Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus.


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:
05 2021
Historique:
received: 30 09 2020
revised: 04 11 2020
accepted: 11 11 2020
pubmed: 5 12 2020
medline: 11 9 2021
entrez: 4 12 2020
Statut: ppublish

Résumé

Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations. We newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations. We identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10 This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.

Identifiants

pubmed: 33272962
pii: annrheumdis-2020-219209
doi: 10.1136/annrheumdis-2020-219209
pmc: PMC8053352
doi:

Types de publication

Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

632-640

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI024717
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR073228
Pays : United States

Informations de copyright

© Author(s) (or their employer(s)) 2021. 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.

Auteurs

Xianyong Yin (X)

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

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, Kanagawa, Japan.
Laboratory for Statistical and Translational Genetics Analysis, RIKEN Center for Integrative Medical Sciences, Kanagawa, 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, Korea.
Hanyang University Institute for Rheumatology Research, Seoul, Korea.

Leilei Wen (L)

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

Masaru Koido (M)

Laboratory for Statistical and Translational Genetics Analysis, RIKEN Center for Integrative Medical Sciences, Kanagawa, 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, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
Institute of Dermatology, Anhui Medical University, Hefei, Anhui, China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, China.

Yuma Sakamoto (Y)

Koga Hospital 21, Fukuoka, Japan.

Sungsin Jo (S)

Hanyang University Institute for Rheumatology Research, Seoul, Korea.

Rui-Xue Leng (RX)

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.

Nao Otomo (N)

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

Viktoryia Laurynenka (V)

Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Young-Chang Kwon (YC)

Hanyang University Institute for Rheumatology Research, Seoul, Korea.

Yujun Sheng (Y)

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

Nobuhiko Sugano (N)

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

Mi Yeong Hwang (MY)

Division of Genome Research, Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Cheongju, Korea.

Weiran Li (W)

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

Masaya Mukai (M)

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

Kyungheon Yoon (K)

Division of Genome Research, Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Cheongju, Korea.

Minglong Cai (M)

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

Kazuyoshi Ishigaki (K)

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

Won Tae Chung (WT)

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

He Huang (H)

Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
Institute of Dermatology, Anhui Medical University, Hefei, Anhui, China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, 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, Korea.

Mengwei Wang (M)

Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
Institute of Dermatology, Anhui Medical University, Hefei, Anhui, China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, 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, Korea.

Xiaodong Zheng (X)

Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
Institute of Dermatology, Anhui Medical University, Hefei, Anhui, China.
Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, 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, Korea.

Dongqing Ye (D)

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, 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, Korea.

Yuanjia Tang (Y)

Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine (SJTUSM), Shanghai, 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, Korea.

Huihua Ding (H)

Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine (SJTUSM), Shanghai, 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, Korea.

Chengxu Li (C)

Department of Dermatology, China-Japan Friendship Hospital, Beijing, China.

Hiroaki Niiro (H)

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

Youngho Park (Y)

Hanyang University Institute for Rheumatology Research, Seoul, Korea.

Changbing Shen (C)

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

Wenmin Fei (W)

Department of Dermatology, China-Japan Friendship Hospital, Beijing, 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, Korea.

Keke Li (K)

Department of Dermatology, China-Japan Friendship Hospital, Beijing, 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, Korea.

Yongfei Wang (Y)

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong, 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, Korea.

Wanling Yang (W)

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong, China.

Yoshifumi Tada (Y)

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

Ken Yamaji (K)

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

Masato Shimizu (M)

Hokkaido Medical Center for Rheumatic Disease, Hokkaido, 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.
Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPi-iFReC), Osaka University, Osaka, Japan.

Koichi Matsuda (K)

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

Leah C Kottyan (LC)

Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.

Matthew T Weirauch (MT)

Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.

Sreeja Parameswaran (S)

Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Shruti Eswar (S)

Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Hanan Salim (H)

Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Xiaoting Chen (X)

Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Kazuhiko Yamamoto (K)

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

John B Harley (JB)

Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.
US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA.

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

Sen Yang (S)

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

Takuaki Yamamoto (T)

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

Bong-Jo Kim (BJ)

Division of Genome Research, Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Cheongju, Korea.

Nan Shen (N)

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

Shiro Ikegawa (S)

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

Hye-Soon Lee (HS)

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

Xuejun Zhang (X)

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

Chikashi Terao (C)

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

Yong Cui (Y)

Department of Dermatology, China-Japan Friendship Hospital, Beijing, 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, Korea chikashi.terao@riken.jp wuhucuiyong@vip.163.com scbae@hanyang.ac.kr.
Hanyang University Institute for Rheumatology Research, Seoul, Korea.

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