Sequencing of over 100,000 individuals identifies multiple genes and rare variants associated with Crohns disease susceptibility
Authors: Sazonovs Aleksejs , Stevens Christine R. , Venkataraman Guhan R. , Yuan Kai , Avila Brandon , Abreu Maria T. , Ahmad Tariq , Allez Matthieu , Ananthakrishnan Ashwin N. , Atzmon Gil , Baras Aris , Barrett Jeffrey C. , Barzilai Nir , Beaugerie Laurent , Beecham Ashley , Bernstein Charles N. , Bitton Alain , Bokemeyer Bernd , Chan Andrew , Chung Daniel , Cleynen Isabelle , Cosnes Jacques , Cutler David J. , Daly Allan , Damas Oriana M. , Datta Lisa W. , Dawany Noor , Devoto Marcella , Dodge Sheila , Ellinghaus Eva , Fachal Laura , Farkkila Martti , Faubion William , Ferreira Manuel , Franchimont Denis , Gabriel Stacey B. , Georges Michel , Gettler Kyle , Giri Mamta , Glaser Benjamin , Goerg Siegfried , Goyette Philippe , Graham Daniel , Hämäläinen Eija , Haritunians Talin , Heap Graham A. , Hiltunen Mikko , Hoeppner Marc , Horowitz Julie E. , Irving Peter , Iyer Vivek , Jalas Chaim , Kelsen Judith , Khalili Hamed , Kirschner Barbara S. , Kontula Kimmo , Koskela Jukka T. , Kugathasan Subra , Kupcinskas Juozas , Lamb Christopher A. , Laudes Matthias , Levine Adam P. , Lewis James , Liefferinckx Claire , Loescher Britt-Sabina , Louis Edouard , Mansfield John , May Sandra , McCauley Jacob L. , Mengesha Emebet , Mni Myriam , Moayyedi Paul , Moran Christopher J. , Newberry Rodney , O’Charoen Sirimon , Okou David T. , Oldenburg Bas , Ostrer Harry , Palotie Aarno , Pekow Joel , Peter Inga , Pierik Marieke J. , Ponsioen Cyriel Y. , Pontikos Nikolas , Prescott Natalie , Pulver Ann E. , Rahmouni Souad , Rice Daniel L. , Saavalainen Päivi , Sands Bruce , Sartor R. Balfour , Schiff Elena R. , Schreiber Stefan , Schuum L. Philip , Segal Anthony W. , Seksik Philippe , Shawky Rasha , Sheikh Shehzad Z. , Silverberg Mark , Simmons Alison , Skeiceviciene Jurgita , Sokol Harry , Solomonson Matthew , Somineni Hari , Sun Dylan , Targan Stephan , Turner Dan , Uhlig Holm H. , van der Meulen Andrea E. , Vermeire Severine , Verstockt Sare , Voskuil Michiel D. , Winter Harland S. , Young Justine ,   Belgium IBD Consortium,   Cedars-Sinai IBD,   International IBD Genetics Consortium,   NIDDK IBD Genetics Consortium,   NIHR IBD BioResource,   Regeneron Genetics Center,   SHARE Consortium,   SPARC IBD Network,   UK IBD Genetics Consortium, Duerr Richard H. , Franke Andre , Brant Steven R. , Cho Judy , Weersma Rinse K. , Parkes Miles , Xavier Ramnik , Rivas Manuel A. , Rioux John D. , McGovern Dermot , Huang Hailiang , Anderson Carl A. , Daly Mark J. 
Published: June 2021

AbstractGenome-wide association studies (GWAS) have identified hundreds of loci associated with Crohns disease (CD), however, as with all complex diseases, deriving pathogenic mechanisms from these non-coding GWAS discoveries has been challenging. To complement GWAS and better define actionable biological targets, we analysed sequenced data from more than 30,000 CD patients and 80,000 population controls. We observe rare coding variants in established CD susceptibility genes as well as ten genes where coding variation directly implicates the gene in disease risk for the first time.