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; Jian Jun Liu

doi:10.1038/ncomms8270

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 LinTin 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^*, Jian Jun Liu

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

113 Citations (Scopus)

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.

Original language	English
Article number	7270
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8270
Publication status	Published - Jun 1 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.

ASJC Scopus Subject Areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Li, M., Foo, J. N., Wang, J. Q., Low, H. Q., Tang, X. Q., Toh, K. Y., Yin, P. R., Khor, C. C., Goh, Y. F., Irwan, I. D., Xu, R. C., Andiappan, A. K., Bei, J. X., Rotzschke, O., Chen, M. H., Cheng, C. Y., Sun, L. D., Jiang, G. R., Wong, T. Y., ... Liu, J. J. (2015). Identification of new susceptibility loci for IgA nephropathy in Han Chinese. Nature Communications, 6, Article 7270. https://doi.org/10.1038/ncomms8270

@article{75123955080b4e2d952af1823803f4ba,

title = "Identification of new susceptibility loci for IgA nephropathy in Han Chinese",

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.",

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

year = "2015",

month = jun,

day = "1",

doi = "10.1038/ncomms8270",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

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, Tai, ES, Wang, L, Chen, N, Zhang, XJ, Zeng, YX, Zhang, H, Liu, ZH, Yu, XQ & Liu, JJ 2015, 'Identification of new susceptibility loci for IgA nephropathy in Han Chinese', Nature Communications, vol. 6, 7270. https://doi.org/10.1038/ncomms8270

TY - JOUR

T1 - Identification of new susceptibility loci for IgA nephropathy in Han Chinese

AU - Li, Ming

AU - Foo, Jia Nee

AU - Wang, Jin Quan

AU - Low, Hui Qi

AU - Tang, Xue Qing

AU - Toh, Kai Yee

AU - Yin, Pei Ran

AU - Khor, Chiea Chuen

AU - Goh, Yu Fen

AU - Irwan, Ishak D.

AU - Xu, Ri Cong

AU - Andiappan, Anand K.

AU - Bei, Jin Xin

AU - Rotzschke, Olaf

AU - Chen, Meng Hua

AU - Cheng, Ching Yu

AU - Sun, Liang Dan

AU - Jiang, Geng Ru

AU - Wong, Tien Yin

AU - Lin, Hong Li

AU - Aung, Tin

AU - Liao, Yun Hua

AU - Saw, Seang Mei

AU - Ye, Kun

AU - Ebstein, Richard P.

AU - Chen, Qin Kai

AU - Shi, Wei

AU - Chew, Soo Hong

AU - Chen, Jian

AU - Zhang, Fu Ren

AU - Li, Sheng Ping

AU - Xu, Gang

AU - Tai, E. Shyong

AU - Wang, Li

AU - Chen, Nan

AU - Zhang, Xue Jun

AU - Zeng, Yi Xin

AU - Zhang, Hong

AU - Liu, Zhi Hong

AU - Yu, Xue Qing

AU - Liu, Jian Jun

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

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DO - 10.1038/ncomms8270

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SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 7270

ER -

Identification of new susceptibility loci for IgA nephropathy in Han Chinese

Abstract

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ASJC Scopus Subject Areas

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