PMID- 28314753
OWN - NLM
STAT- MEDLINE
DCOM- 20170814
LR  - 20200225
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Print)
IS  - 0003-4967 (Linking)
VI  - 76
IP  - 6
DP  - 2017 Jun
TI  - Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to 
      systemic sclerosis.
PG  - 1150-1158
LID - 10.1136/annrheumdis-2016-210645 [doi]
AB  - OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease characterised by 
      skin and systemic fibrosis culminating in organ damage. Previous genetic studies 
      including genome-wide association studies (GWAS) have identified 12 
      susceptibility loci satisfying genome-wide significance. Transethnic 
      meta-analyses have successfully expanded the list of susceptibility genes and 
      deepened biological insights for other autoimmune diseases. METHODS: We performed 
      transethnic meta-analysis of GWAS in the Japanese and European populations, 
      followed by a two-staged replication study comprising a total of 4436 cases and 
      14 751 controls. Associations between significant single nuclear polymorphisms 
      (SNPs) and neighbouring genes were evaluated. Enrichment analysis of H3K4Me3, a 
      representative histone mark for active promoter was conducted with an expanded 
      list of SSc susceptibility genes. RESULTS: We identified two significant SNP in 
      two loci, GSDMA and PRDM1, both of which are related to immune functions and 
      associated with other autoimmune diseases (p=1.4x10(-10) and 6.6x10(-10), 
      respectively). GSDMA also showed a significant association with limited cutaneous 
      SSc. We also replicated the associations of previously reported loci including a 
      non-GWAS locus, TNFAIP3. PRDM1 encodes BLIMP1, a transcription factor regulating 
      T-cell proliferation and plasma cell differentiation. The top SNP in GSDMA was a 
      missense variant and correlated with gene expression of neighbouring genes, and 
      this could explain the association in this locus. We found different human 
      leukocyte antigen (HLA) association patterns between the two populations. 
      Enrichment analysis suggested the importance of CD4-naive primary T cell. 
      CONCLUSIONS: GSDMA and PRDM1 are associated with SSc. These findings provide 
      enhanced insight into the genetic and biological basis of SSc.
CI  - Published by the BMJ Publishing Group Limited. For permission to use (where not 
      already granted under a licence) please go to 
      http://www.bmj.com/company/products-services/rights-and-licensing/.
FAU - Terao, Chikashi
AU  - Terao C
AD  - Department of Center for Genomic Medicine, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
AD  - Center for the Promotion of Interdisciplinary Education and Research, Kyoto 
      University Graduate School of Medicine, Kyoto, Japan.
AD  - Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, 
      Boston, Massachusetts, USA.
AD  - Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, Massachusetts, USA.
AD  - Program in Medical and Population Genetics, Broad Institute, Cambridge, 
      Massachusetts, USA.
FAU - Kawaguchi, Takahisa
AU  - Kawaguchi T
AD  - Department of Center for Genomic Medicine, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Dieude, Philippe
AU  - Dieude P
AD  - Rheumatology Bichat Hospital, Paris 7 University, Paris, France.
FAU - Varga, John
AU  - Varga J
AD  - Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
FAU - Kuwana, Masataka
AU  - Kuwana M
AD  - Division of Rheumatology, Department of Internal Medicine, Keio University School 
      of Medicine, Tokyo, Japan.
FAU - Hudson, Marie
AU  - Hudson M
AD  - Jewish General Hospital and Lady Davis Research Institute, Montreal, Quebec, 
      Canada.
FAU - Kawaguchi, Yasushi
AU  - Kawaguchi Y
AD  - Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
FAU - Matucci-Cerinic, Marco
AU  - Matucci-Cerinic M
AD  - Division of Rheumatology AOUC, Department of Experimental and Clinical Medicine, 
      Department of Medical & Geriatrics Medicine, University of Florence, Firenze, 
      Italy.
FAU - Ohmura, Koichiro
AU  - Ohmura K
AD  - Department of Rheumatology and Clinical Immunology, Kyoto University Graduate 
      School of Medicine, Kyoto, Japan.
FAU - Riemekasten, Gabriela
AU  - Riemekasten G
AD  - Clinic for Rheumatology, University of Lubeck, Lubeck, Germany.
AD  - German Lung Center Borstel, Leibniz Institute, Germany.
FAU - Kawasaki, Aya
AU  - Kawasaki A
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, Tsukuba, Japan.
FAU - Airo, Paolo
AU  - Airo P
AD  - Rheumatology Unit, Spedali Civili, Brescia, Italy.
FAU - Horita, Tetsuya
AU  - Horita T
AD  - Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University 
      Graduate School of Medicine, Sapporo, Japan.
FAU - Oka, Akira
AU  - Oka A
AD  - The Institute of Medical Science, Tokai University, Isehara, Japan.
FAU - Hachulla, Eric
AU  - Hachulla E
AD  - Internal Medicine Department, FHU Immune-Mediated Inflammatory Diseases and 
      Targeted Therapies, Lille University, Lille, France.
FAU - Yoshifuji, Hajime
AU  - Yoshifuji H
AD  - Department of Rheumatology and Clinical Immunology, Kyoto University Graduate 
      School of Medicine, Kyoto, Japan.
FAU - Caramaschi, Paola
AU  - Caramaschi P
AD  - Rheumatology Department, University of Verona, Azienda Ospedaliera Universitaria 
      Integrata, Italy.
FAU - Hunzelmann, Nicolas
AU  - Hunzelmann N
AD  - Dermatology Department, University of Koln, Koln, Germany.
FAU - Baron, Murray
AU  - Baron M
AD  - Jewish General Hospital and Lady Davis Research Institute, Montreal, Quebec, 
      Canada.
FAU - Atsumi, Tatsuya
AU  - Atsumi T
AD  - Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University 
      Graduate School of Medicine, Sapporo, Japan.
FAU - Hassoun, Paul
AU  - Hassoun P
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns 
      Hopkins University, Baltimore, Maryland, USA.
FAU - Torii, Takeshi
AU  - Torii T
AD  - Torii Clinic, Kyoto, Japan.
FAU - Takahashi, Meiko
AU  - Takahashi M
AD  - Department of Center for Genomic Medicine, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Tabara, Yasuharu
AU  - Tabara Y
AD  - Department of Center for Genomic Medicine, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Shimizu, Masakazu
AU  - Shimizu M
AD  - Department of Center for Genomic Medicine, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Tochimoto, Akiko
AU  - Tochimoto A
AD  - Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
FAU - Ayuzawa, Naho
AU  - Ayuzawa N
AD  - Department of Rheumatology, National Hospital Organization, Utano National 
      Hospital, Kyoto, Japan.
FAU - Yanagida, Hidetoshi
AU  - Yanagida H
AD  - Department of Rheumatology, National Hospital Organization, Utano National 
      Hospital, Kyoto, Japan.
FAU - Furukawa, Hiroshi
AU  - Furukawa H
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, Tsukuba, Japan.
AD  - Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, 
      National Hospital Organization, Sagamihara, Japan.
FAU - Tohma, Shigeto
AU  - Tohma S
AD  - Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, 
      National Hospital Organization, Sagamihara, Japan.
FAU - Hasegawa, Minoru
AU  - Hasegawa M
AD  - Division of Medicine, Faculty of Medical Sciences, Department of Dermatology, 
      University of Fukui, Fukui, Japan.
FAU - Fujimoto, Manabu
AU  - Fujimoto M
AD  - Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, 
      Ibaraki, Japan.
FAU - Ishikawa, Osamu
AU  - Ishikawa O
AD  - Department of Dermatology, Gunma University Graduate School of Medicine, Gunma, 
      Japan.
FAU - Yamamoto, Toshiyuki
AU  - Yamamoto T
AD  - Department of Dermatology, Fukushima Medical University, Fukushima, Japan.
FAU - Goto, Daisuke
AU  - Goto D
AD  - Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, 
      Tsukuba, Japan.
FAU - Asano, Yoshihide
AU  - Asano Y
AD  - Department of Dermatology, University of Tokyo Graduate School of Medicine, 
      Tokyo, Japan.
FAU - Jinnin, Masatoshi
AU  - Jinnin M
AD  - Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto 
      University, Kumamoto, Japan.
FAU - Endo, Hirahito
AU  - Endo H
AD  - Division of Rheumatology, Department of Internal Medicine, School of Medicine, 
      Toho University, Tokyo, Japan.
FAU - Takahashi, Hiroki
AU  - Takahashi H
AD  - Department of Rheumatology and Clinical Immunology, Sapporo Medical University 
      School of Medicine, Sapporo, Hokkaido, Japan.
FAU - Takehara, Kazuhiko
AU  - Takehara K
AD  - Department of Dermatology, Faculty of Medicine, Institute of Medical, 
      Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, 
      Japan.
FAU - Sato, Shinichi
AU  - Sato S
AD  - Department of Dermatology, University of Tokyo Graduate School of Medicine, 
      Tokyo, Japan.
FAU - Ihn, Hironobu
AU  - Ihn H
AD  - Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto 
      University, Kumamoto, Japan.
FAU - Raychaudhuri, Soumya
AU  - Raychaudhuri S
AD  - Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, 
      Boston, Massachusetts, USA.
AD  - Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, Massachusetts, USA.
AD  - Program in Medical and Population Genetics, Broad Institute, Cambridge, 
      Massachusetts, USA.
AD  - Arthritis Research UK Centre for Genetics and Genomics, Centre for 
      Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester 
      Academic Health Science Centre, The University of Manchester, Manchester, UK.
FAU - Liao, Katherine
AU  - Liao K
AD  - Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, 
      Boston, Massachusetts, USA.
FAU - Gregersen, Peter
AU  - Gregersen P
AD  - Robert S. Boas Center for Genomics and Human Genetics, The Feinstein Institute 
      for Medical Research, Manhasset, New York, USA.
FAU - Tsuchiya, Naoyuki
AU  - Tsuchiya N
AUID- ORCID: 0000-0002-6776-5580
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, Tsukuba, Japan.
FAU - Riccieri, Valeria
AU  - Riccieri V
AD  - Sapienza University of Rome, Rome, Italy.
FAU - Melchers, Inga
AU  - Melchers I
AD  - University Medical Center, Freiburg, Germany.
FAU - Valentini, Gabriele
AU  - Valentini G
AD  - Department of Clinical and Experimental Medicine, Rheumatology Section, Second 
      University of Naples, Naples, Italy.
FAU - Cauvet, Anne
AU  - Cauvet A
AD  - INSERM U1016/UMR 8104, Cochin Institute, Paris Descartes University, Paris, 
      France.
FAU - Martinez, Maria
AU  - Martinez M
AD  - INSERM U1220-IRSD-Batiment B Purpan Hospital Toulouse, Paris, France.
FAU - Mimori, Tsuneyo
AU  - Mimori T
AD  - Department of Rheumatology and Clinical Immunology, Kyoto University Graduate 
      School of Medicine, Kyoto, Japan.
FAU - Matsuda, Fumihiko
AU  - Matsuda F
AD  - Department of Center for Genomic Medicine, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Allanore, Yannick
AU  - Allanore Y
AD  - Rheumatology A Department, INSERM U1016/UMR 8104, Cochin Institute, Paris 
      Descartes University, Paris, France.
LA  - eng
GR  - R01 AR063759/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
DEP - 20170317
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (GSDMA protein, human)
RN  - 0 (HLA Antigens)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Repressor Proteins)
RN  - 138415-26-6 (PRDM1 protein, human)
RN  - EC 2.1.1.- (Positive Regulatory Domain I-Binding Factor 1)
SB  - IM
MH  - Case-Control Studies
MH  - Europe/epidemiology
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - HLA Antigens/genetics
MH  - Humans
MH  - Japan/epidemiology
MH  - Neoplasm Proteins/*genetics
MH  - Polymorphism, Single Nucleotide
MH  - Positive Regulatory Domain I-Binding Factor 1
MH  - Repressor Proteins/*genetics
MH  - Scleroderma, Systemic/ethnology/*genetics
PMC - PMC6733404
MID - NIHMS1047771
OTO - NOTNLM
OT  - Autoimmune Diseases
OT  - Gene Polymorphism
OT  - Systemic Sclerosis
COIS- Competing interests: None declared.
EDAT- 2017/03/21 06:00
MHDA- 2017/08/15 06:00
PMCR- 2019/09/09
CRDT- 2017/03/19 06:00
PHST- 2016/10/06 00:00 [received]
PHST- 2017/01/08 00:00 [revised]
PHST- 2017/02/21 00:00 [accepted]
PHST- 2017/03/21 06:00 [pubmed]
PHST- 2017/08/15 06:00 [medline]
PHST- 2017/03/19 06:00 [entrez]
PHST- 2019/09/09 00:00 [pmc-release]
AID - annrheumdis-2016-210645 [pii]
AID - 10.1136/annrheumdis-2016-210645 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2017 Jun;76(6):1150-1158. doi: 10.1136/annrheumdis-2016-210645. 
      Epub 2017 Mar 17.