Using this strategy, we estimated significant causal effects between serum IgA levels and IgA nephropathy (inverse variance-weighted OR 9.70 per SD of exposure, 95%CI: 6.80–13.8, P < 0.001; Fig. 5c), supporting IgA level as a strong causal mediator of disease risk for these loci. This evidence concerns the gene CD79A and IgA glomerulonephritis.