@article{26a1d5be1640429bb951488c68a6a976,
title = "Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis",
abstract = "We present a genome-wide association study of ileal Crohn disease and two independent replication studies that identify several new regions of association to Crohn disease. Specifically, in addition to the previously established CARD15 and IL23R associations, we identified strong and significantly replicated associations (combined P < 10-10) with an intergenic region on 10q21.1 and a coding variant in ATG16L1, the latter of which was also recently reported by another group. We also report strong associations with independent replication to variation in the genomic regions encoding PHOX2B, NCF4 and a predicted gene on 16q24.1 (FAM92B). Finally, we demonstrate that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium. Together, these findings suggest that autophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease.",
author = "Rioux, {John D.} and Xavier, {Ramnik J.} and Taylor, {Kent D.} and Silverberg, {Mark S.} and Philippe Goyette and Alan Huett and Todd Green and Petric Kuballa and Barmada, {M. Michael} and Datta, {Lisa Wu} and Shugart, {Yin Yao} and Griffiths, {Anne M.} and Targan, {Stephan R.} and Ippoliti, {Andrew F.} and Bernard, {Edmond Jean} and Ling Mei and Nicolae, {Dan L.} and Miguel Regueiro and Schumm, {L. Philip} and Steinhart, {A. Hillary} and Rotter, {Jerome I.} and Duerr, {Richard H.} and Cho, {Judy H.} and Daly, {Mark J.} and Brant, {Steven R.}",
note = "Funding Information: J. Adams for help with immunohistochemistry; A. Landry for expression studies and D. Altshuler for his critical reading of the manuscript. The NIDDK IBDGC is funded by the following grants: DK62431 (S.R.B.), DK62420 (R.H.D.), DK62432 (J.D.R.), DK62423 (M.S.S.), DK62413 (K.D.T.) and DK62422 and DK62429 (J.H.C.). The work on the Cedars-Sinai cohort was supported by project 1 of DK 46763 (J.I.R.). R.J.X. is supported by the following grants: AI062773 and DK43351.",
year = "2007",
month = may,
doi = "10.1038/ng2032",
language = "English (US)",
volume = "39",
pages = "596--604",
journal = "Nature genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "5",
}