Biobehavioral Genetics of CVD Risk

描述(由申请人提供)： 这个K99ROO应用程序描述了应聘者将进行的培训和研究。在K99阶段的头两年，申请人将继续她的博士后培训，学习统计学和心理学的课程，并完成一个有指导的研究项目。在Roo阶段的3年中，申请者将过渡到一个独立的终身教职研究职位，并从K99阶段继续研究。该项目为期五年的研究项目集中于多种生物、心理和生活方式相关的心血管危险因素在个体中聚集的原因及其在人群中的协变性。与5-羟色胺和炎症通路等中枢生理机制相关的遗传变异可能部分介导了CVD危险表型的聚集。这项拟议的研究项目旨在全面测试5-羟色胺途径基因(SLC6A4、MAOA、TPH1、TPH2、HTR1A、HTR1B、HTR2A、HTR2C)和炎症标志基因(IL1B、IL6、TNFa、CRP、SELEE、SELF、ICAM1、VCAM1)与多个CVD风险域的关联。本项目的具体目的是：1)使用多变量和单变量模型，在1173名欧洲裔美国人(EA)和861名非洲裔美国人(AA)样本中，检验上述基因的多态(个体和单倍型)与心理、生物和生活方式相关的心血管疾病危险因素之间的关联；2)使用EA中的基因组对照方法和AA中基于个体混合的方法，在控制人群分层后，确认基因型之间的关联。3)用结构方程模型检验所调查的基因多态性是否构成心血管疾病危险因素的协变。4)用多元统计和混合模型确定所研究的多态性是否可以预测EA和AA的生物学危险因素的进展。在K99阶段，申请者将通过专注于SLC6A4、HTR2A和CRP基因来解决这些目标，同时获得完成K99和RoO项目所需的分析方法和行为科学方面的培训。Roo阶段将包括检查所有基因，以全面评估途径 (摘要结束)

DESCRIPTION (provided by applicant): This K99ROO application describes the training and research that will be carried out by the candidate. During the first 2 years on the K99 phase, the applicant will continue her postdoctoral training by taking courses in statistics and psychology and completing a guided research project. During the 3 years on ROO phase, the applicant will transition into an independent, tenure-track research position and continue the research from the K99 phase. The research project for the five years on this project focuses on the causes of aggregation of multiple biological, psychological and lifestyle related cardiovascular risk factors in individuals and their covariation in populations. It is possible that genetic variation associated with central physiological mechanisms like the serotonin and inflammation pathways may partially mediate aggregation of CVD risk phenotypes. The proposed research project aims to comprehensively test genes in the serotonin pathway (SLC6A4, MAOA, TPH1, TPH2, HTR1A, HTR1B, HTR2A, HTR2C) and inflammatory marker genes (IL1B, IL6,TNFa, CRP, SELE, SELF, ICAM1, VCAM1) for association with multiple CVD risk domains. Specifically this project aims: 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. In the K99 phase the applicant will address these aims by focusing on SLC6A4, HTR2A and CRP genes, while acquiring the training in analytical methods and behavioral sciences that will be needed to complete the K99 and ROO projects. The ROO phase will involve examining all genes for a comprehensive evaluation of the pathways (End of Abstract)