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Hanchard NA, Moulds JM, Belmont JW, et al. A Genome-Wide Screen for Large-Effect Alloimmunization Susceptibility Loci among Red Blood Cell Transfusion Recipients with Sickle Cell Disease. Transfus Med Hemother. 2014;41(6):453-61doi: 10.1159/000369079.
Hanchard, N. A., Moulds, J. M., Belmont, J. W., & Chen, A. (2014). A Genome-Wide Screen for Large-Effect Alloimmunization Susceptibility Loci among Red Blood Cell Transfusion Recipients with Sickle Cell Disease. Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie, 41(6), 453-61. https://doi.org/10.1159/000369079
Hanchard, Neil A, et al. "A Genome-Wide Screen for Large-Effect Alloimmunization Susceptibility Loci among Red Blood Cell Transfusion Recipients with Sickle Cell Disease." Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie vol. 41,6 (2014): 453-61. doi: https://doi.org/10.1159/000369079
Hanchard NA, Moulds JM, Belmont JW, Chen A. A Genome-Wide Screen for Large-Effect Alloimmunization Susceptibility Loci among Red Blood Cell Transfusion Recipients with Sickle Cell Disease. Transfus Med Hemother. 2014 Nov;41(6):453-61. doi: 10.1159/000369079. Epub 2014 Nov 07. PMID: 25670933; PMCID: PMC4280456.
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Transfus Med Hemother. 2014 Nov;41(6):453-61. doi: 10.1159/000369079. Epub 2014 Nov 07.

A Genome-Wide Screen for Large-Effect Alloimmunization Susceptibility Loci among Red Blood Cell Transfusion Recipients with Sickle Cell Disease.

Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie

Neil A Hanchard, Joann M Moulds, John W Belmont, Alice Chen

Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA ; ARS/USDA/Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
  2. Scientific Support Services, LifeShare Blood Centers, Shreveport, LA, USA.
  3. Department of Pathology, Texas Heart Institute, Baylor St. Luke's Medical Center, Houston, TX, USA.

PMID: 25670933 PMCID: PMC4280456 DOI: 10.1159/000369079

Abstract

BACKGROUND: A selective susceptibility of certain individuals to form multiple alloantibodies in response to red cell transfusion is well-recognized in clinical practice, and is a particular problem in persons with sickle cell disease (SCD). The reason for this differential susceptibility is unclear, but inter-individual genetic differences are likely to contribute.

METHODS: We conducted a pilot case-control genome-wide association study using 1,000,000 SNPs in 94 alloimmune responders (cases) and non-responders (controls) with SCD in order to identify loci of large effect size associated with alloimmunization.

RESULTS: No loci showed evidence of association at a genome-wide significance cut-off (p < 0.5 × 10(-8)). SNPs in the ARAP1/STARD10 region showed suggestive association (p < 1 × 10(-6)), but no association was observed at previously implicated loci TRIM21 or HLA. In analyses of the number of accumulated antibodies, a modest association was found with SNPs in the Toll-like receptor gene TLR10 (p < 1 × 10(-4)).

CONCLUSIONS: Alloimmunization in persons with SCD is unlikely to be mediated by loci of very large effect size; however, larger and more comprehensive studies are required to fully evaluate loci with more moderate effects. This study provides a working approach to such future studies in SCD.

Keywords: African American; GWAS; Genome-wide association studies; Genomics; Responders

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