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Variations in adult HbF levels are partly explained by the co\u2010inheritance of genetic variants that regulate globin expression. In this study, we investigated the association of\n                    <jats:italic>BCL11A<\/jats:italic>\n                    rs4671393, rs1427407, rs11886868 and\n                    <jats:italic>HBS1L\u2010MYB<\/jats:italic>\n                    rs9399137 polymorphisms with HbF levels and clinical complications in a cohort of 409 adult Brazilian SCA patients. Our findings reveal that variant alleles of all four single\u2010nucleotide polymorphisms (SNPs) were significantly associated with higher HbF levels. Moreover, homozygosity for the major alleles was independently associated with higher risk and cumulative incidence of stroke, avascular necrosis, leg ulcers, priapism and acute chest syndrome. Haplotype analysis with\n                    <jats:italic>BCL11A<\/jats:italic>\n                    variants was also associated with HbF and the patient's phenotype. A genetic risk score (GRS) combining the risk genotypes was significantly associated with lower HbF levels (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and increased complication risk (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). A model integrating the GRS with clinical variables demonstrated superior discriminatory performance (area under the curve (AUC): 0.72) compared to models based solely on clinical factors. In summary, this study underscores the clinical relevance of HbF\u2010related genetic variants and supports their integration into risk stratification and personalized management strategies for SCA.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70489","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T12:44:23Z","timestamp":1776343463000},"page":"2203-2211","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A genetic risk score based on\n                    <i>BCL11A<\/i>\n                    and\n                    <i>HBS1L\u2010MYB<\/i>\n                    variants predicts clinical severity in Brazilian sickle cell anaemia patients"],"prefix":"10.1111","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1736-0227","authenticated-orcid":false,"given":"Gabriela S.","family":"Arcanjo","sequence":"first","affiliation":[{"name":"Genetics and Molecular Biology Postgraduate Program Federal University of Pernambuco  Recife Pernambuco Brazil"},{"name":"Hematology and Hemotherapy Center State University of Campinas  Campinas S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6226-2941","authenticated-orcid":false,"given":"Alexsandro P.","family":"Silva","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Biology Postgraduate Program Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5599-2989","authenticated-orcid":false,"given":"Madi V.","family":"Diniz","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Biology Postgraduate Program Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5292-5417","authenticated-orcid":false,"given":"Igor F.","family":"Domingos","sequence":"additional","affiliation":[{"name":"Cardiology Emergency Unit of Pernambuco University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3302-4311","authenticated-orcid":false,"given":"Diego A.","family":"Pereira\u2010Martins","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cancer Research Centre Groningen University Medical Centre Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6645-9322","authenticated-orcid":false,"given":"Amanda B.","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Biology Postgraduate Program Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talita S. S.","family":"Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Biology Postgraduate Program Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C.","family":"Anjos","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Biology Postgraduate Program Federal University of Pernambuco  Recife Pernambuco Brazil"},{"name":"Department of Internal Medicine Hematology and Hemotherapy Foundation of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1733-5053","authenticated-orcid":false,"given":"Aderson S.","family":"Araujo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Hematology and Hemotherapy Foundation of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6478-8173","authenticated-orcid":false,"given":"Edis","family":"Belini\u2010Junior","sequence":"additional","affiliation":[{"name":"Molecular Biology and Genetics Laboratory Federal University of Mato Grosso do Sul (UFMS)  Tr\u00eas Lagoas MS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0809-8068","authenticated-orcid":false,"given":"Sara T. 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