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

Yong-Fei Wang, et al.

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Received Date: 26th April 20

Yong-Fei WangYan ZhangZhiming LinHuoru ZhangTing-You WangYujie CaoDavid L. MorrisYujun ShengXianyong YinShi-Long ZhongXiaoqiong GuYao LeiJing HeQi WuJiangshan Jane ShenJing YangTai-Hing LamJia-Huang LinZhi-Ming MaiMengbiao GuoYuanjia TangYanhui ChenQin SongBo BanChi Chiu MokYong CuiLiangjing LuNan ShenPak C. ShamChak Sing LauDavid K. SmithTimothy J. VyseXuejun ZhangYu Lung LauWanling Yang

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.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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