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

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

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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.

Original languageEnglish (US)
Pages (from-to)1118-1125
Number of pages8
JournalNature genetics
Volume42
Issue number12
DOIs
StatePublished - Dec 2010

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ASJC Scopus subject areas

  • Genetics

Cite this

Franke, A., McGovern, D. P. B., Barrett, J. C., Wang, K., Radford-Smith, G. L., Ahmad, T., Lees, C. W., Balschun, T., Lee, J., Roberts, R., Anderson, C. A., Bis, J. C., Bumpstead, S., Ellinghaus, D., Festen, E. M., Georges, M., Green, T., Haritunians, T., Jostins, L., ... Parkes, M. (2010). Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nature genetics, 42(12), 1118-1125. https://doi.org/10.1038/ng.717