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

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 biol...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053352/
https://www.ncbi.nlm.nih.gov/pubmed/33272962
http://dx.doi.org/10.1136/annrheumdis-2020-219209
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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
author_facet 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
author_sort Yin, Xianyong
collection PubMed
description 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.
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spelling pubmed-80533522021-05-05 Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus 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 Ann Rheum Dis Systemic Lupus Erythematosus 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. BMJ Publishing Group 2021-05 2020-12-03 /pmc/articles/PMC8053352/ /pubmed/33272962 http://dx.doi.org/10.1136/annrheumdis-2020-219209 Text en © 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. https://creativecommons.org/licenses/by-nc/4.0/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/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Systemic Lupus Erythematosus
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
Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus
title Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus
title_full Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus
title_fullStr Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus
title_full_unstemmed Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus
title_short Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus
title_sort meta-analysis of 208370 east asians identifies 113 susceptibility loci for systemic lupus erythematosus
topic Systemic Lupus Erythematosus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053352/
https://www.ncbi.nlm.nih.gov/pubmed/33272962
http://dx.doi.org/10.1136/annrheumdis-2020-219209
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