Genetics research in systemic lupus erythematosus for clinicians: methodology, progress, and controversies

Clinical journals are reporting genetic associations with systemic lupus erythematosus (SLE) with increasing frequency. Interpreting these studies is difficult for clinicians without rigorous training in epidemiology, statistics, and genetics. In this review, we discuss basic issues important to understanding and contextualizing new genetic association studies. We, therefore, highlight literature related to methodology as well as recent genetic discoveries in SLE.

Functional single nucleotide polymorphisms (SNPs) and/or haplotypes have now been identified for ITGAM, PTPN22, and IRF5, and several additional loci have been highlighted in recent genome-wide association studies in SLE. Recent work also indicates that several regions within the extended major histocompatibility complex contribute independently to SLE risk. Evidence of additive statistical interaction has been found between IRF5 and TYK2, IRF5, and STAT4, and between NAT2 and exposure to tobacco smoke.

Many new genes have been associated with SLE susceptibility, revealing insight into SLE pathophysiology. Current research is focusing on further refining the initial genetic association results and extending this work to non-European populations. Research is also expanding beyond SNP associations to investigate the contribution of copy number variants (CNVs) and DNA methylation to SLE risk.