The genetics of blood pressure and hypertension: the role of rare variation.
The role of heredity in influencing blood pressure and risk of hypertension is well recognized. However, progress in identifying specific genetic variation that contributes to heritability is very limited. This is in spite of completion of the human genome sequence, the development of extraordinary amounts of information about genome sequence variation and the investigation of blood pressure inheritance in linkage analysis, candidate gene studies and, most recently genome-wide association studies. This paper considers the progress of this research and the obstacles that have been encountered. This work has made clear that the genetic architecture of blood pressure regulation in the population is not likely to be shaped by commonly occurring genetic variation in a discrete set of blood pressure-influencing genes. Rather heritability may be accounted for by rare variation that has its biggest impact within pedigrees rather than on the population at large. Rare variants in a wide range of genes are likely to be the focus of high blood pressure genetics for the next several years and the emerging strategies that can be applied to uncover this genetic variation and the problems that must confronted are considered.