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Patients show substantial differences in their predisposition to alloimmunization, and genetic variability is one proposed component. Although several genetic association studies have been conducted for alloimmunization, the results have been inconsistent, and the genetic determinants of alloimmunization remain largely unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design and Methods<\/jats:title><jats:p>We performed a genome\u2010wide association study (GWAS) in 236 African American (AA) SCD patients from the Outcome Modifying Genes in Sickle Cell Disease (OMG\u2010SCD) cohort, which is part of Trans\u2010Omics for Precision Medicine (TOPMed), with whole\u2010genome sequencing data available. We also performed sensitivity analyses adjusting for different sets of covariates and applied different sample grouping strategies based on the number of alloantibodies patients developed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified one genome\u2010wide significant locus on chr12 (<jats:italic>p<\/jats:italic>\u2009=\u20093.1e\u20109) with no evidence of genomic inflation (lambda\u2009=\u20091.003). Further leveraging QTL evidence from GTEx whole blood and\/or Jackson Heart Study PBMC RNA\u2010Seq data, we identified a number of potential genes, such as <jats:italic>ARHGAP9<\/jats:italic>, <jats:italic>STAT6<\/jats:italic>, and <jats:italic>ATP23<\/jats:italic>, that may be driving the association signal. We also discovered some suggestive loci using different analysis strategies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We call for the community to collect additional alloantibody information within SCD cohorts to further the understanding of the genetic basis of alloimmunization in order to improve transfusion outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.17944","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T08:20:58Z","timestamp":1720167658000},"page":"1772-1783","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A genome\u2010wide association study of alloimmunization in the <scp>TOPMed OMG<\/scp>\u2010<scp>SCD<\/scp> cohort identifies a locus on chromosome 12"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8324-2803","authenticated-orcid":false,"given":"Quan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Biostatistics University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Karafin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie E.","family":"Garrett","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Department of Genetics University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Ashley\u2010Koch","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn J.","family":"Telen","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Duke Comprehensive Sickle Cell Center Duke University Medical Center  Durham North Carolina 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