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Nat Commun. 2015 Jun 1;6:7270. doi: 10.1038/ncomms8270.

Identification of new susceptibility loci for IgA nephropathy in Han Chinese.

Author information

1
Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou , Guangdong 510080, China.
2
Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, Guangdong 510080, China.
3
Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
4
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, China.
5
Singapore Eye Research Institute, Singapore 169856, Singapore.
6
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore.
7
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
8
Department of Nephrology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
9
Institute of Dermatology and Department of Dermatology, No.1 Hospital, Anhui Medical University, Hefei, Anhui, 230032, China.
10
State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Hefei, Anhui 230032, China.
11
Department of Nephrology, XinHua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
12
Department of Nephrology, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, China.
13
Department of Nephrology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
14
Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore 117549, Singapore.
15
Department of Nephrology, The People's Hospital of Guangxi Autonomous Region, Nanning, Guangxi 530021, China.
16
Department of Psychology, National University of Singapore, Singapore 117570, Singapore.
17
Department of Nephrology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
18
Department of Nephrology, Guangdong General Hospital, Guangzhou, Guangdong 510080, China.
19
Department of Economics, National University of Singapore, Singapore 117570, Singapore.
20
Department of Nephrology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian 350025, China.
21
Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Science, Jinan, Shandong 250000, China.
22
Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510080, China.
23
Department of Nephrology, Tongji Hospital, Tongji Medical College of Huazhong University of science &Technology, Wuhan, Hubei 430030, China.
24
Duke-National University of Singapore Graduate Medical School, Singapore 169857, Singapore.
25
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 119228, Singapore.
26
Department of Nephrology, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
27
Department of Nephrology, RuiJin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
28
State Key Laboratory of oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510080, China.
29
Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China.
30
Renal Division, Peking University First Hospital, Peking University, Institute of Nephrology, Beijing 100034, China.
31
School of Biological Sciences, Anhui Medical University, Hefei, Anhui 230032, China.
32
Institute of Dermatology and Department of Dermatology, No.1 Hospital, Anhui Medical University, Hefei, Anhui 230032, China.

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.

PMID:
26028593
PMCID:
PMC4458882
DOI:
10.1038/ncomms8270
[Indexed for MEDLINE]
Free PMC Article

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