Genome-wide association studies of chronic kidney disease: what have we learned?

Abstract

Genome-wide association studies (GWASs) have led to the identification of genes underlying renal traits such as glomerular filtration rate, and improved our understanding of the pathogenesis of chronic kidney disease. In this Review, O'Seaghdha and Fox discuss how GWASs have revolutionized genetic research, using several large-scale studies as examples, and explain how the knowledge derived from these studies can be applied to improve our understanding of the pathogenesis of kidney disease and to identify novel therapeutic targets. The past 3 years have witnessed a dramatic expansion in our knowledge of the genetic determinants of estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD). However, heritability estimates of eGFR indicate that we have only identified a small proportion of the total heritable contribution to the phenotypic variation. The majority of associations reported from genome-wide association studies identify genomic regions of interest and further work will be required to identify the causal variants responsible for a specific phenotype. Progress in this area is likely to stem from the identification of novel risk genotypes, which will offer insight into the pathogenesis of disease and potential novel therapeutic targets. Follow-up studies stimulated by findings from genome-wide association studies of kidney disease are already yielding promising results, such as the identification of an association between urinary uromodulin levels and incident CKD. Although this work is at an early stage, prospects for progress in our understanding of CKD and its treatment look more promising now than at any point in the past.