TY - JOUR
T1 - Construction of a population-specific HLA imputation reference panel and its application to Graves' disease risk in Japanese
AU - Okada, Yukinori
AU - Momozawa, Yukihide
AU - Ashikawa, Kyota
AU - Kanai, Masahiro
AU - Matsuda, Koichi
AU - Kamatani, Yoichiro
AU - Takahashi, Atsushi
AU - Kubo, Michiaki
N1 - Funding Information:
We thank N. Kumasaka who originally developed the Disentangler software. We acknowledge T. Aoi and C. Inai for technical assistance and the members of BioBank Japan and the Rotary Club of Osaka-Midosuji District 2660 Rotary International for supporting our study. Y.O. was supported by the Japan Science and Technology Agency (JST), the Japan Society of the Promotion of Science (JSPS), the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Takeda Science Foundation, the Gout Research Foundation, the Tokyo Biochemical Research Foundation and the Japan Rheumatism Foundation. The BioBank Japan Project was supported by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government.
Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.
PY - 2015/6/26
Y1 - 2015/6/26
N2 - 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.
AB - 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.
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U2 - 10.1038/ng.3310
DO - 10.1038/ng.3310
M3 - Article
C2 - 26029868
AN - SCOPUS:84933278837
VL - 47
SP - 798
EP - 802
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 7
ER -