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

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

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.

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.

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.