We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.
- MeSH
- antigeny CD11b genetika MeSH
- celogenomová asociační studie MeSH
- genetická pleiotropie genetika MeSH
- genetické lokusy genetika MeSH
- HLA-D antigeny genetika MeSH
- IgA nefropatie genetika MeSH
- imunita genetika MeSH
- interakce hostitele a patogenu genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- protoonkogenní proteiny c-vav genetika MeSH
- signální adaptorové proteiny CARD genetika MeSH
- střeva imunologie parazitologie MeSH
- věk při počátku nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
