Cellular and Molecular Life Sciences

, Volume 69, Issue 22, pp 3751–3763

Genetic susceptibility to hypertensive renal disease



Hypertensive renal disease occurs at increased frequency among the relatives of patients with this disease compared to individuals who lack a family history of disease. This suggests a heritable risk in which genetic variation may play a role. These observations have motivated a search for genetic variation contributing to this risk in both experimental animal models and in human populations. Studies of animal models indicate the capacity of natural genetic variants to contribute to disease risk and have produced a few insights into the disease mechanism. In its current phase, human population genetic studies have sought to associate genetic variation with disease in large populations by testing genotypes at a large number of common genetic variations in the genome, expecting that common genetic variants contributing to renal disease risk will be identified. These genome-wide association studies (GWAS) have been productive and are a clear technical success; they have also identified narrowly defined loci and genes containing variation contributing to disease risk. Further extension and refinement of these GWAS are likely to extend this success. However, it is also clear that few additional variants with substantial effects accounting for the greatest part of heritability will be uncovered by GWAS. This raises an interesting biological question regarding where the remaining unaccounted heritable risk may be located. At present, much consideration is being given to this question and to the challenge of testing hypotheses that lead from the various alternative mechanisms under consideration. One result of the progress of GWAS is likely to be a renewed interest in mechanisms by which related individuals can share and transmit traits independently of Mendelian inheritance. This paper reviews the current progress in this area and considers other mechanisms by which familial aggregation of risk for renal disease may arise.


Epigenetics Epistasis Genome mapping Heritability Linkage analysis Transgenerational inheritance 



African American


Estimated glomerular filtration rate


End-stage renal disease


Genome-wide association study


Spontaneously hypertensive rat


Single-nucleotide polymorphism

Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  1. 1.Institute of Molecular MedicineUniversity of Texas HSC at HoustonHoustonUSA

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