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Recent advances in understanding the genetic basis of systemic lupus erythematosus

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Abstract

Systemic lupus erythematosus (SLE) is a polygenic chronic autoimmune disease leading to multiple organ damage. A large heritability of up to 66% is estimated in SLE, with roughly 180 reported susceptibility loci that have been identified mostly by genome-wide association studies (GWASs) and account for approximately 30% of genetic heritability. A vast majority of risk variants reside in non-coding regions, which makes it quite challenging to interpret their functional implications in the SLE-affected immune system, suggesting the importance of understanding cell type–specific epigenetic regulation around SLE GWAS variants. The latest genetic studies have been highly fruitful as several dozens of SLE loci were newly discovered in the last few years and many loci have come to be understood in systemic approaches integrating GWAS signals with other biological resources. In this review, we summarize SLE-associated genetic variants in both the major histocompatibility complex (MHC) and non-MHC loci, examining polygenetic risk scores for SLE and their associations with clinical features. Finally, variant-driven pathogenetic functions underlying genetic associations are described, coupled with discussion about challenges and future directions in genetic studies on SLE.

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Funding

This research was supported in part by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1A6A1A03038899).

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Authors and Affiliations

  1. Department of Biology, Kyung Hee University, Seoul, Republic of Korea

    Eunji Ha & Kwangwoo Kim

  2. Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea

    Eunji Ha & Kwangwoo Kim

  3. Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea

    Sang-Cheol Bae

  4. Hanyang University Institute for Rheumatology Research, Seoul, Republic of Korea

    Sang-Cheol Bae

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  1. Eunji Ha
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This article is a contribution to the special issue on: Genetics and functional genetics of Autoimmune diseases - Guest Editors: Yukinori Okada & Kazuhiko Yamamoto

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Ha, E., Bae, SC. & Kim, K. Recent advances in understanding the genetic basis of systemic lupus erythematosus. Semin Immunopathol 44, 29–46 (2022). https://doi.org/10.1007/s00281-021-00900-w

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