Systemic lupus erythematosus genetics: what’s new?

摘要

The last 6 months has witnessed staggeringrnadvances in our understanding of the genetics ofrnsystemic lupus erythematosus (SLE). New andrnimportant genes have been identified through classicalrnassociation studies; two independent wholegenomernassociation analyses have been published;rnwe have made inroads into the dissection of complexrngenetic effects arising from the major histocompatibilityrncomplex (MHC); and we arernincreasingly recognizing that large-scale genomicrnalteration in the form of copy-number variationrn(CNV) is an important risk factor for SLE.rnIt has been known for at least 30 years that SLErnhas a strong genetic basis, and the results of earlyrnfamily studies are frequently quoted; a disease concordancernrate of 2–5% for dizygotic twins, comparedrnwith 24–48% for monozygotic twins, and arnsibling risk ratio (λs) up to 29 [1–3]. The inheritancernof SLE is complex and does not follow simplernMendelian rules, which suggests multiple genesrncontribute to disease susceptibility. Occasional rarernbut highly penetrant mutations occur, such asrncomplement C1q deficiency and the recentlyrndescribed variation in the TREX1 exonuclease;rnhowever, in most cases, SLE risk is likely to berndetermined by common variants occurring in a