GENETIC EPIDEMIOLOGICAL INVESTIGATIONS OF CORONARY ARTERY DISEASE AND ITS RISK FACTORS

Abstract

Many single nucleotide polymorphisms (SNPs) have been reported to be associated with CAD. Rs6903956 on androgen-dependent tissue factor pathway inhibitor (TFPI) regulating protein (ADTRP) gene was identified to associate with CAD in Chinese. The association has been replicated in the Singaporean Chinese and we investigated whether the genetic variant was associated with coagulation factors.

The identification of SNPs associated with CAD and its related traits provides a chance to evaluate whether the inclusion of genetic variants into phenotypic based risk prediction models could improve prediction accuracy. We construct Genetic Risk Score (GRS) for augmenting the Adult Treatment Panel III (ATPIII) model. C-statistics and net reclassification improvement (NRI) index were used to evaluate the model performance.

Gene-gene and gene-environment interactions play a role in determining the outcome of CAD and its risk factors. The last component of the dissertation included interaction study for BMI and lipids.