In search of cardiovascular candidate genes: interactions between phenotypes and genotypes.

Most cardiovascular traits of interest can be defined as "complex traits," with the first step in the identification of genetic factors affecting such traits being the detection of quantitative trait loci (QTLs). Animal models have proven particularly useful in this regard. However, only very few of the QTLs identified to date have led to the identification of candidate genes. We describe an example of our own work where the combination of anatomical and a biochemical intermediate phenotypes have led to the identification of the natriuretic peptide precursor A (Nppa) gene as a candidate gene for left ventricular hypertrophy (LVH). Combined with the power of comparative genetics, these strategies will continue to improve the chances of finding candidate genes for cardiovascular traits such as susceptibility to heart diseases, hypertension, and hypertension-induced end-organ damage.