{
  "abstract": "Background: Pain is one of the most common and disabling manifestations of sickle cell disease (SCD), significantly affecting patients' quality of life. While several genetic variants have been associated with pain phenotypes in SCD, the biological mechanisms underlying chronic non-crisis pain remain incompletely understood. Previous studies have reported associations between acute pain and variants in genes such as ICAM1, COMT, DRD3, and NR3C1, whereas ADRB2 and S100B have been implicated in persistent pain outside vaso-occlusive crises. Methods: Whole-genome sequencing (WGS) data from Brazilian individuals with HbSS or HbSβ⁰ genotypes, aged over 12 years, were analyzed. Chronic non-crisis pain was defined by continuous use of analgesic medication for at least 30 consecutive days during the year preceding enrollment. A genome-wide association study (GWAS) was conducted using a logistic mixed-effects model adjusted for genetic ancestry and relatedness among participants. Results: Three single-nucleotide variants (SNVs) demonstrated suggestive evidence of association with chronic non-crisis pain, with p-values ranging from approximately 10 -8 to 10 -7 . The strongest association signals were observed within DPP10, a gene involved in neuronal excitability and pain regulation. Additional candidate loci were identified in GRAMD1C and TLR4, genes previously linked to inflammatory responses, vaso-occlusive complications, and acute chest syndrome in individuals with SCD. Conclusions: Our findings identify promising genetic loci associated with susceptibility to chronic non-crisis pain in sickle cell disease. These results contribute to a better understanding of the genetic architecture of pain in SCD and may support future studies aimed at identifying biomarkers and developing personalized therapeutic strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Universidade de São Paulo (USP), São Paulo, SP, Brazil",
    "Fundação Hemominas (FH), Belo Horizonte, MG, Brazil",
    "Fundação de Hematologia e Hemoterapia de Pernambuco (Hemope), Recife, PE, Brazil",
    "Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil",
    "UCSF Benioff Children's Hospital Oakland, United States",
    "Vitalant, United States",
    "Pró-Sangue, São Paulo, SP, Brazil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mina CINTHO OZAHATA"
    },
    {
      "affs": [
        0
      ],
      "name": "Carlos Henrique PASSOS"
    },
    {
      "affs": [
        1
      ],
      "name": "André ROLIM BELISáRIO"
    },
    {
      "affs": [
        2
      ],
      "name": "Alessandra FERRAZ"
    },
    {
      "affs": [
        3
      ],
      "name": "Ester CERDEIRA SABINO"
    },
    {
      "affs": [
        4
      ],
      "name": "Shannon KELLY"
    },
    {
      "affs": [
        5
      ],
      "name": "Brian CUSTER"
    },
    {
      "affs": [
        6
      ],
      "name": "Carla Luana DINARDO"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9rkr42mar1bxd.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.106654",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926004013",
  "id": "9rkr42mar1bxd",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.106654",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2716|Hemoglobinopathies and Related Disorders"
    ]
  ],
  "openalex": "W7223138584",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/9rkr42mar1bxd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:29Z",
      "native_id": "f8c739f333b7403d9b3f02f1574e125f",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.106654"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2716|Hemoglobinopathies and Related Disorders",
      "subfield": "human-genetics"
    }
  ],
  "title": "GENOME-WIDE ASSOCIATION STUDY OF NON-CRISIS PAIN IN PATIENTS WITH SICKLE CELL DISEASE",
  "title_text": "GENOME-WIDE ASSOCIATION STUDY OF NON-CRISIS PAIN IN PATIENTS WITH SICKLE CELL DISEASE",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:29Z",
  "url": "https://research.draconitic.com/paper/9rkr42mar1bxd",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}