Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease
Laura J. Smyth, Emma H. Dahlström, Anna Syreeni, Katie Kerr, Jill Kilner, Ross Doyle, Eoin Brennan, Viji Nair, Damian Fermin, Robert G. Nelson, Helen C. Looker, Christopher Wooster, Darrell Andrews, Kerry Anderson, Gareth J. McKay, Joanne B. Cole, Rany M. Salem, Peter J. Conlon, Matthias Kretzler, Joel N. Hirschhorn, Denise M. Sadlier, Catherine Godson, José C. Florez, Carol Forsblom, Alexander P. Maxwell, Per‐Henrik Groop, Niina Sandholm, Amy Jayne McKnight
Abstract
Type 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.