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- W2905930450 endingPage "3647" @default.
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- W2905930450 abstract "Abstract Red blood cell (RBC) transfusion remains a critical therapeutic intervention in sickle cell disease (SCD); however, the apparent propensity of some patients to regularly develop RBC alloantibodies after transfusion presents a significant challenge to finding compatible blood for so-called alloimmunization responders. Predisposing genetic loci have long been thought to contribute to the responder phenomenon, but to date, no definitive loci have been identified. We undertook a genome-wide association study of alloimmunization responder status in 267 SCD multiple transfusion recipients, using genetic estimates of ancestral admixture to bolster our findings. Analyses revealed single nucleotide polymorphisms (SNPs) on chromosomes 2 and 5 approaching genome-wide significance (minimum P = 2.0 × 10−8 and 8.4 × 10−8, respectively), with local ancestry analysis demonstrating similar levels of admixture in responders and nonresponders at implicated loci. Association at chromosome 5 was nominally replicated in an independent cohort of 130 SCD transfusion recipients, with meta-analysis surpassing genome-wide significance (rs75853687, Pmeta = 6.6 × 10−9), and this extended to individuals forming multiple (>3) alloantibodies (Pmeta = 9.4 × 10−5). The associated variant is rare outside of African populations, and orthogonal genome-wide haplotype analyses, contingent on local ancestry, revealed genome-wide significant sharing of a ∼60-kb haplotype of African ancestry at the chromosome 5 locus (Bayes Factor = 4.95). This locus overlaps a putative cis-acting enhancer predicted to regulate transcription of ADRA1B and the lncRNA LINC01847, both members of larger ontologies associated with immune regulation. Our findings provide potential insights to the pathophysiology underlying the development of alloantibodies and implicate non-RBC ancestry-limited loci in the susceptibility to alloimmunization." @default.
- W2905930450 created "2019-01-01" @default.
- W2905930450 creator A5024029845 @default.
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- W2905930450 date "2018-12-21" @default.
- W2905930450 modified "2023-10-17" @default.
- W2905930450 title "A locus on chromosome 5 shows African ancestry–limited association with alloimmunization in sickle cell disease" @default.
- W2905930450 cites W145680385 @default.
- W2905930450 cites W1481813776 @default.
- W2905930450 cites W1499422972 @default.
- W2905930450 cites W1522600439 @default.
- W2905930450 cites W1551870152 @default.
- W2905930450 cites W1583337622 @default.
- W2905930450 cites W1764651538 @default.
- W2905930450 cites W1816832019 @default.
- W2905930450 cites W1819753035 @default.
- W2905930450 cites W1822614937 @default.
- W2905930450 cites W1912672559 @default.
- W2905930450 cites W1978967539 @default.
- W2905930450 cites W1983774106 @default.
- W2905930450 cites W1984621034 @default.
- W2905930450 cites W1991129132 @default.
- W2905930450 cites W1992436001 @default.
- W2905930450 cites W1997775525 @default.
- W2905930450 cites W2006564041 @default.
- W2905930450 cites W2009162031 @default.
- W2905930450 cites W2012034410 @default.
- W2905930450 cites W2012758550 @default.
- W2905930450 cites W2031573639 @default.
- W2905930450 cites W2035718279 @default.
- W2905930450 cites W2035728929 @default.
- W2905930450 cites W2038694212 @default.
- W2905930450 cites W2041088116 @default.
- W2905930450 cites W2044216777 @default.
- W2905930450 cites W2044227662 @default.
- W2905930450 cites W2044728514 @default.
- W2905930450 cites W2046547008 @default.
- W2905930450 cites W2053832525 @default.
- W2905930450 cites W2056768166 @default.
- W2905930450 cites W2058401000 @default.
- W2905930450 cites W2059817933 @default.
- W2905930450 cites W2061539393 @default.
- W2905930450 cites W2064957954 @default.
- W2905930450 cites W2070251534 @default.
- W2905930450 cites W2081567960 @default.
- W2905930450 cites W2082508932 @default.
- W2905930450 cites W2087497959 @default.
- W2905930450 cites W2087546077 @default.
- W2905930450 cites W2092304285 @default.
- W2905930450 cites W2093011816 @default.
- W2905930450 cites W2102294296 @default.
- W2905930450 cites W2104549677 @default.
- W2905930450 cites W2105349784 @default.
- W2905930450 cites W2107121611 @default.
- W2905930450 cites W2110755408 @default.
- W2905930450 cites W2115837368 @default.
- W2905930450 cites W2116828514 @default.
- W2905930450 cites W2119279196 @default.
- W2905930450 cites W2125479029 @default.
- W2905930450 cites W2125933377 @default.
- W2905930450 cites W2127135127 @default.
- W2905930450 cites W2127757090 @default.
- W2905930450 cites W2129011493 @default.
- W2905930450 cites W2129316818 @default.
- W2905930450 cites W2129375421 @default.
- W2905930450 cites W2134121494 @default.
- W2905930450 cites W2134543755 @default.
- W2905930450 cites W2146183901 @default.
- W2905930450 cites W2150182456 @default.
- W2905930450 cites W2154470508 @default.
- W2905930450 cites W2156174439 @default.
- W2905930450 cites W2161485037 @default.
- W2905930450 cites W2161633633 @default.
- W2905930450 cites W2162530578 @default.
- W2905930450 cites W2163013660 @default.
- W2905930450 cites W2226775845 @default.
- W2905930450 cites W2259938310 @default.
- W2905930450 cites W2281993660 @default.
- W2905930450 cites W2326956261 @default.
- W2905930450 cites W2339456402 @default.
- W2905930450 cites W2341005078 @default.
- W2905930450 cites W2423205648 @default.
- W2905930450 cites W2499873627 @default.
- W2905930450 cites W2506588867 @default.
- W2905930450 cites W2529924676 @default.
- W2905930450 cites W2532435486 @default.
- W2905930450 cites W2538361155 @default.
- W2905930450 cites W2621164587 @default.
- W2905930450 cites W2625501045 @default.