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

doi:10.1136/annrheumdis-2020-219209

Meta-Analysis

. 2021 May;80(5):632-640.

doi: 10.1136/annrheumdis-2020-219209. Epub 2020 Dec 3.

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

Xianyong Yin^#^{1

2

3

4

5

6}, Kwangwoo Kim^#⁷, Hiroyuki Suetsugu^#^{8

9

10}, So-Young Bang^{11

12}, Leilei Wen^{1

2

3}, Masaru Koido^{9

13}, Eunji Ha⁷, Lu Liu^{1

2

3}, Yuma Sakamoto¹⁴, Sungsin Jo¹², Rui-Xue Leng¹⁵, Nao Otomo^{8

9

16}, Viktoryia Laurynenka¹⁷, Young-Chang Kwon¹², Yujun Sheng^{1

2

3}, Nobuhiko Sugano¹⁸, Mi Yeong Hwang¹⁹, Weiran Li^{1

2

3}, Masaya Mukai²⁰, Kyungheon Yoon¹⁹, Minglong Cai^{1

2

3}, Kazuyoshi Ishigaki^{9

21

22

23}, Won Tae Chung²⁴, He Huang^{1

2

3}, Daisuke Takahashi²⁵, Shin-Seok Lee²⁶, Mengwei Wang^{1

2

3}, Kohei Karino²⁷, Seung-Cheol Shim²⁸, Xiaodong Zheng^{1

2

3}, Tomoya Miyamura²⁹, Young Mo Kang³⁰, Dongqing Ye¹⁵, Junichi Nakamura³¹, Chang-Hee Suh³², Yuanjia Tang³³, Goro Motomura¹⁰, Yong-Beom Park³⁴, Huihua Ding³³, Takeshi Kuroda³⁵, Jung-Yoon Choe³⁶, Chengxu Li⁵, Hiroaki Niiro³⁷, Youngho Park¹², Changbing Shen^{38

39}, Takeshi Miyamoto⁴⁰, Ga-Young Ahn¹¹, Wenmin Fei⁵, Tsutomu Takeuchi⁴¹, Jung-Min Shin¹¹, Keke Li⁵, Yasushi Kawaguchi⁴², Yeon-Kyung Lee¹¹, Yongfei Wang⁴³, Koichi Amano⁴⁴, Dae Jin Park¹¹, Wanling Yang⁴³, Yoshifumi Tada⁴⁵, Ken Yamaji⁴⁶, Masato Shimizu⁴⁷, Takashi Atsumi⁴⁸, Akari Suzuki⁴⁹, Takayuki Sumida⁵⁰, Yukinori Okada^{51

52}, Koichi Matsuda^{53

54}, Keitaro Matsuo^{55

56}, Yuta Kochi⁵⁷; Japanese Research Committee on Idiopathic Osteonecrosis of the Femoral Head; Leah C Kottyan^{17

58}, Matthew T Weirauch^{17

58}, Sreeja Parameswaran¹⁷, Shruti Eswar¹⁷, Hanan Salim¹⁷, Xiaoting Chen¹⁷, Kazuhiko Yamamoto⁴⁹, John B Harley^{17

58

59}, Koichiro Ohmura⁶⁰, Tae-Hwan Kim^{11

12}, Sen Yang^{1

2

3}, Takuaki Yamamoto⁶¹, Bong-Jo Kim¹⁹, Nan Shen^{17

33

62}, Shiro Ikegawa⁸, Hye-Soon Lee^{11

12}, Xuejun Zhang^{1

2

3

63}, Chikashi Terao^{64

65

66}, Yong Cui⁶⁷, Sang-Cheol Bae^{68

12}

Affiliations

¹ Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
² Institute of Dermatology, Anhui Medical University, Hefei, Anhui, China.
³ Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, China.
⁴ Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui, China.
⁵ Department of Dermatology, China-Japan Friendship Hospital, Beijing, China.
⁶ Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
⁷ Department of Biology and Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Korea.
⁸ Laboratory for Bone and Joint Diseases, RIKEN Center for Medical Sciences, Kanagawa, Japan.
⁹ Laboratory for Statistical and Translational Genetics Analysis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
¹⁰ Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
¹¹ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.
¹² Hanyang University Institute for Rheumatology Research, Seoul, Korea.
¹³ Division of Molecular Pathology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹⁴ Koga Hospital 21, Fukuoka, Japan.
¹⁵ Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
¹⁶ Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
¹⁷ Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁸ Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Osaka, Japan.
¹⁹ Division of Genome Research, Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Cheongju, Korea.
²⁰ Department of Rheumatology & Clinical Immunology, Sapporo City General Hospital, Hokkaido, Japan.
²¹ Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
²² Center for Data Sciences, Harvard Medical School, Boston, Massachusetts, USA.
²³ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
²⁴ Department of Internal Medicine, Dong-A University Hospital, Busan, Korea.
²⁵ Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
²⁶ Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School and Hospital, Gwangju, Korea.
²⁷ Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
²⁸ Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea.
²⁹ Department of Internal Medicine and Rheumatology, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan.
³⁰ Division of Rheumatology, Department of Internal medicine, Kyungpook National University Hospital, Daegu, Korea.
³¹ Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
³² Department of Rheumatology, Ajou University School of Medicine, Suwon, Korea.
³³ Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine (SJTUSM), Shanghai, China.
³⁴ Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
³⁵ Niigata University Health Administration Center, Niigata, Japan.
³⁶ Department of Rheumatology, Catholic University of Daegu School of Medicine, Daegu, Korea.
³⁷ Department of Medical Education, Kyushu University Graduate School of Medical Sciences, Fukuoka City, Japan.
³⁸ Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.
³⁹ Shenzhen Key Laboratory for Translational Medicine of Dermatology, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China.
⁴⁰ Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
⁴¹ Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
⁴² Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
⁴³ Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong, China.
⁴⁴ Department of Rheumatology & Clinical Immunology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
⁴⁵ Department of Rheumatology, Faculty of Medicine, Saga University, Saga, Japan.
⁴⁶ Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
⁴⁷ Hokkaido Medical Center for Rheumatic Disease, Hokkaido, Japan.
⁴⁸ Department of Orthopaedic Surgery, Showa University School of Medicine, Tokyo, Japan.
⁴⁹ Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
⁵⁰ Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
⁵¹ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
⁵² Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPi-iFReC), Osaka University, Osaka, Japan.
⁵³ Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁵⁴ Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
⁵⁵ Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
⁵⁶ Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁵⁷ Department of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
⁵⁸ Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.
⁵⁹ US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA.
⁶⁰ Department of Rheumatology and Clinical immunology, Kyoto University Graduate school of Medicine, Kyoto, Japan.
⁶¹ Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
⁶² State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
⁶³ Department of Dermatology, Institute of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
⁶⁴ 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.
⁶⁵ Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan.
⁶⁶ The Department of Applied Genetics, The School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
⁶⁷ Department of Dermatology, China-Japan Friendship Hospital, Beijing, China chikashi.terao@riken.jp wuhucuiyong@vip.163.com scbae@hanyang.ac.kr.
⁶⁸ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea chikashi.terao@riken.jp wuhucuiyong@vip.163.com scbae@hanyang.ac.kr.

^# Contributed equally.

PMID: 33272962
PMCID: PMC8053352
DOI: 10.1136/annrheumdis-2020-219209

Meta-Analysis

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

Xianyong Yin et al. Ann Rheum Dis. 2021 May.

. 2021 May;80(5):632-640.

doi: 10.1136/annrheumdis-2020-219209. Epub 2020 Dec 3.

Authors

Affiliations

¹ Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
² Institute of Dermatology, Anhui Medical University, Hefei, Anhui, China.
³ Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, China.
⁴ Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui, China.
⁵ Department of Dermatology, China-Japan Friendship Hospital, Beijing, China.
⁶ Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
⁷ Department of Biology and Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Korea.
⁸ Laboratory for Bone and Joint Diseases, RIKEN Center for Medical Sciences, Kanagawa, Japan.
⁹ Laboratory for Statistical and Translational Genetics Analysis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
¹⁰ Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
¹¹ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.
¹² Hanyang University Institute for Rheumatology Research, Seoul, Korea.
¹³ Division of Molecular Pathology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹⁴ Koga Hospital 21, Fukuoka, Japan.
¹⁵ Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
¹⁶ Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
¹⁷ Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁸ Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Osaka, Japan.
¹⁹ Division of Genome Research, Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Cheongju, Korea.
²⁰ Department of Rheumatology & Clinical Immunology, Sapporo City General Hospital, Hokkaido, Japan.
²¹ Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
²² Center for Data Sciences, Harvard Medical School, Boston, Massachusetts, USA.
²³ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
²⁴ Department of Internal Medicine, Dong-A University Hospital, Busan, Korea.
²⁵ Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
²⁶ Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School and Hospital, Gwangju, Korea.
²⁷ Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
²⁸ Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea.
²⁹ Department of Internal Medicine and Rheumatology, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan.
³⁰ Division of Rheumatology, Department of Internal medicine, Kyungpook National University Hospital, Daegu, Korea.
³¹ Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
³² Department of Rheumatology, Ajou University School of Medicine, Suwon, Korea.
³³ Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine (SJTUSM), Shanghai, China.
³⁴ Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
³⁵ Niigata University Health Administration Center, Niigata, Japan.
³⁶ Department of Rheumatology, Catholic University of Daegu School of Medicine, Daegu, Korea.
³⁷ Department of Medical Education, Kyushu University Graduate School of Medical Sciences, Fukuoka City, Japan.
³⁸ Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.
³⁹ Shenzhen Key Laboratory for Translational Medicine of Dermatology, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China.
⁴⁰ Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
⁴¹ Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
⁴² Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
⁴³ Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong, China.
⁴⁴ Department of Rheumatology & Clinical Immunology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
⁴⁵ Department of Rheumatology, Faculty of Medicine, Saga University, Saga, Japan.
⁴⁶ Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
⁴⁷ Hokkaido Medical Center for Rheumatic Disease, Hokkaido, Japan.
⁴⁸ Department of Orthopaedic Surgery, Showa University School of Medicine, Tokyo, Japan.
⁴⁹ Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
⁵⁰ Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
⁵¹ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
⁵² Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPi-iFReC), Osaka University, Osaka, Japan.
⁵³ Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁵⁴ Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
⁵⁵ Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
⁵⁶ Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁵⁷ Department of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
⁵⁸ Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.
⁵⁹ US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA.
⁶⁰ Department of Rheumatology and Clinical immunology, Kyoto University Graduate school of Medicine, Kyoto, Japan.
⁶¹ Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
⁶² State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
⁶³ Department of Dermatology, Institute of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
⁶⁴ 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.
⁶⁵ Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan.
⁶⁶ The Department of Applied Genetics, The School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
⁶⁷ Department of Dermatology, China-Japan Friendship Hospital, Beijing, China chikashi.terao@riken.jp wuhucuiyong@vip.163.com scbae@hanyang.ac.kr.
⁶⁸ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea chikashi.terao@riken.jp wuhucuiyong@vip.163.com scbae@hanyang.ac.kr.

^# Contributed equally.

PMID: 33272962
PMCID: PMC8053352
DOI: 10.1136/annrheumdis-2020-219209

Abstract

Objective: 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.

Methods: 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.

Results: We identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10^-8). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (r_g=-0.242) and non-albumin protein (r_g=0.238).

Conclusion: 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.

Keywords: epidemiology; genetic; lupus erythematosus; polymorphism; systemic.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

**Figure 1**
Summary of meta-analysis association results and comparison of MAFs for lead variants within the 46 novel loci between East Asians and Europeans. (A) Manhattan plot of genome-wide association meta-analysis results from 208 370 SLE East Asians including 13 377 SLE cases and 194 993 controls. Minus log10-transformed association p values (y-axis) are plotted along chromosomal positions (x-axis). Known and novel loci are highlighted in light blue and pink, respectively. The red dashed line denotes the genome-wide association significance threshold of p=5×10⁻⁸. The grey dashed line represents p=10⁻³⁰, at which the y-axis breaks. (B) Comparison of MAFs of lead variants within the 46 novel loci between East Asians (y-axis) and non-Finnish Europeans (x-axis) in the Genome Aggregation Database (gnomAD) v3. Variants with more than 10 times higher MAFs in East Asians are coloured purple above a red dashed line. MAF, minor allele frequency.

**Figure 2**
New lead exonic variants identified at three known (*CSK*, *IKBKB* and *TYK2*) and two novel (*CHD23* and *LRRK1*) loci. (A) rs11553760 (synonymous variant) at *CSK*. (B) rs2272736 (p.Arg303Gln, missense variant) at *IKBKB*. (C) rs55882956 (p.Arg703Trp, missense variant) at *TYK2*. (D) rs10823829 (synonymous variant) at *CHD23*. (E) rs35985016 (p.Lys203Glu, missense variant) at *LRRK1*. The lead SNP is labelled as purple diamond. The LD is estimated from 7021 Chinese samples. LD, linkage disequilibrium; Mb, megabases; SNP, single nucleotide polymorphism.

**Figure 3**
Two independent association signals identified. (A) At two intronic variants within known *STAT4* locus. (B) At known (rs7097397, p.Arg1816Gln) and new (rs7072606, p.Ser214Pro) missense variants within *WDFY4* locus. (C) A known intronic variant within *ATXN2* gene and a new (rs1131476, p.Ala352Thr) missense variant within *OAS1* gene. The lead and secondary index variants are labelled in diamond. The lead variant and its LD proxies are in red while the secondary signal index variant and its LD proxies are in blue. The LD is estimated from 7021 Chinese samples. LD, linkage disequilibrium; Mb, megabases.

**Figure 4**
Results of statistical fine-mapping analysis. (A) Number of 95% credible sets of putative causal variants, binned by their sizes. (B) Number of potential causal variants with posterior probabilities (PP) ≥0.1, which are considered to be the true causal variants.

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References

1. Carter EE, Barr SG, Clarke AE. The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol 2016;12:605–20. 10.1038/nrrheum.2016.137 - DOI - PubMed
1. Guerra SG, Vyse TJ, Cunninghame Graham DS. The genetics of lupus: a functional perspective. Arthritis Res Ther 2012;14:211. 10.1186/ar3844 - DOI - PMC - PubMed
1. Gateva V, Sandling JK, Hom G, et al. . A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 2009;41:1228–33. 10.1038/ng.468 - DOI - PMC - PubMed
1. Han J-W, Zheng H-F, Cui Y, et al. . Genome-Wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet 2009;41:1234–7. 10.1038/ng.472 - DOI - PubMed
1. Cunninghame Graham DS, Morris DL, Bhangale TR, et al. . Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with systemic lupus erythematosus. PLoS Genet 2011;7:e1002341. 10.1371/journal.pgen.1002341 - DOI - PMC - PubMed

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[1] Carter EE, Barr SG, Clarke AE. The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol 2016;12:605–20. 10.1038/nrrheum.2016.137 - DOI - PubMed

[2] Carter EE, Barr SG, Clarke AE. The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol 2016;12:605–20. 10.1038/nrrheum.2016.137 - DOI - PubMed

[3] Guerra SG, Vyse TJ, Cunninghame Graham DS. The genetics of lupus: a functional perspective. Arthritis Res Ther 2012;14:211. 10.1186/ar3844 - DOI - PMC - PubMed

[4] Guerra SG, Vyse TJ, Cunninghame Graham DS. The genetics of lupus: a functional perspective. Arthritis Res Ther 2012;14:211. 10.1186/ar3844 - DOI - PMC - PubMed

[5] Gateva V, Sandling JK, Hom G, et al. . A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 2009;41:1228–33. 10.1038/ng.468 - DOI - PMC - PubMed

[6] Gateva V, Sandling JK, Hom G, et al. . A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 2009;41:1228–33. 10.1038/ng.468 - DOI - PMC - PubMed

[7] Han J-W, Zheng H-F, Cui Y, et al. . Genome-Wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet 2009;41:1234–7. 10.1038/ng.472 - DOI - PubMed

[8] Han J-W, Zheng H-F, Cui Y, et al. . Genome-Wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet 2009;41:1234–7. 10.1038/ng.472 - DOI - PubMed

[9] Cunninghame Graham DS, Morris DL, Bhangale TR, et al. . Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with systemic lupus erythematosus. PLoS Genet 2011;7:e1002341. 10.1371/journal.pgen.1002341 - DOI - PMC - PubMed

[10] Cunninghame Graham DS, Morris DL, Bhangale TR, et al. . Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with systemic lupus erythematosus. PLoS Genet 2011;7:e1002341. 10.1371/journal.pgen.1002341 - DOI - PMC - PubMed

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

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

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Abstract

Conflict of interest statement

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Cited by

References

Publication types

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Grants and funding

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Full Text Sources

Medical