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. 2019 Jun 18;51(3):459-466.
doi: 10.19723/j.issn.1671-167X.2019.03.013.

[Trans-ethnic analysis of susceptibility variants in IgA nephropathy]

[Article in Chinese]
Y Q Kang  1   2 , Y M Zhang  1 , P Hou  1 , S F Shi  1 , L J Liu  1 , X J Zhou  1 , J C Lv  1 , H Zhang  1
Affiliations

[Trans-ethnic analysis of susceptibility variants in IgA nephropathy]

[Article in Chinese]
Y Q Kang et al. Beijing Da Xue Xue Bao Yi Xue Ban. .

Abstract
in English, Chinese

Objective: To compare the genetic architecture of susceptibility variants of IgA nephropathy (IgAN) in Chinese and Europeans.

Methods: We selected the independent genome-wide significant variants of IgAN in European population as candidate variants. Their associations, risk alleles, risk allele frequencies, odds ratios and population attributable risk scores were derived and calculated, then compared with those in the current Chinese population, including 1 194 IgAN patients and 902 controls. Using the significant variants, genetic risk scores were calculated and compared between the East Asians and the Europeans. The correlation between the genetic risk scores and clinical manifestations was also evaluated.

Results: There were 16 independent single nucleotide polymorphisms (SNPs) located in 11 loci showing significantly association with susceptibility to IgAN in the Europeans. 93.75% (15/16) of them also showed significant associations in the Chinese (P<0.05). The effects of all the associated SNPs were in the same direction, either risk or being protective for IgAN, between the Chinese and the Europeans. On the contrary, remarkable higher risk allelic odds ratio (P=1.94×10-2), higher risk allele frequency (P=3.09×10-2), and higher population attributable risk (P=3.03×10-4) were observed for most of the associated SNPs in the Chinese than in the Europeans. Furthermore, genetic risk scores were significantly larger in the Asian populations compared with the Europeans (P=1.78×10-163). While there was no significance among the subpopulations in both the East Asians and the Europeans. Compared with the healthy controls, the genetic risk score in the IgAN patients was significantly larger (P=3.60×10-27). Clinical analysis showed the genetic risk score was positively associated with serum levels of IgA and IgA1, phases of chronic kidney disease and Haas grades.

Conclusion: Our study provides further evidence in the shared genetic architecture between Chinese and Europeans, while differences with respect to the effect sizes and risk allele frequencies across ethnicities, contributing partially to the differences of disease prevalence.

目的: 在中国和欧洲人群中比较IgA肾病易感基因遗传多态性的种族差异。

方法: 检索欧洲人群中已报道的IgA肾病易感基因遗传位点,验证其在中国人群(1 194例患者和902例对照)中的关联性,比较两个人群中显著相关位点的危险等位基因型及其基因型频率、效应OR值、人群归因风险百分比之间的差异。利用所有相关位点计算遗传危险度评分,比较其在亚欧人群中的分布,分析其与临床表型的关联。

结果: 共有11个遗传座位上16个独立相关遗传位点与欧洲人群中IgA肾病的遗传易感性显著相关。93.75%(15/16)欧洲人相关遗传位点在中国人群中得到独立验证(P<0.05),且危险等位基因型在两个人群中一致。与欧洲人群相比,中国人群遗传位点拥有更高的危险等位基因型频率(P=3.09×10 -2)、OR值(P=1.94×10 -2)和人群归因风险百分比(P=3.03×10 -4)。中国人群IgA肾病患者与健康对照、东亚人群与欧洲人群相比遗传危险度评分更高(P值分别为3.60×10 -27和1.78×10 -163),东亚人群和欧洲人群各亚组之间差异无统计学意义。研究人群中IgA肾病遗传危险度评分与血浆IgA1水平、慢性肾脏病(chronic kidney disease,CKD)分期和Hass分级显著相关。

结论: IgA肾病相关易感基因在欧洲人群和中国人群相似,中国人群有更高遗传风险,提示亚洲人群中IgA肾病高患病率具有遗传基础。

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Figures

1
1
IgAN易感基因遗传性位点在中国人群和欧洲人群的疾病风险比较 Comparison of OR, PARP and RAF between the Chinese and Europeans
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IgAN患者和健康对照遗传危险度评分比较 Comparison of genetic risk score between the IgAN patients and controls
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东亚人群和欧洲人群IgAN遗传危险度评分比较 Comparison of genetic risk score between East Asians and Europeans
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东亚人群之间IgAN遗传危险度评分比较 Comparison of genetic risk score among subpopulations in East Asians
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欧洲人群之间IgAN遗传危险度评分比较 Comparison of genetic risk score among subpopulations in Europeans
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References

    1. Scolari F. Familial IgA nephropathy. J Nephrol. 1999;12(4):213–219. - PubMed
    1. Scolari F, Amoroso A, Savoldi S, et al. Familial clustering of IgA nephropathy: further evidence in an Italian population. Am J Kidney Dis. 1999;33(5):857–865. - PubMed
    1. Kiryluk K, Li Y, Sanna-Cherchi S, et al. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis. PLoS Genet. 2012;8(6):e1002765. - PMC - PubMed
    1. Feehally J, Farrall M, Boland A, et al. HLA has strongest association with IgA nephropathy in genome-wide analysis. J Am Soc Nephrol. 2010;21(10):1791–1797. - PMC - PubMed
    1. Gharavi AG, Kiryluk K, Choi M, et al. Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet. 2011;43(4):321–327. - PMC - PubMed