Mendelian and trans-generational inheritance in hypertensive renal disease.

Familial risk in hypertensive renal disease has stimulated a search for genetic variation contributing to this risk. The current phase of population genetic studies has 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. It is also clear that narrowly defined loci and genes containing variation contributing to disease risk have been identified. Further extension and refinement of these GWAS are likely to extend this success. However, it is also clear that few if any 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 heritable risk may be located. 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 current progress in this area and considers other mechanisms by which familial aggregation of risk for renal disease may arise.