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Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups

Author

Listed:
  • Yong-Fei Wang

    (The University of Hong Kong)

  • Yan Zhang

    (Guangzhou Medical University)

  • Zhiming Lin

    (The Third Affiliated Hospital of Sun Yat-Sen University)

  • Huoru Zhang

    (The University of Hong Kong)

  • Ting-You Wang

    (The University of Hong Kong
    University of Minnesota)

  • Yujie Cao

    (The University of Hong Kong)

  • David L. Morris

    (King’s College London)

  • Yujun Sheng

    (Anhui Medical University)

  • Xianyong Yin

    (Anhui Medical University)

  • Shi-Long Zhong

    (Guangdong Provincial People’s Hospital)

  • Xiaoqiong Gu

    (Guangzhou Women and Children’s Medical Center)

  • Yao Lei

    (The University of Hong Kong)

  • Jing He

    (Guangzhou Medical University)

  • Qi Wu

    (Guangzhou Medical University)

  • Jiangshan Jane Shen

    (The University of Hong Kong)

  • Jing Yang

    (The University of Hong Kong)

  • Tai-Hing Lam

    (The University of Hong Kong)

  • Jia-Huang Lin

    (The University of Hong Kong)

  • Zhi-Ming Mai

    (The University of Hong Kong
    National Institutes of Health)

  • Mengbiao Guo

    (The University of Hong Kong)

  • Yuanjia Tang

    (Shanghai Jiao Tong University School of Medicine)

  • Yanhui Chen

    (Union Hospital Affiliated to Fujian Medical University)

  • Qin Song

    (Affiliated Hospital of Jining Medical University)

  • Bo Ban

    (Affiliated Hospital of Jining Medical University)

  • Chi Chiu Mok

    (Tuen Mun Hospital)

  • Yong Cui

    (China-Japan Friendship Hospital)

  • Liangjing Lu

    (Shanghai Jiao Tong University School of Medicine)

  • Nan Shen

    (Shanghai Jiao Tong University School of Medicine)

  • Pak C. Sham

    (The University of Hong Kong)

  • Chak Sing Lau

    (The University of Hong Kong)

  • David K. Smith

    (The University of Hong Kong)

  • Timothy J. Vyse

    (King’s College London)

  • Xuejun Zhang

    (Anhui Medical University)

  • Yu Lung Lau

    (The University of Hong Kong)

  • Wanling Yang

    (The University of Hong Kong
    The University of Hong Kong)

Abstract

Systemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underlie the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated. To address this, we undertake a genome-wide association study, increasing the sample size of Chinese populations to the level of existing European studies. Thirty-eight novel SLE-associated loci and incomplete sharing of genetic architecture are identified. In addition to the human leukocyte antigen (HLA) region, nine disease loci show clear ancestral differences and implicate antibody production as a potential mechanism for differences in disease manifestation. Polygenic risk scores perform significantly better when trained on ancestry-matched data sets. These analyses help to reveal the genetic basis for disparities in SLE among ancestral groups.

Suggested Citation

  • Yong-Fei Wang & Yan Zhang & Zhiming Lin & Huoru Zhang & Ting-You Wang & Yujie Cao & David L. Morris & Yujun Sheng & Xianyong Yin & Shi-Long Zhong & Xiaoqiong Gu & Yao Lei & Jing He & Qi Wu & Jiangshan, 2021. "Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21049-y
    DOI: 10.1038/s41467-021-21049-y
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    Cited by:

    1. Chachrit Khunsriraksakul & Qinmengge Li & Havell Markus & Matthew T. Patrick & Renan Sauteraud & Daniel McGuire & Xingyan Wang & Chen Wang & Lida Wang & Siyuan Chen & Ganesh Shenoy & Bingshan Li & Xue, 2023. "Multi-ancestry and multi-trait genome-wide association meta-analyses inform clinical risk prediction for systemic lupus erythematosus," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Tian Zhou & Xinyi Zhu & Zhizhong Ye & Yong-Fei Wang & Chao Yao & Ning Xu & Mi Zhou & Jianyang Ma & Yuting Qin & Yiwei Shen & Yuanjia Tang & Zhihua Yin & Hong Xu & Yutong Zhang & Xiaoli Zang & Huihua D, 2022. "Lupus enhancer risk variant causes dysregulation of IRF8 through cooperative lncRNA and DNA methylation machinery," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Yuki Ishikawa & Nao Tanaka & Yoshihide Asano & Masanari Kodera & Yuichiro Shirai & Mitsuteru Akahoshi & Minoru Hasegawa & Takashi Matsushita & Kazuyoshi Saito & Sei-ichiro Motegi & Hajime Yoshifuji & , 2024. "GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Kensuke Yamaguchi & Kazuyoshi Ishigaki & Akari Suzuki & Yumi Tsuchida & Haruka Tsuchiya & Shuji Sumitomo & Yasuo Nagafuchi & Fuyuki Miya & Tatsuhiko Tsunoda & Hirofumi Shoda & Keishi Fujio & Kazuhiko , 2022. "Splicing QTL analysis focusing on coding sequences reveals mechanisms for disease susceptibility loci," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Alesha A. Hatton & Fei-Fei Cheng & Tian Lin & Ren-Juan Shen & Jie Chen & Zhili Zheng & Jia Qu & Fan Lyu & Sarah E. Harris & Simon R. Cox & Zi-Bing Jin & Nicholas G. Martin & Dongsheng Fan & Grant W. M, 2024. "Genetic control of DNA methylation is largely shared across European and East Asian populations," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    6. Qiang Wang & Taehyeung Kim & Marta Martínez-Bonet & Vitor R. C. Aguiar & Sangwan Sim & Jing Cui & Jeffrey A. Sparks & Xiaoting Chen & Marc Todd & Brian Wauford & Miranda C. Marion & Carl D. Langefeld , 2024. "High-throughput identification of functional regulatory SNPs in systemic lupus erythematosus," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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