Terao, Chikashi, Kawaguchi, Takahisa, Dieude, Philippe ORCID: 0000-0002-4814-0307, Varga, John, Kuwana, Masataka, Hudson, Marie, Kawaguchi, Yasushi, Matucci-Cerinic, Marco, Ohmura, Koichiro, Riemekasten, Gabriela, Kawasaki, Aya, Airo, Paolo, Horita, Tetsuya ORCID: 0000-0003-2332-3841, Oka, Akira, Hachulla, Eric, Yoshifuji, Hajime, Caramaschi, Paola, Hunzelmann, Nicolas, Baron, Murray, Atsumi, Tatsuya, Hassoun, Paul, Torii, Takeshi, Takahashi, Meiko, Tabara, Yasuharu, Shimizu, Masakazu, Tochimoto, Akiko, Ayuzawa, Naho, Yanagida, Hidetoshi, Furukawa, Hiroshi, Tohma, Shigeto, Hasegawa, Minoru ORCID: 0000-0003-3738-2682, Fujimoto, Manabu ORCID: 0000-0002-3062-4872, Ishikawa, Osamu, Yamamoto, Toshiyuki, Goto, Daisuke, Asano, Yoshihide, Jinnin, Masatoshi, Endo, Hirahito, Takahashi, Hiroki, Takehara, Kazuhiko, Sato, Shinichi, Ihn, Hironobu, Raychaudhuri, Soumya ORCID: 0000-0002-1901-8265, Liao, Katherine, Gregersen, Peter, Tsuchiya, Naoyuki ORCID: 0000-0002-6776-5580, Riccieri, Valeria, Melchers, Inga, Valentini, Gabriele, Cauvet, Anne, Martinez, Maria ORCID: 0000-0003-2180-4537, Mimori, Tsuneyo, Matsuda, Fumihiko and Allanore, Yannick (2017). Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis. Ann. Rheum. Dis., 76 (6). S. 1150 - 1159. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-2060

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Terao, ChikashiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kawaguchi, TakahisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dieude, PhilippeUNSPECIFIEDorcid.org/0000-0002-4814-0307UNSPECIFIED
Varga, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuwana, MasatakaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hudson, MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kawaguchi, YasushiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Matucci-Cerinic, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ohmura, KoichiroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riemekasten, GabrielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kawasaki, AyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Airo, PaoloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horita, TetsuyaUNSPECIFIEDorcid.org/0000-0003-2332-3841UNSPECIFIED
Oka, AkiraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hachulla, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yoshifuji, HajimeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caramaschi, PaolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hunzelmann, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baron, MurrayUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Atsumi, TatsuyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hassoun, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Torii, TakeshiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Takahashi, MeikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tabara, YasuharuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shimizu, MasakazuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tochimoto, AkikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ayuzawa, NahoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yanagida, HidetoshiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Furukawa, HiroshiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tohma, ShigetoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hasegawa, MinoruUNSPECIFIEDorcid.org/0000-0003-3738-2682UNSPECIFIED
Fujimoto, ManabuUNSPECIFIEDorcid.org/0000-0002-3062-4872UNSPECIFIED
Ishikawa, OsamuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yamamoto, ToshiyukiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goto, DaisukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Asano, YoshihideUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jinnin, MasatoshiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Endo, HirahitoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Takahashi, HirokiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Takehara, KazuhikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sato, ShinichiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ihn, HironobuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raychaudhuri, SoumyaUNSPECIFIEDorcid.org/0000-0002-1901-8265UNSPECIFIED
Liao, KatherineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gregersen, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tsuchiya, NaoyukiUNSPECIFIEDorcid.org/0000-0002-6776-5580UNSPECIFIED
Riccieri, ValeriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Melchers, IngaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Valentini, GabrieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cauvet, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martinez, MariaUNSPECIFIEDorcid.org/0000-0003-2180-4537UNSPECIFIED
Mimori, TsuneyoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Matsuda, FumihikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Allanore, YannickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-229502
DOI: 10.1136/annrheumdis-2016-210645
Journal or Publication Title: Ann. Rheum. Dis.
Volume: 76
Number: 6
Page Range: S. 1150 - 1159
Date: 2017
Publisher: BMJ PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1468-2060
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; RHEUMATOID-ARTHRITIS; LUPUS-ERYTHEMATOSUS; RISK-FACTOR; LOCI; VARIANTS; VISUALIZATION; REPLICATION; SCANMultiple languages
RheumatologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22950

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