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 GuoYuanjia 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, Wanling Yang

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

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.

Original languageEnglish (US)
Article number772
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 1 2021

Bibliographical note

Funding Information:
We thank grant support from National Key Research and Development Program of China (2017YFC0909001), Hong Kong PhD fellowship scheme (HKPF), HKU Post-graduate Scholarships and the Edward and Yolanda Wong Fund for supporting post-graduate students who participated in this work. We also thank the Hong Kong Area of Excellence (AoE) NPC case-control study partially funded by the World Cancer Research Fund (WCRF) for sharing their GWAS data. Y.-F.W. thanks grant support from National Natural Science Foundation of China (Grant No. 81801636). Y.Z. thanks grant support from National Natural Science Foundation of China (Grant No. 81970450) and the Science and Technology Project of Guangzhou (Grant No. 201903010074). W.Y. and Y.L.L. thank Research Grant Council of Hong Kong for support on genetic studies of SLE (GRF 17146616,17106320).

Publisher Copyright:
© 2021, The Author(s).

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