Evidence map›Paper›PMID 33933144›Full record

ArticleClinical epigenetics2021

Assessment of differentially methylated loci in individuals with end-stage kidney disease attributed to diabetic kidney disease: an exploratory study.

L J Smyth, J Kilner, V Nair, H Liu, E Brennan, K Kerr, N Sandholm, J Cole, E Dahlström, A Syreeni and 18 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 2 pooled it
8.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.

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  18. Integrated multiomic analyses: An approach to improve understanding of diabetic kidney disease.Diabetic medicine : a journal of the British Diabetic Association · 2025
    Review
  19. Advances in the Epigenetic Mechanisms of Diabetic Nephropathy Pathogenesis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 8 institutions in 5 countries.

L J SmythMolecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK. laura.smyth@qub.ac.uk.ORCID 0000-0001-6419-4826
J KilnerMolecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK.
V NairInternal Medicine, Department of Nephrology, University of Michigan, Ann Arbor, MI, USA.
H LiuDepartment of Department of Medicine/ Nephrology, Department of Genetics, Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
E BrennanDiabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Research, School of Medicine, University College Dublin, Dublin 4, Ireland.
K KerrMolecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK.
N SandholmFolkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
J ColePrograms in Metabolism and Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
E DahlströmFolkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
A SyreeniFolkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
R M SalemDepartment of Family Medicine and Public Health, UC San Diego, San Diego, CA, USA.
R G NelsonChronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA.
H C LookerChronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA.
C WoosterMolecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK.
K AndersonMolecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK.
G J McKayMolecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK.
F KeeMolecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK.
I YoungMolecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK.
D AndrewsDiabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Research, School of Medicine, University College Dublin, Dublin 4, Ireland.
C ForsblomFolkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
J N HirschhornPrograms in Metabolism and Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
C GodsonDiabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Research, School of Medicine, University College Dublin, Dublin 4, Ireland.
P H GroopFolkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
A P MaxwellMolecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK.
K SusztakDepartment of Department of Medicine/ Nephrology, Department of Genetics, Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
M KretzlerInternal Medicine, Department of Nephrology, University of Michigan, Ann Arbor, MI, USA.
J C FlorezPrograms in Metabolism and Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
A J McKnightMolecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK.
Queen's University Belfast · GBUniversity of Helsinki · FIBroad Institute · USUniversity College Dublin · IENational Institute of Diabetes and Digestive and Kidney Diseases · USUniversity of Michigan · USUniversity of Pennsylvania · USUC San Diego Health System · US

Funding

University of Michigan O'Brien Kidney Translational Core CenterP30DK081943 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PENNATHUR, SUBRAMANIAM · 2008 to 2022
$12.9M
Integrative genomic, epigenetic and functional studies in diabetic kidney diseaseR01DK105154 · NIDDK · BROAD INSTITUTE, INC. · PI FLOREZ, JOSE CARLOS, HIRSCHHORN, JOEL N · 2016 to 2019
$3.0M
Genome-Wide Association Studies of Diabetic NephropathyR01DK081923 · NIDDK · BROAD INSTITUTE, INC. · PI HIRSCHHORN, JOEL N · 2009 to 2012
$2.3M
Genetically harmonized dietary intake and causal relationships with diabetes-related outcomesK99DK127196 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI COLE, JOANNE BURNETTE · 2021 to 2022
$178k
Medical Research Council MC_PC_15025Medical Research Council MC_PC_20026NIDDK NIH HHS K99 DK127196NIDDK NIH HHS P30 DK081943NIDDK NIH HHS R01 DK081923NIDDK NIH HHS R01 DK105154Science Foundation Ireland SFI15/US/B3130Wellcome Trust
6 · The paper itself

Abstract

backgroundA subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this exploratory investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing to identify potential blood-based biomarkers. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina's Infinium MethylationEPIC BeadChip arrays (n = 862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p ≤ × 10

resultsTop-ranked genes within which several dmCpGs were located and supported by functional data with methylation look-ups in other cohorts include: AFF3, ARID5B, CUX1, ELMO1, FKBP5, HDAC4, ITGAL, LY9, PIM1, RUNX3, SEPTIN9 and UPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-β signalling and Th17 cell differentiation.

conclusionsEpigenetic alterations provide a dynamic link between an individual's genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM.

Indexed as

AdultDiabetes Mellitus, Type 1Diabetic NephropathiesDNA MethylationEpigenesis, GeneticEpigenomicsFemaleHumansKidney Failure, ChronicMaleAssociationDiabetesEnd-stageEPICKidneyMethylationNephropathy

Identifiers

PMID33933144
PMCPMC8088646
OpenAlexW3159791029

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.