期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms8270
关键词
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资金
- Guangdong Department of Science & Technology Translational Medicine Center [2011A080300002]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [20130171130008]
- Science and Technology Planning Project of Guangdong Province, China [2013B051000019]
- Guangzhou Committee of Science and Technology, China [2012J5100031]
- Young Scientists Fund of National Natural Science Foundation of China [81200489]
- Yong Scholars Fund for the Doctoral Program of Higher Education of China [20120171120087]
- Natural Science Foundation of Guangdong Province, China [2014A030313136]
- Agency for Science & Technology and Research (A*STAR) of Singapore
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 x 10(-10)), ACCS on 11p11.2 (rs2074038, OR = 1.14, P = 3.93 x 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR = 1.13, P = 1.41 x 10(-9)), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR = 1.22, P = 2.26 x 10(-19)), and identify three independent signals within the DEFA locus (rs2738058, P = 1.15 x 10(-19); rs12716641, P = 9.53 x 10(-9); s9314614, P = 4.25 x 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.
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