Our hypothesis is that important genetic factors that contribute to VTE risk have not yet been identified, particularly within the African American (AA) population. We propose to utilize a novel, inexpensive optical biosensor assay for screening multiple single nucleotide polymorphisms (SNPs) or Indels (short insertions/deletions) simultaneously in samples made available through collaboration with Drs. Richard Marlar and Carolyn Welsh in order to identify such genetic factors. Both a case/control population (700 cases; 1,400 controls) and families (410) with Hereditary Thrombolic Disorder (HTD) will be used in these studies. The relative contribution of individual or multiple polymorphisms inherited simultaneously on VTE risk will be statistically assessed by our biostatistician, Dr. Hongyu Zhao. SNPs that have been reported to contribute to VTE, and SNPs that are in promoter regions or create nonconservative amino acid substitutions in genes associated with coagulation homeostasis will be analyzed. The extensive set of new genetic data will be incorporated into the VA Merit Review study of acquired and physiological VTE risk factors and collective risk parameters assessed in collaboration with Dr. Marlar and his associates. We propose to focus additional work on analysis of VTE in African American (AA) cases, both individuals from the 34 AA families from the HTD family study and AA individuals from the case/control study. These samples will be analyzed by admixture mapping to identify genomic regions containing disease related alleles that are present in the African genome and of lower abundance or absent in the European. This will be followed by analysis of VTE associated gene haplotypes in the AA VTE families and AA individuals in the case/control study. ? ?
