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学科主题: 临床医学
题名:
Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens
作者: Kiryluk, Krzysztof1; Li, Yifu1; Scolari, Francesco2,3; Sanna-Cherchi, Simone1; Choi, Murim4,5; Verbitsky, Miguel1; Fasel, David1; Lata, Sneh1; Prakash, Sindhuri1; Shapiro, Samantha1; Fischman, Clara1; Snyder, Holly J.1; Appel, Gerald1; Izzi, Claudia2,6; Viola, Battista Fabio7; Dallera, Nadia2,3; Del Vecchio, Lucia8; Barlassina, Cristina8; Salvi, Erika8; Bertinetto, Francesca Eleonora9,10; Amoroso, Antonio9,10; Savoldi, Silvana11,12; Rocchietti, Marcella11,12; Amore, Alessandro13; Peruzzi, Licia13; Coppo, Rosanna13; Salvadori, Maurizio14; Ravani, Pietro15,16; Magistroni, Riccardo17; Ghiggeri, Gian Marco18; Caridi, Gianluca18; Bodria, Monica18; Lugani, Francesca18; Allegri, Landino19,20; Delsante, Marco19,20; Maiorana, Mariarosa19,20; Magnano, Andrea19,20; Frasca, Giovanni21; Boer, Emanuela22; Boscutti, Giuliano23; Ponticelli, Claudio24; Mignani, Renzo25; Marcantoni, Carmelita26; Di Landro, Domenico26; Santoro, Domenico27; Pani, Antonello28; Polci, Rosaria29; Feriozzi, Sandro29; Chicca, Silvana30; Galliani, Marco30; Gigante, Maddalena31; Gesualdo, Loreto32; Zamboli, Pasquale33; Battaglia, Giovanni Giorgio34; Garozzo, Maurizio34; Maixnerova, Dita35,36; Tesar, Vladimir35,36; Eitner, Frank37,38; Rauen, Thomas37; Floege, Juergen37; Kovacs, Tibor39,40; Nagy, Judit39,40; Mucha, Krzysztof41; Paczek, Leszek41; Zaniew, Marcin42; Mizerska-Wasiak, Malgorzata43; Roszkowska-Blaim, Maria43; Pawlaczyk, Krzysztof44; Gale, Daniel45; Barratt, Jonathan46,47; Thibaudin, Lise48; Berthoux, Francois48; Canaud, Guillaume49; Boland, Anne50,51; Metzger, Marie52,53; Panzer, Ulf54; Suzuki, Hitoshi55; Goto, Shin56; Narita, Ichiei56; Caliskan, Yasar57; Xie, Jingyuan58; Hou, Ping59; Chen, Nan58; Zhang, Hong59; Wyatt, Robert J.60,61; Novak, Jan62; Julian, Bruce A.63; Feehally, John46,47; Stengel, Benedicte52,53; Cusi, Daniele8; Lifton, Richard P.4,64; Gharavi, Ali G.1
刊名: NATURE GENETICS
发表日期: 2014-11-01
DOI: 10.1038/ng.3118
卷: 46, 期:11, 页:1187-1196
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Genetics & Heredity
研究领域[WOS]: Genetics & Heredity
关键词[WOS]: GENOME-WIDE ASSOCIATION ; INFLAMMATORY-BOWEL-DISEASE ; LEUKEMIA INHIBITORY FACTOR ; ULCERATIVE-COLITIS ; CROHNS-DISEASE ; SUSCEPTIBILITY LOCI ; COMMON VARIANTS ; DENDRITIC CELLS ; VAV PROTEINS ; KAPPA-B
英文摘要:

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.

语种: 英语
所属项目编号: R01DK082753 ; R01DK095510 ; K23DK090207 ; R03DK099564 ; R21DK098531 ; 13GRNT14680075 ; SROP-4.2.2/B-10/1/2010-0029
项目资助者: US National Institutes of Health (NIH) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ; Center for Glomerular Diseases at Columbia University ; NIH/NIDDK ; Carl W Gottschalk Research Scholar Grant from the American Society of Nephrology (ASN) ; American Heart Association (AHA) ; Italian Ministry of Health and NIH Ricerca Finalizzata ; Fondazione Malattie Renali nel Bambino ; InterOmics (PB05 MIUR-CNR Italian Flagship Project)
WOS记录号: WOS:000344131900009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53983
Appears in Collections:北京大学第一临床医学院_肾脏内科_期刊论文

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作者单位: 1.Univ Parma, Chair Nephrol, I-43100 Parma, Italy
2.Riuniti Hosp, Div Nephrol Dialysis & Renal Transplantat, Ancona, Italy
3.Gorizia Hosp, Div Nephrol & Dialysis, Gorizia, Italy
4.Humanitas Clin & Res Ctr, Nephrol & Dialysis Unit, Milan, Italy
5.Univ Pecs, Fac Med, Nephrol Ctr, Pecs, Hungary
6.Niigata Univ, Div Clin Nephrol & Rheumatol, Niigata, Japan
7.Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA
8.Infermi Hosp, Div Nephrol & Dialysis, Rimini, Italy
9.Univ Pecs, Fac Med, Dept Internal Med 2, Pecs, Hungary
10.Istanbul Univ, Istanbul Fac Med, Div Nephrol, Istanbul, Turkey
11.Cannizzaro Hosp, Div Nephrol, Catania, Italy
12.G Brotzu Hosp, Dept Nephrol & Dialysis, Cagliari, Italy
13.Hosp Viterbo, Viterbo, Italy
14.Sandro Pertini Hosp, Div Nephrol & Dialysis, Rome, Italy
15.Krysiewicza Childrens Hosp, Poznan, Poland
16.Le Bonheur Childrens Hosp, Childrens Fdn Res Ctr, Memphis, TN USA
17.Univ Hosp Turin, Citta Salute & Sci, Turin, Italy
18.Univ Turin, Dept Med Sci, Turin, Italy
19.Osped Cirie, Nephrol & Dialysis Unit, Turin, Italy
20.Osped Chivasso, Turin, Italy
21.Univ Foggia, Dept Med & Surg Sci, Foggia, Italy
22.Med Univ Warsaw, Dept Pediat & Nephrol, Warsaw, Poland
23.Univ Naples 2, Dept Nephrol, Naples, Italy
24.Osped Acireale, Unita Operat Nefrol & Dialisi, Acireale, Italy
25.Charles Univ Prague, Gen Univ Hosp, Prague, Czech Republic
26.UCL, Ctr Nephrol, London, England
27.CEA, Ctr Natl Genotypage, Inst Genom, Evry, France
28.Univ Paris 11, Villejuif, France
29.Azienda Osped Univ, Div Nephrol, Parma, Italy
30.Bayer Pharma, Kidney Dis Res, Wuppertal, Germany
31.Univ Klinikum Hamburg Eppendorf, Med Klin 3, Hamburg, Germany
32.Careggi Hosp, Div Nephrol & Renal Transplantat, Florence, Italy
33.Univ Calgary, Dept Med, Calgary, AB, Canada
34.Univ Calgary, Dept Community Hlth Sci, Calgary, AB, Canada
35.Univ Brescia, Dept Med & Surg Specialties, Brescia, Italy
36.Columbia Univ, Coll Phys & Surg, Dept Med, Div Nephrol, New York, NY 10027 USA
37.Univ Brescia, Div Nephrol, Azienda Osped Spedali Civili Brescia, Montichiari Hosp, Brescia, Italy
38.Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea
39.Univ Brescia, Dept Obstet & Gynecol, Prenatal Diag Unit, Brescia, Italy
40.Univ Brescia, Div Nephrol, Azienda Osped Spedali Civili Brescia, Spedali Civili Hosp, Brescia, Italy
41.Univ Milan, Div Renal, Dipartimento Med Chirurg & Odontoiatria, San Paolo Hosp,Sch Med, Milan, Italy
42.Regina Margheritra Hosp, Nephrol Dialysis & Transplantat Unit, Turin, Italy
43.Univ Modena & Reggio Emilia, Azienda Osped Univ Policlin Modena, Div Nephrol Dialysis & Transplantat, Modena, Italy
44.Giannina Gaslini Inst, Div Nephrol Dialysis & Transplantat, Genoa, Italy
45.Azienda Osped Univ Osped Riuniti Trieste, Div Nephrol, Trieste, Italy
46.Univ Messina, Chair Nephrol, Div Nephol & Dialysis, Azienda Osped Univ Policlin, Messina, Italy
47.Univ Bari, Dept Emergency & Organ Transplantat, Nephrol Sect, Bari, Italy
48.Charles Univ Prague, Fac Med 1, Dept Nephrol, Prague, Czech Republic
49.Univ Aachen, Dept Nephrol, Rhein Westfal Tech Hsch, Aachen, Germany
50.Med Univ Warsaw, Dept Immunol Transplantol & Internal Med, Warsaw, Poland
51.Poznan Med Univ, Dept Nephrol Transplantol & Internal Med, Poznan, Poland
52.Univ Hosp Leicester, John Walls Renal Unit, Leicester, Leics, England
53.Univ Leicester, Dept Infect Immun & Inflammat, Leicester, Leics, England
54.Univ North Hosp, Dept Nephrol Dialysis & Renal Transplantat, St Etienne, France
55.Hop Necker Enfants Malad, Serv Nephrol Transplantat Adultes, Paris, France
56.Univ Paris 05, INSERM, Inst Necker Enfants Malades, Sorbonne Paris Cite, Paris, France
57.INSERM, Ctr Res Epidemiol & Populat Hlth, Villejuif, France
58.Juntendo Univ, Fac Med, Dept Internal Med, Div Nephrol, Tokyo, Japan
59.Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Nephrol, Shanghai 200030, Peoples R China
60.Peking Univ, Inst Nephrol, Peking Univ Hosp 1, Div Renal, Beijing 100871, Peoples R China
61.Univ Tennessee, Hlth Sci Ctr, Div Pediat Nephrol, Memphis, TN USA
62.Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA
63.Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
64.Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA

Recommended Citation:
Kiryluk, Krzysztof,Li, Yifu,Scolari, Francesco,et al. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens[J]. NATURE GENETICS,2014,46(11):1187-1196.
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