We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 à 10(-11), OR = 1.21; rs4227, P = 4.31 à 10(-10), OR = 1.23) and 8p23 (rs2738048, P = 3.18 à 10(-14), OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 à 10(-20), OR = 1.34; rs1794275, P = 3.43 à 10(-13), OR = 1.30; rs2523946, P = 1.74 à 10(-11), OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 à 10(-11), OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.