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

Xianyong Yin, Kwangwoo Kim, Hiroyuki Suetsugu, So Young Bang, Leilei Wen, Masaru Koido, Eunji Ha, Lu Liu, Yuma Sakamoto, Sungsin Jo, Rui Xue Leng, Nao Otomo, Viktoryia Laurynenka, Young Chang Kwon, Yujun Sheng, Nobuhiko Sugano, Mi Yeong Hwang, Weiran Li, Masaya Mukai, Kyungheon YoonMinglong Cai, Kazuyoshi Ishigaki, Won Tae Chung, He Huang, Daisuke Takahashi, Shin Seok Lee, Mengwei Wang, Kohei Karino, Seung Cheol Shim, Xiaodong Zheng, Tomoya Miyamura, Young Mo Kang, Dongqing Ye, Junichi Nakamura, Chang Hee Suh, Yuanjia Tang, Goro Motomura, Yong Beom Park, Huihua Ding, Takeshi Kuroda, Jung Yoon Choe, Chengxu Li, Hiroaki Niiro, Youngho Park, Changbing Shen, Takeshi Miyamoto, Ga Young Ahn, Wenmin Fei, Tsutomu Takeuchi, Jung Min Shin, Keke Li, Yasushi Kawaguchi, Yeon Kyung Lee, Yongfei Wang, Koichi Amano, Dae Jin Park, Wanling Yang, Yoshifumi Tada, Ken Yamaji, Masato Shimizu, Takashi Atsumi, Akari Suzuki, Takayuki Sumida, Yukinori Okada, Koichi Matsuda, Keitaro Matsuo, Yuta Kochi, Leah C. Kottyan, Matthew T. Weirauch, Sreeja Parameswaran, Shruti Eswar, Hanan Salim, Xiaoting Chen, Kazuhiko Yamamoto, John B. Harley, Koichiro Ohmura, Tae Hwan Kim, Sen Yang, Takuaki Yamamoto, Bong Jo Kim, Nan Shen, Shiro Ikegawa, Hye Soon Lee, Xuejun Zhang, Chikashi Terao, Yong Cui, Sang Cheol Bae

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Objective Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated withnearly 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 Thisstudy 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.

Original languageEnglish
Pages (from-to)632-640
Number of pages9
JournalAnnals of the rheumatic diseases
Volume80
Issue number5
DOIs
Publication statusPublished - 2021 May 1
Externally publishedYes

Keywords

  • epidemiology
  • genetic
  • lupus erythematosus
  • polymorphism
  • systemic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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