Abstract
The discovery of genetic variation associated with pediatric kidney disease has shed light on the biology underlying these conditions and, in some cases, has improved our clinical management of patients. We are challenged to continue the momentum of the genomic era in pediatric nephrology by identifying novel disease-associated genetic variation and translating these discoveries into clinical applications. This article reviews the diverse forms of genetic architecture that have been found to be associated with kidney diseases and traits. These include rare, fully penetrant variants responsible for Mendelian forms of disease, copy number variants, and more common variants associated with increased risk of disease. These discoveries have provided us with a greater understanding of the molecular mechanisms underlying these conditions and highlighted key pathways for potential intervention. In a number of areas, the identification of rare, fully penetrant variants is immediately clinically relevant, whether in regard to diagnostic testing, prediction of outcomes, or choice of therapies and interventions. This article discusses limitations in the deterministic view of rare, putatively causal mutations, a challenge increasing in importance as sequencing expands to many more genes and patients. This article also focusses on common genetic variants, using those found to be associated with focal segmental glomerulosclerosis in African-Americans, IgA nephropathy, chronic kidney disease (CKD), and estimated glomerular filtration rate (eGFR) as examples. Identifying common genetic variants associated with disease will complement other areas of genomic inquiry, lead to a greater biological understanding of disease, and will benefit pediatric nephrology patients.
Keywords genetics - risk variant - genome-wide association - nephrotic syndrome
