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Construction of a population-specific HLA imputation reference panel and its application to Graves' disease risk in Japanese.
- Source :
-
Nature genetics [Nat Genet] 2015 Jul; Vol. 47 (7), pp. 798-802. Date of Electronic Publication: 2015 Jun 01. - Publication Year :
- 2015
-
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, ɛ, 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.
- Subjects :
- Case-Control Studies
Gene Frequency
Genetic Predisposition to Disease
Genetic Testing standards
Genome-Wide Association Study
Humans
Japan
Linkage Disequilibrium
Mutation, Missense
Polymorphism, Single Nucleotide
Reference Standards
Risk
Sequence Analysis, DNA
Graves Disease genetics
Histocompatibility Antigens Class I genetics
Histocompatibility Antigens Class II genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1546-1718
- Volume :
- 47
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Nature genetics
- Publication Type :
- Academic Journal
- Accession number :
- 26029868
- Full Text :
- https://doi.org/10.1038/ng.3310