{
  "abstract": "Purpose: To characterize the genetically supported candidate gene landscape of age-related macular degeneration (AMD), identify robust candidate genes, and evaluate the potential roles of cholesteryl ester transfer protein (CETP)-related lipid traits in AMD susceptibility and progression.\n\nMethods: Large-scale AMD genome-wide association study discovery and replication cohorts were analyzed using an integrative framework combining single-tissue and cross-tissue transcriptome-wide association studies (TWASs) with MAGMA gene-based analysis. Candidate genes were further evaluated using GTEx expression quantitative trait loci data with summary-data–based Mendelian randomization (SMR) and colocalization analyses. Mendelian randomization (MR), multivariable MR (MVMR), and MR–Bayesian model averaging (MR-BMA) were used to assess CETP-related lipid traits in AMD risk and progression.\n\nResults: Integrated evidence from TWASs and MAGMA prioritized seven AMD-associated genes, including CFH, CETP, PLEKHA1, RDH5, HTRA1, AFF1, and ZBTB41. Two-sample MR indicated that genetically predicted CETP-related high-density lipoprotein cholesterol (HDL-C) was associated with increased AMD risk (odds ratio = 1.51; 95% confidence interval, 1.40–1.62; P = 7.0 × 10−27). In MVMR analyses, CETP-related HDL-C retained an independent association, and MR-BMA ranked it as the lipid trait with the highest posterior support. Exploratory analyses suggested that genetically predicted CETP-related HDL-C was associated with AMD progression, including choroidal neovascularization and geographic atrophy.\n\nConclusions: Across discovery and replication cohorts, this multi-cohort, multi-method study prioritized CETP as a genetically supported candidate effector gene for AMD and implicates HDL-C–related genetic variation at the CETP locus in AMD susceptibility and exploratory progression outcomes. These findings support the potential relevance of CETP-related lipid biology but require further mechanistic validation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Retinal and Vitreous Diseases, Aier Eye Hospital of Wuhan University, Wuhan, Hubei, China",
    "Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China",
    "Department of Internal Medicine, Changsha Eighth Hospital, Changsha, Hunan, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Changzhong Xu"
    },
    {
      "affs": [
        2
      ],
      "name": "Qiulin Yan"
    },
    {
      "affs": [
        0
      ],
      "name": "Chao Feng"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanzi Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiangyun Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Rui Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Junwen He"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianhua Wu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9bsvyk72e04ah.bib",
  "cited_by": 0,
  "doi": "10.1167/iovs.67.12.54",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13715911/",
  "id": "9bsvyk72e04ah",
  "issns": [
    "0146-0404",
    "1552-5783"
  ],
  "landing_url": "https://doi.org/10.1167/iovs.67.12.54",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Genetics"
    ],
    [
      "openalex",
      "2731|Retinal Diseases and Treatments"
    ]
  ],
  "openalex": "W7223371009",
  "pdf_url": null,
  "pmcid": "PMC13715911",
  "pmid": "42924995",
  "published": "2026-10-23",
  "publisher": "Association for Research in Vision and Ophthalmology",
  "ris": "https://research.draconitic.com/paper/9bsvyk72e04ah.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:23:05Z",
      "native_id": "PMC13715911",
      "source": "pmc",
      "url": "https://doi.org/10.1167/iovs.67.12.54"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Genetics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Integrative Genomic Analyses Prioritize CETP-Related Lipid Traits in Age-Related Macular Degeneration",
  "title_text": "Integrative Genomic Analyses Prioritize CETP-Related Lipid Traits in Age-Related Macular Degeneration",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:23:05Z",
  "url": "https://research.draconitic.com/paper/9bsvyk72e04ah",
  "venue": "Investigative Ophthalmology & Visual Science",
  "versions": []
}