{
  "abstract": "Standard polygenic risk scores capture overall genetic liability to coronary artery disease (CAD) but do not reveal the biological processes contributing to risk in an individual. Here, we applied data-driven latent factor decomposition to 526 genome-wide significant CAD-associated variants, using their associations with 78 CAD-related phenotypic traits. We identified eight genetic components corresponding to cholesterol-enriched lipoproteins, triglyceride-rich lipoproteins, lipoprotein(a), metabolically unhealthy normal weight, obesity, endothelial dysfunction, coagulation and cardiac remodeling. Process-specific polygenic risk scores (pPRSs) captured biological profiles beyond those reflected by conventional risk factors. In UK Biobank (n = 458,905), the Swedish CArdioPulmonary bioImage Study (n = 24,904) and Mass General Brigham Biobank (n = 53,848), pPRSs were consistently associated with clinical and subclinical CAD and showed distinct biomarker, proteomic and comorbidity profiles. These findings establish a framework for biologically resolved genetic CAD risk and may inform process-specific approaches to precision prevention.",
  "abstract_shown": true,
  "affiliations": [
    "Chalmers University of Technology"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "name": "J. Morze"
    },
    {
      "name": "K. Smith"
    },
    {
      "name": "M. Kierczak"
    },
    {
      "name": "G. Bergstrom"
    },
    {
      "name": "H. Li"
    },
    {
      "name": "A. Gummesson"
    },
    {
      "name": "T. Fall"
    },
    {
      "name": "S. Soderberg"
    },
    {
      "name": "T. Ebbers"
    },
    {
      "name": "J. G. Smith"
    },
    {
      "name": "R. Landberg"
    },
    {
      "name": "P. Franks"
    },
    {
      "name": "T. Lappalainen"
    },
    {
      "name": "M. Udler"
    },
    {
      "affs": [
        0
      ],
      "name": "C. Wittenbecher"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6q89wptvqfqh8.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.08.26365088",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.08.26365088v1.full",
  "id": "6q89wptvqfqh8",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.08.26365088v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "genetic and genomic medicine"
    ],
    [
      "openalex",
      "1311|Genetic Associations and Epidemiology"
    ]
  ],
  "openalex": "W7221466098",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.08.26365088v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6q89wptvqfqh8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:38Z",
      "native_id": "10.64898/2026.10.08.26365088",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.08.26365088v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:genetic and genomic medicine",
      "subfield": "human-genetics"
    }
  ],
  "title": "Decomposing polygenic risk of coronary artery disease into distinct biological processes",
  "title_text": "Decomposing polygenic risk of coronary artery disease into distinct biological processes",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:38Z",
  "url": "https://research.draconitic.com/paper/6q89wptvqfqh8",
  "venue": "medRxiv",
  "versions": []
}