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• W4229366946 abstract "Heparin, a widely used anticoagulant, carries the risk of an antibody-mediated adverse drug reaction, heparin-induced thrombocytopenia (HIT). A subset of heparin-treated patients produces detectable levels of antibodies against complexes of heparin bound to circulating platelet factor 4 (PF4). Using a genome-wide association study (GWAS) approach, we aimed to identify genetic variants associated with anti-PF4/heparin antibodies that account for the variable antibody response seen in HIT. We performed a GWAS on anti-PF4/heparin antibody levels determined via polyclonal enzyme-linked immunosorbent assays. Our discovery cohort (n = 4237) and replication cohort (n = 807) constituted patients with European ancestry and clinical suspicion of HIT, with cases confirmed via functional assay. Genome-wide significance was considered at α = 5 × 10-8. No variants were significantly associated with anti-PF4/heparin antibody levels in the discovery cohort at a genome-wide significant level. Secondary GWAS analyses included the identification of variants with suggestive associations in the discovery cohort (α = 1 × 10-4). The top variant in both cohorts was rs1555175145 (discovery β = -0.112 [0.018], P = 2.50 × 10-5; replication β = -0.104 [0.051], P = .041). In gene set enrichment analysis, 3 gene sets reached false discovery rate-adjusted significance (q < 0.05) in both discovery and replication cohorts: Leukocyte Transendothelial Migration, Innate Immune Response, and Lyase Activity. Our results indicate that genomic variation is not significantly associated with anti-PF4/heparin antibody levels. Given our power to identify variants with moderate frequencies and effect sizes, this evidence suggests genetic variation is not a primary driver of variable antibody response in heparin-treated patients with European ancestry." @default.
• W4229366946 created "2022-05-10" @default.
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• W4229366946 date "2022-07-18" @default.
• W4229366946 modified "2023-09-27" @default.
• W4229366946 title "Genome-wide association study of platelet factor 4/heparin antibodies in heparin-induced thrombocytopenia" @default.
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• W4229366946 doi "https://doi.org/10.1182/bloodadvances.2022007673" @default.
• W4229366946 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35533259" @default.
• W4229366946 hasPublicationYear "2022" @default.
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