Xavier, Ramnik J
Mayo Clinic
Kurt Isselbacher Professor of Medicine at Harvard Medical School, Cambridge, MA, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Molecular Biology, Massachusetts General Hospital, Bosto.
Citations 1
Exome sequencing directly implicates 68 genes in inflammatory bowel disease
Zhu, Ruifei , Zhang, Qian , Yuan, Kai , Zhang, Rui , Turvey, Alexandra K. , Stevens, Christine R , Ahmad, Tariq, Bernstein, Çharles N. , Bokemeyer, Bernd , Brooks, Johanne , Butterworth, Jeffrey, Clark, Katie, Cummings, F, Ennis, Sarah, Färkkilä, M, Faubion, William A. , Foley, Stephen, Franchimont, Denis , Hancock, L, Hart, Ailsa, Hooper, Patricia, Irving, Peter, Jarvis, Mark , Johnston, EL, Karlson, Elizabeth W, Kemp, Cheryl, Kennedy, Nick, Lees, Charlie, Lewis, James D. , Li, Andy, Louis, Édouard , McGovern, Dermot P.B., Oglesby, Arabis, Perez, Kate J, Pollok, R, Raine, Tim, Ramadas, Arvind, Ramakrishnan, S., Sands, Bruce, Satsangi, Jack, Schreiber, Stefan, Selinger, Christian, Shedwell, Sophy, Silverberg, M, Singh, Salil, Steel, Alan, Uhlig, H, Verma, Ajay, Vermeire, Séverine , Weersma, Rinse K. , Xavier, Ramnik, Parkes, Miles, Rioux, John D. , Anderson, Carl A. , Raine, Tim , Uhlig, Holm H. , Fachal, Laura , Bernstein, Charles Noah , Bokemeyer, Bernd , Brant, Steven R , Cho, Judy H , Duerr, Richard H , Faubion, William , Franchimont, Denis , Franke, André , Kupcinskas, Juozas , Lamb, Christopher A , Lewis, James D , Loescher, Britt-Sabina , Louis, Edouard , McCauley, Jacob L , Moayyedi, Paul , Newberry, Rodney D , Palotie, Aarno V. , Pekow, Joel , Prescott, Natalie , Sabic, Ksenija , Sands, Bruce E , Silverberg, Mark S , Sokol, Harry , Vermeire, Séverine , Weersma, Rinse K , Xavier, Ramnik J , Yu, Mingrui , Rioux, John D , Daly, Mark J. , Huang, Hailiang , Anderson, Carl A , Raine, Tim , Zhang, Qian , Yuan, Kai , Stevens, Christine R. , Fachal, Laura , Ahmad, Tariq , Kok, Klaartje Bel , Butterworth, Jeffrey R., Cummings, Fraser , Ennis, Sarah A. , Färkkilâ, Martti , Hart, Ailsa , Hooper, Patricia, Irving, Peter Miles , Karlson, Elizabeth W. , Kennedy, Nicholas Alexander , Lees, Charlie W. , McCauley, Jacob L. , McGovern, Dermot P.B. , McLaughlin, John , Moayyedi, Paul , Moran, G , Newberry, Rodney D. , Pekow, Joel , Satsangi, Jack, Sazonovs, Aleksejs , Schreiber, Stefan , Selinger, Christian P. , Steed, Helen , Parkes, Miles
No container title available | May 12, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder of the gastrointestinal tract whose genetic basis is only partly resolved because most risk variants identified by genome-wide association studies (GWAS) lie in non-coding regions, limiting direct gene assignment and biological interpretation 1,2 . Here we analysed whole-exome and whole-genome sequencing data from 86,213 IBD cases and 478,363 controls of European ancestry. We identified 68 IBD genes directly implicated by conditionally independent protein-coding associations across the allele frequency spectrum. Many newly implicated IBD genes are supported by orthogonal genomic or pleiotropic evidence, pointing to disease-related pathways and nominating targets with therapeutic relevance. We further identified allelic series and non-additive effects at key loci such as NOD2 and TYK2. These results show that large-scale sequencing can resolve disease genes and pathways that remain ambiguous from non-coding association alone, providing a more direct route from human genetics to biological insight and therapeutic hypotheses.