Identification of new susceptibility loci for IgA nephropathy in Han Chinese

IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, odds ratio (OR)=1.13, P =7.27 × 10 −10 ), ACCS on 11p11.2 (rs2074038, OR=1.14, P =3.93 × 10 −9 ) and ODF1-KLF10 on 8q22.3 (rs2033562, OR=1.13, P =1.41 × 10 −9 ), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR=1.22, P =2.26 × 10 −19 ), and identify three independent signals within the DEFA locus (rs2738058, P =1.15 × 10 −19 ; rs12716641, P =9.53 × 10 −9 ; rs9314614, P =4.25 × 10 −9 , multivariate association). The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants within ST6GAL1 , ACCS and DEFA correlate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.