Biobehavioral Genetics of CVD Risk

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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)