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Identification of new susceptibility loci for IgA nephropathy in Han Chinese

Author

Listed:
  • Ming Li

    (The First Affiliated Hospital, Sun Yat-sen University
    Key Laboratory of Nephrology, Ministry of Health and Guangdong Province)

  • 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
    Key Laboratory of Nephrology, Ministry of Health and Guangdong Province)

  • 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
    Key Laboratory of Nephrology, Ministry of Health and Guangdong Province)

  • Chiea-Chuen Khor

    (Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research
    Singapore Eye Research Institute
    Yong Loo Lin School of Medicine, National University of Singapore and National University Health System)

  • 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
    Key Laboratory of Nephrology, Ministry of Health and Guangdong Province)

  • 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
    Yong Loo Lin School of Medicine, National University of Singapore and National University Health System)

  • Liang-Dan Sun

    (No.1 Hospital, Anhui Medical University
    State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology)

  • Geng-Ru Jiang

    (XinHua Hospital, School of Medicine, Shanghai Jiao Tong University)

  • Tien-Yin Wong

    (Singapore Eye Research Institute
    Yong Loo Lin School of Medicine, National University of Singapore and National University Health System)

  • Hong-Li Lin

    (The First Affiliated Hospital, Dalian Medical University)

  • Tin Aung

    (Singapore Eye Research Institute
    Yong Loo Lin School of Medicine, National University of Singapore and National University Health System)

  • Yun-Hua Liao

    (The First Affiliated Hospital, Guangxi Medical University)

  • Seang-Mei Saw

    (Singapore Eye Research Institute
    Yong Loo Lin School of Medicine, National University of Singapore and National University Health System
    Saw Swee Hock School of Public Health, National University of Singapore, National University Health System)

  • 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
    Yong Loo Lin School of Medicine, National University of Singapore, National University Health System)

  • 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
    State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology)

  • Yi-Xin Zeng

    (State Key Laboratory of oncology in South China, Sun Yat-sen University Cancer Center
    Peking Union Medical College, Chinese Academy of Medical Science)

  • 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
    Saw Swee Hock School of Public Health, National University of Singapore, National University Health System
    School of Biological Sciences, Anhui Medical University
    No.1 Hospital, Anhui Medical University)

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.

Suggested Citation

  • 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 R, 2015. "Identification of new susceptibility loci for IgA nephropathy in Han Chinese," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8270
    DOI: 10.1038/ncomms8270
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