期刊
NATURE GENETICS
卷 46, 期 11, 页码 1187-1196出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3118
关键词
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资金
- US National Institutes of Health (NIH) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01DK082753, R01DK095510]
- Center for Glomerular Diseases at Columbia University
- NIH/NIDDK [K23DK090207, R03DK099564, R21DK098531]
- Carl W Gottschalk Research Scholar Grant from the American Society of Nephrology (ASN)
- American Heart Association (AHA) [13GRNT14680075]
- Italian Ministry of Health and NIH Ricerca Finalizzata
- Fondazione Malattie Renali nel Bambino
- InterOmics (PB05 MIUR-CNR Italian Flagship Project)
- [SROP-4.2.2/B-10/1/2010-0029]
- Grants-in-Aid for Scientific Research [24591213, 26293201, 26670429] Funding Source: KAKEN
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.
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