We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci / Franke, Andre; Mcgovern, Dermot P. B.; Barrett, Jeffrey C.; Wang, Kai; Radford Smith, Graham L.; Ahmad, Tariq; Lees, Charlie W.; Balschun, Tobias; Lee, James; Roberts, Rebecca; Anderson, Carl A.; Bis, Joshua C.; Bumpstead, Suzanne; Ellinghaus, David; Festen, Eleonora M.; Georges, Michel; Green, Todd; Haritunians, Talin; Jostins, Luke; Latiano, Anna; Mathew, Christopher G.; Montgomery, Grant W.; Prescott, Natalie J.; Raychaudhuri, Soumya; Rotter, Jerome I.; Schumm, Philip; Sharma, Yashoda; Simms, Lisa A.; Taylor, Kent D.; Whiteman, David; Wijmenga, Cisca; Baldassano, Robert N.; Barclay, Murray; Bayless, Theodore M.; Brand, Stephan; Büning, Carsten; Cohen, Albert; Colombel, Jean Frederick; Cottone, Mario; Stronati, Laura; Denson, Ted; De Vos, Martine; D'Inca, Renata; Dubinsky, Marla; Edwards, Cathryn; Florin, Tim; Franchimont, Denis; Gearry, Richard; Glas, Jürgen; Van Gossum, Andre; Guthery, Stephen L.; Halfvarson, Jonas; Verspaget, Hein W.; Hugot, Jean Pierre; Karban, Amir; Laukens, Debby; Lawrance, Ian; Lemann, Marc; Levine, Arie; Libioulle, Cecile; Louis, Edouard; Mowat, Craig; Newman, William; Panés, Juliãn; Phillips, Anne; Proctor, Deborah D.; Regueiro, Miguel; Russell, Richard; Rutgeerts, Paul; Sanderson, Jeremy; Sans, Miquel; Seibold, Frank; Steinhart, A. Hillary; Stokkers, Pieter C. F.; Torkvist, Leif; Kullak Ublick, Gerd; Wilson, David; Walters, Thomas; Targan, Stephan R.; Brant, Steven R.; Rioux, John D.; D'Amato, Mauro; Weersma, Rinse K.; Kugathasan, Subra; Griffiths, Anne M.; Mansfield, John C.; Vermeire, Severine; Duerr, Richard H.; Silverberg, Mark S.; Satsangi, Jack; Schreiber, Stefan; Cho, Judy H.; Annese, Vito; Hakonarson, Hakon; Daly, Mark J.; Parkes, Miles. - In: NATURE GENETICS. - ISSN 1061-4036. - STAMPA. - 42:12(2010), pp. 1118-1125. [10.1038/ng.717]

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

STRONATI, LAURA;
2010

Abstract

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
2010
We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
Computational Biology; Crohn Disease; Genetic Linkage; Genetic Loci; Genetic Variation; Genome, Human; Humans; Reproducibility of Results; Genetic Predisposition to Disease; Genome-Wide Association Study; Genetics
01 Pubblicazione su rivista::01a Articolo in rivista
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci / Franke, Andre; Mcgovern, Dermot P. B.; Barrett, Jeffrey C.; Wang, Kai; Radford Smith, Graham L.; Ahmad, Tariq; Lees, Charlie W.; Balschun, Tobias; Lee, James; Roberts, Rebecca; Anderson, Carl A.; Bis, Joshua C.; Bumpstead, Suzanne; Ellinghaus, David; Festen, Eleonora M.; Georges, Michel; Green, Todd; Haritunians, Talin; Jostins, Luke; Latiano, Anna; Mathew, Christopher G.; Montgomery, Grant W.; Prescott, Natalie J.; Raychaudhuri, Soumya; Rotter, Jerome I.; Schumm, Philip; Sharma, Yashoda; Simms, Lisa A.; Taylor, Kent D.; Whiteman, David; Wijmenga, Cisca; Baldassano, Robert N.; Barclay, Murray; Bayless, Theodore M.; Brand, Stephan; Büning, Carsten; Cohen, Albert; Colombel, Jean Frederick; Cottone, Mario; Stronati, Laura; Denson, Ted; De Vos, Martine; D'Inca, Renata; Dubinsky, Marla; Edwards, Cathryn; Florin, Tim; Franchimont, Denis; Gearry, Richard; Glas, Jürgen; Van Gossum, Andre; Guthery, Stephen L.; Halfvarson, Jonas; Verspaget, Hein W.; Hugot, Jean Pierre; Karban, Amir; Laukens, Debby; Lawrance, Ian; Lemann, Marc; Levine, Arie; Libioulle, Cecile; Louis, Edouard; Mowat, Craig; Newman, William; Panés, Juliãn; Phillips, Anne; Proctor, Deborah D.; Regueiro, Miguel; Russell, Richard; Rutgeerts, Paul; Sanderson, Jeremy; Sans, Miquel; Seibold, Frank; Steinhart, A. Hillary; Stokkers, Pieter C. F.; Torkvist, Leif; Kullak Ublick, Gerd; Wilson, David; Walters, Thomas; Targan, Stephan R.; Brant, Steven R.; Rioux, John D.; D'Amato, Mauro; Weersma, Rinse K.; Kugathasan, Subra; Griffiths, Anne M.; Mansfield, John C.; Vermeire, Severine; Duerr, Richard H.; Silverberg, Mark S.; Satsangi, Jack; Schreiber, Stefan; Cho, Judy H.; Annese, Vito; Hakonarson, Hakon; Daly, Mark J.; Parkes, Miles. - In: NATURE GENETICS. - ISSN 1061-4036. - STAMPA. - 42:12(2010), pp. 1118-1125. [10.1038/ng.717]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/840750
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