Genetic Variation in Coagulation Factors and Risk of Haemorrhage
Ms Erlinda Dedgjonaj
Institution or company
Imperial College London
Genomics and Rare Diseases, Haematology
The function of the coagulation system is to ameliorate blood loss (haemorrhage) by clotting when the integrity of a blood vessel wall has been breached. The formation of a blood clot depends on a cascade of interactions between numerous proteins in the blood to generate fibrin which stabilises the primary platelet plug. The concentrations of these proteins vary considerably between individuals and it has been hypothesised that the concentration of certain coagulation factors in the blood may be a significant determinant of the risk of bleeding or haemorrhage, including the risk of major haemorrhage during surgery and after trauma. Recent advances in molecular measuring technology have allowed the systematic measurement of concentrations of selected proteins in blood plasma, in thousand of participants in epidemiological cohorts. Genome-wide association studies have identified hundreds of alleles associated with concretions of proteins, many of which are coagulation factors (e.g. Sun et al 2018). We will use genetic data from the INTERVAL cohort to build models to predict variation in coagulation factor levels. We will apply these models to the NIHR rare disease sequencing cohort and determine whether the genetically predicted coagulation factor levels are are associated with bleeding phenotypes.