Genomic Landscape of Systemic Lupus Erythematosus and Lupus Nephritis Globally and the Gaps in Africa

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a strong genetic component, and lupus nephritis (LN) represents one of its most common and severe organ-specific manifestations. This review synthesises current evidence on the genetic architecture of SLE and LN, with a particular focus on identifying shared and distinct genetic susceptibility loci and highlighting knowledge and data gaps in highly burdened African populations. Across studies, most risk loci, including HLA-DRB1, TNFSF4, IRF5, STAT4, TNFAIP3, BANK1, BLK, ITGAM, and FcγR2A/FcγR3A, converge on key immune pathways such as antigen presentation, type I IFN signalling, B-cell activation, and immune complex clearance. The findings support a substantial genomic overlap between SLE and LN, with most variants contributing to systemic immune dysregulation rather than kidney-specific susceptibility. A limited number of loci, including PDGFRA, HAS2, and SLC5A11, have been implicated in renal involvement, while APOL1 G1/G2 risk variants are associated with renal disease progression and adverse kidney outcomes among individuals of African ancestry. Despite these advances, relatively few loci have been definitively linked to LN independent of SLE, reflecting both biological overlap and limitations in study design. Moreover, the existing literature is heavily skewed toward European, Asian, and admixed populations, with minimal representation of continental African cohorts. Given the high genetic diversity and disproportionate disease burden in African populations, this represents a critical knowledge gap. Improved inclusion of diverse populations, coupled with high-resolution genomic and functional studies, will be essential to refine causal variant identification and enhance understanding of disease mechanisms. Ultimately, insights into population-specific genetic risk may enable earlier identification of high-risk individuals and support the development of precision medicine strategies for SLE, specifically LN.