PMID- 26029868
OWN - NLM
STAT- MEDLINE
DCOM- 20150909
LR  - 20220409
IS  - 1546-1718 (Electronic)
IS  - 1061-4036 (Linking)
VI  - 47
IP  - 7
DP  - 2015 Jul
TI  - Construction of a population-specific HLA imputation reference panel and its 
      application to Graves' disease risk in Japanese.
PG  - 798-802
LID - 10.1038/ng.3310 [doi]
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, varepsilon, 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 x 10(-6)), with the strongest 
      impact at HLA-DPB1 (P = 1.6 x 10(-42)). Our study illustrates the value of 
      population-specific HLA reference panels.
FAU - Okada, Yukinori
AU  - Okada Y
AD  - 1] Department of Human Genetics and Disease Diversity, Graduate School of Medical 
      and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. [2] 
      Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical 
      Sciences, Yokohama, Japan.
FAU - Momozawa, Yukihide
AU  - Momozawa Y
AD  - Laboratory for Genotyping Development, RIKEN Center for Integrative Medical 
      Sciences, Yokohama, Japan.
FAU - Ashikawa, Kyota
AU  - Ashikawa K
AD  - Laboratory for Genotyping Development, RIKEN Center for Integrative Medical 
      Sciences, Yokohama, Japan.
FAU - Kanai, Masahiro
AU  - Kanai M
AD  - Department of Human Genetics and Disease Diversity, Graduate School of Medical 
      and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Matsuda, Koichi
AU  - Matsuda K
AUID- ORCID: 0000000172922686
AD  - Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical 
      Science, The University of Tokyo, Tokyo, Japan.
FAU - Kamatani, Yoichiro
AU  - Kamatani Y
AD  - Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical 
      Sciences, Yokohama, Japan.
FAU - Takahashi, Atsushi
AU  - Takahashi A
AD  - Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical 
      Sciences, Yokohama, Japan.
FAU - Kubo, Michiaki
AU  - Kubo M
AD  - Laboratory for Genotyping Development, RIKEN Center for Integrative Medical 
      Sciences, Yokohama, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150601
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Case-Control Studies
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - Genetic Testing/standards
MH  - Genome-Wide Association Study
MH  - Graves Disease/*genetics
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Histocompatibility Antigens Class II/*genetics
MH  - Humans
MH  - Japan
MH  - Linkage Disequilibrium
MH  - Mutation, Missense
MH  - Polymorphism, Single Nucleotide
MH  - Reference Standards
MH  - Risk
MH  - Sequence Analysis, DNA
EDAT- 2015/06/02 06:00
MHDA- 2015/09/10 06:00
CRDT- 2015/06/02 06:00
PHST- 2014/11/28 00:00 [received]
PHST- 2015/04/27 00:00 [accepted]
PHST- 2015/06/02 06:00 [entrez]
PHST- 2015/06/02 06:00 [pubmed]
PHST- 2015/09/10 06:00 [medline]
AID - ng.3310 [pii]
AID - 10.1038/ng.3310 [doi]
PST - ppublish
SO  - Nat Genet. 2015 Jul;47(7):798-802. doi: 10.1038/ng.3310. Epub 2015 Jun 1.