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GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region

Author

Listed:
  • Yuki Ishikawa

    (The Laboratory for Statistical and Translational Genetics)

  • Nao Tanaka

    (The Laboratory for Statistical and Translational Genetics
    Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University)

  • Yoshihide Asano

    (Tohoku University Graduate School of Medicine
    The University of Tokyo)

  • Masanari Kodera

    (Chukyo Hospital, Japan Community Health Care Organization)

  • Yuichiro Shirai

    (Nippon Medical School Graduate School of Medicine)

  • Mitsuteru Akahoshi

    (Kyushu University Graduate School of Medical Sciences
    Saga University Hospital)

  • Minoru Hasegawa

    (University of Fukui)

  • Takashi Matsushita

    (Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University)

  • Kazuyoshi Saito

    (University of Occupational and Environmental Health, Japan)

  • Sei-ichiro Motegi

    (Gunma University Graduate School of Medicine)

  • Hajime Yoshifuji

    (Graduate School of Medicine, Kyoto University)

  • Ayumi Yoshizaki

    (The University of Tokyo)

  • Tomohiro Kohmoto

    (Division of Molecular Genetics)

  • Kae Takagi

    (Tokyo Women’s Medical University, Adachi Medical Center)

  • Akira Oka

    (Tokai University School of Medicine)

  • Miho Kanda

    (Chukyo Hospital, Japan Community Health Care Organization)

  • Yoshihito Tanaka

    (Chukyo Hospital, Japan Community Health Care Organization)

  • Yumi Ito

    (Chukyo Hospital, Japan Community Health Care Organization)

  • Kazuhisa Nakano

    (University of Occupational and Environmental Health, Japan)

  • Hiroshi Kasamatsu

    (University of Fukui)

  • Akira Utsunomiya

    (University of Fukui)

  • Akiko Sekiguchi

    (Gunma University Graduate School of Medicine)

  • Hiroaki Niiro

    (Kyushu University Graduate School of Medical Sciences)

  • Masatoshi Jinnin

    (Wakayama Medical University Graduate School of Medicine)

  • Katsunari Makino

    (Faculty of Life Sciences, Kumamoto University)

  • Takamitsu Makino

    (Faculty of Life Sciences, Kumamoto University)

  • Hironobu Ihn

    (Faculty of Life Sciences, Kumamoto University)

  • Motohisa Yamamoto

    (The University of Tokyo)

  • Chisako Suzuki

    (Sapporo Medical University School of Medicine)

  • Hiroki Takahashi

    (Sapporo Medical University School of Medicine)

  • Emi Nishida

    (Nagoya City University Graduate School of Medical Sciences
    Okazaki City Hospital)

  • Akimichi Morita

    (Nagoya City University Graduate School of Medical Sciences)

  • Toshiyuki Yamamoto

    (Fukushima Medical University, School of Medicine)

  • Manabu Fujimoto

    (Osaka University)

  • Yuya Kondo

    (Institute of Medicine, University of Tsukuba)

  • Daisuke Goto

    (Institute of Medicine, University of Tsukuba)

  • Takayuki Sumida

    (Institute of Medicine, University of Tsukuba)

  • Naho Ayuzawa

    (National Hospital Organization, Utano National Hospital)

  • Hidetoshi Yanagida

    (National Hospital Organization, Utano National Hospital)

  • Tetsuya Horita

    (Hokkaido University)

  • Tatsuya Atsumi

    (Hokkaido University)

  • Hirahito Endo

    (Toho University, Rheumatic Disease Center)

  • Yoshihito Shima

    (Osaka University Graduate School of Medicine)

  • Atsushi Kumanogoh

    (Osaka University Graduate School of Medicine)

  • Jun Hirata

    (Osaka University, Statistical Immunology)

  • Nao Otomo

    (The Laboratory for Statistical and Translational Genetics)

  • Hiroyuki Suetsugu

    (The Laboratory for Statistical and Translational Genetics)

  • Yoshinao Koike

    (The Laboratory for Statistical and Translational Genetics)

  • Kohei Tomizuka

    (The Laboratory for Statistical and Translational Genetics)

  • Soichiro Yoshino

    (The Laboratory for Statistical and Translational Genetics)

  • Xiaoxi Liu

    (The Laboratory for Statistical and Translational Genetics)

  • Shuji Ito

    (The Laboratory for Statistical and Translational Genetics)

  • Keiko Hikino

    (The Laboratory for Pharmacogenomics)

  • Akari Suzuki

    (The Laboratory for Autoimmune Diseases)

  • Yukihide Momozawa

    (The Laboratory for Genotyping Development)

  • Shiro Ikegawa

    (The Laboratory for Bone and Joint Diseases)

  • Yoshiya Tanaka

    (University of Occupational and Environmental Health, Japan)

  • Osamu Ishikawa

    (Gunma University Graduate School of Medicine)

  • Kazuhiko Takehara

    (Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University)

  • Takeshi Torii

    (Torii Clinic)

  • Shinichi Sato

    (The University of Tokyo)

  • Yukinori Okada

    (Osaka University, Statistical Immunology)

  • Tsuneyo Mimori

    (Graduate School of Medicine, Kyoto University
    Ijinkai Takeada General Hospital)

  • Fumihiko Matsuda

    (Kyoto University, Center for Genomic Medicine)

  • Koichi Matsuda

    (The University of Tokyo, Laboratory of Genome Technology, Human Genome Center
    The University of Tokyo)

  • Tiffany Amariuta

    (Harvard Medical School
    Brigham and Women’s Hospital, Harvard Medical School
    Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Issei Imoto

    (Aichi Cancer Center Research Institute)

  • Keitaro Matsuo

    (Division of Cancer Epidemiology and Prevention)

  • Masataka Kuwana

    (Nippon Medical School Graduate School of Medicine)

  • Yasushi Kawaguchi

    (Tokyo Women’s Medical University, Division of Rheumatology, Department of Internal Medicine)

  • Koichiro Ohmura

    (Graduate School of Medicine, Kyoto University)

  • Chikashi Terao

    (The Laboratory for Statistical and Translational Genetics
    The Clinical Research Center
    University of Shizuoka)

Abstract

Here we report the largest Asian genome-wide association study (GWAS) for systemic sclerosis performed to date, based on data from Japanese subjects and comprising of 1428 cases and 112,599 controls. The lead SNP is in the FCGR/FCRL region, which shows a penetrating association in the Asian population, while a complete linkage disequilibrium SNP, rs10917688, is found in a cis-regulatory element for IRF8. IRF8 is also a significant locus in European GWAS for systemic sclerosis, but rs10917688 only shows an association in the presence of the risk allele of IRF8 in the Japanese population. Further analysis shows that rs10917688 is marked with H3K4me1 in primary B cells. A meta-analysis with a European GWAS detects 30 additional significant loci. Polygenic risk scores constructed with the effect sizes of the meta-analysis suggest the potential portability of genetic associations beyond populations. Prioritizing the top 5% of SNPs of IRF8 binding sites in B cells improves the fitting of the polygenic risk scores, underscoring the roles of B cells and IRF8 in the development of systemic sclerosis. The results also suggest that systemic sclerosis shares a common genetic architecture across populations.

Suggested Citation

  • Yuki Ishikawa & Nao Tanaka & Yoshihide Asano & Masanari Kodera & Yuichiro Shirai & Mitsuteru Akahoshi & Minoru Hasegawa & Takashi Matsushita & Kazuyoshi Saito & Sei-ichiro Motegi & Hajime Yoshifuji & , 2024. "GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44541-z
    DOI: 10.1038/s41467-023-44541-z
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