Genetic Analysis Provides Evidence for Increased Disease Prevalence of Systemic Lupus Erythematosus in Chinese Populations compared to Europeans

Abstract

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with strong genetic contribution and ethnic differences, characterized by recurrent inflammatory response and multipleorgan damage. Worldwide epidemiology studies have showed that the prevalence of SLE in Asians is about 23 times higher than that in European ancestry. We have conducted a transethnic metaanalysis using Genome Wide Association Study (GWAS) datasets from Chinese and Europeans, and identified 10 novel SLE risk loci, bringing the total to more than Sixty. In this study, we compared those established risk loci between Asians and Europeans, and observed a significant increase in population frequency of SLE risk alleles in Chinese, providing strong evidence that genetics explains the discrepant population prevalence. In addition, we integrated multidimensional biologically annotation to prioritize SLE risk genes and demonstrated that these genes are more likely to be the interactors of targets for the approved drugs for SLE, supporting the role of genetic studies in drug discovery. Through scanning the drug databases, we suggest that those approved drugs for other diseases may be repositioned for SLE treatment. In summary, on the basis of genetic findings, our analysis sheds light on the pathways and cell types that contribute to SLE pathogenesis, and provides genetic evidence for the discrepant population prevalence and supports the role of association studies in drug discovery.