title: A Genome-Wide Screen for Large-Effect Alloimmunization Susceptibility Loci among Red Blood Cell Transfusion Recipients with Sickle Cell Disease.
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.
authors: 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.
authors: Neil A
authors: NA
authors: Hanchard
authors: Scientific Support Services, LifeShare Blood Centers, Shreveport, LA, USA.
authors: Joann M
authors: JM
authors: Moulds
authors: 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.
authors: John W
authors: JW
authors: Belmont
authors: Department of Pathology, Texas Heart Institute, Baylor St. Luke's Medical Center, Houston, TX, USA.
authors: Alice
authors: A
authors: Chen
keywords: African American; GWAS; Genome-wide association studies; Genomics; Responders