Identification of new susceptibility loci for IgA nephropathy in Han Chinese

作者：Li Ming; Foo Jia Nee; Wang Jin Quan; Low Hui Qi; Tang Xue Qing; Toh Kai Yee; Yin Pei Ran; Khor Chiea Chuen; Goh Yu Fen; Irwan Ishak D; Xu Ri Cong; Andiappan Anand K; Bei Jin Xin; Rotzschke Olaf; Chen Meng Hua; Cheng Ching Yu; Sun Liang Dan; Jiang Geng Ru; Wong Tien Yin; Lin Hong Li; Aung Tin; Liao Yun Hua; Saw Seang Mei; Ye Kun; Ebstein Richard P; Chen Qin Kai; Shi Wei; Chew Soo Hong; Chen Jian; Zhang Fu Ren; Li Sheng Ping; Xu Gang; Tai E Shyong; Wang Li

来源：Nature Communications, 2015, 6: UNSP 7270.

DOI：10.1038/ncomms8270

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.

• 单位
  1; 北京大学; 中国人民解放军南京军区福州总医院; 南京大学; 中国医学科学院; 上海市闵行区中心医院; 广西壮族自治区人民医院; 大连医科大学1; 安徽医科大学; 中国医学科学院北京协和医院; 上海交通大学; 中山大学; 宁夏医科大学; 广西医科大学; 南昌大学; 山东省医学科学院; 广东省人民医院; 四川省医学科学院（四川省人民医院）