{
  "abstract": "Blood lipids are well-established risk factors for cardiovascular and other chronic diseases, yet the underlying functional mechanisms remain unclear. We conducted a large-scale, genome-wide transcriptome analysis of serum lipid levels using whole blood RNA-sequencing data from 6898 individuals of diverse races and ethnicities (17% Black or African American, 15% Hispanic Latino/a, 68% White). We utilized mixed-effects linear regression and meta-analyzed four discovery datasets (n = 4398 participants), identifying significant associations for 27 genes with low-density lipoproteins (LDL), 974 with high-density lipoproteins (HDL), 1229 with triglycerides (TRIG), and 276 with total cholesterol (TCHO). Two replication datasets (n = 2500 participants) confirmed 3, 55, 380, and 31 genes, respectively. Enrichment analysis revealed lipid metabolic processes for LDL, HDL, and TCHO associated genes, including LDLR, NPC2, and SQLE for LDL and TCHO, while TRIG associated genes highlighted immune and allergic response, cancer, and molecular signaling gene enrichment pathways. To infer causality, we performed bidirectional two-sample Mendelian randomization (MR) and colocalization analyses. MR identified the expression of 8 genes as possibly causal for lipid levels; notable EEPD1 expression, linked with cellular cholesterol homeostasis, was inversely linked with TRIG levels. We also identified novel variants shared with LDL levels and gene expression of DDAH2, associated with cardiovascular disease, and TRIG level and expression of FCGRT, linked with maintaining triglyceride homeostasis. Phenome-wide enrichment analyses reported TRIG associated genes were enriched in secondary malignancy of bone suggesting broader systemic health implications of modified lipid levels. These findings highlight novel associations and genetic regulatory mechanisms as potential therapeutic targets for lipid dysregulation.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Public Health Sciences, Fred Hutchinson Cancer Center, 1100 Fairview Avenue N, Seattle, WA 98109, United States.",
    "Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 170 Rosenau Hall, CB #7400, 135 Dauer Drive, Chapel Hill, NC 27599, United States.",
    "Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, 72 E. Concord St Robinson (B), Boston, MA 02118, United States.",
    "Framingham Heart Study, 73 Mt. Wayte Ave, Ste 2, Framingham, Massachusetts, Boston, MA 01702, United States.",
    "Population Sciences Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD 20892, United States.",
    "Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, 2215 Garland Ave, 507 Light Hall, Nashville, TN 37232, United States.",
    "Vanderbilt Genetics Institute, Vanderbilt University Medical Center, 2215 Garland Ave, 507 Light Hall, Nashville, TN 37232, United States.",
    "Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Ave, Boston, MA 02118, United States.",
    "The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, 1468 Madison Ave, New York, NY 10029, United States.",
    "Department of Epidemiology, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35233, United States.",
    "Department of Epidemiology, School of Public Health, University of Washington, Box #351619, Seattle, WA 98195, United States."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jessica I Lundin",
      "orcid": "0000-0003-4892-6235"
    },
    {
      "affs": [
        1
      ],
      "name": "Mariaelisa Graff"
    },
    {
      "affs": [
        0
      ],
      "name": "Jeff Haessler"
    },
    {
      "affs": [
        1
      ],
      "name": "Xinruo Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanwei Cai"
    },
    {
      "affs": [
        0
      ],
      "name": "Harriett Fuller"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Nancy Heard-Costa"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Tianxiao Huan"
    },
    {
      "affs": [
        4
      ],
      "name": "Roby Joehanes"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Joshua M Landman"
    },
    {
      "affs": [
        7
      ],
      "name": "Gina Marie Peloso"
    },
    {
      "affs": [
        7
      ],
      "name": "Yuxuan Wang"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Zhe Wang"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Jennifer E Below"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Daniel Levy"
    },
    {
      "affs": [
        1
      ],
      "name": "Kari E North"
    },
    {
      "affs": [
        10
      ],
      "name": "Alex P Reiner"
    },
    {
      "affs": [
        7
      ],
      "name": "Ryan Zukowski"
    },
    {
      "affs": [
        0,
        10
      ],
      "name": "Ulrike Peters",
      "orcid": "0000-0001-5666-9318"
    },
    {
      "affs": [
        0
      ],
      "name": "Charles Kooperberg",
      "orcid": "0000-0002-7986-8560"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8qm5qxcbkeppq.bib",
  "cited_by": 0,
  "doi": "10.1093/hmg/ddag113",
  "fulltext_url": "https://europepmc.org/articles/PMC13718429",
  "id": "8qm5qxcbkeppq",
  "issns": [
    "0964-6906",
    "1460-2083"
  ],
  "landing_url": "https://europepmc.org/article/MED/42955849",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "AcademicSubjects/SCI01140"
    ],
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "1311|Genetic Associations and Epidemiology"
    ]
  ],
  "openalex": "W7224420806",
  "pdf_url": "https://europepmc.org/articles/PMC13718429?pdf=render",
  "pmcid": "PMC13718429",
  "pmid": "42955849",
  "published": "2026-10-01",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/8qm5qxcbkeppq.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:44Z",
      "native_id": "MED:42955849",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42955849"
    },
    {
      "first_seen": "2026-11-02T12:22:27Z",
      "native_id": "PMC13718429",
      "source": "pmc",
      "url": "https://doi.org/10.1093/hmg/ddag113"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetic Associations and Epidemiology",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Transcriptomic signatures of lipids in blood provide hypotheses of functional mechanisms linked to lipid metabolism and immune-cell regulation.",
  "title_text": "Transcriptomic signatures of lipids in blood provide hypotheses of functional mechanisms linked to lipid metabolism and immune-cell regulation.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:27Z",
  "url": "https://research.draconitic.com/paper/8qm5qxcbkeppq",
  "venue": "Human molecular genetics",
  "versions": []
}