1. Identification of new susceptibility loci for IgA nephropathy in Han Chinese.
- Author
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Li M, Foo JN, Wang JQ, Low HQ, Tang XQ, Toh KY, Yin PR, Khor CC, Goh YF, Irwan ID, Xu RC, Andiappan AK, Bei JX, Rotzschke O, Chen MH, Cheng CY, Sun LD, Jiang GR, Wong TY, Lin HL, Aung T, Liao YH, Saw SM, Ye K, Ebstein RP, Chen QK, Shi W, Chew SH, Chen J, Zhang FR, Li SP, Xu G, Shyong Tai E, Wang L, Chen N, Zhang XJ, Zeng YX, Zhang H, Liu ZH, Yu XQ, and Liu JJ
- Subjects
- Adult, Antigens, CD genetics, CD11b Antigen genetics, CD11c Antigen genetics, Case-Control Studies, China, DEFICIENS Protein genetics, Early Growth Response Transcription Factors genetics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Heat-Shock Proteins genetics, Humans, Kruppel-Like Transcription Factors genetics, Lyases genetics, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Sialyltransferases genetics, Young Adult, Asian People genetics, Glomerulonephritis, IGA genetics
- Abstract
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.
- Published
- 2015
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