{
  "abstract": "Hemoglobin A1c (HbA1c), an important diagnostic biomarker for type 2 diabetes (T2D), is also associated with aging, cognitive performance, and mortality. To identify epistatic interactions, we assessed 133 known gene variants associated with HbA1c among 3778 non-diabetic subjects of European ancestry in the Long Life Family Study (LLFS). We applied Bayesian imputation based association mapping (BIMBAM) to identify significant pairwise epistatic interactions among 133 genetic variants. To take into account confounding effects, we adjusted age, sex, field centers, body mass index (BMI), and genetic principal components (PCs). This analysis yielded seven pairs with log10(BF) > 10; of those, six pairs were confirmed using a full-term mixed regression model. Specifically, these included significant interactions of HK1-rs17476364 with variants in GCK (rs2971670, rs4607517) or G6PC2 (rs560887), as well as between HK1-rs16926246 and the same variants (p values for each term ≤ 7.14 × 10−3). All epistatic interactions between HK1 and GCK, and between HK1 and G6PC2 were replicated at p < 0.05 in at least one of two large independent studies (namely, Framingham Offspring Study; Health and Retirement Study). The present study revealed that HK1 and GCK interact to contribute to regulating levels of HbA1c and are likely to be involved in molecular mechanisms underlying healthy aging processes.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, 4444 Forest Park Ave, St. Louis, MO 63108, USA",
    "G. H. Sergievsky Center, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Departments of Neurology and Epidemiology, Columbia University Irving Medical Center, New York, NY 10032, USA",
    "Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA",
    "Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC 27708, USA",
    "Department of Medicine, Section of Geriatrics, Boston Medical Center, Boston University School of Medicine, Boston, MA 02118, USA",
    "Unit of Epidemiology, Biostatistics and Biodemography, Department of Public Health, Southern Denmark University, 5230 Odense, Denmark",
    "Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15260, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Lihua Wang",
      "orcid": "0000-0002-0125-1544"
    },
    {
      "affs": [
        1
      ],
      "name": "Joseph H. Lee",
      "orcid": "0000-0002-2000-4821"
    },
    {
      "affs": [
        2
      ],
      "name": "Bharat Thyagarajan",
      "orcid": "0000-0001-6968-6985"
    },
    {
      "affs": [
        3
      ],
      "name": "Anatoliy I. Yashin",
      "orcid": "0000-0003-4262-8894"
    },
    {
      "affs": [
        0
      ],
      "name": "E. Warwick Daw"
    },
    {
      "affs": [
        4
      ],
      "name": "Thomas T. Perls"
    },
    {
      "affs": [
        5
      ],
      "name": "Kaare Christensen",
      "orcid": "0000-0002-5429-5292"
    },
    {
      "affs": [
        6
      ],
      "name": "Joseph M. Zmuda"
    },
    {
      "affs": [
        0
      ],
      "name": "Michael A. Province",
      "orcid": "0000-0001-6102-774X"
    },
    {
      "affs": [
        0
      ],
      "name": "Ping An"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2ac2s5jy0m1qj.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219797",
  "fulltext_url": null,
  "id": "2ac2s5jy0m1qj",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9797",
  "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": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-31",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/2ac2s5jy0m1qj.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T00:20:58Z",
      "native_id": "10.3390/ijms27219797",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9797"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "Evidence of Epistatic Interactive Effects of HK1 and GCK Genes on Circulating Hemoglobin A1c Levels in Humans",
  "title_text": "Evidence of Epistatic Interactive Effects of HK1 and GCK Genes on Circulating Hemoglobin A1c Levels in Humans",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T00:21:14Z",
  "url": "https://research.draconitic.com/paper/2ac2s5jy0m1qj",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}