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

Wang, Y.-F.; Zhang, Y.; Lin, Z.; Zhang, H.; Wang, T.-Y.; Cao, Y.; Morris, D. L.; Sheng, Y.; Yin, X.; Zhong, S.-L.; Gu, X.; Yao, L.; He, J.; Wu, Q.; Shen, J. J.; Yang, J.; Lam, T.-H.; Lin, J.-H.; Mai, Z.-M.; Guo, M.; Tang, Y.; Chen, Y.; Song, Q.; Ban, B.; Mok, C. C.; Cui, Y.; Lu, L.; Shen, N.; Sham, P. C.; Lau, C. S.; Smith, D. K.; Vyse, T. J.; Zhang, X.; Lau, Y. L.; Yang, W.

doi:10.1101/2020.04.12.037622

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bioRxiv · 10.1101/2020.04.12.037622

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

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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 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.

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Wang, Y.-F., Zhang, Y., Lin, Z., Zhang, H., Wang, T.-Y., Cao, Y., Morris, D. L., Sheng, Y., Yin, X., Zhong, S.-L., Gu, X., Yao, L., He, J., Wu, Q., Shen, J. J., Yang, J., Lam, T.-H., Lin, J.-H., Mai, Z.-M., Guo, M., Tang, Y., Chen, Y., Song, Q., Ban, B., Mok, C. C., Cui, Y., Lu, L., Shen, N., Sham, P. C., Lau, C. S., Smith, D. K., Vyse, T. J., Zhang, X., Lau, Y. L., Yang, W.. 2020-04-12. Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity that may underly population disparities in this disease. https://doi.org/10.1101/2020.04.12.037622

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