Genetic architecture of complex traits predisposing to nephropathy: hypertension

Blood pressure and hypertension have significant genetic underpinnings that may be age-dependent. The age-dependency, significant contributions from environmental factors such as diet and exercise, and inherent moment-to-moment variability complicate the identification of the genes contributing to the development of hypertension. Although genetic abnormalities may have moderate effects, the physiologic pathways involving these genes have redundant compensating mechanisms to bring the system back into equilibrium. This has the effect of reducing or completely masking the initial genetic defects, one of the hypothesized reasons for the small genetic effects found by the recent genome-wide association studies. This review article discusses the concept of initiators versus compensators in the context of finding genes related to hypertension development. A brief review is provided of some key genes found to be associated with hypertension, including the genes identified from the nine genome-wide association studies published to date.