Kiryluk, Krzysztof;
Li, Yifu;
Scolari, Francesco;
Sanna-Cherchi, Simone;
Choi, Murim;
Verbitsky, Miguel;
Fasel, David;
... Gharavi, Ali G; + view all
(2014)
Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.
Nature Genetics
, 46
(11)
pp. 1187-1196.
10.1038/ng.3118.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ng.3118 |
| Publisher version: | http://dx.doi.org/10.1038/ng.3118 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, GENOME-WIDE ASSOCIATION, LEUKEMIA INHIBITORY FACTOR, ULCERATIVE-COLITIS, COMMON VARIANTS, DENDRITIC CELLS, CROHNS-DISEASE, VAV PROTEINS, SUSCEPTIBILITY, ALPHA, EXPRESSION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10196195 |
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