title: Performance of HLA allele prediction methods in African Americans for class II genes HLA-DRB1, -DQB1, and -DPB1.
abstract: BACKGROUND
  The expense of human leukocyte antigen (HLA) allele genotyping has motivated the development of imputation methods that use dense single nucleotide polymorphism (SNP) genotype data and the region's haplotype structure, but the performance of these methods in admixed populations (such as African Americans) has not been adequately evaluated. We compared genotype-based-derived from both genome-wide genotyping and targeted sequencing-imputation results to existing allele data for HLA-DRB1, -DQB1, and -DPB1.
  
  
  RESULTS
  In European Americans, the newly-developed HLA Genotype Imputation with Attribute Bagging (HIBAG) method outperformed HLA*IMP:02. In African Americans, HLA*IMP:02 performed marginally better than HIBAG pre-built models, but HIBAG models constructed using a portion of our African American sample with both SNP genotyping and four-digit HLA class II allele typing had consistently higher accuracy than HLA*IMP:02. However, HIBAG was significantly less accurate in individuals heterozygous for local ancestry (p ≤0.04). Accuracy improved in models with equal numbers of African and European chromosomes. Variants added by targeted sequencing and SNP imputation further improved both imputation accuracy and the proportion of high quality calls.
  
  
  CONCLUSIONS
  Combining the HIBAG approach with local ancestry and dense variant data can produce highly-accurate HLA class II allele imputation in African Americans.
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, 1 Ford Place, 3E, 48202 Detroit, MI, USA. alevin1@hfhs.org.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Levin
authors.forename: Indra
authors.initials: I
authors.lastname: Adrianto
authors.forename: Indrani
authors.initials: I
authors.lastname: Datta
authors.forename: Michael C
authors.initials: MC
authors.lastname: Iannuzzi
authors.forename: Sheri
authors.initials: S
authors.lastname: Trudeau
authors.forename: Paul
authors.initials: P
authors.lastname: McKeigue
authors.forename: Courtney G
authors.initials: CG
authors.lastname: Montgomery
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Rybicki
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D060005:Genotyping Techniques / Q000379:methods*; D059868:HLA-DP beta-Chains / Q000235:genetics*; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics
chemical_list: D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains