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 Sadlier; Catherine Godson; Jose C. Florez; GENIE Consortium; Carol Forsblom; Alexander P. Maxwell; Per Henrik Groop; Niina Sandholm; Amy Jayne McKnight

doi:10.1038/s41467-022-34963-6

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. HirschhornDenise Sadlier, Catherine Godson, Jose C. Florez, GENIE Consortium, Carol Forsblom, Alexander P. Maxwell, Per Henrik Groop, Niina Sandholm, Amy Jayne McKnight^*

^*Corresponding author for this work

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	7891
Number of pages	16
Journal	Nature Communications
Volume	13
DOIs	https://doi.org/10.1038/s41467-022-34963-6
Publication status	Published - 22 Dec 2022

Keywords

Biomarkers
CpG Islands
DNA
DNA Methylation - genetics
Diabetes Mellitus, Type 1 - complications - genetics
Diabetic Nephropathies - genetics
Epigenesis, Genetic
Epigenome
Genome-Wide Association Study
Humans

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10.1038/s41467-022-34963-6Licence: CC BY

Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease
Copyright 2022 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 2.05 MBLicence: CC BY

1 Finished
2 Active

R4015CPH: Social Circumstances and Epigenomics Promoting Health in Three Countries
McKnight, A. J. (PI), Cruise, S. (CoI), Kee, F. (CoI) & McGuinness, B. (CoI)
06/11/2020 → …
Project: Research
R3789CPH: Discovery of an integrated risk profile for chronic kidney disease and development of a clinical biomarker panel for personalising medicine (Stratified medicine for chronic kidney disease)
McKnight, A. J. (PI) & Maxwell, P. (CoI)
15/06/2016 → …
Project: Research
R4744CPH: Integrative genomic, epigenetic and functional studies in diabetic kidney disease
Maxwell, P. (PI), McKay, G. (CoI) & McKnight, A. J. (CoI)
27/01/2016 → 31/03/2023
Project: Research

Cite this

Smyth, L. J., Dahlström, E. H., Syreeni, A., Kerr, K., Kilner, J., Doyle, R., Brennan, E., Nair, V., Fermin, D., Nelson, R. G., Looker, H. C., Wooster, C., Andrews, D., Anderson, K., McKay, G. J., Cole, J. B., Salem, R. M., Conlon, P. J., Kretzler, M., ... McKnight, A. J. (2022). Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease. Nature Communications, 13, Article 7891. https://doi.org/10.1038/s41467-022-34963-6

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title = "Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease",

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.",

keywords = "Biomarkers, CpG Islands, DNA, DNA Methylation - genetics, Diabetes Mellitus, Type 1 - complications - genetics, Diabetic Nephropathies - genetics, Epigenesis, Genetic, Epigenome, Genome-Wide Association Study, Humans",

author = "Smyth, {Laura J.} and Dahlstr{\"o}m, {Emma H.} and Anna Syreeni and Katie Kerr and Jill Kilner and Ross Doyle and Eoin Brennan and Viji Nair and Damian Fermin and Nelson, {Robert G.} and Looker, {Helen C.} and Christopher Wooster and Darrell Andrews and Kerry Anderson and McKay, {Gareth J.} and Cole, {Joanne B.} and Salem, {Rany M.} and Conlon, {Peter J.} and Matthias Kretzler and Hirschhorn, {Joel N.} and Denise Sadlier and Catherine Godson and Florez, {Jose C.} and {GENIE Consortium} and Carol Forsblom and Maxwell, {Alexander P.} and Groop, {Per Henrik} and Niina Sandholm and McKnight, {Amy Jayne}",

year = "2022",

month = dec,

day = "22",

doi = "10.1038/s41467-022-34963-6",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

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Smyth, LJ, Dahlström, EH, Syreeni, A, Kerr, K , Kilner, J, Doyle, R, Brennan, E, Nair, V, Fermin, D, Nelson, RG, Looker, HC, Wooster, C, Andrews, D, Anderson, K, McKay, GJ, Cole, JB, Salem, RM, Conlon, PJ, Kretzler, M, Hirschhorn, JN, Sadlier, D, Godson, C, Florez, JC, GENIE Consortium, Forsblom, C, Maxwell, AP, Groop, PH, Sandholm, N & McKnight, AJ 2022, 'Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease', Nature Communications, vol. 13, 7891. https://doi.org/10.1038/s41467-022-34963-6

TY - JOUR

T1 - Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease

AU - Smyth, Laura J.

AU - Dahlström, Emma H.

AU - Syreeni, Anna

AU - Kerr, Katie

AU - Kilner, Jill

AU - Doyle, Ross

AU - Brennan, Eoin

AU - Nair, Viji

AU - Fermin, Damian

AU - Nelson, Robert G.

AU - Looker, Helen C.

AU - Wooster, Christopher

AU - Andrews, Darrell

AU - Anderson, Kerry

AU - McKay, Gareth J.

AU - Cole, Joanne B.

AU - Salem, Rany M.

AU - Conlon, Peter J.

AU - Kretzler, Matthias

AU - Hirschhorn, Joel N.

AU - Sadlier, Denise

AU - Godson, Catherine

AU - Florez, Jose C.

AU - GENIE Consortium

AU - Forsblom, Carol

AU - Maxwell, Alexander P.

AU - Groop, Per Henrik

AU - Sandholm, Niina

AU - McKnight, Amy Jayne

PY - 2022/12/22

Y1 - 2022/12/22

N2 - 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.

AB - 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.

KW - Biomarkers

KW - CpG Islands

KW - DNA

KW - DNA Methylation - genetics

KW - Diabetes Mellitus, Type 1 - complications - genetics

KW - Diabetic Nephropathies - genetics

KW - Epigenesis, Genetic

KW - Epigenome

KW - Genome-Wide Association Study

KW - Humans

U2 - 10.1038/s41467-022-34963-6

DO - 10.1038/s41467-022-34963-6

M3 - Article

C2 - 36550108

AN - SCOPUS:85144517080

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

M1 - 7891

ER -

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

Abstract

Keywords

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Projects

R4015CPH: Social Circumstances and Epigenomics Promoting Health in Three Countries

R3789CPH: Discovery of an integrated risk profile for chronic kidney disease and development of a clinical biomarker panel for personalising medicine (Stratified medicine for chronic kidney disease)

R4744CPH: Integrative genomic, epigenetic and functional studies in diabetic kidney disease

Cite this