.

脑卒中是我国居民首位致死致残病因，缺血性脑卒中作为脑卒中的主要类型，严重危害人群健康。缺血性脑卒中受遗传因素、环境因素及其交互作用共同影响。通过基因-环境交互作用的研究可为疾病的生物学机制研究提供线索，有助于筛选高危人群。然而，基因-环境交互作用对缺血性脑卒中影响的相关研究在我国较为局限。本研究拟在已募集的1072个缺血性脑卒中家系的基础上开展随访，采用现场采集的流行病学资料、体格检查资料、血生化检测和基因多态性检测数据，探讨既往研究发现的易感基因位点对缺血性脑卒中及其大动脉粥样硬化型和小动脉闭塞型发病风险的影响；利用基于家系的关联分析、广义多因子降维法、稀疏网络等统计学方法，探讨上述易感基因之间以及易感基因与吸烟、饮酒、体育锻炼、膳食习惯等环境因素交互作用的规律和特点。通过对遗传因素和环境因素的综合研究，为筛选和识别缺血性脑卒中高危人群，开展疾病的针对性防治提供科学依据。

缺血性脑卒中受遗传因素、环境因素及其交互作用共同影响。通过基因-环境交互作用的研究可为疾病的生物学机制研究提供线索，有助于筛选高危人群。然而，基因-环境交互作用对缺血性脑卒中影响的相关研究在我国较为局限。本研究在已募集的1072个缺血性脑卒中家系的基础上开展随访，对社区人群的常见慢性非传染性疾病及其常见危险因素的疾病负担及其危险因素进行了调查，广泛探索了环境污染物及其他传统行为危险因素与疾病的关系。在此基础上，基于脑卒中家系、糖尿病家系样本重点验证既往报告的遗传易感基因在中国人群中与疾病的关联，并深入探索遗传易感基因与环境因素的交互作用，同时基于多种疾病和危险因素表型，探索遗传易感基因与不同表型及危险因素的遗传多效性。通过对遗传因素和环境因素的综合研究，为筛选和识别缺血性脑卒中高危人群，开展疾病的针对性防治提供科学依据。