Nature Communications (Jan 2024)
GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region
- Yuki Ishikawa,
- Nao Tanaka,
- Yoshihide Asano,
- Masanari Kodera,
- Yuichiro Shirai,
- Mitsuteru Akahoshi,
- Minoru Hasegawa,
- Takashi Matsushita,
- Kazuyoshi Saito,
- Sei-ichiro Motegi,
- Hajime Yoshifuji,
- Ayumi Yoshizaki,
- Tomohiro Kohmoto,
- Kae Takagi,
- Akira Oka,
- Miho Kanda,
- Yoshihito Tanaka,
- Yumi Ito,
- Kazuhisa Nakano,
- Hiroshi Kasamatsu,
- Akira Utsunomiya,
- Akiko Sekiguchi,
- Hiroaki Niiro,
- Masatoshi Jinnin,
- Katsunari Makino,
- Takamitsu Makino,
- Hironobu Ihn,
- Motohisa Yamamoto,
- Chisako Suzuki,
- Hiroki Takahashi,
- Emi Nishida,
- Akimichi Morita,
- Toshiyuki Yamamoto,
- Manabu Fujimoto,
- Yuya Kondo,
- Daisuke Goto,
- Takayuki Sumida,
- Naho Ayuzawa,
- Hidetoshi Yanagida,
- Tetsuya Horita,
- Tatsuya Atsumi,
- Hirahito Endo,
- Yoshihito Shima,
- Atsushi Kumanogoh,
- Jun Hirata,
- Nao Otomo,
- Hiroyuki Suetsugu,
- Yoshinao Koike,
- Kohei Tomizuka,
- Soichiro Yoshino,
- Xiaoxi Liu,
- Shuji Ito,
- Keiko Hikino,
- Akari Suzuki,
- Yukihide Momozawa,
- Shiro Ikegawa,
- Yoshiya Tanaka,
- Osamu Ishikawa,
- Kazuhiko Takehara,
- Takeshi Torii,
- Shinichi Sato,
- Yukinori Okada,
- Tsuneyo Mimori,
- Fumihiko Matsuda,
- Koichi Matsuda,
- Tiffany Amariuta,
- Issei Imoto,
- Keitaro Matsuo,
- Masataka Kuwana,
- Yasushi Kawaguchi,
- Koichiro Ohmura,
- Chikashi Terao
Affiliations
- Yuki Ishikawa
- RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics
- Nao Tanaka
- RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics
- Yoshihide Asano
- Department of Dermatology, Tohoku University Graduate School of Medicine
- Masanari Kodera
- Department of Dermatology, Chukyo Hospital, Japan Community Health Care Organization
- Yuichiro Shirai
- Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine
- Mitsuteru Akahoshi
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences
- Minoru Hasegawa
- Faculty of Medical Sciences, Department of Dermatology, University of Fukui
- Takashi Matsushita
- Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
- Kazuyoshi Saito
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan
- Sei-ichiro Motegi
- Department of Dermatology, Gunma University Graduate School of Medicine
- Hajime Yoshifuji
- Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University
- Ayumi Yoshizaki
- Department of Dermatology, The University of Tokyo
- Tomohiro Kohmoto
- Aichi Cancer Center Research Institute, Division of Molecular Genetics
- Kae Takagi
- Tokyo Women’s Medical University, Adachi Medical Center
- Akira Oka
- Department of Molecular Life Sciences, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine
- Miho Kanda
- Department of Dermatology, Chukyo Hospital, Japan Community Health Care Organization
- Yoshihito Tanaka
- Department of Dermatology, Chukyo Hospital, Japan Community Health Care Organization
- Yumi Ito
- Department of Dermatology, Chukyo Hospital, Japan Community Health Care Organization
- Kazuhisa Nakano
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan
- Hiroshi Kasamatsu
- Faculty of Medical Sciences, Department of Dermatology, University of Fukui
- Akira Utsunomiya
- Faculty of Medical Sciences, Department of Dermatology, University of Fukui
- Akiko Sekiguchi
- Department of Dermatology, Gunma University Graduate School of Medicine
- Hiroaki Niiro
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences
- Masatoshi Jinnin
- Department of Dermatology, Wakayama Medical University Graduate School of Medicine
- Katsunari Makino
- Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University
- Takamitsu Makino
- Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University
- Hironobu Ihn
- Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University
- Motohisa Yamamoto
- Department of Rheumatology and Allergy, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo
- Chisako Suzuki
- Department of Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine
- Hiroki Takahashi
- Department of Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine
- Emi Nishida
- Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences
- Akimichi Morita
- Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences
- Toshiyuki Yamamoto
- Department of Dermatology, Fukushima Medical University, School of Medicine
- Manabu Fujimoto
- Department of Dermatology, Graduate School of Medicine, Osaka University
- Yuya Kondo
- Department of Rheumatology, Institute of Medicine, University of Tsukuba
- Daisuke Goto
- Department of Rheumatology, Institute of Medicine, University of Tsukuba
- Takayuki Sumida
- Department of Rheumatology, Institute of Medicine, University of Tsukuba
- Naho Ayuzawa
- Department of Clinical Immunology, National Hospital Organization, Utano National Hospital
- Hidetoshi Yanagida
- Department of Clinical Immunology, National Hospital Organization, Utano National Hospital
- Tetsuya Horita
- Faculty of Medicine and Graduate School of Medicine, Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University
- Tatsuya Atsumi
- Faculty of Medicine and Graduate School of Medicine, Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University
- Hirahito Endo
- Omori Medical Center, Toho University, Rheumatic Disease Center
- Yoshihito Shima
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine
- Atsushi Kumanogoh
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine
- Jun Hirata
- Immunology Frontier Center, Osaka University, Statistical Immunology
- Nao Otomo
- RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics
- Hiroyuki Suetsugu
- RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics
- Yoshinao Koike
- RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics
- Kohei Tomizuka
- RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics
- Soichiro Yoshino
- RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics
- Xiaoxi Liu
- RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics
- Shuji Ito
- RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics
- Keiko Hikino
- RIKEN Center for Integrative Medical Sciences, The Laboratory for Pharmacogenomics
- Akari Suzuki
- RIKEN Center for Integrative Medical Sciences, The Laboratory for Autoimmune Diseases
- Yukihide Momozawa
- RIKEN Center for Integrative Medical Sciences, The Laboratory for Genotyping Development
- Shiro Ikegawa
- RIKEN Center for Integrative Medical Sciences, The Laboratory for Bone and Joint Diseases
- Yoshiya Tanaka
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan
- Osamu Ishikawa
- Department of Dermatology, Gunma University Graduate School of Medicine
- Kazuhiko Takehara
- Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
- Takeshi Torii
- Torii Clinic
- Shinichi Sato
- Department of Dermatology, The University of Tokyo
- Yukinori Okada
- Immunology Frontier Center, Osaka University, Statistical Immunology
- Tsuneyo Mimori
- Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University
- Fumihiko Matsuda
- Graduate School of Medicine, Kyoto University, Center for Genomic Medicine
- Koichi Matsuda
- Institute of Medical Science, The University of Tokyo, Laboratory of Genome Technology, Human Genome Center
- Tiffany Amariuta
- Center for Data Sciences, Harvard Medical School
- Issei Imoto
- Aichi Cancer Center Research Institute
- Keitaro Matsuo
- Aichi Cancer Center Research Institute, Division of Cancer Epidemiology and Prevention
- Masataka Kuwana
- Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine
- Yasushi Kawaguchi
- Tokyo Women’s Medical University, Division of Rheumatology, Department of Internal Medicine
- Koichiro Ohmura
- Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University
- Chikashi Terao
- RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics
- DOI
- https://doi.org/10.1038/s41467-023-44541-z
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 16
Abstract
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.
