STUDIES ON THE GENETIC PREDISPOSITION TO COMMON THROMBOTIC DISEASES

Common thrombotic diseases (i.e. myocardial infarction, MI; ischemic stroke; deep vein thrombosis, DVT) are the main cause of death and disability worldwide. These diseases are highly heritable. From a genetic standpoint common thrombotic diseases are classified as complex, because their inheritance is believed to arise from several different genetic variants, interacting among themselves and with environmental exposures. Genome-wide association studies (GWAS) have represented a major step forward in deciphering the genetics of such complex traits as cardiovascular diseases, having identified several hundred SNPs associated with common diseases. In spite of these recent advances, however, genetic variants established to influence the risk for common thrombotic diseases explain only a fraction of disease heritability. Using early-onset disease as a model, we studied the predisposition to common thrombotic diseases using different approaches for genetic and association analysis. We also conducted an exploratory study using cutting-edge next-generation sequencing technology for the identification of causal genes/variants in DVT. We confirmed associations of candidate variants with predisposition to common cardiovascular diseases and we identified several novel variants potentially associated with the development of these common, life-threatening diseases.