Why Have Genetic Studies for Arterial Thrombosis Risk Factors Been So Unsuccessful?
As noted above, the identification of genetic susceptibility factors for arterial thrombosis and atherosclerosis has received enormous attention and has been the subject of extensive clinical investigation, with surprisingly disappointing results. A number of key factors may contribute to this observation. Many of the reported positive association studies are likely to represent false positives, which are to be expected, given the extremely large number of studies that have been undertaken and the anticipated publication bias toward positive studies. It is also possible that we may often be looking at the wrong gene. Workers in the cardiovascular field generally assume that genetic polymorphisms contributing to variation in gene X will lie in or around the gene X structural gene. However, it is becoming increasingly clear that genetic variation at other loci, for example in critical transcription factors that regulate the expression of gene X, could also be responsible.14 Such genes wi
