Construction of a population-specific HLA imputation reference panel and its application to Graves' disease risk in Japanese

Yukinori Okada, Yukihide Momozawa, Kyota Ashikawa, Masahiro Kanai, Koichi Matsuda, Yoichiro Kamatani, Atsushi Takahashi, Michiaki Kubo

Research output: Contribution to journalArticle

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Abstract

To fine map association signals of human leukocyte antigen (HLA) variants in the major histocompatibility complex (MHC) region, we constructed a Japanese population-specific reference panel (n = 908). We conducted trans-ancestry comparisons of linkage disequilibrium (LD) and haplotype structure for HLA variants using an entropy-based LD measurement, I, and a visualization tool to capture high-dimensional variables. Our Japanese reference panel exhibited stronger LD between HLA genes than European or other East Asian populations, characterized by one population-specific common long-range HLA haplotype. We applied HLA imputation to genome-wide association study (GWAS) data for Graves' disease in Japanese (n = 9,003) and found that amino acid polymorphisms of multiple class I and class II HLA genes independently contribute to disease risk (HLA-DPB1, HLA-A, HLA-B and HLA-DRB1; P < 2.3 × 10 '6), with the strongest impact at HLA-DPB1 (P = 1.6 × 10 '42). Our study illustrates the value of population-specific HLA reference panels.

Original languageEnglish
Pages (from-to)798-802
Number of pages5
JournalNature Genetics
Volume47
Issue number7
DOIs
Publication statusPublished - 26-06-2015

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Graves Disease
HLA Antigens
Population
Linkage Disequilibrium
Haplotypes
HLA-D Antigens
Genome-Wide Association Study
Entropy
Major Histocompatibility Complex
Genes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Okada, Yukinori ; Momozawa, Yukihide ; Ashikawa, Kyota ; Kanai, Masahiro ; Matsuda, Koichi ; Kamatani, Yoichiro ; Takahashi, Atsushi ; Kubo, Michiaki. / Construction of a population-specific HLA imputation reference panel and its application to Graves' disease risk in Japanese. In: Nature Genetics. 2015 ; Vol. 47, No. 7. pp. 798-802.
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Okada, Y, Momozawa, Y, Ashikawa, K, Kanai, M, Matsuda, K, Kamatani, Y, Takahashi, A & Kubo, M 2015, 'Construction of a population-specific HLA imputation reference panel and its application to Graves' disease risk in Japanese', Nature Genetics, vol. 47, no. 7, pp. 798-802. https://doi.org/10.1038/ng.3310

Construction of a population-specific HLA imputation reference panel and its application to Graves' disease risk in Japanese. / Okada, Yukinori; Momozawa, Yukihide; Ashikawa, Kyota; Kanai, Masahiro; Matsuda, Koichi; Kamatani, Yoichiro; Takahashi, Atsushi; Kubo, Michiaki.

In: Nature Genetics, Vol. 47, No. 7, 26.06.2015, p. 798-802.

Research output: Contribution to journalArticle

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AU - Kubo, Michiaki

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