Genetic advances in systemic lupus erythematosus: an update

Current Opinion in Rheumatology
Lingyan ChenTimothy J Vyse

Abstract

More than 80 susceptibility loci are now reported to show robust genetic association with systemic lupus erythematosus (SLE). The differential functional effects of the risk alleles for the majority of these loci remain to be defined. Here, we review current SLE association findings and the recent progress in the annotation of noncoding regions of the human genome as well as the new technologies and statistical methods that can be applied to further the understanding of SLE genetics. Genome-wide association studies (GWAS) have markedly expanded the catalogue of genetic signals contributing to SLE development; we can now explain more than 50% of the disease's heritability. Expression quantitative trait loci mapping with colocalization analysis of GWAS results help to identify the underlying causal genes. The Encyclopedia of DNA elements, Roadmap Epigenome, and the Blueprint Epigenome projects have jointly annotated more than 80% of the noncoding genome, providing a wealth of information (from healthy individuals) to define the functional elements within the risk loci. Technologies, such as next-generation sequencing, chromatin structure determination, and genome editing, will help elucidate the actual mechanisms that underpin SL...Continue Reading

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