A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy

Xue Qing Yu; Ming Li; Hong Zhang; Hui Qi Low; Xin Wei; Jin Quan Wang; Liang Dan Sun; Kar Seng Sim; Yi Li; Jia Nee Foo; Wei Wang; Zhi Jian Li; Xian Yong Yin; Xue Qing Tang; Li Fan; Jian Chen; Rong Shan Li; Jian Xin Wan; Zhang Suo Liu; Tan Qi Lou; Li Zhu; Xiao Jun Huang; Xue Jun Zhang; Zhi Hong Liu; Jian Jun Liu

doi:10.1038/ng.1047

A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy

Xue Qing Yu, Ming Li, Hong Zhang, Hui Qi Low, Xin Wei, Jin Quan Wang, Liang Dan Sun, Kar Seng Sim, Yi Li, Jia Nee Foo, Wei Wang, Zhi Jian Li, Xian Yong Yin, Xue Qing Tang, Li Fan, Jian Chen, Rong Shan Li, Jian Xin Wan, Zhang Suo Liu, Tan Qi LouLi Zhu, Xiao Jun Huang, Xue Jun Zhang, Zhi Hong Liu, Jian Jun Liu^*

^*Corresponding author for this work

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

258 Citations (Scopus)

Abstract

We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10 ^-11, OR = 1.21; rs4227, P = 4.31 × 10 ^-10, OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10 ^-14, OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10-20, OR = 1.34; rs1794275, P = 3.43 × 10 ^-13, OR = 1.30; rs2523946, P = 1.74 × 10 ^-11, OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10 ^-11, OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.

Original language	English
Pages (from-to)	178-182
Number of pages	5
Journal	Nature Genetics
Volume	44
Issue number	2
DOIs	https://doi.org/10.1038/ng.1047
Publication status	Published - Feb 2012
Externally published	Yes

ASJC Scopus Subject Areas

Genetics

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Yu, X. Q., Li, M., Zhang, H., Low, H. Q., Wei, X., Wang, J. Q., Sun, L. D., Sim, K. S., Li, Y., Foo, J. N., Wang, W., Li, Z. J., Yin, X. Y., Tang, X. Q., Fan, L., Chen, J., Li, R. S., Wan, J. X., Liu, Z. S., ... Liu, J. J. (2012). A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy. Nature Genetics, 44(2), 178-182. https://doi.org/10.1038/ng.1047

@article{34fcf15fd7e84ed6b6cbb23f4ddac8be,

title = "A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy",

abstract = "We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10 -11, OR = 1.21; rs4227, P = 4.31 × 10 -10, OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10 -14, OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10-20, OR = 1.34; rs1794275, P = 3.43 × 10 -13, OR = 1.30; rs2523946, P = 1.74 × 10 -11, OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10 -11, OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.",

author = "Yu, {Xue Qing} and Ming Li and Hong Zhang and Low, {Hui Qi} and Xin Wei and Wang, {Jin Quan} and Sun, {Liang Dan} and Sim, {Kar Seng} and Yi Li and Foo, {Jia Nee} and Wei Wang and Li, {Zhi Jian} and Yin, {Xian Yong} and Tang, {Xue Qing} and Li Fan and Jian Chen and Li, {Rong Shan} and Wan, {Jian Xin} and Liu, {Zhang Suo} and Lou, {Tan Qi} and Li Zhu and Huang, {Xiao Jun} and Zhang, {Xue Jun} and Liu, {Zhi Hong} and Liu, {Jian Jun}",

year = "2012",

month = feb,

doi = "10.1038/ng.1047",

language = "English",

volume = "44",

pages = "178--182",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "2",

}

Yu, XQ, Li, M, Zhang, H, Low, HQ, Wei, X, Wang, JQ, Sun, LD, Sim, KS, Li, Y, Foo, JN, Wang, W, Li, ZJ, Yin, XY, Tang, XQ, Fan, L, Chen, J, Li, RS, Wan, JX, Liu, ZS, Lou, TQ, Zhu, L, Huang, XJ, Zhang, XJ, Liu, ZH & Liu, JJ 2012, 'A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy', Nature Genetics, vol. 44, no. 2, pp. 178-182. https://doi.org/10.1038/ng.1047

TY - JOUR

T1 - A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy

AU - Yu, Xue Qing

AU - Li, Ming

AU - Zhang, Hong

AU - Low, Hui Qi

AU - Wei, Xin

AU - Wang, Jin Quan

AU - Sun, Liang Dan

AU - Sim, Kar Seng

AU - Li, Yi

AU - Foo, Jia Nee

AU - Wang, Wei

AU - Li, Zhi Jian

AU - Yin, Xian Yong

AU - Tang, Xue Qing

AU - Fan, Li

AU - Chen, Jian

AU - Li, Rong Shan

AU - Wan, Jian Xin

AU - Liu, Zhang Suo

AU - Lou, Tan Qi

AU - Zhu, Li

AU - Huang, Xiao Jun

AU - Zhang, Xue Jun

AU - Liu, Zhi Hong

AU - Liu, Jian Jun

PY - 2012/2

Y1 - 2012/2

N2 - We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10 -11, OR = 1.21; rs4227, P = 4.31 × 10 -10, OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10 -14, OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10-20, OR = 1.34; rs1794275, P = 3.43 × 10 -13, OR = 1.30; rs2523946, P = 1.74 × 10 -11, OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10 -11, OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.

AB - We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10 -11, OR = 1.21; rs4227, P = 4.31 × 10 -10, OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10 -14, OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10-20, OR = 1.34; rs1794275, P = 3.43 × 10 -13, OR = 1.30; rs2523946, P = 1.74 × 10 -11, OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10 -11, OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.

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A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy

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