title: High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci.
abstract: OBJECTIVE
  A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data.
  
  
  METHODS
  We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data for a total sample size of 9299 Korean and 45,790 European case-control samples.
  
  
  RESULTS
  We identified eight new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1-FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5×10(-8)), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the seven new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of single nucleotide polymorphisms (SNPs) that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs.
  
  
  CONCLUSIONS
  This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases.
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
authors.forename: Kwangwoo
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Bang
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Hye-Soon
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Cho
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Chan-Bum
authors.initials: CB
authors.lastname: Choi
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Yoon-Kyoung
authors.initials: YK
authors.lastname: Sung
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Jae-Bum
authors.initials: JB
authors.lastname: Jun
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Yoo
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Arthritis & Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea.
authors.forename: Seong-Kyu
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Rheumatology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Chang-Hee
authors.initials: CH
authors.lastname: Suh
authors.affiliation: Division of Rheumatology, Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, Republic of Korea.
authors.forename: Seung-Cheol
authors.initials: SC
authors.lastname: Shim
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
authors.forename: Shin-Seok
authors.initials: SS
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authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jisoo
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authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Department of internal medicine, Dong-A University, Busan, Republic of Korea.
authors.forename: Won Tae
authors.initials: WT
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authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Arthritis & Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea.
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Choe
authors.affiliation: Department of Life Science, Sogang University, Seoul, Republic of Korea.
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.affiliation: Center for Genome Science, Korea National Institute of Health, Osong Health Technology, Chungcheongbuk-do, Republic of Korea.
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Center for Genome Science, Korea National Institute of Health, Osong Health Technology, Chungcheongbuk-do, Republic of Korea.
authors.forename: Bok-Ghee
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authors.affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
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authors.initials: SK
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authors.affiliation: Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, UK.
authors.forename: Steve
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authors.affiliation: Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, UK.
authors.forename: John
authors.initials: J
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authors.affiliation: Department of Medicine, Division of Rheumatology, Columbia University, New York, New York, USA.
authors.forename: Dimitrios A
authors.initials: DA
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authors.affiliation: The Center of Rheumatology, Albany, New York, USA.
authors.forename: Joel M
authors.initials: JM
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authors.affiliation: Department of Rheumatology, Hospital Marques de Valdecilla, IFIMAV, Santander, Spain.
authors.forename: Miguel A
authors.initials: MA
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authors.affiliation: Department of Rheumatology, Hospital Clinico San Carlos, Madrid, Spain.
authors.forename: Luis
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authors.affiliation: Department of Clinical Medicine/Rheumatoloy, Umeå University, Umeå, Sweden.
authors.forename: Lisbeth
authors.initials: L
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authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Yukinori
authors.initials: Y
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authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Diogo
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Katherine P
authors.initials: KP
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authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Karlson
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, UK.
authors.forename: Soumya
authors.initials: S
authors.lastname: Raychaudhuri
authors.affiliation: Department of Clinical Medicine/Rheumatoloy, Umeå University, Umeå, Sweden.
authors.forename: Solbritt
authors.initials: S
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authors.affiliation: Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Granada, Spain.
authors.forename: Javier
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authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Lars
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authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Leonid
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authors.affiliation: The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York, USA.
authors.forename: Peter K
authors.initials: PK
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authors.affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
authors.forename: Jane
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authors.lastname: Worthington
authors.affiliation: Division of Rheumatology, New York University School of Medicine, New York, New York, USA.
authors.forename: Jeffrey D
authors.initials: JD
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authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
authors.forename: Robert M
authors.initials: RM
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authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
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mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D056910:Republic of Korea / Q000208:ethnology; D044465:White People / Q000235:genetics*; D055815:Young Adult
keywords: Ant-CCP; Gene Polymorphism; Rheumatoid Arthritis