{
  "abstract": "BackgroundCoronary atherosclerosis is shaped by immune, vascular, and metabolic interactions, but genetic links between circulating protein networks and immune-regulatory mechanisms remain incompletely resolved.MethodsIn an exploratory MR screen using a suggestive instrument threshold, we screened 2,821 genetically proxied plasma protein ratios for association with coronary heart disease (CHD) and evaluated the leading signal using bidirectional Mendelian randomization, two-step mediation analysis, Bayesian colocalization, expression quantitative trait locus colocalization, regulatory annotation, and plasma-based phenotypic evaluation in a case-control cohort.ResultsA higher genetically predicted MED18/SH2B3 ratio was associated with CHD after Bonferroni correction (inverse-variance weighted odds ratio = 1.13, 95% confidence interval 1.07-1.18; P = 4.93 × 10-6). The ratio rQTL and SH2B3 protein signal colocalized with CHD at the chromosome 12 SH2B3 locus (PP.H4 = 0.984 and 0.985, respectively). SH2B3 eQTLs also colocalized with CHD in Whole Blood (PP.H4 = 0.937) and EBV-transformed lymphocytes (PP.H4 = 0.932), supporting a blood and lymphocyte context. In 168 clinical participants, the highest ratio tertile remained associated with CHD after multivariable adjustment (odds ratio = 2.81, 95% confidence interval 1.16-7.09). Adding the continuous ratio to clinical covariates increased the AUC from 0.696 to 0.785 (paired DeLong P = 0.013), whereas either protein alone did not significantly improve discrimination. Post hoc subtype-versus-control analyses showed an association for CCS, whereas the AMI estimates were imprecise. Exploratory profiling further identified ratio-group differences in selected hematological indices and circulating inflammatory cytokines.ConclusionThese convergent genetic, transcript-level, and clinical findings prioritize an SH2B3-centered immunogenetic signal in CHD. They do not establish a cell-specific immune mechanism and require external and functional validation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "Xin Lin"
    },
    {
      "name": "Yajuan Ren"
    },
    {
      "name": "Qin Luo"
    },
    {
      "name": "Rui Bai"
    },
    {
      "name": "Yang Feng"
    },
    {
      "name": "Yao Zhao"
    },
    {
      "name": "Jiani Xiong"
    },
    {
      "name": "Yunfei Bian"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4tjffjvs0ar2p.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1949795",
  "fulltext_url": null,
  "id": "4tjffjvs0ar2p",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1949795",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4tjffjvs0ar2p.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T06:20:07Z",
      "native_id": "10.3389/fimmu.2026.1949795",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1949795"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Integrative plasma proteomic and Mendelian randomization analyses prioritize an SH2B3-centered immunogenetic signal in coronary heart disease",
  "title_text": "Integrative plasma proteomic and Mendelian randomization analyses prioritize an SH2B3-centered immunogenetic signal in coronary heart disease",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T06:20:07Z",
  "url": "https://research.draconitic.com/paper/4tjffjvs0ar2p",
  "venue": "Frontiers in Immunology",
  "versions": []
}