{
  "abstract": "Background: The shared genetic etiology underlying the comorbidity of skeletal degeneration and metabolic dysregulation remains poorly understood. This study aims to decipher the pleiotropic genetic architecture of multivariate metabolic bone diseases (mvMBDs) through an integrative summary-statistics framework. Methods: We applied Genomic Structural Equation Modeling (Genomic SEM) to integrate genome-wide association study (GWAS) summary statistics for six complex traits: osteoporosis (OP), chronic kidney disease (CKD), type 2 diabetes (T2D), alkaline phosphatase (ALP), high-density lipoprotein (HDL), and C-reactive protein (CRP). Subsequent analyses incorporated robust fine-mapping (SuSiE/FINEMAP), transcriptome-wide association studies (TWAS), and partitioned heritability assessments to identify putative functional loci and regulatory mechanisms. Results: Genomic SEM revealed significant genetic covariance among the six traits, successfully deriving a latent mvMBD construct. We identified 197 genomic risk loci, including 193 lead SNPs that did not achieve genome-wide significance in the six constituent univariate GWAS, predominantly localized in non-coding cis-regulatory elements (e.g., super-enhancers and intronic regions). Fine-mapping and TWAS prioritized critical pleiotropic genes (e.g., MACF1, CETP, SPP1, and HNF1A). Gene-set enrichment analyses identified enrichment for terms related to bone biology, lipid metabolism, and inflammation. Conclusion: Our findings robustly demonstrate that mvMBDs are not isolated clinical entities but rather interconnected systemic syndromes underpinned by glycolipid metabolic dysregulation and shared pleiotropic regulatory networks. This study establishes a novel theoretical paradigm for the genetic basis of metabolic bone diseases, offering promising functional targets for future precision medicine interventions.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopedics, Affiliated Rehabilitation Hospital of Nanchang University, Nanchang University, Nanchang, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kun Yi"
    },
    {
      "affs": [
        0
      ],
      "name": "Fan Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Feiping Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenlong Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yang Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Bowen Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Sining Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lang Jiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiaxin Ding"
    },
    {
      "affs": [
        0
      ],
      "name": "Daoping Lei"
    },
    {
      "affs": [
        0
      ],
      "name": "Junjie Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Siyuan Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Binghua Wu",
      "orcid": "0000-0002-2595-8595"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/axm15mnvv4dca.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0360386",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13712618/",
  "id": "axm15mnvv4dca",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0360386",
  "language": "en",
  "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": [
    [
      "heading",
      "Biochemistry"
    ],
    [
      "heading",
      "Biology and Life Sciences"
    ],
    [
      "heading",
      "Bone and Mineral Metabolism"
    ],
    [
      "heading",
      "Computational Biology"
    ],
    [
      "heading",
      "Covariance"
    ],
    [
      "heading",
      "Genetic Loci"
    ],
    [
      "heading",
      "Genetics"
    ],
    [
      "heading",
      "Genetics of Disease"
    ],
    [
      "heading",
      "Genome Analysis"
    ],
    [
      "heading",
      "Genome-Wide Association Studies"
    ],
    [
      "heading",
      "Genomics"
    ],
    [
      "heading",
      "Human Genetics"
    ],
    [
      "heading",
      "Mathematics"
    ],
    [
      "heading",
      "Metabolism"
    ],
    [
      "heading",
      "Physical Sciences"
    ],
    [
      "heading",
      "Probability Theory"
    ],
    [
      "heading",
      "Random Variables"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "heading",
      "Single Nucleotide Polymorphisms"
    ],
    [
      "openalex",
      "1311|Genetic Associations and Epidemiology"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Metabolism/Bone and mineral metabolism"
    ],
    [
      "plos",
      "/Biology and life sciences/Computational biology/Genome analysis/Genome-wide association studies"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genetic loci"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genetics of disease"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Genome analysis/Genome-wide association studies"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Human genetics/Genome-wide association studies"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Single nucleotide polymorphisms"
    ],
    [
      "plos",
      "/Physical sciences/Mathematics/Probability theory/Random variables/Covariance"
    ]
  ],
  "openalex": "W7223802324",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0360386&type=printable",
  "pmcid": "PMC13712618",
  "pmid": "42945232",
  "published": "2026-10-27",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/axm15mnvv4dca.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.1371/journal.pone.0360386",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0360386"
    },
    {
      "first_seen": "2026-10-31T12:23:09Z",
      "native_id": "PMC13712618",
      "source": "pmc",
      "url": "https://doi.org/10.1371/journal.pone.0360386"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "heading:Metabolism",
      "subfield": "enzymology-metabolism"
    },
    {
      "field": "biology",
      "origin": "heading:Computational Biology",
      "subfield": "bioinformatics"
    },
    {
      "field": "biology",
      "origin": "plos:genetics",
      "subfield": "genetics-genomics"
    },
    {
      "field": "mathematics",
      "origin": "heading:Probability Theory",
      "subfield": "probability"
    },
    {
      "field": "medicine",
      "origin": "heading:Human Genetics",
      "subfield": "human-genetics"
    }
  ],
  "title": "Unraveling the shared genetic architecture of metabolic bone diseases via genomic structural equation modeling and multi-omics integration",
  "title_text": "Unraveling the shared genetic architecture of metabolic bone diseases via genomic structural equation modeling and multi-omics integration",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:23:09Z",
  "url": "https://research.draconitic.com/paper/axm15mnvv4dca",
  "venue": "PLOS One",
  "versions": []
}