A genome-wide association study on a southern European population identifies a new Crohn's disease susceptibility locus at RBX1-EP300

被引：36

作者：

Julia, Antonio ^{[1
]}

Domenech, Eugeni ^{[2
]}

Ricart, Elena ^{[3
]}

Tortosa, Rauel ^{[1
]}

Garcia-Sanchez, Valle ^{[4
]}

Gisbert, Javier P. ^{[5
]}

Nos Mateu, Pilar ^{[6
]}

Gutierrez, Ana ^{[7
]}

Gomollon, Fernando ^{[8
]}

Luis Mendoza, Juan ^{[9
]}

Garcia-Planella, Esther ^{[10
]}

Barreiro-de Acosta, Manuel ^{[11
]}

Munoz, Fernando ^{[12
]}

Vera, Maribel ^{[13
]}

Saro, Cristina ^{[14
]}

Esteve, Maria ^{[15
]}

Andreu, Montserrat ^{[16
]}

Alonso, Arnald ^{[1
]}

Lopez-Lasanta, Maria ^{[1
]}

Codo, Laia ^{[17
]}

Lluis Gelpi, Josep ^{[17
,18
]}

Garcia-Montero, Andres C. ^{[19
]}

Bertranpetit, Jaume ^{[20
]}

Absher, Devin ^{[21
]}

Panes, Julian ^{[3
]}

Marsal, Sara ^{[1
]}

机构：

[1] Vall dHebron Res Inst, Rheumatol Res Grp, Barcelona, Spain

[2] Hosp Badalona Germans Trias & Pujol, Digest Syst Serv, Badalona 08196, Spain

[3] IDIBAPS, Hosp Clin Barcelona, Gastroenterol Dept, Barcelona, Spain

[4] Hosp Univ Reina Sofia, Digest Syst Serv, Cordoba, Spain

[5] Hosp Univ Princesa & IP, Gastroenterol Serv, Madrid, Spain

[6] Hosp la Fe, Digest Med Serv, Valencia, Spain

[7] Hosp Gen Alicante, Gastroenterol Serv, Alicante, Spain

[8] Hosp Clin Univ, Digest Syst Serv, Zaragoza, Spain

[9] Hosp Clin San Carlos, Gastroenterol Serv, Madrid, Spain

[10] Hosp Santa Creu & Sant Pau, Gastroenterol Dept, Barcelona, Spain

[11] Hosp Clin Univ, Gastroenterol Serv, Santiago De Compostela, Spain

[12] Complejo Hosp Leon, Gastroenterol Serv, Leon, Spain

[13] Hosp Univ Puerta de Hierro, Gastroenterol Serv, Madrid, Spain

[14] Hosp Cabuenes, Internal Med Serv, Gijon, Spain

[15] Hosp Univ Mutua de Terrassa, Gastroenterol Serv, Barcelona, Spain

[16] Pompeu Fabra Univ, Inst Res Hosp del Mar, IMIM, Dept Gastroenterol, Barcelona, Spain

[17] Natl Inst Bioinformat, Barcelona Supercomp Ctr, Barcelona, Spain

[18] Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain

[19] Univ Salamanca, Banco Nacl ADN Carlos 3, E-37008 Salamanca, Spain

[20] Univ Pompeu Fabra, Nacl Genotyping Ctr CeGen, Barcelona, Spain

[21] HudsonAlpha Inst Biotechnol, Huntsville, AL USA

来源：

GUT | 2013年 / 62卷 / 10期

关键词：

Crohn's Disease; Genetics; Genetic Polymorphisms; INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; ULCERATIVE-COLITIS; T-CELLS; GENETICS; VARIANTS; LINKAGE; EXPRESSION; GENOTYPES; PATHWAYS;

D O I：

10.1136/gutjnl-2012-302865

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Objective Genome-wide association studies (GWAS) have identified multiple risk loci for Crohn's disease (CD). However, the cumulative risk exerted by these loci is low, and the likelihood that additional, as-yet undiscovered loci contribute to the risk of CD is very high. We performed a GWAS on a southern European population to identify new CD risk loci. Design We genotyped 620901 genome markers on 1341 CD patients and 1518 controls from Spain. The top association signals representing new candidate risk loci were subsequently analysed in an independent replication cohort of 1365 CD patients and 1396 controls. Results We identified a genome-wide significant association on chromosome 22q13.2 in the intergenic region between the RBX1 and EP300 genes (single nucleotide polymorphism rs4820425, OR 1.27, 95% CI 1.17 to 1.38, p=3.42E-8). We also found suggestive evidence for the association of the IFNGR2 (21q22.11), FOXP2 (7q31), MACROD2 (20p12.1) and AIF1 (6p21.3) loci with CD risk. Conclusions In this GWAS performed on a southern European cohort, we have identified a new risk locus for CD between RBX1 and EP300. This study demonstrates that using populations of different ancestry is a useful strategy to identify new risk loci for CD.

引用

页码：1440 / 1445

页数：6

共 40 条

[21] Genetics and pathogenesis of inflammatory bowel disease [J].

Khor, Bernard ;

Gardet, Agnes ;

Xavier, Ramnik J. .

NATURE, 2011, 474 (7351) :307-317

[22] New IBD genetics: common pathways with other diseases [J].

Lees, C. W. ;

Barrett, J. C. ;

Parkes, M. ;

Satsangi, J. .

GUT, 2011, 60 (12) :1739-1753

[23] CLASSIFICATION OF INFLAMMATORY BOWEL-DISEASE [J].

LENNARDJONES, JE .

SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 1989, 24 :2-6

[24] MaCH: Using Sequence and Genotype Data to Estimate Haplotypes and Unobserved Genotypes [J].

Li, Yun ;

Willer, Cristen J. ;

Ding, Jun ;

Scheet, Paul ;

Abecasis, Goncalo R. .

GENETIC EPIDEMIOLOGY, 2010, 34 (08) :816-834

[25] Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4 [J].

Libioulle, Cecile ;

Louis, Edouard ;

Hansoul, Sarah ;

Sandor, Cynthia ;

Farnir, Frederic ;

Franchimont, Denis ;

Vermeire, Severine ;

Dewit, Olivier ;

de Vos, Martine ;

Dixon, Anna ;

Demarche, Bruno ;

Gut, Ivo ;

Heath, Simon ;

Foglio, Mario ;

Liang, Liming ;

Laukens, Debby ;

Mni, Myriam ;

Zelenika, Diana ;

Van Gossum, Andre ;

Rutgeerts, Paul ;

Belaiche, Jacques ;

Lathrop, Mark ;

Georges, Michel .

PLOS GENETICS, 2007, 3 (04) :0538-0543

[26]

Liu L, 1999, MOL CELL BIOL, V19, P1202

[27] Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences [J].

Loftus, EV .

GASTROENTEROLOGY, 2004, 126 (06) :1504-1517

[28] Population-Specific Susceptibility to Crohn's Disease and Ulcerative Colitis; Dominant and Recessive Relative Risks in the Japanese Population [J].

Nakagome, Shigeki ;

Takeyama, Yasuaki ;

Mano, Shuhei ;

Sakisaka, Shotaro ;

Matsui, Toshiyuki ;

Kawamura, Shoji ;

Oota, Hiroki .

ANNALS OF HUMAN GENETICS, 2010, 74 :126-136

[29] Genetic Structure of Europeans: A View from the North-East [J].

Nelis, Mari ;

Esko, Tonu ;

Magi, Reedik ;

Zimprich, Fritz ;

Zimprich, Alexander ;

Toncheva, Draga ;

Karachanak, Sena ;

Piskackova, Tereza ;

Balascak, Ivan ;

Peltonen, Leena ;

Jakkula, Eveliina ;

Rehnstrom, Karola ;

Lathrop, Mark ;

Heath, Simon ;

Galan, Pilar ;

Schreiber, Stefan ;

Meitinger, Thomas ;

Pfeufer, Arne ;

Wichmann, H-Erich ;

Melegh, Bela ;

Polgar, Noemi ;

Toniolo, Daniela ;

Gasparini, Paolo ;

D'Adamo, Pio ;

Klovins, Janis ;

Nikitina-Zake, Liene ;

Kucinskas, Vaidutis ;

Kasnauskiene, Jurate ;

Lubinski, Jan ;

Debniak, Tadeusz ;

Limborska, Svetlana ;

Khrunin, Andrey ;

Estivill, Xavier ;

Rabionet, Raquel ;

Marsal, Sara ;

Julia, Antonio ;

Antonarakis, Stylianos E. ;

Deutsch, Samuel ;

Borel, Christelle ;

Attar, Homa ;

Gagnebin, Maryline ;

Macek, Milan ;

Krawczak, Michael ;

Remm, Maido ;

Metspalu, Andres .

PLOS ONE, 2009, 4 (05)

[30] Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility [J].

Parkes, Miles ;

Barrett, Jeffrey C. ;

Prescott, Natalie J. ;

Tremelling, Mark ;

Anderson, Carl A. ;

Fisher, Sheila A. ;

Roberts, Roland G. ;

Nimmo, Elaine R. ;

Cummings, Fraser R. ;

Soars, Dianne ;

Drummond, Hazel ;

Lees, Charlie W. ;

Khawaja, Saud A. ;

Bagnall, Richard ;

Burke, Denis A. ;

Todhunter, Catherine E. ;

Ahmad, Tariq ;

Onnie, Clive M. ;

McArdle, Wendy ;

Strachan, David ;

Bethel, Graeme ;

Bryan, Claire ;

Lewis, Cathryn M. ;

Deloukas, Panos ;

Forbes, Alastair ;

Sanderson, Jeremy ;

Jewell, Derek P. ;

Satsangi, Jack ;

Mansfield, John C. ;

Cardon, Lon ;

Mathew, Christopher G. .

NATURE GENETICS, 2007, 39 (07) :830-832

← 1 2 3 4 →