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

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 Jane Shen, Jing Yang, Tai-Hing Lam, Jia-Huang Lin, Zhi-Ming Mai, Mengbiao Guo, Yuanjia Tang, Yanhui Chen, Qin Song, Bo Ban, Chi Chiu Mok, Yong Cui, Liangjing Lu, Nan Shen, Pak C. Sham, Chak Sing Lau, David K. Smith, Timothy J. Vyse, Xuejun Zhang, Yu Lung Lau () and Wanling Yang ()
Additional contact information
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
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
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

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21049-y

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