This study aimed to identify genetic loci associated with systemic lupus erythematosus (SLE) by genotyping over 500,000 single-nucleotide polymorphisms (SNPs) in DNA samples from 1,311 SLE cases and 1,783 controls, all of European descent. The authors also replicated findings in 793 SLE cases and 857 controls from Sweden. They identified two new genetic loci associated with SLE: the C8orf13-BLK locus on chromosome 8p23.1 and the ITGAM-ITGAX locus on chromosome 16p11.22. The C8orf13-BLK locus, associated with altered mRNA levels of BLK and C8orf13, showed a combined odds ratio of 1.39 (P=1×10−10) in the U.S. and Swedish samples. The ITGAM-ITGAX locus, which includes the genes encoding integrin alpha M (ITGAM) and integrin alpha X (ITGAX), showed a combined odds ratio of 1.33 (P=3×10−11). These findings suggest that variations in these loci contribute to SLE risk and may provide insights into the pathogenesis of the disease.This study aimed to identify genetic loci associated with systemic lupus erythematosus (SLE) by genotyping over 500,000 single-nucleotide polymorphisms (SNPs) in DNA samples from 1,311 SLE cases and 1,783 controls, all of European descent. The authors also replicated findings in 793 SLE cases and 857 controls from Sweden. They identified two new genetic loci associated with SLE: the C8orf13-BLK locus on chromosome 8p23.1 and the ITGAM-ITGAX locus on chromosome 16p11.22. The C8orf13-BLK locus, associated with altered mRNA levels of BLK and C8orf13, showed a combined odds ratio of 1.39 (P=1×10−10) in the U.S. and Swedish samples. The ITGAM-ITGAX locus, which includes the genes encoding integrin alpha M (ITGAM) and integrin alpha X (ITGAX), showed a combined odds ratio of 1.33 (P=3×10−11). These findings suggest that variations in these loci contribute to SLE risk and may provide insights into the pathogenesis of the disease.