Gateva V, Sandling JK, Hom G et al. Nat Genet 2009;41:1228–33.
This study was a targeted replication of a previous genome-wide study in which systemic lupus erythematosus (SLE) risk loci were identified. The present study confirmed the earlier data, and additionally identified five novel SLE risk loci, providing new insights into the pathogenesis of the disease.
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with a strong genetic predisposition. Several association studies have identified 15 SLE risk alleles that achieved a high significance level (p<5×10–8). However, the complete spectrum of SLE risk loci remains to be defined. The present study aimed to identify additional SLE risk loci. Two independent SLE case–control cohorts from the US (1129 SLE cases and 2991 controls) and Sweden (834 SLE cases and 1338 controls) were genotyped for a total of 3735 single nucleotide polymorphisms (SNPs). These SNPs were identified from 2466 loci that reached a p value of 0.05 in a previous genome-wide association study (GWAS; 3188 SNPs) [1], from 23 previously reported SLE risk loci (505 SNPs), and from 35 loci associated with other autoimmune diseases (42 SNPs). A meta-analysis of the published GWAS and present data enabled calculation of a combined p value of association, as well as identification of additional risk loci. The genotyping was performed using a custom Illumina (Illumina Inc., San Diego, CA, USA) SNP array with >12 000 genetic variants; 7113 ancestry-informative markers were used to correct for population stratification.