Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease

Author:

Smyth Laura J.ORCID,Dahlström Emma H.ORCID,Syreeni AnnaORCID,Kerr Katie,Kilner JillORCID,Doyle Ross,Brennan EoinORCID,Nair Viji,Fermin Damian,Nelson Robert G.,Looker Helen C.,Wooster ChristopherORCID,Andrews Darrell,Anderson Kerry,McKay Gareth J.,Cole Joanne B.ORCID,Salem Rany M.ORCID,Conlon Peter J.,Kretzler MatthiasORCID,Hirschhorn Joel N.,Sadlier Denise,Godson Catherine,Florez Jose C.ORCID,Forsblom CarolORCID,Maxwell Alexander P.ORCID,Groop Per-HenrikORCID,Sandholm NiinaORCID,McKnight Amy JayneORCID,

Abstract

AbstractType 1 diabetes affects over nine million individuals globally, with approximately 40% developing diabetic kidney disease. Emerging evidence suggests that epigenetic alterations, such as DNA methylation, are involved in diabetic kidney disease. Here we assess differences in blood-derived genome-wide DNA methylation associated with diabetic kidney disease in 1304 carefully characterised individuals with type 1 diabetes and known renal status from two cohorts in the United Kingdom-Republic of Ireland and Finland. In the meta-analysis, we identify 32 differentially methylated CpGs in diabetic kidney disease in type 1 diabetes, 18 of which are located within genes differentially expressed in kidneys or correlated with pathological traits in diabetic kidney disease. We show that methylation at 21 of the 32 CpGs predict the development of kidney failure, extending the knowledge and potentially identifying individuals at greater risk for diabetic kidney disease in type 1 diabetes.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

Reference75 articles.

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