Genetic studies on metabolic disorder-associated kidney diseases

Abstract

Diabetic kidney disease (DKD) and obesity-related kidney diseases are the representative chronic kidney diseases related to metabolic disorders. Genome-wide association studies have been extensively performed, and a substantial number of confirmed loci have been identified to be associated with many common diseases or quantitative traits, including type 2 diabetes, obesity, and chronic kidney diseases. By contrast, genome-wide association studies for DKD have identified a limited number of susceptible loci, and the robust replication of these loci in independent studies has not yet been accomplished. As of 2024, no genome-wide association study has been reported on obesity-related kidney diseases. Therefore, the genetic studies on DKD or obesity-related kidney diseases have not provided satisfiable results. However, genetic correlation studies and Mendelian randomization studies, that were performed using multitrait genome-wide association study data, suggested that DKD, obesity-related kidney diseases, and obesity share common genetic mechanisms. Because obesity or overweight is a reversible condition, the effective interventions to reduce body weights might contribute to the prevention of the development of not only obesity-related kidney diseases, but also DKD or other types of chronic kidney diseases. Further genetic studies are necessary to understand the genetic architecture of DKD and obesity-related kidney diseases and should be expanded.

Keywords: diabetic kidney disease; genomic-wide association studies; metabolic disorders; obesity.