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Statements

Subject Item
n2:RIV%2F00216208%3A11110%2F14%3A10282619%21RIV15-MSM-11110___
rdf:type
n16:Vysledek skos:Concept
rdfs:seeAlso
http://dx.doi.org/10.1038/ng.3118
dcterms:description
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. 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.
dcterms:title
Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens
skos:prefLabel
Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens
skos:notation
RIV/00216208:11110/14:10282619!RIV15-MSM-11110___
n4:aktivita
n9:V
n4:aktivity
V
n4:cisloPeriodika
11
n4:dodaniDat
n6:2015
n4:domaciTvurceVysledku
n8:8180229 n8:5909627
n4:druhVysledku
n15:J
n4:duvernostUdaju
n14:S
n4:entitaPredkladatele
n10:predkladatel
n4:idSjednocenehoVysledku
11682
n4:idVysledku
RIV/00216208:11110/14:10282619
n4:jazykVysledku
n17:eng
n4:klicovaSlova
kappa-b; vav proteins; dendritic cells; common variants; susceptibility loci; crohns-disease; ulcerative-colitis; leukemia inhibitory factor; inflammatory-bowel-disease; genome-wide association
n4:klicoveSlovo
n5:vav%20proteins n5:inflammatory-bowel-disease n5:crohns-disease n5:genome-wide%20association n5:common%20variants n5:ulcerative-colitis n5:dendritic%20cells n5:leukemia%20inhibitory%20factor n5:kappa-b n5:susceptibility%20loci
n4:kodStatuVydavatele
US - Spojené státy americké
n4:kontrolniKodProRIV
[CE0537303F08]
n4:nazevZdroje
Nature Genetics
n4:obor
n12:EB
n4:pocetDomacichTvurcuVysledku
2
n4:pocetTvurcuVysledku
92
n4:rokUplatneniVysledku
n6:2014
n4:svazekPeriodika
46
n4:tvurceVysledku
Magistroni, Riccardo Salvi, Erika Barlassina, Cristina Izzi, Claudia Sanna-Cherchi, Simone Savoldi, Silvana Fischman, Clara Viola, Battista Fabio Dallera, Nadia Lata, Sneh Rocchietti, Marcella Ravani, Pietro Appel, Gerald Del Vecchio, Lucia Ghiggeri, Gian Marco Kiryluk, Krzysztof Scolari, Francesco Verbitsky, Miguel Bertinetto, Francesca Eleonora Choi, Murim Snyder, Holly J. Peruzzi, Licia Fasel, David Amoroso, Antonio Li, Yifu Prakash, Sindhuri Shapiro, Samantha Salvadori, Maurizio Coppo, Rosanna Tesař, Vladimír Maixnerová, Dita Amore, Alessandro
n4:wos
000344131900009
s:issn
1061-4036
s:numberOfPages
10
n11:doi
10.1038/ng.3118
n19:organizacniJednotka
11110