| Literature DB >> 36038634 |
Aleksejs Sazonovs1, Christine R Stevens2,3,4, Guhan R Venkataraman5, Kai Yuan3,4, Brandon Avila2, Maria T Abreu6, Tariq Ahmad7, Matthieu Allez8, Ashwin N Ananthakrishnan9, Gil Atzmon10,11, Aris Baras12, Jeffrey C Barrett13, Nir Barzilai11,14, Laurent Beaugerie15, Ashley Beecham16,17, Charles N Bernstein18, Alain Bitton19, Bernd Bokemeyer20, Andrew Chan21,22, Daniel Chung23, Isabelle Cleynen24, Jacques Cosnes25, David J Cutler26,27, Allan Daly28, Oriana M Damas29, Lisa W Datta30, Noor Dawany31, Marcella Devoto31,32,33,34, Sheila Dodge35, Eva Ellinghaus36, Laura Fachal1, Martti Farkkila37, William Faubion38, Manuel Ferreira12, Denis Franchimont39, Stacey B Gabriel35, Tian Ge3,40,41, Michel Georges42, Kyle Gettler43, Mamta Giri43, Benjamin Glaser44, Siegfried Goerg45, Philippe Goyette46, Daniel Graham47,48,49, Eija Hämäläinen50, Talin Haritunians51, Graham A Heap7, Mikko Hiltunen52, Marc Hoeppner53, Julie E Horowitz12, Peter Irving54,55, Vivek Iyer28, Chaim Jalas56, Judith Kelsen31, Hamed Khalili21, Barbara S Kirschner57, Kimmo Kontula58, Jukka T Koskela50, Subra Kugathasan27, Juozas Kupcinskas59, Christopher A Lamb60,61, Matthias Laudes45, Chloé Lévesque46, Adam P Levine62, James D Lewis34,63, Claire Liefferinckx39, Britt-Sabina Loescher36, Edouard Louis42, John Mansfield60,61, Sandra May36, Jacob L McCauley16,17, Emebet Mengesha51, Myriam Mni42, Paul Moayyedi64, Christopher J Moran23, Rodney D Newberry65, Sirimon O'Charoen63, David T Okou27,66, Bas Oldenburg67, Harry Ostrer68, Aarno Palotie2,3,4,50,69,70, Jean Paquette46, Joel Pekow57, Inga Peter43, Marieke J Pierik71, Cyriel Y Ponsioen72, Nikolas Pontikos62, Natalie Prescott73, Ann E Pulver74, Souad Rahmouni42, Daniel L Rice1, Päivi Saavalainen75, Bruce Sands43, R Balfour Sartor76, Elena R Schiff62, Stefan Schreiber36, L Philip Schumm77, Anthony W Segal62, Philippe Seksik15, Rasha Shawky78, Shehzad Z Sheikh76, Mark S Silverberg79, Alison Simmons80, Jurgita Skeiceviciene59, Harry Sokol15, Matthew Solomonson2, Hari Somineni81, Dylan Sun12, Stephan Targan51, Dan Turner82, Holm H Uhlig83,84, Andrea E van der Meulen85, Séverine Vermeire86,87, Sare Verstockt87, Michiel D Voskuil88, Harland S Winter23, Justine Young63, Richard H Duerr89, Andre Franke36, Steven R Brant30,90, Judy Cho43, Rinse K Weersma88, Miles Parkes91, Ramnik J Xavier47,48,49,92,93,94,95,96, Manuel A Rivas5, John D Rioux46,97, Dermot P B McGovern51, Hailiang Huang98,99, Carl A Anderson100, Mark J Daly101,102,103,104.
Abstract
Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.Entities:
Mesh：
Year: 2022 PMID： 36038634 DOI： 10.1038/s41588-022-01156-2
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 41.307