title: Human leucocyte antigen class I and II imputation in a multiracial population.
abstract: Human leucocyte antigen (HLA) genes play a central role in response to pathogens and in autoimmunity. Research to understand the effects of HLA genes on health has been limited because HLA genotyping protocols are labour intensive and expensive. Recently, algorithms to impute HLA genotype data using genome-wide association study (GWAS) data have been published. However, imputation accuracy for most of these algorithms was based primarily on training data sets of European ancestry individuals. We considered performance of two HLA-dedicated imputation algorithms - SNP2HLA and HIBAG - in a multiracial population of n = 1587 women with HLA genotyping data by gold standard methods. We first compared accuracy - defined as the percentage of correctly predicted alleles - of HLA-B and HLA-C imputation using SNP2HLA and HIBAG using a breakdown of the data set into an 80% training group and a 20% testing group. Estimates of accuracy for HIBAG were either the same or better than those for SNP2HLA. We then conducted a more thorough test of HIBAG imputation accuracy using five independent 10-fold cross-validation procedures with delineation of ancestry groups using ancestry informative markers. Overall accuracy for HIBAG was 89%. Accuracy by HLA gene was 93% for HLA-A, 84% for HLA-B, 94% for HLA-C, 83% for HLA-DQA1, 91% for HLA-DQB1 and 88% for HLA-DRB1. Accuracy was highest in the African ancestry group (the largest group) and lowest in the Hispanic group (the smallest group). Despite suboptimal imputation accuracy for some HLA gene/ancestry group combinations, the HIBAG algorithm has the advantage of providing posterior estimates of accuracy which enable the investigator to analyse subsets of the population with high predicted (e.g. >95%) imputation accuracy.
authors: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
authors: M H
authors: MH
authors: Kuniholm
authors: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
authors: X
authors: X
authors: Xie
authors: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors: K
authors: K
authors: Anastos
authors: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
authors: X
authors: X
authors: Xue
authors: Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA.
authors: L
authors: L
authors: Reimers
authors: Ruth M. Rothstein CORE Center, Stroger Hospital of Cook County, Chicago, IL, USA.
authors: A L
authors: AL
authors: French
authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors: S J
authors: SJ
authors: Gange
authors: Department of Medicine, Georgetown University Medical Center, Washington, DC, USA.
authors: S G
authors: SG
authors: Kassaye
authors: Department of Pediatrics, University of Southern California, Los Angeles, CA, USA.
authors: A
authors: A
authors: Kovacs
authors: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
authors: T
authors: T
authors: Wang
authors: Bluestone Center for Clinical Research, New York University, New York, NY, USA.|Department of Oral and Maxillofacial Surgery, New York University, New York, NY, USA.
authors: B E
authors: BE
authors: Aouizerat
authors: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
authors: H D
authors: HD
authors: Strickler
mesh_terms: D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D044465:White People
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens