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Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity that may underly population disparities in this disease

By 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, Wanling Yang

Posted 12 Apr 2020
bioRxiv DOI: 10.1101/2020.04.12.037622

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 underly the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated. To address this, we undertook 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 were identified. Nine disease loci showed clear ancestral group heterogeneity and implicated antibody production as a potential mechanism for differences in disease manifestation. Polygenic risk scores performed significantly better when trained on matched ancestral data sets. These analyses help to reveal the genetic bases for disparities in SLE among ancestral groups. ### Competing Interest Statement The authors have declared no competing interest.

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