Biobehavioral Genetics of CVD Risk

心脏病仍然是美国死亡的主要原因，也是健康教育的一个重要重点领域。 “人民2020”倡议。本申请的长期目标是确定 多种生物、心理和生活方式相关的心血管疾病（CVD）风险因素， 个体及其在群体中的协变。可能与中枢神经系统相关的遗传变异 生理机制，如肾上腺素能和炎症途径，可能部分介导 CVD风险表型的聚集。拟议的项目旨在全面测试几个基因， 5-羟色胺途径（SLC 6A 4、MAOA、TPH 1、TPH 2、HTR 1A、HTR 1B、HTR 2A、HTR 2C）和 用于与多种炎症相关的炎症标志物（ILIp、IL 6、CRP、TNFa、SELE、SELP、ICAM 1、VCAM 1） CVD风险域。具体而言，本项目旨在：1）研究多态性之间的关联 （单独和作为单倍型）在上述基因和心理，生物和 1173名欧洲裔美国人（EA）和861名非洲裔美国人样本中的生活方式相关CVD风险因素 (AA)个体登记在HeartSCORE项目，使用多变量和单变量模型; 2） 在使用基因组控制方法控制群体分层后确认基因型关联， AA中的EA和基于个体混合物的方法。3)为了检验所研究的多态性是否 基于CVD危险因素的协变，使用结构方程模型。（4）确定是否 研究的多态性预测了EA和AA生物危险因素的进展， 统计和混合模型。ROO阶段的工作将遵循 目前的K99阶段，重点是SLC 6A 4、HTR 2A和CRP基因以及目标1-3。一旦确定，A 心血管疾病风险的多个维度下的常见遗传变异可能提供途径， 开发新的和新颖的疗法。同时调查两个不同的人群， 预计将提供深入了解潜在的原因undedying种族差异心血管疾病的风险和患病率。

Heart diseases remain the leading cause of death in the US and is an important focus area for the Healthy People 2020 initiative. The long term goal ofthis application is to determine the causes of aggregation of multiple biological, psychological and life-style related cardiovascular disease (CVD) risk factors in individuals and their covariation in populations. It is possible that genetic variation associated with central physiological mechanisms, lil<e the serotonergic and inflammatory pathways, may partially mediate the aggregation of CVD risk phenotypes. The proposed project aims to comprehensively test several genes in the serotonin pathway (SLC6A4, MAOA, TPH1, TPH2, HTR1A, HTR1B, HTR2A, HTR2C) and genes of inflammatory markers (ILIp, IL6, CRP, TNFa, SELE, SELP, ICAM 1, VCAM 1) for association with multiple CVD risk domains. Specifically, this project aims to: 1)To examine the association between polymorphisms (individually and as haplotypes) in the above mentioned genes and psychological, biological and lifestyle-related CVD risk factors in samples of 1173 European American (EA) and 861 African American (AA) individuals enrolled in the HeartSCORE project, using multivariate and univariate models; 2) To confirm genotype associations after controlling for population stratification using genomic control methods in EA and individual admixture based methods in AA. 3) To examine whether investigated polymorphisms underlie the covariation of CVD risk factors, using structural equation modeling. 4)To determine whether studied polymorphisms predict progression of biological risk factors in EA and AA using multivariate statistics and mixed models. The work during the ROO phase will follow from the work done during the current K99 phase which focused on SLC6A4, HTR2A and CRP genes and on aims 1-3. Once identified, a common genetic variant underlying multiple dimensions of CVD risk may provide avenues towards development of new and novel therapeutics. Simultaneous investigation in two different populations is also expected to provide insights into potential causes undedying racial disparities in CVD risk and prevalence.