{
  "abstract": "In the United States, sickle cell disease (SCD) is a rare inherited hemoglobinopathy affecting ∼100 000 individuals, mostly with African ancestry. SCD causes damage to multiple organ systems, and SCD nephropathy (SCDN) is a common complication associated with early mortality. We previously performed a genome-wide association study (GWAS) for SCDN and identified a modest number of genome-wide significant loci. Here, we leveraged the ancestral composition of participants from 2 well-characterized adult SCD cohorts to boost statistical power and perform a local ancestry–aware GWAS for estimated glomerular filtration rate, resulting in the identification of novel genome-wide significant loci within the African and European ancestral components of participants. Meta-analysis identified 12 significant genomic regions in the African tract, including peptidylprolyl isomerase like 6, ARHGAP24, RAB11A, and STEAP3, and 38 regions in the European tract, including UBLCP1, a disintegrin and metalloproteinase with thrombospondin motifs 6, JAZF1, MYO7B, MYO1C, PDGFA, GPC5, LRP1B, KANK1, and TRPV5. The identified regions encompass genes affecting inflammation, extracellular matrix integrity, iron metabolism, magnesium ion homeostasis, B-cell apoptosis, tumor necrosis factor production, and estrogen signaling. Many of these genes and pathways are important not only for renal function but also for SCD biology, providing additional support for the hypothesis that SCDN pathophysiology is unique from other forms of kidney disease. This study represents the largest local ancestry–aware analysis of SCDN to date, furthers our understanding of the genetic risk factors underlying SCDN, and proposes new targets that could be useful for the early identification and treatment of kidney dysfunction in patients with SCD.",
  "abstract_shown": true,
  "affiliations": [
    "Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC",
    "Department of Medicine, University of Pittsburgh, Pittsburgh, PA",
    "School of Medicine, University of Maryland, Baltimore, MD",
    "Department of Medicine, University of Illinois at Chicago, Chicago, IL",
    "Division of Hematology, Department of Medicine, Duke University Medical Center, Durham, NC"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 325,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Melanie E. Garrett"
    },
    {
      "affs": [
        1
      ],
      "name": "Seyed Mehdi Nouraie"
    },
    {
      "affs": [
        2
      ],
      "name": "Roberto F. Machado"
    },
    {
      "affs": [
        3
      ],
      "name": "Victor R. Gordeuk"
    },
    {
      "affs": [
        2
      ],
      "name": "Mark T. Gladwin"
    },
    {
      "affs": [
        4
      ],
      "name": "Marilyn J. Telen"
    },
    {
      "affs": [
        0
      ],
      "name": "Allison E. Ashley-Koch"
    },
    {
      "name": "Gonçalo Abecasis"
    },
    {
      "name": "Gonçalo Abecasis"
    },
    {
      "name": "Francois Aguet"
    },
    {
      "name": "Christine Albert"
    },
    {
      "name": "Laura Almasy"
    },
    {
      "name": "Alvaro Alonso"
    },
    {
      "name": "Seth Ament"
    },
    {
      "name": "Peter Anderson"
    },
    {
      "name": "Pramod Anugu"
    },
    {
      "name": "Kristin Ardlie"
    },
    {
      "name": "Dan Arking"
    },
    {
      "name": "Donna K. Arnett"
    },
    {
      "name": "Allison Ashley-Koch"
    },
    {
      "name": "Stella Aslibekyan"
    },
    {
      "name": "Tim Assimes"
    },
    {
      "name": "Paul Auer"
    },
    {
      "name": "Dimitrios Avramopoulos"
    },
    {
      "name": "Najib Ayas"
    },
    {
      "name": "John Barnard"
    },
    {
      "name": "Kathleen Barnes"
    },
    {
      "name": "R. Graham Barr"
    },
    {
      "name": "Emily Barron-Casella"
    },
    {
      "name": "Terri Beaty"
    },
    {
      "name": "Gerald Beck"
    },
    {
      "name": "Diane Becker"
    },
    {
      "name": "Lewis Becker"
    },
    {
      "name": "Amber Beitelshees"
    },
    {
      "name": "Panagiotis Benos"
    },
    {
      "name": "Marcos Bezerra"
    },
    {
      "name": "Larry Bielak"
    },
    {
      "name": "Joshua Bis"
    },
    {
      "name": "John Blangero"
    },
    {
      "name": "Nathan Blue"
    },
    {
      "name": "Donald W. Bowden"
    },
    {
      "name": "Russell Bowler"
    },
    {
      "name": "Jennifer Brody"
    },
    {
      "name": "Ulrich Broeckel"
    },
    {
      "name": "Deborah Brown"
    },
    {
      "name": "Esteban Burchard"
    },
    {
      "name": "Carlos Bustamante"
    },
    {
      "name": "Brian Cade"
    },
    {
      "name": "Jonathan Cardwell"
    },
    {
      "name": "Vincent Carey"
    },
    {
      "name": "April P. Carson"
    },
    {
      "name": "Cara Carty"
    },
    {
      "name": "Richard Casaburi"
    },
    {
      "name": "James Casella"
    },
    {
      "name": "Peter Castaldi"
    },
    {
      "name": "Mark Chaffin"
    },
    {
      "name": "Yi-Cheng Chang"
    },
    {
      "name": "Daniel Chasman"
    },
    {
      "name": "Wei Min Chen"
    },
    {
      "name": "Yii-Der Ida Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4gbtb9k7j6xy6.bib",
  "cited_by": 1,
  "doi": "10.1182/bloodadvances.2026020894",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731904/",
  "id": "4gbtb9k7j6xy6",
  "issns": [
    "2473-9529",
    "2473-9537"
  ],
  "landing_url": "https://doi.org/10.1182/bloodadvances.2026020894",
  "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",
      "Red Cells, Iron, and Erythropoiesis"
    ],
    [
      "openalex",
      "2716|Hemoglobinopathies and Related Disorders"
    ]
  ],
  "openalex": "W7162865381",
  "pdf_url": null,
  "pmcid": "PMC13731904",
  "pmid": "42616615",
  "published": "2026-10-17",
  "publisher": "The American Society of Hematology",
  "ris": "https://research.draconitic.com/paper/4gbtb9k7j6xy6.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:00Z",
      "native_id": "PMC13731904",
      "source": "pmc",
      "url": "https://doi.org/10.1182/bloodadvances.2026020894"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2716|Hemoglobinopathies and Related Disorders",
      "subfield": "human-genetics"
    }
  ],
  "title": "Local ancestry–aware genome-wide meta-analysis uncovers novel genetic loci for sickle cell disease nephropathy",
  "title_text": "Local ancestry–aware genome-wide meta-analysis uncovers novel genetic loci for sickle cell disease nephropathy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:00Z",
  "url": "https://research.draconitic.com/paper/4gbtb9k7j6xy6",
  "venue": "Blood Advances",
  "versions": []
}