{
  "abstract": "Background Abnormal foveal pit formation is a hallmark of foveal hypoplasia (FH), a key feature of conditions such as albinism and PAX6-related aniridia. While rare, high-penetrance variants in these disorders are well described, the broader genetic architecture of foveal development, including contributions from common variation, is poorly understood.Methods We conducted the first genome-wide association study (GWAS) of foveal pit depth, applying a deep-learning pipeline to quantify this measure from right-eye OCT scans in 61,269 European participants in the UK Biobank. Fine mapping analysis identified sentinel variants within 1Mb of lead signals (P < 5 × 10 -8) which were mapped to putative causal genes using 12 lines of evidence. Whole-exome sequencing from 59,313 European individuals was used for single-variant and gene-based rare-variant association testing.Results GWAS and fine mapping identified 126 sentinel variants, including 47 not previously associated with macular development. Variant-to-gene mapping prioritised 129 putative causal genes, of which 64 represent novel associations with foveal development. Rare-variant analyses implicated two additional genes ( ESYT3 and ACTN3). Collectively, the implicated genes are involved in newly highlighted pathways (e.g., retinoic acid metabolism and cell fate determination) as well as established foveal pathways (e.g., retinal pigmentation and photoreceptor development).Conclusion These findings substantially expand the known genetic architecture of human foveal development, uncovering both common and rare variant contributions. This work establishes a foundation for functional studies of the molecular mechanisms underlying FH and related visual disorders.",
  "authors": [
    {
      "affiliations": [
        "The University of Leicester, Ulverscroft Eye Unit, School of Psychology and Vision Sciences, University of Leicester, Leicester, UK"
      ],
      "name": "Callum Hunt"
    },
    {
      "affiliations": [
        "The University of Leicester, Ulverscroft Eye Unit, School of Psychology and Vision Sciences, University of Leicester, Leicester, UK"
      ],
      "name": "Ha-Jun Yoon"
    },
    {
      "affiliations": [
        "The University of Leicester, Ulverscroft Eye Unit, School of Psychology and Vision Sciences, University of Leicester, Leicester, UK"
      ],
      "name": "Alvin Lirio"
    },
    {
      "affiliations": [
        "Department of Population Health Sciences, University of Leicester, Leicester, UK",
        "University Hospitals of Leicester NHS Trust, Leicester, UK"
      ],
      "name": "Kayesha Coley"
    },
    {
      "affiliations": [
        "Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas, 77030, U.S.A"
      ],
      "name": "Jun Wang"
    },
    {
      "affiliations": [
        "Department of Population Health Sciences, University of Leicester, Leicester, UK"
      ],
      "name": "Nick Shrine"
    },
    {
      "affiliations": [
        "Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas, 77030, U.S.A"
      ],
      "name": "Jianming Shao"
    },
    {
      "affiliations": [
        "The University of Leicester, Ulverscroft Eye Unit, School of Psychology and Vision Sciences, University of Leicester, Leicester, UK",
        "School of Allied Health Professions, Nursing and Midwifery, Faculty of Health, University of Sheffield, Sheffield, UK"
      ],
      "name": "Gail DE Maconachie"
    },
    {
      "affiliations": [
        "The University of Leicester, Ulverscroft Eye Unit, School of Psychology and Vision Sciences, University of Leicester, Leicester, UK"
      ],
      "name": "Zhanhan Tu"
    },
    {
      "affiliations": [
        "Department of Dermatology, Weill Cornell Medical College of Cornell University, New York, NY"
      ],
      "name": "Jonathan H Zippin"
    },
    {
      "affiliations": [
        "Section of Ophthalmology and Department of Twin Research and Genetic Epidemiology, King’s College London",
        "Sørlandet Sykehus Arendal, Arendal, Norway"
      ],
      "name": "Pirro G Hysi"
    },
    {
      "affiliations": [
        "Section of Ophthalmology and Department of Twin Research and Genetic Epidemiology, King’s College London",
        "Sørlandet Sykehus Arendal, Arendal, Norway"
      ],
      "name": "Christopher J Hammond"
    },
    {
      "affiliations": [
        "Department of Ophthalmology and Vision Science, University of California Davis School of Medicine, Sacramento, CA, USA, 95616"
      ],
      "name": "Ala Moshiri"
    },
    {
      "affiliations": [
        "Gavin Herbert Eye Institute – Center for Translational Vision Research, Department of Ophthalmology, University of California Irvine, Irvine, USA"
      ],
      "name": "Rui Chen"
    },
    {
      "affiliations": [
        "Department of Population Health Sciences, University of Leicester, Leicester, UK",
        "University Hospitals of Leicester NHS Trust, Leicester, UK"
      ],
      "name": "Martin D Tobin"
    },
    {
      "affiliations": [
        "Department of Population Health Sciences, University of Leicester, Leicester, UK",
        "University Hospitals of Leicester NHS Trust, Leicester, UK"
      ],
      "name": "Chiara Batini"
    },
    {
      "affiliations": [
        "The University of Leicester, Ulverscroft Eye Unit, School of Psychology and Vision Sciences, University of Leicester, Leicester, UK",
        "University Hospitals of Leicester NHS Trust, Leicester, UK",
        "Department of Genetics and Genome Biology, University of Leicester, Leicestershire, UK",
        "Neurogenetics Group, University of Leicester, Leicester, UK"
      ],
      "name": "Mervyn G Thomas"
    }
  ],
  "title": "#ECR-Paper-05 Genome-wide insights into the genes and pathways shaping human foveal development",
  "uid": "8d79c99b-2604-5de7-8912-dbb884103e16"
}