Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with strong genetic and environmental components. The study identifies two new genetic loci associated with SLE: C8orf13-BLK and ITGAM-ITGAX. These loci were discovered through genome-wide association studies (GWAS) involving 1311 SLE patients and 3340 control subjects of European descent. The study also included replication in 793 SLE patients and 857 control subjects from Sweden. The C8orf13-BLK locus was associated with increased expression of C8orf13 and reduced expression of BLK. Variants in the ITGAM-ITGAX region were linked to SLE risk. The study found that the A allele of rs13277113 in the C8orf13-BLK region was associated with increased SLE risk, with an odds ratio of 1.39 (P=1×10⁻¹⁰). Similarly, the C allele of rs11574637 in the ITGAM-ITGAX region was associated with SLE, with an odds ratio of 1.33 (P=3×10⁻¹¹). The study also found that variants in the ITGAM-ITGAX region were associated with altered levels of messenger RNA in B-cell lines. The ITGAM gene is expressed in various myeloid cells, including dendritic cells, macrophages, and neutrophils. ITGAM forms a heterodimer with ITGB2 and mediates adhesion between immune cells. Mice deficient in ITGAM showed enhanced disease progression in autoimmune models, including lupus. ITGAM may suppress differentiation of Th17 cells, which are involved in autoimmunity. The study confirms that the BLK gene, a tyrosine kinase in the src family, is highly expressed in B cells and may influence B-cell tolerance, potentially predisposing individuals to systemic autoimmunity. The C8orf13 gene, which is ubiquitously expressed, was also found to be associated with SLE risk. The study highlights the importance of genetic factors in SLE susceptibility and suggests that further research is needed to understand the functional roles of these genes in the disease. The findings contribute to the understanding of the genetic basis of SLE and may have implications for the development of new therapeutic strategies.Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with strong genetic and environmental components. The study identifies two new genetic loci associated with SLE: C8orf13-BLK and ITGAM-ITGAX. These loci were discovered through genome-wide association studies (GWAS) involving 1311 SLE patients and 3340 control subjects of European descent. The study also included replication in 793 SLE patients and 857 control subjects from Sweden. The C8orf13-BLK locus was associated with increased expression of C8orf13 and reduced expression of BLK. Variants in the ITGAM-ITGAX region were linked to SLE risk. The study found that the A allele of rs13277113 in the C8orf13-BLK region was associated with increased SLE risk, with an odds ratio of 1.39 (P=1×10⁻¹⁰). Similarly, the C allele of rs11574637 in the ITGAM-ITGAX region was associated with SLE, with an odds ratio of 1.33 (P=3×10⁻¹¹). The study also found that variants in the ITGAM-ITGAX region were associated with altered levels of messenger RNA in B-cell lines. The ITGAM gene is expressed in various myeloid cells, including dendritic cells, macrophages, and neutrophils. ITGAM forms a heterodimer with ITGB2 and mediates adhesion between immune cells. Mice deficient in ITGAM showed enhanced disease progression in autoimmune models, including lupus. ITGAM may suppress differentiation of Th17 cells, which are involved in autoimmunity. The study confirms that the BLK gene, a tyrosine kinase in the src family, is highly expressed in B cells and may influence B-cell tolerance, potentially predisposing individuals to systemic autoimmunity. The C8orf13 gene, which is ubiquitously expressed, was also found to be associated with SLE risk. The study highlights the importance of genetic factors in SLE susceptibility and suggests that further research is needed to understand the functional roles of these genes in the disease. The findings contribute to the understanding of the genetic basis of SLE and may have implications for the development of new therapeutic strategies.