Genetic and epigenetic background of diabetic kidney disease

Niina Sandholm; Emma H Dahlström; Per-Henrik Groop

doi:10.3389/fendo.2023.1163001

Genetic and epigenetic background of diabetic kidney disease

Front Endocrinol (Lausanne). 2023 May 30:14:1163001. doi: 10.3389/fendo.2023.1163001. eCollection 2023.

Authors

Niina Sandholm^{1

2

3}, Emma H Dahlström^{1

2

3}, Per-Henrik Groop^{1

2

3

4}

Affiliations

¹ Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
² Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
³ Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴ Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia.

Abstract

Diabetic kidney disease (DKD) is a severe diabetic complication that affects up to half of the individuals with diabetes. Elevated blood glucose levels are a key underlying cause of DKD, but DKD is a complex multifactorial disease, which takes years to develop. Family studies have shown that inherited factors also contribute to the risk of the disease. During the last decade, genome-wide association studies (GWASs) have emerged as a powerful tool to identify genetic risk factors for DKD. In recent years, the GWASs have acquired larger number of participants, leading to increased statistical power to detect more genetic risk factors. In addition, whole-exome and whole-genome sequencing studies are emerging, aiming to identify rare genetic risk factors for DKD, as well as epigenome-wide association studies, investigating DNA methylation in relation to DKD. This article aims to review the identified genetic and epigenetic risk factors for DKD.

Keywords: EWAS; GWAS; diabetic kidney disease; epigenetics; epigenome-wide association study; exome sequencing; genome sequencing; kidney failure.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Complications* / genetics
Diabetes Mellitus* / genetics
Diabetic Nephropathies* / genetics
Epigenesis, Genetic
Genome-Wide Association Study
Humans
Risk Factors

Grants and funding

This work was supported by grants from Folkhälsan Research Foundation, Wilhelm and Else Stockmann Foundation, “Liv och Hälsa” Society, Sigrid Jusélius Foundation, Helsinki University Central Hospital Research Funds (TYH2023403), and Academy of Finland (316664).