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 language | English |
|---|---|
| Pages (from-to) | 798-802 |
| Number of pages | 5 |
| Journal | Nature Genetics |
| Volume | 47 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 26-06-2015 |
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All Science Journal Classification (ASJC) codes
- Genetics
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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 journal › Article
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
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
VL - 47
SP - 798
EP - 802
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 7
ER -