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Review
. 2023 May 30:14:1163001.
doi: 10.3389/fendo.2023.1163001. eCollection 2023.

Genetic and epigenetic background of diabetic kidney disease

Niina Sandholm  1   2   3 , Emma H Dahlström  1   2   3 , Per-Henrik Groop  1   2   3   4
Affiliations
Review

Genetic and epigenetic background of diabetic kidney disease

Niina Sandholm et al. Front Endocrinol (Lausanne). .

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.

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Conflict of interest statement

P-HG has received investigator-initiated research grants from Eli Lilly and Roche; is an advisory board member for AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Cebix, Eli Lilly, Janssen, Medscape, Merck Sharp & Dohme, Mundipharma, Nestlé, Novartis, Novo Nordisk, and Sanofi; and has received lecture fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Elo Water, Genzyme, Merck Sharp & Dohme, Medscape, Novartis, Novo Nordisk, PeerVoice, Sanofi, and Sciarc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
GWAS on DKD, albuminuria, and eGFR in diabetes. Point size indicates the number of samples. Studies with individuals with T1D are colored red, T2D with blue, and combined T1D + T2D, any type of diabetes or unspecified type of diabetes with gray. Gene names indicate loci reaching genome-wide significance (p-value < 5 × 10−8).
Figure 2
Figure 2
Chromosomal ideogram including CpGs methylation associated with kidney disease (DKD and ESKD), fibrosis, eGFR, or albuminuria in diabetes. For intergenic CpGs (*), the nearest gene is given. Hypermethylated CpGs (in kidney disease vs. controls) are denoted by a dark blue colour and hypomethylated by a light blue colour. CpGs appearing among top loci in multiple studies on kidney disease in diabetes denoted by a red color.
See this image and copyright information in PMC

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