Genetic and epigenetic risk factors for diabetic kidney disease

Diabetes is increasing at daunting rates worldwide, and approximately 40% of affected individuals will develop kidney complications. Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, and there are significant healthcare costs providing appropriate renal replacement therapies to affected individuals. For several decades, investigators have sought to discover inherited risk factors and biomarkers for DKD. In recent years, advances in high-throughput laboratory techniques and computational analyses, coupled with the establishment of multicenter consortia, have helped to identify genetic loci that are replicated across multiple populations. Several genome-wide association studies (GWAS) have been conducted for DKD with further meta-analysis of GWAS and comprehensive "single gene" meta-analyses now published. Despite these efforts, much of the inherited predisposition to DKD remains unexplained. Meta-analyses and integrated-omics pathway studies are being used to help elucidate underlying genetic risks. Epigenetic phenomena are increasingly recognized as important drivers of disease risk, and several epigenome-wide association studies have now been completed. This review describes key findings and ongoing genetic and epigenetic initiatives for DKD.