Construction and application of a Korean reference panel for imputing classical alleles and amino acids of human leukocyte antigen genes

Kwangwoo Kim; So-Young Bang; Hye-Soon Lee; Sang-Cheol Bae

doi:10.1371/journal.pone.0112546

Construction and application of a Korean reference panel for imputing classical alleles and amino acids of human leukocyte antigen genes

PLoS One. 2014 Nov 14;9(11):e112546. doi: 10.1371/journal.pone.0112546. eCollection 2014.

Authors

Kwangwoo Kim¹, So-Young Bang², Hye-Soon Lee², Sang-Cheol Bae²

Affiliations

¹ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America.
² Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.

Abstract

Genetic variations of human leukocyte antigen (HLA) genes within the major histocompatibility complex (MHC) locus are strongly associated with disease susceptibility and prognosis for many diseases, including many autoimmune diseases. In this study, we developed a Korean HLA reference panel for imputing classical alleles and amino acid residues of several HLA genes. An HLA reference panel has potential for use in identifying and fine-mapping disease associations with the MHC locus in East Asian populations, including Koreans. A total of 413 unrelated Korean subjects were analyzed for single nucleotide polymorphisms (SNPs) at the MHC locus and six HLA genes, including HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1. The HLA reference panel was constructed by phasing the 5,858 MHC SNPs, 233 classical HLA alleles, and 1,387 amino acid residue markers from 1,025 amino acid positions as binary variables. The imputation accuracy of the HLA reference panel was assessed by measuring concordance rates between imputed and genotyped alleles of the HLA genes from a subset of the study subjects and East Asian HapMap individuals. Average concordance rates were 95.6% and 91.1% at 2-digit and 4-digit allele resolutions, respectively. The imputation accuracy was minimally affected by SNP density of a test dataset for imputation. In conclusion, the Korean HLA reference panel we developed was highly suitable for imputing HLA alleles and amino acids from MHC SNPs in East Asians, including Koreans.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alleles*
Amino Acid Sequence
Asian People / genetics*
Gene Library*
Genetic Variation*
HLA Antigens / genetics*
Humans
Molecular Sequence Data
Polymorphism, Single Nucleotide
Republic of Korea

Substances

HLA Antigens

Grants and funding

This work was supported by grants from the Korea Healthcare Technology R&D project of the Ministry for Health & Welfare (HI13C2124). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.