A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy

Xue-Qing Yu, Jian-Jun Liu and colleagues report results of a genome-wide association study of IgA nephropathy in Han Chinese. They identify two new susceptibility loci at 8p23 and 17p13 and replicate previously reported signals in the MHC region and at 22q12. 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 × 10 −11 , OR = 1.21; rs4227, P = 4.31 × 10 −10 , OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 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 × 10 −20 , OR = 1.34; rs1794275, P = 3.43 × 10 −13 , OR = 1.30; rs2523946, P = 1.74 × 10 −11 , OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 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.