No abstract

Since the Oxford Classification of IgA nephropathy (IgAN)

We performed a genome-wide association study of IgA nephropathy (IgAN), a major cause of kidney failure worldwide. Discovery was in 1,194 cases and 902 controls of Chinese Han ancestry, with targeted follow-up in Chinese and European cohorts comprising 1,950 cases and 1,920 controls. We identified three independent loci in the major histocompatibility complex (MHC), a common deletion of CFHR1 and CFHR3 at Chr. 1q32 and a locus at Chr. 22q12 that each surpassed genome-wide significance (p-values for association between 1.59 × 10−26 and 4.84 × 10−9 and minor allele odds ratios of 0.63–0.80). These five loci explain 4–7% of the disease variance and up to a 10-fold variation in interindividual risk. Many of the IgAN–protective alleles impart increased risk of other autoimmune or infectious diseases, and IgAN risk allele frequencies closely parallel the variation in disease prevalence among Asian, European and African populations, suggesting complex selective pressures.

National Health and Medical Research Council of Australia.