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Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus.
| Content Provider | Europe PMC |
|---|---|
| Author | Yin, Xianyong Kim, Kwangwoo Suetsugu, Hiroyuki Bang, So-Young Wen, Leilei Koido, Masaru Ha, Eunji Liu, Lu Sakamoto, Yuma Jo, Sungsin Leng, Rui-Xue Otomo, Nao Laurynenka, Viktoryia Kwon, Young-Chang Sheng, Yujun Sugano, Nobuhiko Hwang, Mi Yeong Li, Weiran Mukai, Masaya Yoon, Kyungheon Cai, Minglong Ishigaki, Kazuyoshi Chung, Won Tae Huang, He Takahashi, Daisuke Lee, Shin-Seok Wang, Mengwei Karino, Kohei Shim, Seung-Cheol Zheng, Xiaodong Miyamura, Tomoya Kang, Young Mo Ye, Dongqing Nakamura, Junichi Suh, Chang-Hee Tang, Yuanjia Motomura, Goro Park, Yong-Beom Ding, Huihua Kuroda, Takeshi Choe, Jung-Yoon Li, Chengxu Niiro, Hiroaki Park, Youngho Shen, Changbing Miyamoto, Takeshi Ahn, Ga-Young Fei, Wenmin Takeuchi, Tsutomu Shin, Jung-Min Li, Keke Kawaguchi, Yasushi Lee, Yeon-Kyung Wang, Yongfei Amano, Koichi Park, Dae Jin Yang, Wanling Tada, Yoshifumi Yamaji, Ken Shimizu, Masato Atsumi, Takashi Suzuki, Akari Sumida, Takayuki Okada, Yukinori Matsuda, Koichi Matsuo, Keitaro Kochi, Yuta Kottyan, Leah C Weirauch, Matthew T Parameswaran, Sreeja Eswar, Shruti Salim, Hanan Chen, Xiaoting Yamamoto, Kazuhiko Harley, John B Ohmura, Koichiro Kim, Tae-Hwan Yang, Sen Yamamoto, Takuaki Kim, Bong-Jo Shen, Nan Ikegawa, Shiro Lee, Hye-Soon Zhang, Xuejun Terao, Chikashi Cui, Yong Bae, Sang-Cheol |
| Copyright Year | 2021 |
| Abstract | ObjectiveSystemic 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.MethodsWe 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.ResultsWe 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 (rg=−0.242) and non-albumin protein (rg=0.238).ConclusionThis 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. |
| ISSN | 00034967 |
| Journal | Annals of the Rheumatic Diseases |
| Volume Number | 80 |
| PubMed Central reference number | PMC8053352 |
| Issue Number | 5 |
| PubMed reference number | 33272962 |
| e-ISSN | 14682060 |
| DOI | 10.1136/annrheumdis-2020-219209 |
| Language | English |
| Publisher | BMJ Publishing Group |
| Publisher Date | 2020-12-03 |
| Publisher Place | BMA House, Tavistock Square, London, WC1H 9JR |
| Access Restriction | Open |
| Rights License | This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. © 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. |
| Subject Keyword | lupus erythematosus systemic polymorphism genetic epidemiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Biochemistry, Genetics and Molecular Biology Immunology Rheumatology |
