PMID- 28207879 OWN - NLM STAT- MEDLINE DCOM- 20170901 LR - 20230731 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 2 DP - 2017 TI - Comparison of HLA allelic imputation programs. PG - e0172444 LID - 10.1371/journal.pone.0172444 [doi] LID - e0172444 AB - Imputation of human leukocyte antigen (HLA) alleles from SNP-level data is attractive due to importance of HLA alleles in human disease, widespread availability of genome-wide association study (GWAS) data, and expertise required for HLA sequencing. However, comprehensive evaluations of HLA imputations programs are limited. We compared HLA imputation results of HIBAG, SNP2HLA, and HLA*IMP:02 to sequenced HLA alleles in 3,265 samples from BioVU, a de-identified electronic health record database coupled to a DNA biorepository. We performed four-digit HLA sequencing for HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1 using long-read 454 FLX sequencing. All samples were genotyped using both the Illumina HumanExome BeadChip platform and a GWAS platform. Call rates and concordance rates were compared by platform, frequency of allele, and race/ethnicity. Overall concordance rates were similar between programs in European Americans (EA) (0.975 [SNP2HLA]; 0.939 [HLA*IMP:02]; 0.976 [HIBAG]). SNP2HLA provided a significant advantage in terms of call rate and the number of alleles imputed. Concordance rates were lower overall for African Americans (AAs). These observations were consistent when accuracy was compared across HLA loci. All imputation programs performed similarly for low frequency HLA alleles. Higher concordance rates were observed when HLA alleles were imputed from GWAS platforms versus the HumanExome BeadChip, suggesting that high genomic coverage is preferred as input for HLA allelic imputation. These findings provide guidance on the best use of HLA imputation methods and elucidate their limitations. FAU - Karnes, Jason H AU - Karnes JH AUID- ORCID: 0000-0001-5001-3334 AD - Department of Pharmacy Practice and Science, University of Arizona College of Pharmacy, Tucson, Arizona, United States of America. FAU - Shaffer, Christian M AU - Shaffer CM AD - Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. FAU - Bastarache, Lisa AU - Bastarache L AD - Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America. FAU - Gaudieri, Silvana AU - Gaudieri S AD - Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. AD - School of Anatomy, Physiology and Human Biology, University of Western Australia, Nedlands, Western Australia, Australia. AD - Institute for Immunology & Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia. FAU - Glazer, Andrew M AU - Glazer AM AD - Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. FAU - Steiner, Heidi E AU - Steiner HE AD - Department of Pharmacy Practice and Science, University of Arizona College of Pharmacy, Tucson, Arizona, United States of America. FAU - Mosley, Jonathan D AU - Mosley JD AD - Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. FAU - Mallal, Simon AU - Mallal S AD - Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. AD - Institute for Immunology & Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia. AD - Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America. FAU - Denny, Joshua C AU - Denny JC AD - Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. AD - Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America. FAU - Phillips, Elizabeth J AU - Phillips EJ AD - Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. AD - Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. AD - Institute for Immunology & Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia. FAU - Roden, Dan M AU - Roden DM AD - Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. AD - Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America. AD - Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America. LA - eng GR - UL1 TR000445/TR/NCATS NIH HHS/United States GR - T32 GM007569/GM/NIGMS NIH HHS/United States GR - U19 HL065962/HL/NHLBI NIH HHS/United States GR - R01 LM010685/LM/NLM NIH HHS/United States GR - U01 HG004603/HG/NHGRI NIH HHS/United States GR - U01 GM092691/GM/NIGMS NIH HHS/United States GR - 16FTF30130005/AHA/American Heart Association-American Stroke Association/United States GR - RC2 GM092618/GM/NIGMS NIH HHS/United States GR - P50 GM115305/GM/NIGMS NIH HHS/United States GR - R01 AR062886/AR/NIAMS NIH HHS/United States PT - Journal Article DEP - 20170216 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (HLA Antigens) SB - IM MH - Black or African American MH - Alleles MH - Female MH - Gene Frequency MH - Genome-Wide Association Study MH - Genotype MH - HLA Antigens/*genetics MH - Haplotypes/*genetics MH - Humans MH - Male MH - Middle Aged MH - Polymorphism, Single Nucleotide/*genetics MH - White People PMC - PMC5312875 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/02/17 06:00 MHDA- 2017/09/02 06:00 PMCR- 2017/02/16 CRDT- 2017/02/17 06:00 PHST- 2016/12/09 00:00 [received] PHST- 2017/02/03 00:00 [accepted] PHST- 2017/02/17 06:00 [entrez] PHST- 2017/02/17 06:00 [pubmed] PHST- 2017/09/02 06:00 [medline] PHST- 2017/02/16 00:00 [pmc-release] AID - PONE-D-16-48785 [pii] AID - 10.1371/journal.pone.0172444 [doi] PST - epublish SO - PLoS One. 2017 Feb 16;12(2):e0172444. doi: 10.1371/journal.pone.0172444. eCollection 2017.