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Performance of HLA allele prediction methods in African Americans for class II genes HLA-DRB1, −DQB1, and –DPB1

Albert M Levin12*, Indra Adrianto3, Indrani Datta12, Michael C Iannuzzi4, Sheri Trudeau1, Paul McKeigue5, Courtney G Montgomery3 and Benjamin A Rybicki1

Author Affiliations

1 Department of Public Health Sciences, Henry Ford Health System, 1 Ford Place, 3E, 48202 Detroit, MI, USA

2 Center for Bioinformatics, Henry Ford Health System, Detroit, MI, USA

3 Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

4 Department of Medicine, Upstate Medical University, Syracuse, NY, USA

5 Public Health Sciences Section, University of Edinburgh Medical School, Edinburgh, Scotland

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BMC Genetics 2014, 15:72  doi:10.1186/1471-2156-15-72

Published: 16 June 2014



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.


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.


Combining the HIBAG approach with local ancestry and dense variant data can produce highly-accurate HLA class II allele imputation in African Americans.

HLA; African American; Single nucleotide polymorphisms; Imputation; Admixture