PMID- 21900946
OWN - NLM
STAT- MEDLINE
DCOM- 20120322
LR  - 20221207
IS  - 1435-232X (Electronic)
IS  - 1434-5161 (Linking)
VI  - 56
IP  - 11
DP  - 2011 Nov
TI  - Identification of independent risk loci for Graves' disease within the MHC in the 
      Japanese population.
PG  - 772-8
LID - 10.1038/jhg.2011.99 [doi]
AB  - To identify genetic variants that confer the risk of Graves' disease (GD) in the 
      Japanese population, we conducted a two-stage genome-wide association study 
      (GWAS) using 1119 Japanese individuals with GD and 2718 unrelated controls, and a 
      subsequent replication study using independent 432 GD cases and 1157 controls. We 
      identified 34 single nucleotide polymorphisms (SNPs) to be significantly 
      associated with GD in the GWAS phase. Twenty-two out of 34 SNPs remained positive 
      in the replication study. All 22 SNPs were located within the major 
      histocompatibility complex (MHC) locus on chromosome 6p21. No strong long-range 
      linkage disequilibrium (LD) was observed among the 22 SNPs, indicating 
      independent involvement of multiple loci within the MHC with the risk of GD. 
      Multivariate stepwise logistic regression analysis selected rs3893464, rs4313034, 
      rs3132613, rs4248154, rs2273017, rs9394159 and rs4713693, as markers for 
      independent risk loci for GD. The analysis of LD between these seven SNPs and 
      tagging SNPs for GD-associated human leukocyte antigen (HLA) alleles in the 
      Japanese population (HLA-DPB1(*)0501 and HLA-A(*)0206) demonstrated that all of 
      and five of seven SNPs were not in strong LD with HLA-DPB1(*)0501 and 
      HLA-A(*)0206, respectively. Although causal variants remain to be identified, our 
      results demonstrate the existence of multiple GD susceptibility loci within the 
      MHC region.
FAU - Nakabayashi, Kazuhiko
AU  - Nakabayashi K
AD  - Department of Cell Biology, Fukuoka University, Fukuoka, Japan. 
      knakabayashi@nch.go.jp
FAU - Tajima, Atsushi
AU  - Tajima A
FAU - Yamamoto, Ken
AU  - Yamamoto K
FAU - Takahashi, Atsushi
AU  - Takahashi A
FAU - Hata, Kenichiro
AU  - Hata K
FAU - Takashima, Yasuo
AU  - Takashima Y
FAU - Koyanagi, Midori
AU  - Koyanagi M
FAU - Nakaoka, Hirofumi
AU  - Nakaoka H
FAU - Akamizu, Takashi
AU  - Akamizu T
FAU - Ishikawa, Naofumi
AU  - Ishikawa N
FAU - Kubota, Sumihisa
AU  - Kubota S
FAU - Maeda, Shiro
AU  - Maeda S
FAU - Tsunoda, Tatsuhiko
AU  - Tsunoda T
FAU - Kubo, Michiaki
AU  - Kubo M
FAU - Kamatani, Naoyuki
AU  - Kamatani N
FAU - Nakamura, Yusuke
AU  - Nakamura Y
FAU - Sasazuki, Takehiko
AU  - Sasazuki T
FAU - Shirasawa, Senji
AU  - Shirasawa S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110908
PL  - England
TA  - J Hum Genet
JT  - Journal of human genetics
JID - 9808008
SB  - IM
MH  - Alleles
MH  - Asian People/genetics
MH  - Case-Control Studies
MH  - Gene Frequency
MH  - *Genetic Loci
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - Graves Disease/*genetics
MH  - Humans
MH  - Japan/ethnology
MH  - Major Histocompatibility Complex/*genetics
MH  - Polymorphism, Single Nucleotide
EDAT- 2011/09/09 06:00
MHDA- 2012/03/23 06:00
CRDT- 2011/09/09 06:00
PHST- 2011/09/09 06:00 [entrez]
PHST- 2011/09/09 06:00 [pubmed]
PHST- 2012/03/23 06:00 [medline]
AID - jhg201199 [pii]
AID - 10.1038/jhg.2011.99 [doi]
PST - ppublish
SO  - J Hum Genet. 2011 Nov;56(11):772-8. doi: 10.1038/jhg.2011.99. Epub 2011 Sep 8.