{
  "abstract": "Background: Diabetic kidney disease is a leading cause of kidney failure, yet molecular predictors of risk remain poorly defined, particularly among Indigenous Australians who experience a disproportionate burden. We aimed to identify blood-derived candidate DNA methylation signatures associated with Kidney Disease: Improving Global Outcomes (KDIGO) risk categories in the PROPHECY Aboriginal Diabetes Study.\n\nMethods: We applied methyl-CpG binding domain sequencing to blood-derived DNA from 95 participants stratified as non-diabetic (n = 23), low-risk (n = 21), moderate-risk (n = 26), high-risk (n = 14) or very-high-risk (n = 11). Differential MBD-enriched methylated regions were assessed using covariate-adjusted models incorporating clinical, leukocyte-marker and CpG-density covariates. Candidate regions were prioritised using a nominal discovery threshold and explored using annotation, random forest modelling and human podocyte experiments.\n\nResults: For the primary diabetic kidney disease risk contrast, 1,317 regions met the nominal discovery threshold of P < 0.001, but no region reached FDR < 0.10. Across 16 predefined analysis terms - 11 pairwise/grouped contrasts and 5 single-group terms - 22,392 nominal DMR entries met P < 0.001, corresponding to 13,024 unique candidate regions. Exploratory random forest models suggested that methylation features may contribute discriminatory information beyond clinical covariates, although estimates require independent validation. Podocyte analyses provided locus-level functional context but not genome-wide cross-tissue replication.\n\nConclusions: This cross-sectional discovery study nominates research-grade candidate methylation biomarkers and pathways for future longitudinal validation in PROPHECY and external cohorts.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "Scott Maxwell",
      "orcid": "0000-0002-7801-0714"
    },
    {
      "name": "Ishant Khurana"
    },
    {
      "name": "Sam Buckberry",
      "orcid": "0000-0003-2388-6046"
    },
    {
      "name": "Harikrishnan Kaipananickal"
    },
    {
      "name": "James Breen"
    },
    {
      "name": "Natasha J. Howard"
    },
    {
      "name": "Jun Okabe",
      "orcid": "0000-0002-7196-0522"
    },
    {
      "name": "Sorine Birkelund"
    },
    {
      "name": "Moshe Olshansky"
    },
    {
      "name": "Paul Z. Zimmet",
      "orcid": "0000-0003-0627-0776"
    },
    {
      "name": "Mark E. Cooper",
      "orcid": "0000-0002-5953-642X"
    },
    {
      "name": "Alex Brown",
      "orcid": "0000-0003-2112-3918"
    },
    {
      "name": "Assam El-Osta"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/548wk7cpbn1ke.bib",
  "cited_by": 0,
  "doi": "10.1038/s43856-026-01959-y",
  "fulltext_url": null,
  "id": "548wk7cpbn1ke",
  "issns": [
    "2730-664X"
  ],
  "landing_url": "https://www.nature.com/articles/s43856-026-01959-y",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2727|Chronic Kidney Disease and Diabetes"
    ]
  ],
  "openalex": "W7221609797",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-13",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/548wk7cpbn1ke.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:53Z",
      "native_id": "10.1038/s43856-026-01959-y",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s43856-026-01959-y"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2727|Chronic Kidney Disease and Diabetes",
      "subfield": "general"
    }
  ],
  "title": "Blood DNA methylation profiling identifies candidate diabetic kidney disease risk signatures in the PROPHECY Aboriginal Diabetes Study",
  "title_text": "Blood DNA methylation profiling identifies candidate diabetic kidney disease risk signatures in the PROPHECY Aboriginal Diabetes Study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:53Z",
  "url": "https://research.draconitic.com/paper/548wk7cpbn1ke",
  "venue": "Communications Medicine",
  "versions": []
}