Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study.

autoimmunity lupus erythematosus, systemic polymorphism, genetic

Journal

Annals of the rheumatic diseases
ISSN: 1468-2060
Titre abrégé: Ann Rheum Dis
Pays: England
ID NLM: 0372355

Informations de publication

Date de publication:
24 May 2022
Historique:
received: 12 02 2022
accepted: 11 05 2022
entrez: 24 5 2022
pubmed: 25 5 2022
medline: 25 5 2022
Statut: aheadofprint

Résumé

Genome-wide association studies (GWAS) have identified >100 risk loci for systemic lupus erythematosus (SLE), but the disease genes at most loci remain unclear, hampering translation of these genetic discoveries. We aimed to prioritise genes underlying the 110 SLE loci that were identified in the latest East Asian GWAS meta-analysis. We built gene expression predictive models in blood B cells, CD4 TWAS identified 171 genes for SLE (p<1.0×10 Cell-level TWAS in six types of immune cells complemented SLE gene discovery and guided the identification of novel genetic associations. The gene findings shed biological insights into SLE genetic associations.

Identifiants

pubmed: 35609976
pii: annrheumdis-2022-222345
doi: 10.1136/annrheumdis-2022-222345
pmc: PMC9380500
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

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Auteurs

Xianyong Yin (X)

Department of Dermatology and Institute of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, People's Republic of China.
Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui, People's Republic of China.
Department of Dermatology, China-Japan Friendship Hospital, Beijing, People's Republic of China.
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Human Phenome Institute, Fudan University, Shanghai, People's Republic of China.

Kwangwoo Kim (K)

Department of Biology and Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Korea.

Hiroyuki Suetsugu (H)

Laboratory for Bone and Joint Diseases, RIKEN Center for Medical Sciences, Tokyo, Japan.
Laboratory for Statistical and Translational Genetics Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

So-Young Bang (SY)

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
Hanyang University Institute for Rheumatology Research, Seoul, South Korea.

Leilei Wen (L)

Department of Dermatology and Institute of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, People's Republic of China.

Masaru Koido (M)

Laboratory for Statistical and Translational Genetics Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Division of Molecular Pathology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Eunji Ha (E)

Department of Biology and Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Korea.

Lu Liu (L)

Department of Dermatology and Institute of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, People's Republic of China.

Yuma Sakamoto (Y)

Laboratory for Bone and Joint Diseases, RIKEN Center for Medical Sciences, Tokyo, Japan.
Koga Hospital 21, Kurume, Japan.

Sungsin Jo (S)

Hanyang University Institute for Rheumatology Research, Seoul, South Korea.

Rui-Xue Leng (RX)

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.

Nao Otomo (N)

Laboratory for Bone and Joint Diseases, RIKEN Center for Medical Sciences, Tokyo, Japan.
Laboratory for Statistical and Translational Genetics Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.

Young-Chang Kwon (YC)

Hanyang University Institute for Rheumatology Research, Seoul, South Korea.

Yujun Sheng (Y)

Department of Dermatology and Institute of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, People's Republic of China.

Nobuhiko Sugano (N)

Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Osaka, Japan.

Mi Yeong Hwang (MY)

Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju-si, South Korea.

Weiran Li (W)

Department of Dermatology and Institute of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, People's Republic of China.

Masaya Mukai (M)

Department of Rheumatology & Clinical Immunology, Sapporo City General Hospital, Hokkaido, Japan.

Kyungheon Yoon (K)

Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju-si, South Korea.

Minglong Cai (M)

Department of Dermatology and Institute of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, People's Republic of China.

Kazuyoshi Ishigaki (K)

Laboratory for Statistical and Translational Genetics Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Center for Data Sciences, Harvard Medical School, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Won Tae Chung (WT)

Department of Internal Medicine, Dong-A University Hospital, Busan, South Korea.

He Huang (H)

Department of Dermatology and Institute of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, People's Republic of China.

Daisuke Takahashi (D)

Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.

Shin-Seok Lee (SS)

Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School and Hospital, Gwangju, South Korea.

Mengwei Wang (M)

Department of Dermatology and Institute of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, People's Republic of China.

Kohei Karino (K)

Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.

Seung-Cheol Shim (SC)

Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, South Korea.

Xiaodong Zheng (X)

Department of Dermatology and Institute of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, People's Republic of China.

Tomoya Miyamura (T)

Department of Internal Medicine and Rheumatology, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan.

Young Mo Kang (YM)

Division of Rheumatology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, South Korea.

Dongqing Ye (D)

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.

Junichi Nakamura (J)

Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.

Chang-Hee Suh (CH)

Department of Rheumatology, Ajou University School of Medicine, Suwon, South Korea.

Yuanjia Tang (Y)

Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine (SJTUSM), Shanghai, People's Republic of China.

Goro Motomura (G)

Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Yong-Beom Park (YB)

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.

Huihua Ding (H)

Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine (SJTUSM), Shanghai, People's Republic of China.

Takeshi Kuroda (T)

Niigata University Health Administration Center, Niigata, Japan.

Jung-Yoon Choe (JY)

Department of Rheumatology, Catholic University of Daegu School of Medicine, Daegu, South Korea.

Chengxu Li (C)

Department of Dermatology, China-Japan Friendship Hospital, Beijing, People's Republic of China.

Hiroaki Niiro (H)

Department of Medical Education, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.

Youngho Park (Y)

Hanyang University Institute for Rheumatology Research, Seoul, South Korea.

Changbing Shen (C)

Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People's Republic of China.
Shenzhen Key Laboratory for Translational Medicine of Dermatology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, People's Republic of China.

Takeshi Miyamoto (T)

Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

Ga-Young Ahn (GY)

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.

Wenmin Fei (W)

Department of Dermatology, China-Japan Friendship Hospital, Beijing, People's Republic of China.

Tsutomu Takeuchi (T)

Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

Jung-Min Shin (JM)

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.

Keke Li (K)

Department of Dermatology, China-Japan Friendship Hospital, Beijing, People's Republic of China.

Yasushi Kawaguchi (Y)

Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.

Yeon-Kyung Lee (YK)

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.

Yong-Fei Wang (YF)

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.

Koichi Amano (K)

Department of Rheumatology & Clinical Immunology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.

Dae Jin Park (DJ)

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.

Wanling Yang (W)

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.

Yoshifumi Tada (Y)

Department of Rheumatology, Faculty of Medicine, Saga University, Saga, Japan.

Yu Lung Lau (YL)

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.

Ken Yamaji (K)

Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.

Zhengwei Zhu (Z)

Department of Dermatology and Institute of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, People's Republic of China.

Masato Shimizu (M)

Hokkaido Medical Center for Rheumatic Diseases, Sapporo, Japan.

Takashi Atsumi (T)

Department of Orthopaedic Surgery, Showa University School of Medicine, Tokyo, Japan.

Akari Suzuki (A)

Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.

Takayuki Sumida (T)

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

Yukinori Okada (Y)

Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Genome Informatics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.

Koichi Matsuda (K)

Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.

Keitaro Matsuo (K)

Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Yuta Kochi (Y)

Department of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.

Kazuhiko Yamamoto (K)

Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.

Koichiro Ohmura (K)

Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Tae-Hwan Kim (TH)

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
Hanyang University Institute for Rheumatology Research, Seoul, South Korea.

Sen Yang (S)

Department of Dermatology and Institute of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, People's Republic of China.

Takuaki Yamamoto (T)

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Bong-Jo Kim (BJ)

Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju-si, South Korea.

Nan Shen (N)

Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine (SJTUSM), Shanghai, People's Republic of China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, People's Republic of China.
Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Shiro Ikegawa (S)

Laboratory for Bone and Joint Diseases, RIKEN Center for Medical Sciences, Tokyo, Japan.

Hye-Soon Lee (HS)

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
Hanyang University Institute for Rheumatology Research, Seoul, South Korea.

Xuejun Zhang (X)

Department of Dermatology and Institute of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, People's Republic of China.
Department of Dermatology, Institute of Dermatology, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.

Chikashi Terao (C)

Laboratory for Statistical and Translational Genetics Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan chikashi.terao@riken.jp wuhucuiyong@vip.163.com scbae@hanyang.ac.kr.
Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan.
Department of Applied Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.

Yong Cui (Y)

Department of Dermatology, China-Japan Friendship Hospital, Beijing, People's Republic of China chikashi.terao@riken.jp wuhucuiyong@vip.163.com scbae@hanyang.ac.kr.

Sang-Cheol Bae (SC)

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea chikashi.terao@riken.jp wuhucuiyong@vip.163.com scbae@hanyang.ac.kr.
Hanyang University Institute for Rheumatology Research, Seoul, South Korea.

Classifications MeSH