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Journal of Peking University(Health Sciences) ›› 2019, Vol. 51 ›› Issue (3): 459-466. doi: 10.19723/j.issn.1671-167X.2019.03.013

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Trans-ethnic analysis of susceptibility variants in IgA nephropathy

Yu-qi KANG1,2,Yue-miao ZHANG1△(),Ping HOU1,Su-fang SHI1,Li-jun LIU1,Xu-jie ZHOU1,Ji-cheng LV1,Hong ZHANG1   

  • Received:2019-03-18 Online:2019-06-18 Published:2019-06-26
  • Supported by:
    Supported by the National Natural Science Foundation of China (81800636), Beijing Natural Science Foundation (7184253), and the Fundamental Research Funds for the Central Universities: Peking University Medicine Fund of Fostering Young Scholars’ Scientific & Technological Innovation (BMU2017PY007)

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Abstract: 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 diffe-rences with respect to the effect sizes and risk allele frequencies across ethnicities, contributing partially to the differences of disease prevalence.

Key words: IgA nephropathy, Polymorphism, single nucleotide, Chinese, Europeans

CLC Number: 

  • R692.31

Table 1

Baseline clinical manifestations of 1 194 IgA nephrpathy patients"

Characteristic Median or percentage
Age/years, IQR 32 (25, 39)
Gender, male/female 651/543
Systolic blood pressure/mmHg, IQR 120 (110, 130)
Diastolic blood pressure/mmHg, IQR 80 (70, 88)
Hypertension/% 47.90
Urinary protein (g/24 h)/%
<1 33.93
1-2 27.52
2-3.5 15.60
≥3.5 20.95
eGFR/[mL/(min·1.73 m2)], IQR 85.63 (63.52, 106.63)
Haas classification/%
Ⅰ 38.19
Ⅱ 6.71
Ⅲ 38.43
Ⅳ 7.87
Ⅴ 8.80

Table 2

Comparison of associated SNPs in Chinese and European populations"

Figure 1

Comparison of OR, PARP and RAF between the Chinese and Europeans OR, odds ratio; PARP, population attributable risk proportion; RAF, risk allele frequency."

Figure 2

Comparison of genetic risk score between the IgAN patients and controls uwGRS, unweighted genetic risk score; wGRS, weighted genetic risk score; IgAN, IgA nephropathy."

Table 3

Association of genetic risk score and clinical manifestations in lgA nephropathy"

Figure 3

Comparison of genetic risk score between East Asians and Europeans uwGRS, unweighted genetic risk score; wGRS, weighted genetic risk score."

Figure 4

Comparison of genetic risk score among subpopulations in East Asians uwGRS, unweighted genetic risk score; wGRS, weighted genetic risk score; CDX, Chinese Dai in Xishuangbanna; CHB, Chinese Han in Beijing; CHS, Southern Han Chinese; JPT, Japanese in Tokyo; KHT, Kinh in Ho Chi Minh City."

Figure 5

Comparison of genetic risk score among subpopulations in Europeans uwGRS, unweighted genetic risk score; wGRS, weighted genetic risk score; CEU, Utah residents with Northern and Western European Ancestry; FIN, Finnish in Finland; GBR, British in England and Scotland; IBS, Iberian population in Spain; TSI, Toscani in Italia."

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