Identification of new susceptibility loci for IgA nephropathy in Han Chinese.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Li, M; Foo, J-N; Wang, J-Q; Low, H-Q; Tang, X-Q; Toh, K-Y; Yin, P-R; Khor, C-C; Goh, Y-F; Irwan, ID; Xu, R-C; Andiappan, AK; Bei, J-X; Rotzschke, O; Chen, M-H; Cheng, C-Y; Sun, L-D; Jiang, G-R; Wong, T-Y; Lin, H-L; Aung, T; Liao, Y-H; Saw, S-M; Ye, K; Ebstein, RP; Chen, Q-K; Shi, W; Chew, S-H; Chen, J; Zhang, F-R; Li, S-P; Xu, G; Shyong Tai, E; Wang, L; Chen, N; Zhang, X-J; Zeng, Y-X; Zhang, H; Liu, Z-H; Yu, X-Q; Liu, J-J

Published Date

  • June 1, 2015

Published In

Volume / Issue

  • 6 /

Start / End Page

  • 7270 -

PubMed ID

  • 26028593

Pubmed Central ID

  • PMC4458882

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms8270


  • eng

Conference Location

  • England