Identification of new susceptibility loci for IgA nephropathy in Han Chinese

Ming Li, Jia-Nee Foo, Jin-Quan Wang, Hui-Qi Low, Xue-Qing Tang, Kai-Yee Toh, Pei-Ran Yin, Chiea-Chuen Khor, Yu-Fen Goh, Ishak D. Irwan, Ri-Cong Xu, Anand K. Andiappan, Jin-Xin Bei, Olaf Rotzschke, Meng-Hua Chen, Ching-Yu Cheng, Liang-Dan Sun, Geng-Ru Jiang, Tien-Yin Wong, Hong-Li Lin, Tin Aung, Yun-Hua Liao, Seang-Mei Saw, Kun Ye, Richard P. Ebstein, Qin-Kai Chen, Wei Shi, Soo-Hong Chew, Jian Chen, Fu-Ren Zhang, Sheng-Ping Li, Gang Xu, E. Shyong Tai, Li Wang, Nan Chen, Xue-Jun Zhang, Yi-Xin Zeng, Hong Zhang, Zhi-Hong Liu, Xue-Qing Yu () and Jian-Jun Liu ()
Additional contact information
Ming Li: The First Affiliated Hospital, Sun Yat-sen University
Jia-Nee Foo: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research
Jin-Quan Wang: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine
Hui-Qi Low: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research
Xue-Qing Tang: The First Affiliated Hospital, Sun Yat-sen University
Kai-Yee Toh: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research
Pei-Ran Yin: The First Affiliated Hospital, Sun Yat-sen University
Chiea-Chuen Khor: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research
Yu-Fen Goh: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research
Ishak D. Irwan: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research
Ri-Cong Xu: The First Affiliated Hospital, Sun Yat-sen University
Anand K. Andiappan: Singapore Immunology Network, Agency for Science, Technology and Research
Jin-Xin Bei: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research
Olaf Rotzschke: Singapore Immunology Network, Agency for Science, Technology and Research
Meng-Hua Chen: General Hospital of Ningxia Medical University
Ching-Yu Cheng: Singapore Eye Research Institute
Liang-Dan Sun: No.1 Hospital, Anhui Medical University
Geng-Ru Jiang: XinHua Hospital, School of Medicine, Shanghai Jiao Tong University
Tien-Yin Wong: Singapore Eye Research Institute
Hong-Li Lin: The First Affiliated Hospital, Dalian Medical University
Tin Aung: Singapore Eye Research Institute
Yun-Hua Liao: The First Affiliated Hospital, Guangxi Medical University
Seang-Mei Saw: Singapore Eye Research Institute
Kun Ye: The People’s Hospital of Guangxi Autonomous Region
Richard P. Ebstein: National University of Singapore
Qin-Kai Chen: the First Affiliated Hospital of Nanchang University
Wei Shi: Guangdong General Hospital
Soo-Hong Chew: National University of Singapore
Jian Chen: Fuzhou General Hospital of Nanjing Military Command
Fu-Ren Zhang: Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Science
Sheng-Ping Li: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center
Gang Xu: Tongji Hospital, Tongji Medical College of Huazhong University of science & Technology
E. Shyong Tai: Duke-National University of Singapore Graduate Medical School
Li Wang: Sichuan Provincial People’s Hospital
Nan Chen: RuiJin Hospital, School of Medicine, Shanghai Jiao Tong University
Xue-Jun Zhang: No.1 Hospital, Anhui Medical University
Yi-Xin Zeng: State Key Laboratory of oncology in South China, Sun Yat-sen University Cancer Center
Hong Zhang: Peking University First Hospital, Peking University, Institute of Nephrology
Zhi-Hong Liu: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine
Xue-Qing Yu: The First Affiliated Hospital, Sun Yat-sen University
Jian-Jun Liu: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8270

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