PMID- 27486778
OWN - NLM
STAT- MEDLINE
DCOM- 20170509
LR  - 20221207
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 99
IP  - 2
DP  - 2016 Aug 4
TI  - Contribution of a Non-classical HLA Gene, HLA-DOA, to the Risk of Rheumatoid 
      Arthritis.
PG  - 366-74
LID - S0002-9297(16)30223-3 [pii]
LID - 10.1016/j.ajhg.2016.06.019 [doi]
AB  - Despite the progress in human leukocyte antigen (HLA) causal variant mapping, 
      independent localization of major histocompatibility complex (MHC) risk from 
      classical HLA genes is challenging. Here, we conducted a large-scale MHC 
      fine-mapping analysis of rheumatoid arthritis (RA) in a Japanese population 
      (6,244 RA cases and 23,731 controls) population by using HLA imputation, followed 
      by a multi-ethnic validation study including east Asian and European populations 
      (n = 7,097 and 23,149, respectively). Our study identified an independent risk of 
      a synonymous mutation at HLA-DOA, a non-classical HLA gene, on anti-citrullinated 
      protein autoantibody (ACPA)-positive RA risk (p = 1.4 x 10(-9)), which 
      demonstrated a cis-expression quantitative trait loci (cis-eQTL) effect on 
      HLA-DOA expression. Trans-ethnic comparison revealed different linkage 
      disequilibrium (LD) patterns in HLA-DOA and HLA-DRB1, explaining the observed 
      HLA-DOA variant risk heterogeneity among ethnicities, which was most evident in 
      the Japanese population. Although previous HLA fine-mapping studies have 
      identified amino acid polymorphisms of the classical HLA genes as driving genetic 
      susceptibility to disease, our study additionally identifies the dosage 
      contribution of a non-classical HLA gene to disease etiology. Our study 
      contributes to the understanding of HLA immunology in human diseases and suggests 
      the value of incorporating additional ancestry in MHC fine-mapping.
CI  - Copyright (c) 2016. Published by Elsevier Inc.
FAU - Okada, Yukinori
AU  - Okada Y
AD  - Department of Human Genetics and Disease Diversity, Graduate School of Medical 
      and Dental Sciences, Tokyo Medical and Dental University, 113-0034 Tokyo, Japan; 
      Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan; Department of Statistical Genetics, Graduate 
      School of Medicine, Osaka University, Osaka 565-0871, Japan. Electronic address: 
      yokada@sg.med.osaka-u.ac.jp.
FAU - Suzuki, Akari
AU  - Suzuki A
AD  - Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan.
FAU - Ikari, Katsunori
AU  - Ikari K
AD  - Institute of Rheumatology, Tokyo Women's Medical University, Tokyo 162-0054, 
      Japan; Core Research for Evolutional Science and Technology (CREST), Japan 
      Science and Technology Agency (JST), Tokyo 162-0054, Japan.
FAU - Terao, Chikashi
AU  - Terao C
AD  - Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and 
      Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Program in 
      Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA; 
      Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 
      606-8507, Japan; Center for the Promotion of Interdisciplinary Education and 
      Research, Kyoto University, Kyoto 606-8501, Japan.
FAU - Kochi, Yuta
AU  - Kochi Y
AD  - Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan; Core Research for Evolutional Science and 
      Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 162-0054, 
      Japan.
FAU - Ohmura, Koichiro
AU  - Ohmura K
AD  - Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, 
      Kyoto University, Kyoto 606-8507, Japan.
FAU - Higasa, Koichiro
AU  - Higasa K
AD  - Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 
      606-8507, Japan.
FAU - Akiyama, Masato
AU  - Akiyama M
AD  - Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan.
FAU - Ashikawa, Kyota
AU  - Ashikawa K
AD  - Laboratory for Genotyping Development, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, 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, 113-0034 Tokyo, Japan; 
      Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan.
FAU - Hirata, Jun
AU  - Hirata J
AD  - Department of Human Genetics and Disease Diversity, Graduate School of Medical 
      and Dental Sciences, Tokyo Medical and Dental University, 113-0034 Tokyo, Japan; 
      Pharmaceutical Discovery Research Laboratories, Teijin Pharma, Hino 191-8512, 
      Japan.
FAU - Suita, Naomasa
AU  - Suita N
AD  - Department of Human Genetics and Disease Diversity, Graduate School of Medical 
      and Dental Sciences, Tokyo Medical and Dental University, 113-0034 Tokyo, Japan; 
      Advanced Medicinal Research Laboratories, Tsukuba Research Institute, Ono 
      Pharmaceutical, Tsukuba 300-4247, Japan.
FAU - Teo, Yik-Ying
AU  - Teo YY
AD  - Saw Swee Hock School of Public Health, National University of Singapore, 
      Singapore 117549.
FAU - Xu, Huji
AU  - Xu H
AD  - Department of Rheumatology and Immunology, Shanghai Changzheng Hospital and The 
      Second Military Medical University, Shanghai 200433, China.
FAU - Bae, Sang-Cheol
AU  - Bae SC
AD  - Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 
      Seoul 04763, South Korea.
FAU - Takahashi, Atsushi
AU  - Takahashi A
AD  - Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan.
FAU - Momozawa, Yukihide
AU  - Momozawa Y
AD  - Laboratory for Genotyping Development, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan.
FAU - Matsuda, Koichi
AU  - Matsuda K
AD  - Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical 
      Science, The University of Tokyo, 108-8639 Tokyo, Japan.
FAU - Momohara, Shigeki
AU  - Momohara S
AD  - Institute of Rheumatology, Tokyo Women's Medical University, Tokyo 162-0054, 
      Japan.
FAU - Taniguchi, Atsuo
AU  - Taniguchi A
AD  - Institute of Rheumatology, Tokyo Women's Medical University, Tokyo 162-0054, 
      Japan.
FAU - Yamada, Ryo
AU  - Yamada R
AD  - Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 
      606-8507, Japan.
FAU - Mimori, Tsuneyo
AU  - Mimori T
AD  - Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, 
      Kyoto University, Kyoto 606-8507, Japan.
FAU - Kubo, Michiaki
AU  - Kubo M
AD  - Laboratory for Genotyping Development, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan.
FAU - Brown, Matthew A
AU  - Brown MA
AD  - University of Queensland Diamantina Institute, Translational Research Institute, 
      Princess Alexandra Hospital, Brisbane, Queensland 4072, Australia.
FAU - Raychaudhuri, Soumya
AU  - Raychaudhuri S
AD  - Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and 
      Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Program in 
      Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA; 
      Partners Center for Personalized Genetic Medicine, Boston, MA 02115, USA; Faculty 
      of Medical and Human Sciences, University of Manchester, Manchester M13 9PL, UK.
FAU - Matsuda, Fumihiko
AU  - Matsuda F
AD  - Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 
      606-8507, Japan.
FAU - Yamanaka, Hisashi
AU  - Yamanaka H
AD  - Institute of Rheumatology, Tokyo Women's Medical University, Tokyo 162-0054, 
      Japan.
FAU - Kamatani, Yoichiro
AU  - Kamatani Y
AD  - Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan.
FAU - Yamamoto, Kazuhiko
AU  - Yamamoto K
AD  - Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan; Department of Allergy and Rheumatology, 
      Graduate School of Medicine, the University of Tokyo, Tokyo 113-0033, Japan.
LA  - eng
GR  - R01 AR063759/AR/NIAMS NIH HHS/United States
GR  - UH2 AR067677/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Validation Study
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Autoantibodies)
RN  - 0 (HLA-D Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 29VT07BGDA (Citrulline)
SB  - IM
MH  - Arthritis, Rheumatoid/*genetics
MH  - Asian People/*genetics
MH  - Autoantibodies
MH  - Citrulline
MH  - Ethnicity/genetics
MH  - Europe/ethnology
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - HLA-D Antigens/*genetics
MH  - HLA-DRB1 Chains/genetics
MH  - Humans
MH  - Japan/ethnology
MH  - Linkage Disequilibrium/genetics
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide/genetics
MH  - White People/genetics
PMC - PMC4974094
EDAT- 2016/08/04 06:00
MHDA- 2017/05/10 06:00
PMCR- 2017/02/04
CRDT- 2016/08/04 06:00
PHST- 2016/02/19 00:00 [received]
PHST- 2016/06/21 00:00 [accepted]
PHST- 2016/08/04 06:00 [entrez]
PHST- 2016/08/04 06:00 [pubmed]
PHST- 2017/05/10 06:00 [medline]
PHST- 2017/02/04 00:00 [pmc-release]
AID - S0002-9297(16)30223-3 [pii]
AID - 10.1016/j.ajhg.2016.06.019 [doi]
PST - ppublish
SO  - Am J Hum Genet. 2016 Aug 4;99(2):366-74. doi: 10.1016/j.ajhg.2016.06.019.