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1. Interobserver agreement of current and new proposed endoscopic scores for postoperative recurrence in Crohn’s disease

Author

Bak, Michiel T.J., Hammoudi, Nassim, Allez, Matthieu, Silverberg, Mark S., Schellekens, Isa M., Erler, Nicole S., Dijkstra, Gerard, Romberg-Camps, Mariëlle, de Boer, Nanne K.H., Jansen, Sita V., van der Marel, Sander, Horjus, Carmen S., Visschedijk, Marijn C., Goetgebuer, Rogier L., van Dop, Willemijn A., Hoekstra, Jildou, Bodelier, Alexander G.L., Molendijk, Ilse, Derikx, Lauranne A.A.P., van Schaik, Fiona D.M., West, Rachel L., Duijvestein, Marjolijn, Janneke van der Woude, C., van Ruler, Oddeke, and de Vries, Annemarie C.

Published
2024
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2. Patients With Low Drug Levels or Antibodies to a Prior Anti–Tumor Necrosis Factor Are More Likely to Develop Antibodies to a Subsequent Anti–Tumor Necrosis Factor

Author

Vande Casteele, Niels, Abreu, Maria T, Flier, Sarah, Papamichael, Konstantinos, Rieder, Florian, Silverberg, Mark S, Khanna, Reena, Okada, Lauren, Yang, Lei, Jain, Anjali, and Cheifetz, Adam S

Subjects
Biomedical and Clinical Sciences, Immunology, Autoimmune Disease, Digestive Diseases, Biotechnology, Prevention, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Good Health and Well Being, Adalimumab, Autoantibodies, Drug Monitoring, Genome-Wide Association Study, Humans, Inflammatory Bowel Diseases, Infliximab, Tumor Necrosis Factor Inhibitors, Clinical Sciences, Gastroenterology & Hepatology, Clinical sciences
Abstract

Therapeutic drug monitoring (TDM) with measurement of serum drug and antidrug antibodies (ADAb) is used widely to confirm therapeutic exposure, rule out immunogenicity, and optimize treatment of biologics in patients with inflammatory bowel diseases.1 A recent genome-wide association study found the variant HLA-DQA1∗05 to increase the risk of development of antibodies against infliximab (IFX) and adalimumab (ADM) 2-fold, regardless of concomitant immunomodulator use.2,3 However, there is currently limited evidence showing whether patients who develop antibodies to 1 anti-tumor necrosis factor (TNF) are prone to develop antibodies to the subsequent anti-TNF. Our aim was to investigate the risk of subsequent antibody development in cases (with ADAb to prior anti-TNF) versus control subjects (without ADAb to prior anti-TNF) using a large cohort of patients with inflammatory bowel diseases who underwent TDM with a drug-tolerant assay.

Published
2022

3. Development and Validation of an Integrative Risk Score for Future Risk of Crohn’s Disease in Healthy First-Degree Relatives: A Multicenter Prospective Cohort Study

Author

Lee, Sun-Ho, Turpin, Williams, Espin-Garcia, Osvaldo, Xu, Wei, Leibovitzh, Haim, Xue, Mingyue, Raygoza Garay, Juan Antonio, Graña-Miraglia, Lucía, Smith, Michelle I., Goethel, Ashleigh, Madsen, Karen L., Avni-Biron, Irit, Dotan, Iris, Weiss, Batia, Panaccione, Remo, Huynh, Hien, Jacobson, Kevan, Aumais, Guy, Mack, David, Griffiths, Anne M., Steinhart, A. Hillary, Silverberg, Mark S., Turner, Dan, Bernstein, Charles N., Feagan, Brian G., Moayyedi, Paul, Paterson, Andrew, Guttman, David S., Abreu, Maria, Beck, Paul, Dieleman, Leo, Kaplan, Gilaad, Krause, Denis O., Marshall, John, Ropeleski, Mark, Seidman, Ernest, Snapper, Scott, Stadnyk, Andy, Surette, Michael, Walters, Thomas, Vallance, Bruce, Bitton, Alain, Cino, Maria, Critch, Jeff, Denson, Lee, Deslandres, Colette, El-Matary, Wael, Herfarth, Hans, Higgins, Peter, Hyams, Jeff, McGrath, Jerry, Otley, Anthony, and Croitoru, Kenneth

Published
2024
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4. Healthy First-Degree Relatives From Multiplex Families vs Simplex Families Have a Higher Subclinical Intestinal Inflammation, a Distinct Fecal Microbial Signature, and Harbor a Higher Risk of Developing Crohn’s Disease

Author

Abreu, Maria T., Beck, Paul, Bernstein, Charles, Croitoru, Kenneth, Dieleman, Levinus, Feagan, Brian, Griffiths, Anne, Guttman, David S., Jacobson, Kevan, Kaplan, Gilaad, Krause, Denis O., Madsen, Karen L., Marshall, John K., Moayyedi, Paul, Ropeleski, Mark, Seidman, Ernest, Silverberg, Mark S., Snapper, Scott, Stadnyk, Andy, Steinhart, A. Hillary, Surette, Michael, Turner, Dan, Walters, Thomas, Vallance, Bruce, Aumais, Guy, Bitton, Alain, Cino, Maria, Critch, Jeff, Denson, Lee, Deslandres, Colette, El-Matary, Wael, Herfarth, Hans, Higgins, Peter, Huynh, Hien Q., Hyams, Jeff, Mack, David R., McGrath, Jerry, Otley, Anthony, Panaccione, Remo, Olivera, Pablo A., Martinez-Lozano, Helena, Leibovitzh, Haim, Xue, Mingyue, Neustaeter, Anna, Espin-Garcia, Osvaldo, Xu, Wei, Bernstein, Charles N., Yerushalmi, Baruch, Hyams, Jeffrey S., Wrobel, Iwona, Panacionne, Remo, Dieleman, Levinus A., Griffiths, Anne M., Turpin, Williams, and Lee, Sun-Ho

Published
2024
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6. After Surgically Induced Remission, Ileal and Colonic Mucosa-Associated Microbiota Predicts Crohn’s Disease Recurrence

Author

Hernández-Rocha, Cristian, Turpin, Williams, Borowski, Krzysztof, Stempak, Joanne M., Sabic, Ksenija, Gettler, Kyle, Tastad, Christopher, Chasteau, Colleen, Korie, Ujunwa, Hanna, Mary, Khan, Abdul, Mengesha, Emebet, Bitton, Alain, Schwartz, Marc B., Barrie, Arthur, Datta, Lisa W., Lazarev, Mark, Brant, Steven R., Rioux, John D., McGovern, Dermot P.B., Duerr, Richard H., Schumm, L. Phil, Cho, Judy H., and Silverberg, Mark S.

Published
2024
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7. Existing Bowel Preparation Quality Scales Are Reliable in the Setting of Centralized Endoscopy Reading

Author

Hanzel, Jurij, Sey, Michael, Ma, Christopher, Zou, Guangyong, East, James E., Siegel, Corey A., Mosli, Mahmoud, Reinisch, Walter, McDonald, John W. D., Silverberg, Mark S., Van Viegen, Tanja, Shackelton, Lisa M., Clayton, Lucy B., Enns, Robert, Epstein, Ian, Hilsden, Robert J., Hookey, Lawrence, Moffatt, Dana C., Ng Kwet Shing, Richard, Telford, Jennifer J., von Renteln, Daniel, Feagan, Brian G., Barkun, Alan, and Jairath, Vipul

Published
2023
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8. Identifying high-impact variants and genes in exomes of Ashkenazi Jewish inflammatory bowel disease patients

Author

Wu, Yiming, Gettler, Kyle, Kars, Meltem Ece, Giri, Mamta, Li, Dalin, Bayrak, Cigdem Sevim, Zhang, Peng, Jain, Aayushee, Maffucci, Patrick, Sabic, Ksenija, Van Vleck, Tielman, Nadkarni, Girish, Denson, Lee A., Ostrer, Harry, Levine, Adam P., Schiff, Elena R., Segal, Anthony W., Kugathasan, Subra, Stenson, Peter D., Cooper, David N., Philip Schumm, L., Snapper, Scott, Daly, Mark J., Haritunians, Talin, Duerr, Richard H., Silverberg, Mark S., Rioux, John D., Brant, Steven R., McGovern, Dermot P. B., Cho, Judy H., and Itan, Yuval

Published
2023
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9. HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44+ Natural Killer Cells in Ulcerative Colitis

Author

Akar, Alaa, Flemming, Cornelius, Felix, Flomm, Flosbach, Markus, Jäger, Julia, Jeromin, Niklas, Jung, Johannes, Ohms, Mareike, Reinshagen, Konrad, Rische, Johann, Sagebiel, Adrian, Sandfort, Deborah, Steinert, Fenja, Tomuschat, Christian, Wesche, Jasmin, Shifteh Abedian, Abraham, Clara, Achkar, Jean-Paul, Ahmad, Tariq, Alberts, Rudi, Alizadeh, Behrooz, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Anderson, Carl A., Andrews, Jane M., Annese, Vito, Aumais, Guy, Baidoo, Leonard, Baldassano, Robert N., Bampton, Peter A., Barclay, Murray, Barrett, Jeffrey C., Bethge, Johannes, Bewshea, Claire, Bis, Joshua C., Bitton, Alain, BK, Thelma, Boucher, Gabrielle, Brain, Oliver, Brand, Stephan, Brant, Steven R., Cheon, Jae Hee, Chew, Angela, Cho, Judy H., Cleynen, Isabelle, Cohain, Ariella, Cooney, Rachel, Croft, Anthony, Daly, Mark J., D'Amato, Mauro, Danese, Silvio, Daryani, Naser Ebrahim, Datta, Lisa Wu, Degenhardt, Frauke, Denapiene, Goda, Denson, Lee A., Devaney, Kathy L., Dewit, Olivier, D'Inca, Renata, Drummond, Hazel E., Dubinsky, Marla, Duerr, Richard H., Edwards, Cathryn, Ellinghaus, David, Ellul, Pierre, Esaki, Motohiro, Essers, Jonah, Ferguson, Lynnette R., Festen, Eleonora A., Fleshner, Philip, Florin, Tim, Franchimont, Denis, Franke, Andre, Fuyuno, Yuta, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Goyette, Philippe, Green, Todd, Griffiths, Anne M., Guthery, Stephen L., Hakonarson, Hakon, Halfvarson, Jonas, Hanigan, Katherine, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hayward, Nicholas K., Hedl, Matija, Henderson, Paul, Hold, Georgina L., Hong, Myhunghee, Hu, Xinli, Huang, Hailiang, Hugot, Jean-Pierre, Hui, Ken Y., Imielinski, Marcin, Jazayeri, Omid, Jonaitis, Laimas, Jostins, Luke, Juyal, Garima, Chandra Juyal, Ramesh, Kalla, Rahul, Karlsen, Tom H., Kennedy, Nicholas A., Khan, Mohammed Azam, Kim, Won Ho, Kitazono, Takanari, Kiudelis, Gediminas, Kubo, Michiaki, Kugathasan, Subra, Kupcinskas, Limas, Lamb, Christopher A., de Lange, Katrina M., Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lee, James C., Lees, Charlie W., Leja, Marcis, Lewis, Nina, Van Limbergen, Johan, Lionetti, Paolo, Liu, Jimmy Z., Louis, Edouard, Luo, Yang, Mahy, Gillian, Malekzadeh, Masoud Mohammad, Malekzadeh, Reza, Mansfield, John, Marriott, Suzie, Massey, Dunecan, Mathew, Christopher G., Matsui, Toshiyuki, McGovern, Dermot P.B., van der Meulen, Andrea, Midha, Vandana, Milgrom, Raquel, Mirzaei, Samaneh, Mitrovic, Mitja, Montgomery, Grant W., Mowat, Craig, Müller, Christoph, Newman, William G., Ng, Aylwin, Ng, Siew C., Evelyn Ng, Sok Meng, Nikolaus, Susanna, Ning, Kaida, Nöthen, Markus, Oikonomou, Ioannis, Okou, David, Orchard, Timothy R., Palmieri, Orazio, Parkes, Miles, Phillips, Anne, Ponsioen, Cyriel Y., Potocnik, Urõs, Poustchi, Hossein, Prescott, Natalie J., Proctor, Deborah D., Radford-Smith, Graham, Rahier, Jean- Francois, Regueiro, Miguel, Reinisch, Walter, Rieder, Florian, Rioux, John D., Roberts, Rebecca, Rogler, Gerhard, Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schadt, Eric E., Scharl, Michael, Schembri, John, Schreiber, Stefan, Schumm, L. Philip, Scott, Regan, Seielstad, Mark, Shah, Tejas, Sharma, Yashoda, Silverberg, Mark S., Simmons, Alison, Simms, Lisa A., Singh, Abhey, Skieceviciene, Jurgita, van Sommeren, Suzanne, Song, Kyuyoung, Sood, Ajit, Spain, Sarah L., Steinhart, A. Hillary, Stempak, Joanne M., Stronati, Laura, Sung, Joseph J.Y., Targan, Stephan R., Taylor, Kirstin M., Theatre, Emilie, Torkvist, Leif, Torres, Esther A., Tremelling, Mark, Uhlig, Holm H., Umeno, Junji, Vahedi, Homayon, Vasiliauskas, Eric, Velde, Anje ter, Ventham, Nicholas T., Vermeire, Severine, Verspaget, Hein W., De Vos, Martine, Walters, Thomas, Wang, Kai, Wang, Ming-Hsi, Weersma, Rinse K., Wei, Zhi, Whiteman, David, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Wong, Sunny H., Xavier, Ramnik J., Yamazaki, Keiko, Yang, Suk-Kyun, Ye, Byong Duk, Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhang, Hu, Zhang, Wei, Zhao, Hongyu, Zhao, Zhen Z., Baumdick, Martin E., Niehrs, Annika, Schwerk, Maria, Hinrichs, Ole, Jordan-Paiz, Ana, Padoan, Benedetta, Wegner, Lucy H.M., Schloer, Sebastian, Zecher, Britta F., Malsy, Jakob, Joshi, Vinita R., Illig, Christin, Schröder-Schwarz, Jennifer, Möller, Kimberly J., Martin, Maureen P., Yuki, Yuko, Ozawa, Mikki, Sauter, Jürgen, Schmidt, Alexander H., Perez, Daniel, Giannou, Anastasios D., Carrington, Mary, Davis, Randall S., Schumacher, Udo, Sauter, Guido, Huber, Samuel, Puelles, Victor G., Melling, Nathaniel, Altfeld, Marcus, and Bunders, Madeleine J.

Published
2023
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10. Gut Microbiome Composition Is Associated With Future Onset of Crohn’s Disease in Healthy First-Degree Relatives

Author

Abreu, Maria, Beck, Paul, Bernstein, Charles, Croitoru, Kenneth, Dieleman, Levinus A., Feagan, Brian, Griffiths, Anne, Guttman, David, Jacobson, Kevan, Kaplan, Gilaad, Krause, Denis O., Madsen, Karen, Marshall, John, Moayyedi, Paul, Ropeleski, Mark, Seidman, Ernest, Silverberg, Mark, Snapper, Scott, Stadnyk, Andy, Steinhart, Hillary, Surette, Michael, Turner, Dan, Walters, Thomas, Vallance, Bruce, Aumais, Guy, Bitton, Alain, Cino, Maria, Critch, Jeff, Denson, Lee, Deslandres, Colette, El-Matary, Wael, Herfarth, Hans, Higgins, Peter, Huynh, Hien, Hyams, Jeffrey S., Mack, David, McGrath, Jerry, Otley, Anthony, Panancionne, Remo, Raygoza Garay, Juan Antonio, Turpin, Williams, Lee, Sun-Ho, Smith, Michelle I., Goethel, Ashleigh, Griffiths, Anne M., Espin-Garcia, Osvaldo, Aumais, Guy L., Bernstein, Charles N., Biron, Irit A., Dotan, Iris, Guttman, David S., Marshall, John K., Panaccione, Remo, Silverberg, Mark S., Steinhart, A. Hillary, Yerushalmi, Baruch, Paterson, Andrew D., and Xu, Wei

Published
2023
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12. Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility

Author

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., Ge, Tian, 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, Lévesque, Chloé, Levine, Adam P., Lewis, James D., 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 D., O’Charoen, Sirimon, Okou, David T., Oldenburg, Bas, Ostrer, Harry, Palotie, Aarno, Paquette, Jean, 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, Schumm, L. Philip, Segal, Anthony W., Seksik, Philippe, Shawky, Rasha, Sheikh, Shehzad Z., Silverberg, Mark S., 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, Séverine, Verstockt, Sare, Voskuil, Michiel D., Winter, Harland S., Young, Justine, Duerr, Richard H., Franke, Andre, Brant, Steven R., Cho, Judy, Weersma, Rinse K., Parkes, Miles, Xavier, Ramnik J., Rivas, Manuel A., Rioux, John D., McGovern, Dermot P. B., Huang, Hailiang, Anderson, Carl A., and Daly, Mark J.

Published
2022
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13. IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus

Author

Caron, Bénédicte, Abreu, Maria T., Siegel, Corey A., Panaccione, Remo, Sands, Bruce E., Dignass, Axel, Turner, Dan, Dotan, Iris, Hart, Ailsa L., Ahuja, Vineet, Allez, Matthieu, Ananthakrishnan, Ashwin N., Ghosh, Subrata, Griffiths, Anne M., Halfvarson, Jonas, Kaser, Arthur, Kotze, Paulo G., Koutroubakis, Ioannis E., Lakatos, Peter L., Levine, Arie, Lewis, James D., Magro, Fernando, Mantzaris, Gerassimos J., O’Morain, Colm, Ran, Zhihua, Reinisch, Walter, Rogler, Gerhard, Sachar, David B., Siegmund, Britta, Silverberg, Mark S., Sood, Ajit, Spinelli, Antonino, Steinwurz, Flavio, Tysk, Curt, Yamamoto-Furusho, Jesus K., Schreiber, Stefan, Rubin, David T., Sandborn, William J., Danese, Silvio, and Peyrin-Biroulet, Laurent

Published
2022
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14. Management of pouch neoplasia: consensus guidelines from the International Ileal Pouch Consortium

Author

Kiran, Ravi P, Kochhar, Gursimran S, Kariv, Revital, Rex, Douglas K, Sugita, Akira, Rubin, David T, Navaneethan, Udayakumar, Hull, Tracy L, Ko, Huaibin Mabel, Liu, Xiuli, Kachnic, Lisa A, Strong, Scott, Iacucci, Marietta, Bemelman, Willem, Fleshner, Philip, Safyan, Rachael A, Kotze, Paulo G, D'Hoore, André, Faiz, Omar, Lo, Simon, Ashburn, Jean H, Spinelli, Antonino, Bernstein, Charles N, Kane, Sunanda V, Cross, Raymond K, Schairer, Jason, McCormick, James T, Farraye, Francis A, Chang, Shannon, Scherl, Ellen J, Schwartz, David A, Bruining, David H, Philpott, Jessica, Bentley-Hibbert, Stuart, Tarabar, Dino, El-Hachem, Sandra, Sandborn, William J, Silverberg, Mark S, Pardi, Darrell S, Church, James M, and Shen, Bo

Published
2022
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16. Treatment of pouchitis, Crohn's disease, cuffitis, and other inflammatory disorders of the pouch: consensus guidelines from the International Ileal Pouch Consortium

Author

Shen, Bo, Kochhar, Gursimran S, Rubin, David T, Kane, Sunanda V, Navaneethan, Udayakumar, Bernstein, Charles N, Cross, Raymond K, Sugita, Akira, Schairer, Jason, Kiran, Ravi P, Fleshner, Philip, McCormick, James T, D’Hoore, André, Shah, Samir A, Farraye, Francis A, Kariv, Revital, Liu, Xiuli, Rosh, Joel, Chang, Shannon, Scherl, Ellen, Schwartz, David A, Kotze, Paulo Gustavo, Bruining, David H, Philpott, Jessica, Abraham, Bincy, Segal, Jonathan, Sedano, Rocio, Kayal, Maia, Bentley-Hibbert, Stuart, Tarabar, Dino, El-Hachem, Sandra, Sehgal, Priya, Picoraro, Joseph A, Vermeire, Séverine, Sandborn, William J, Silverberg, Mark S, and Pardi, Darrell S

Published
2022
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17. Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis

Author

Alberts, Rudi, de Vries, Elisabeth MG, Goode, Elizabeth C, Jiang, Xiaojun, Sampaziotis, Fotis, Rombouts, Krista, Böttcher, Katrin, Folseraas, Trine, Weismüller, Tobias J, Mason, Andrew L, Wang, Weiwei, Alexander, Graeme, Alvaro, Domenico, Bergquist, Annika, Björkström, Niklas K, Beuers, Ulrich, Björnsson, Einar, Boberg, Kirsten Muri, Bowlus, Christopher L, Bragazzi, Maria C, Carbone, Marco, Chazouillères, Olivier, Cheung, Angela, Dalekos, Georgios, Eaton, John, Eksteen, Bertus, Ellinghaus, David, Färkkilä, Martti, Festen, Eleonora AM, Floreani, Annarosa, Franceschet, Irene, Gotthardt, Daniel Nils, Hirschfield, Gideon M, Hoek, B van, Holm, Kristian, Hohenester, Simon, Hov, Johannes Roksund, Imhann, Floris, Invernizzi, Pietro, Juran, Brian D, Lenzen, Henrike, Lieb, Wolfgang, Liu, Jimmy Z, Marschall, Hanns-Ulrich, Marzioni, Marco, Melum, Espen, Milkiewicz, Piotr, Müller, Tobias, Pares, Albert, Rupp, Christian, Rust, Christian, Sandford, Richard N, Schramm, Christoph, Schreiber, Stefan, Schrumpf, Erik, Silverberg, Mark S, Srivastava, Brijesh, Sterneck, Martina, Teufel, Andreas, Vallier, Ludovic, Verheij, Joanne, Vila, Arnau Vich, Vries, Boudewijn de, Zachou, Kalliopi, Chapman, Roger W, Manns, Michael P, Pinzani, Massimo, Rushbrook, Simon M, Lazaridis, Konstantinos N, Franke, Andre, Anderson, Carl A, Karlsen, Tom H, Ponsioen, Cyriel Y, and Weersma, Rinse K

Subjects
Genetics, Transplantation, Chronic Liver Disease and Cirrhosis, Liver Disease, Clinical Research, Rare Diseases, Digestive Diseases - (Gallbladder), Digestive Diseases, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Adult, Cholangitis, Sclerosing, Cohort Studies, Disease Progression, Female, Humans, Kaplan-Meier Estimate, Logistic Models, Male, Middle Aged, Polymorphism, Single Nucleotide, Proportional Hazards Models, Thrombospondins, International PSC Study Group, The UK PSC Consortium, Primary sclerosing cholangitis, genetics, liver transplantation, Clinical Sciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology
Abstract

ObjectivePrimary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications.DesignWe collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients-obtained using the Illumina immunochip-with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes.ResultsWe identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07×10-9). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells.ConclusionWe present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.

Published
2018

18. Diagnosis and classification of ileal pouch disorders: consensus guidelines from the International Ileal Pouch Consortium

Author

Shen, Bo, Kochhar, Gursimran S, Kariv, Revital, Liu, Xiuli, Navaneethan, Udayakumar, Rubin, David T, Cross, Raymond K, Sugita, Akira, D'Hoore, André, Schairer, Jason, Farraye, Francis A, Kiran, Ravi P, Fleshner, Philip, Rosh, Joel, Shah, Samir A, Chang, Shannon, Scherl, Ellen, Pardi, Darrell S, Schwartz, David A, Kotze, Paulo G, Bruining, David H, Kane, Sunanda V, Philpott, Jessica, Abraham, Bincy, Segal, Jonathan, Sedano, Rocio, Kayal, Maia, Bentley-Hibbert, Stuart, Tarabar, Dino, El-Hachem, Sandra, Sehgal, Priya, McCormick, James T, Picoraro, Joseph A, Silverberg, Mark S, Bernstein, Charles N, Sandborn, William J, and Vermeire, Séverine

Published
2021
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19. Endoscopic evaluation of surgically altered bowel in inflammatory bowel disease: a consensus guideline from the Global Interventional Inflammatory Bowel Disease Group

Author

Shen, Bo, Kochhar, Gursimran S, Navaneethan, Udayakumar, Cross, Raymond K, Farraye, Francis A, Iacucci, Marietta, Schwartz, David A, Gonzalez-Lama, Yago, Schairer, Jason, Kiran, Ravi P, Kotze, Paulo Gustavo, Kobayashi, Taku, Bortlik, Martin, Liu, Xiuli, Levy, Alexander N, González Suárez, Begoña, Tang, Shou-Jiang, Coelho-Prabhu, Nayantara, Lukas, Martin, Bruining, David H, El-Hachem, Sandra, Charles, Roger J, Chen, Yan, Sood, Ajit, Mao, Ren, Loras, Carme, Dulai, Parambir S, Picoraro, Joseph A, Chiorean, Michael, Lukas, Milan, Shergill, Amandeep, Silverberg, Mark S, Sandborn, William J, and Bernstein, Charles N

Published
2021
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21. Anti-microbial antibody response is associated with future onset of Crohn’s disease independent of biomarkers of altered gut barrier function, subclinical inflammation, and genetic risk

Author

Lee, Sun-Ho, Turpin, Williams, Espin-Garcia, Osvaldo, Raygoza Garay, Juan Antonio, Smith, Michelle I., Leibovitzh, Haim, Goethel, Ashleigh, Turner, Dan, Mack, David, Deslandres, Colette, Cino, Maria, Aumais, Guy, Panaccione, Remo, Jacobson, Kevan, Bitton, Alain, Steinhart, A. Hillary, Huynh, Hien Q., Princen, Fred, Moayyedi, Paul, Griffiths, Anne M., Silverberg, Mark S., Paterson, Andrew D., Xu, Wei, and Croitoru, Kenneth

Published
2021
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22. Systematic review:Patient-related, microbial, surgical, and histopathological risk factors for endoscopic post-operative recurrence in patients with Crohn's disease

Author

Bak, Michiel T.J., Demers, Karlijn, Hammoudi, Nassim, Allez, Matthieu, Silverberg, Mark S., Fuhler, Gwenny M., Parikh, Kaushal, Pierik, Marieke J., Stassen, Laurents P.S., van der Woude, C. Janneke, Doukas, Michail, van Ruler, Oddeke, de Vries, Annemarie C., Bak, Michiel T.J., Demers, Karlijn, Hammoudi, Nassim, Allez, Matthieu, Silverberg, Mark S., Fuhler, Gwenny M., Parikh, Kaushal, Pierik, Marieke J., Stassen, Laurents P.S., van der Woude, C. Janneke, Doukas, Michail, van Ruler, Oddeke, and de Vries, Annemarie C.

Abstract

Background: Risk stratification for endoscopic post-operative recurrence (ePOR) in Crohn's disease (CD) is required to identify patients who would benefit most from initiation of prophylactic medication and intensive monitoring of recurrence. Aims:To assess the current evidence on patient-related, microbial, surgical and histopathological risk factors for ePOR in patients with CD after ileocolic (re-)resection. Methods: Multiple online databases (Embase, MEDLINE, Web of Science and Cochrane Library) were searched up to March 2024. Studies with reported associations of patient-related, microbial, surgical and/or histopathological factors for ePOR (i.e., Rutgeerts’ score ≥i2 or modified Rutgeerts’ score ≥i2a) were included. The risk of bias was assessed with the Newcastle-Ottawa Scale for observational cohort studies and case-control studies. Results: In total, 47 studies were included (four RCTs, 29 cohort studies, 12 case–control studies, one cross-sectional study and one individual participant data meta-analysis) including 6006 patients (median sample size 87 patients [interquartile range 46–170]). Risk of bias assessment revealed a poor quality in 41% of the studies. An association was reported in multiple studies of ePOR with active smoking at and post-surgery, male sex and prior bowel resection. A heterogeneous association with ePOR was reported for other risk factors included in the current guidelines (penetrating disease, perianal disease, younger age, extensive small bowel disease and presence of granulomas in the resection specimen or myenteric plexitis in the resection margin), and other patient-related, microbial, surgical and histopathological factors. Conclusion: Risk factors for ePOR in international guidelines are not consistently reported as risk factors in current literature except for active smoking and prior bowel resection. To develop evidence-base

Published
2024

23. Systematic review: Patient‐related, microbial, surgical, and histopathological risk factors for endoscopic post‐operative recurrence in patients with Crohn's disease.

Author

Bak, Michiel T. J., Demers, Karlijn, Hammoudi, Nassim, Allez, Matthieu, Silverberg, Mark S., Fuhler, Gwenny M., Parikh, Kaushal, Pierik, Marieke J., Stassen, Laurents P. S., van der Woude, C. Janneke, Doukas, Michail, van Ruler, Oddeke, and de Vries, Annemarie C.

Subjects
CROHN'S disease, PREOPERATIVE risk factors, DISEASE risk factors, INTESTINAL diseases, ONLINE databases
Abstract

Summary: Background: Risk stratification for endoscopic post‐operative recurrence (ePOR) in Crohn's disease (CD) is required to identify patients who would benefit most from initiation of prophylactic medication and intensive monitoring of recurrence. Aims: To assess the current evidence on patient‐related, microbial, surgical and histopathological risk factors for ePOR in patients with CD after ileocolic (re‐)resection. Methods: Multiple online databases (Embase, MEDLINE, Web of Science and Cochrane Library) were searched up to March 2024. Studies with reported associations of patient‐related, microbial, surgical and/or histopathological factors for ePOR (i.e., Rutgeerts' score ≥i2 or modified Rutgeerts' score ≥i2a) were included. The risk of bias was assessed with the Newcastle‐Ottawa Scale for observational cohort studies and case‐control studies. Results: In total, 47 studies were included (four RCTs, 29 cohort studies, 12 case–control studies, one cross‐sectional study and one individual participant data meta‐analysis) including 6006 patients (median sample size 87 patients [interquartile range 46–170]). Risk of bias assessment revealed a poor quality in 41% of the studies. An association was reported in multiple studies of ePOR with active smoking at and post‐surgery, male sex and prior bowel resection. A heterogeneous association with ePOR was reported for other risk factors included in the current guidelines (penetrating disease, perianal disease, younger age, extensive small bowel disease and presence of granulomas in the resection specimen or myenteric plexitis in the resection margin), and other patient‐related, microbial, surgical and histopathological factors. Conclusion: Risk factors for ePOR in international guidelines are not consistently reported as risk factors in current literature except for active smoking and prior bowel resection. To develop evidence‐based, personalised strategies, large prospective studies are warranted to identify risk factors for ePOR. Validation studies of promising (bio)markers are also required. [ABSTRACT FROM AUTHOR]

Published
2024
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24. When Should I Get My Next COVID-19 Vaccine? Data From the Surveillance of Responses to COVID-19 Vaccines in Systemic Immune-Mediated Inflammatory Diseases (SUCCEED) Study.

Author

Bowdish, Dawn M. E., Chandran, Vinod, Hitchon, Carol A., Kaplan, Gilaad G., Avina-Zubieta, J. Antonio, Fortin, Paul R., Larché, Maggie J., Boire, Gilles, Gingras, Anne-Claude, Dayam, Roya M., Colmegna, Ines, Lukusa, Luck, Lee, Jennifer L. F., Richards, Dawn P., Pereira, Daniel, Watts, Tania H., Silverberg, Mark S., Bernstein, Charles N., Lacaille, Diane, and Benoit, Jenna

Published
2024
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25. Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases

Author

Levine, Arie, Rhodes, Jonathan M., Lindsay, James O., Abreu, Maria T., Kamm, Michael A., Gibson, Peter R., Gasche, Christoph, Silverberg, Mark S., Mahadevan, Uma, Boneh, Rotem Sigall, Wine, Eyton, Damas, Oriana M., Syme, Graeme, Trakman, Gina L., Yao, Chu Kion, Stockhamer, Stefanie, Hammami, Muhammad B., Garces, Luis C., Rogler, Gerhard, Koutroubakis, Ioannis E., Ananthakrishnan, Ashwin N., McKeever, Liam, and Lewis, James D.

Published
2020
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26. Practical guidelines on endoscopic treatment for Crohn's disease strictures: a consensus statement from the Global Interventional Inflammatory Bowel Disease Group

Author

Shen, Bo, Kochhar, Gursimran, Navaneethan, Udayakumar, Farraye, Francis A, Schwartz, David A, Iacucci, Marietta, Bernstein, Charles N, Dryden, Gerald, Cross, Raymond, Bruining, David H, Kobayashi, Taku, Lukas, Martin, Shergill, Amandeep, Bortlik, Martin, Lan, Nan, Lukas, Milan, Tang, Shou-Jiang, Kotze, Paulo Gustavo, Kiran, Ravi P, Dulai, Parambir S, El-Hachem, Sandra, Coelho-Prabhu, Nayantara, Thakkar, Shyam, Mao, Ren, Chen, Guodong, Zhang, Shengyu, Suárez, Begoña González, Lama, Yago Gonzalez, Silverberg, Mark S, and Sandborn, William J

Published
2020
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27. Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial

Author

Jairath, Vipul, primary, Zou, Guangyong, additional, Wang, Zhongya, additional, Adsul, Shashi, additional, Colombel, Jean-Frederic, additional, D’Haens, Geert R, additional, Freire, Marcelo, additional, Moran, Gordon W, additional, Peyrin-Biroulet, Laurent, additional, Sandborn, William J, additional, Sebastian, Shaji, additional, Travis, Simon, additional, Vermeire, Séverine, additional, Radulescu, Gabriela, additional, Sigler, Julie, additional, Hanžel, Jurij, additional, Ma, Christopher, additional, Sedano, Rocio, additional, McFarlane, Stefanie C, additional, Arya, Naveen, additional, Beaton, Melanie, additional, Bossuyt, Peter, additional, Danese, Silvio, additional, Green, Daniel, additional, Harlan, William, additional, Horynski, Marek, additional, Klopocka, Maria, additional, Petroniene, Rima, additional, Silverberg, Mark S, additional, Wolanski, Lukasz, additional, and Feagan, Brian G, additional

Published
2024
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28. A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn’s Disease and Human Gut Microbiome Composition

Author

Li, Dalin, Achkar, Jean-Paul, Haritunians, Talin, Jacobs, Jonathan P, Hui, Ken Y, D'Amato, Mauro, Brand, Stephan, Radford-Smith, Graham, Halfvarson, Jonas, Niess, Jan-Hendrik, Kugathasan, Subra, Büning, Carsten, Schumm, L Philip, Klei, Lambertus, Ananthakrishnan, Ashwin, Aumais, Guy, Baidoo, Leonard, Dubinsky, Marla, Fiocchi, Claudio, Glas, Jürgen, Milgrom, Raquel, Proctor, Deborah D, Regueiro, Miguel, Simms, Lisa A, Stempak, Joanne M, Targan, Stephan R, Törkvist, Leif, Sharma, Yashoda, Devlin, Bernie, Borneman, James, Hakonarson, Hakon, Xavier, Ramnik J, Daly, Mark, Brant, Steven R, Rioux, John D, Silverberg, Mark S, Cho, Judy H, Braun, Jonathan, McGovern, Dermot PB, and Duerr, Richard H

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Nutrition and Dietetics, Genetics, Nutrition, Inflammatory Bowel Disease, Autoimmune Disease, Human Genome, Clinical Research, Digestive Diseases, Crohn's Disease, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Alleles, Case-Control Studies, Cation Transport Proteins, Colitis, Ulcerative, Crohn Disease, Female, Gastrointestinal Microbiome, Genetic Pleiotropy, Genotype, Humans, Male, Mutation, Missense, Risk Factors, Inflammatory Bowel Diseases, Microbiota, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics
Abstract

Background & aimsGenome-wide association studies have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn's disease (CD) and ulcerative colitis remain incompletely defined. Here, we aimed to identify novel associations between IBD and functional genetic variants using the Illumina ExomeChip (San Diego, CA).MethodsGenotyping was performed in 10,523 IBD cases and 5726 non-IBD controls. There were 91,713 functional single-nucleotide polymorphism loci in coding regions analyzed. A novel identified association was replicated further in 2 independent cohorts. We further examined the association of the identified single-nucleotide polymorphism with microbiota from 338 mucosal lavage samples in the Mucosal Luminal Interface cohort measured using 16S sequencing.ResultsWe identified an association between CD and a missense variant encoding alanine or threonine at position 391 in the zinc transporter solute carrier family 39, member 8 protein (SLC39A8 alanine 391 threonine, rs13107325) and replicated the association with CD in 2 replication cohorts (combined meta-analysis P = 5.55 × 10(-13)). This variant has been associated previously with distinct phenotypes including obesity, lipid levels, blood pressure, and schizophrenia. We subsequently determined that the CD risk allele was associated with altered colonic mucosal microbiome composition in both healthy controls (P = .009) and CD cases (P = .0009). Moreover, microbes depleted in healthy carriers strongly overlap with those reduced in CD patients (P = 9.24 × 10(-16)) and overweight individuals (P = 6.73 × 10(-16)).ConclusionsOur results suggest that an SLC39A8-dependent shift in the gut microbiome could explain its pleiotropic effects on multiple complex diseases including CD.

Published
2016

29. A Frameshift in CSF2RB Predominant Among Ashkenazi Jews Increases Risk for Crohn's Disease and Reduces Monocyte Signaling via GM-CSF

Author

Chuang, Ling-Shiang, Villaverde, Nicole, Hui, Ken Y, Mortha, Arthur, Rahman, Adeeb, Levine, Adam P, Haritunians, Talin, Ng, Sok Meng Evelyn, Zhang, Wei, Hsu, Nai-Yun, Facey, Jody-Ann, Luong, Tramy, Fernandez-Hernandez, Heriberto, Li, Dalin, Rivas, Manuel, Schiff, Elena R, Gusev, Alexander, Schumm, L Phillip, Bowen, Beatrice M, Sharma, Yashoda, Ning, Kaida, Remark, Romain, Gnjatic, Sacha, Legnani, Peter, George, James, Sands, Bruce E, Stempak, Joanne M, Datta, Lisa W, Lipka, Seth, Katz, Seymour, Cheifetz, Adam S, Barzilai, Nir, Pontikos, Nikolas, Abraham, Clara, Dubinsky, Marla J, Targan, Stephan, Taylor, Kent, Rotter, Jerome I, Scherl, Ellen J, Desnick, Robert J, Abreu, Maria T, Zhao, Hongyu, Atzmon, Gil, Pe’er, Itsik, Kugathasan, Subra, Hakonarson, Hakon, McCauley, Jacob L, Lencz, Todd, Darvasi, Ariel, Plagnol, Vincent, Silverberg, Mark S, Muise, Aleixo M, Brant, Steven R, Daly, Mark J, Segal, Anthony W, Duerr, Richard H, Merad, Miriam, McGovern, Dermot PB, Peter, Inga, and Cho, Judy H

Subjects
Clinical Research, Genetics, Inflammatory Bowel Disease, Digestive Diseases, Crohn's Disease, 2.1 Biological and endogenous factors, Aetiology, Case-Control Studies, Crohn Disease, Cytokine Receptor Common beta Subunit, Female, Frameshift Mutation, Granulocyte-Macrophage Colony-Stimulating Factor, Humans, Intestines, Jews, Male, Monocytes, Risk Factors, Signal Transduction, IBD, Risk Factor, Ethnic Variation, Clinical Sciences, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology
Abstract

Background & aimsCrohn's disease (CD) has the highest prevalence in Ashkenazi Jewish populations. We sought to identify rare, CD-associated frameshift variants of high functional and statistical effects.MethodsWe performed exome sequencing and array-based genotype analyses of 1477 Ashkenazi Jewish individuals with CD and 2614 Ashkenazi Jewish individuals without CD (controls). To validate our findings, we performed genotype analyses of an additional 1515 CD cases and 7052 controls for frameshift mutations in the colony-stimulating factor 2-receptor β common subunit gene (CSF2RB). Intestinal tissues and blood samples were collected from patients with CD; lamina propria leukocytes were isolated and expression of CSF2RB and granulocyte-macrophage colony-stimulating factor-responsive cells were defined by adenomatous polyposis coli (APC) time-of-flight mass cytometry (CyTOF analysis). Variants of CSF2RB were transfected into HEK293 cells and the expression and functions of gene products were compared.ResultsIn the discovery cohort, we associated CD with a frameshift mutation in CSF2RB (P = 8.52 × 10(-4)); the finding was validated in the replication cohort (combined P = 3.42 × 10(-6)). Incubation of intestinal lamina propria leukocytes with granulocyte-macrophage colony-stimulating factor resulted in high levels of phosphorylation of signal transducer and activator of transcription (STAT5) and lesser increases in phosphorylation of extracellular signal-regulated kinase and AK straining transforming (AKT). Cells co-transfected with full-length and mutant forms of CSF2RB had reduced pSTAT5 after stimulation with granulocyte-macrophage colony-stimulating factor, compared with cells transfected with control CSF2RB, indicating a dominant-negative effect of the mutant gene. Monocytes from patients with CD who were heterozygous for the frameshift mutation (6% of CD cases analyzed) had reduced responses to granulocyte-macrophage colony-stimulating factor and markedly decreased activity of aldehyde dehydrogenase; activity of this enzyme has been associated with immune tolerance.ConclusionsIn a genetic analysis of Ashkenazi Jewish individuals, we associated CD with a frameshift mutation in CSF2RB. Intestinal monocytes from carriers of this mutation had reduced responses to granulocyte-macrophage colony-stimulating factor, providing an additional mechanism for alterations to the innate immune response in individuals with CD.

Published
2016

30. TNFRSF1B Is Associated with ANCA in IBD

Author

Li, Dalin, Silverberg, Mark S, Haritunians, Talin, Dubinsky, Marla C, Landers, Carol, Stempak, Joanne M, Milgrom, Raquel, Guo, Xiuqing, Chen, Yii-Der Ida, Rotter, Jerome I, Taylor, Kent D, McGovern, Dermot PB, and Targan, Stephan R

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Autoimmune Disease, Digestive Diseases, Genetics, Inflammatory Bowel Disease, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, Antibodies, Antineutrophil Cytoplasmic, Child, Colitis, Ulcerative, Crohn Disease, Female, Genome-Wide Association Study, Heterozygote, Humans, Inflammatory Bowel Diseases, Male, Receptors, Tumor Necrosis Factor, Type II, Young Adult, GWAS, inflammatory bowel diseases, ANCA, TNFRSFIB, Gastroenterology & Hepatology, Clinical sciences
Abstract

The genetic basis of antineutrophil cytoplasmic antibody, an important biomarker of inflammatory bowel disease (IBD), has never been thoroughly examined on a genome-wide scale. In this study, we performed a 2-stage genome-wide association study (GWAS) on antineutrophil cytoplasmic antibody in IBD cases. In the 2959 IBD cases in the discovery stage, we observed an association between a variant in the gene TNFRSF1B with antineutrophil cytoplasmic antibody level (rs5745994, minor allele frequency = 0.028, beta = 18.12, 95% CI, 11.82-24.22, P = 1.89 × 10). This association was replicated in an independent cohort of 419 IBD cases (beta = 16.91, 95% CI, 6.13-27.69, P = 2.38 × 10). With a Q-value of 0.036, we performed a fixed-effect meta-analysis for the association of rs5745994 in both cohorts and observed a stronger association signal (beta = 17.81, 95% CI, 12.36-23.25, P = 8.97 × 10). TNFRSF1B gene codes for tumor necrosis factor (TNF) receptor 2 (TNFR2), thereby we examined the reported TNFRSF1B variant with serum TNFR2 level. We observed a negative association with serum TNFR2 level being 8.23 EU/mL in carriers and 9.12 EU/mL in noncarriers (P = 0.033). This finding indicates the functional role of identified TNFRSF1B variant in IBD serology and may be reflective of the underlying biological mechanisms that determine clinical expression and/or response to certain therapies.

Published
2016

31. Characterization of Genetic Loci That Affect Susceptibility to Inflammatory Bowel Diseases in African Americans

Author

Huang, Chengrui, Haritunians, Talin, Okou, David T, Cutler, David J, Zwick, Michael E, Taylor, Kent D, Datta, Lisa W, Maranville, Joseph C, Liu, Zhenqiu, Ellis, Shannon, Chopra, Pankaj, Alexander, Jonathan S, Baldassano, Robert N, Cross, Raymond K, Dassopoulos, Themistocles, Dhere, Tanvi A, Duerr, Richard H, Hanson, John S, Hou, Jason K, Hussain, Sunny Z, Isaacs, Kim L, Kachelries, Kelly E, Kader, Howard, Kappelman, Michael D, Katz, Jeffrey, Kellermayer, Richard, Kirschner, Barbara S, Kuemmerle, John F, Kumar, Archana, Kwon, John H, Lazarev, Mark, Mannon, Peter, Moulton, Dedrick E, Osuntokun, Bankole O, Patel, Ashish, Rioux, John D, Rotter, Jerome I, Saeed, Shehzad, Scherl, Ellen J, Silverberg, Mark S, Silverman, Ann, Targan, Stephan R, Valentine, John F, Wang, Ming-Hsi, Simpson, Claire L, Bridges, S Louis, Kimberly, Robert P, Rich, Stephen S, Cho, Judy H, Di Rienzo, Anna, Kao, Linda WH, McGovern, Dermot PB, Brant, Steven R, and Kugathasan, Subra

Subjects
Genetics, Clinical Research, Crohn's Disease, Digestive Diseases, Inflammatory Bowel Disease, Autoimmune Disease, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Good Health and Well Being, Adult, Black or African American, Aged, Colitis, Ulcerative, Crohn Disease, Female, Genetic Loci, Genetic Predisposition to Disease, Humans, Inflammatory Bowel Diseases, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, United States, White People, Young Adult, Race, Ethnicity, Genetic Variant, Intestinal Inflammation, Clinical Sciences, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology
Abstract

Background & aimsInflammatory bowel disease (IBD) has familial aggregation in African Americans (AAs), but little is known about the molecular genetic susceptibility. Mapping studies using the Immunochip genotyping array expand the number of susceptibility loci for IBD in Caucasians to 163, but the contribution of the 163 loci and European admixture to IBD risk in AAs is unclear. We performed a genetic mapping study using the Immunochip to determine whether IBD susceptibility loci in Caucasians also affect risk in AAs and identify new associated loci.MethodsWe recruited AAs with IBD and without IBD (controls) from 34 IBD centers in the United States; additional controls were collected from 4 other Immunochip studies. Association and admixture loci were mapped for 1088 patients with Crohn's disease, 361 with ulcerative colitis, 62 with IBD type unknown, and 1797 controls; 130,241 autosomal single-nucleotide polymorphisms (SNPs) were analyzed.ResultsThe strongest associations were observed between ulcerative colitis and HLA rs9271366 (P = 7.5 × 10(-6)), Crohn's disease and 5p13.1 rs4286721 (P = 3.5 × 10(-6)), and IBD and KAT2A rs730086 (P = 2.3 × 10(-6)). Additional suggestive associations (P < 4.2 × 10(-5)) were observed between Crohn's disease and IBD and African-specific SNPs in STAT5A and STAT3; between IBD and SNPs in IL23R, IL12B, and C2orf43; and between ulcerative colitis and SNPs near HDAC11 and near LINC00994. The latter 3 loci have not been previously associated with IBD, but require replication. Established Caucasian associations were replicated in AAs (P < 3.1 × 10(-4)) at NOD2, IL23R, 5p15.3, and IKZF3. Significant admixture (P < 3.9 × 10(-4)) was observed for 17q12-17q21.31 (IZKF3 through STAT3), 10q11.23-10q21.2, 15q22.2-15q23, and 16p12.2-16p12.1. Network analyses showed significant enrichment (false discovery rate

Published
2015

34. Analysis of Clinical Trial Screen Failures in Inflammatory Bowel Diseases [IBD]: Real World Results from the International Organization for the study of IBD.

Author

Vieujean, Sophie, Lindsay, James O, D'Amico, Ferdinando, Ahuja, Vineet, Silverberg, Mark S, Sood, Ajit, Yamamoto-Furusho, Jesus K, Nagahori, Masakazu, Watanabe, Mamoru, Koutroubakis, Ioannis E, Foteinogiannopoulou, Kalliopi, Biron, Irit Avni, Walsh, Alissa, Outtier, An, Nordestgaard, Rie Louise Møller, Abreu, Maria T, Dubinsky, Marla, Siegel, Corey, Louis, Edouard, and Dotan, Iris

Abstract

Background Recruitment for randomized controlled trials [RCTs] in inflammatory bowel diseases [IBD] has substantially dropped over time. This study aimed to assess reasons why IBD patients are not included in sponsored multicentre phase IIb–III RCTs. Methods All IOIBD members [ n  = 58] were invited to participate. We divided barriers to participation as follows: [1] reasons patients with active IBD were not deemed appropriate for an RCT; [2] reasons qualified patients did not wish to participate; and [3] reasons for screen failure [SF] in patients agreeing to participate. We assess these in a 4-week prospective study including, consecutively, all patients with symptomatic disease for whom a treatment change was required. In addition, we performed a 6-month retrospective study to further evaluate reasons for SF. Results A total of 106 patients (60 male [56.6%], 63 Crohn's disease [CD] [59.4%]), from ten centres across the world, were included in the prospective study. An RCT has not been proposed to 65 of them [mainly due to eligibility criteria]. Of the 41 patients to whom an RCT was offered, eight refused [mainly due to reluctance to receive placebo] and 28 agreed to participate. Among these 28 patients, five failed their screening and 23 were finally included in an RCT. A total of 107 patients (61 male [57%], 67 CD [62.6%]), from 13 centres worldwide, were included in our retrospective study of SFs. The main reason was insufficient disease activity. Conclusion This first multicentre study analysing reasons for non-enrolment in IBD RCTs shows that we lose patients at each step. Eligibility criteria, the risk of placebo assignment, and insufficient disease activity were part of the main barriers. [ABSTRACT FROM AUTHOR]

Published
2024
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38. Clinical Predictors of Early and Late Endoscopic Recurrence Following Ileocolonic Resection in Crohn’s Disease

Author

Hernández-Rocha, Cristian, primary, Walshe, Margaret, additional, Birch, Sondra, additional, Sabic, Ksenija, additional, Korie, Ujunwa, additional, Chasteau, Colleen, additional, Miladinova, Vessela M, additional, Sabol, William B, additional, Mengesha, Emebet, additional, Hanna, Mary, additional, Pozdnyakova, Valeriya, additional, Datta, Lisa, additional, Kohen, Rita, additional, Milgrom, Raquel, additional, Stempak, Joanne M, additional, Bitton, Alain, additional, Brant, Steven R, additional, Rioux, John D, additional, McGovern, Dermot P B, additional, Duerr, Richard H, additional, Cho, Judy H, additional, Schumm, Phil L, additional, Silverberg, Mark S, additional, and Lazarev, Mark, additional

Published
2023
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39. Analysis of Clinical Trial Screen Failures in Inflammatory Bowel Diseases [IBD]: Real World Results from the International Organization for the study of IBD

Author

Vieujean, Sophie, primary, Lindsay, James O, additional, D’Amico, Ferdinando, additional, Ahuja, Vineet, additional, Silverberg, Mark S, additional, Sood, Ajit, additional, Yamamoto-Furusho, Jesus K, additional, Nagahori, Masakazu, additional, Watanabe, Mamoru, additional, Koutroubakis, Ioannis E, additional, Foteinogiannopoulou, Kalliopi, additional, Avni Biron, Irit, additional, Walsh, Alissa, additional, Outtier, An, additional, Nordestgaard, Rie Louise Møller, additional, Abreu, Maria T, additional, Dubinsky, Marla, additional, Siegel, Corey, additional, Louis, Edouard, additional, Dotan, Iris, additional, Reinisch, Walter, additional, Danese, Silvio, additional, Rubin, David T, additional, and Peyrin-Biroulet, Laurent, additional

Published
2023
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43. Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.

Author

Liu, Jimmy Z, Hov, Johannes Roksund, Folseraas, Trine, Ellinghaus, Eva, Rushbrook, Simon M, Doncheva, Nadezhda T, Andreassen, Ole A, Weersma, Rinse K, Weismüller, Tobias J, Eksteen, Bertus, Invernizzi, Pietro, Hirschfield, Gideon M, Gotthardt, Daniel Nils, Pares, Albert, Ellinghaus, David, Shah, Tejas, Juran, Brian D, Milkiewicz, Piotr, Rust, Christian, Schramm, Christoph, Müller, Tobias, Srivastava, Brijesh, Dalekos, Georgios, Nöthen, Markus M, Herms, Stefan, Winkelmann, Juliane, Mitrovic, Mitja, Braun, Felix, Ponsioen, Cyriel Y, Croucher, Peter JP, Sterneck, Martina, Teufel, Andreas, Mason, Andrew L, Saarela, Janna, Leppa, Virpi, Dorfman, Ruslan, Alvaro, Domenico, Floreani, Annarosa, Onengut-Gumuscu, Suna, Rich, Stephen S, Thompson, Wesley K, Schork, Andrew J, Næss, Sigrid, Thomsen, Ingo, Mayr, Gabriele, König, Inke R, Hveem, Kristian, Cleynen, Isabelle, Gutierrez-Achury, Javier, Ricaño-Ponce, Isis, van Heel, David, Björnsson, Einar, Sandford, Richard N, Durie, Peter R, Melum, Espen, Vatn, Morten H, Silverberg, Mark S, Duerr, Richard H, Padyukov, Leonid, Brand, Stephan, Sans, Miquel, Annese, Vito, Achkar, Jean-Paul, Boberg, Kirsten Muri, Marschall, Hanns-Ulrich, Chazouillères, Olivier, Bowlus, Christopher L, Wijmenga, Cisca, Schrumpf, Erik, Vermeire, Severine, Albrecht, Mario, UK-PSCSC Consortium, Rioux, John D, Alexander, Graeme, Bergquist, Annika, Cho, Judy, Schreiber, Stefan, Manns, Michael P, Färkkilä, Martti, Dale, Anders M, Chapman, Roger W, Lazaridis, Konstantinos N, International PSC Study Group, Franke, Andre, Anderson, Carl A, Karlsen, Tom H, and International IBD Genetics Consortium

Subjects
UK-PSCSC Consortium, International PSC Study Group, International IBD Genetics Consortium, Humans, Cholangitis, Sclerosing, Oligonucleotide Array Sequence Analysis, Risk Factors, Case-Control Studies, Gene Frequency, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Loci, Genetic Pleiotropy, Genotyping Techniques, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases.

Published
2013

44. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Author

Jostins, Luke, Ripke, Stephan, Weersma, Rinse K, Duerr, Richard H, McGovern, Dermot P, Hui, Ken Y, Lee, James C, Philip Schumm, L, Sharma, Yashoda, Anderson, Carl A, Essers, Jonah, Mitrovic, Mitja, Ning, Kaida, Cleynen, Isabelle, Theatre, Emilie, Spain, Sarah L, Raychaudhuri, Soumya, Goyette, Philippe, Wei, Zhi, Abraham, Clara, Achkar, Jean-Paul, Ahmad, Tariq, Amininejad, Leila, Ananthakrishnan, Ashwin N, Andersen, Vibeke, Andrews, Jane M, Baidoo, Leonard, Balschun, Tobias, Bampton, Peter A, Bitton, Alain, Boucher, Gabrielle, Brand, Stephan, Büning, Carsten, Cohain, Ariella, Cichon, Sven, D’Amato, Mauro, De Jong, Dirk, Devaney, Kathy L, Dubinsky, Marla, Edwards, Cathryn, Ellinghaus, David, Ferguson, Lynnette R, Franchimont, Denis, Fransen, Karin, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hedl, Matija, Hu, Xinli, Karlsen, Tom H, Kupcinskas, Limas, Kugathasan, Subra, Latiano, Anna, Laukens, Debby, Lawrance, Ian C, Lees, Charlie W, Louis, Edouard, Mahy, Gillian, Mansfield, John, Morgan, Angharad R, Mowat, Craig, Newman, William, Palmieri, Orazio, Ponsioen, Cyriel Y, Potocnik, Uros, Prescott, Natalie J, Regueiro, Miguel, Rotter, Jerome I, Russell, Richard K, Sanderson, Jeremy D, Sans, Miquel, Satsangi, Jack, Schreiber, Stefan, Simms, Lisa A, Sventoraityte, Jurgita, Targan, Stephan R, Taylor, Kent D, Tremelling, Mark, Verspaget, Hein W, De Vos, Martine, Wijmenga, Cisca, Wilson, David C, Winkelmann, Juliane, Xavier, Ramnik J, Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K, Zhao, Hongyu, Silverberg, Mark S, Annese, Vito, Hakonarson, Hakon, Brant, Steven R, Radford-Smith, Graham, Mathew, Christopher G, Rioux, John D, and Schadt, Eric E

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Digestive Diseases, Human Genome, Inflammatory Bowel Disease, Biotechnology, Autoimmune Disease, Crohn's Disease, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Oral and gastrointestinal, Colitis, Ulcerative, Crohn Disease, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Haplotypes, Host-Pathogen Interactions, Humans, Inflammatory Bowel Diseases, Mycobacterium, Mycobacterium Infections, Mycobacterium tuberculosis, Phenotype, Polymorphism, Single Nucleotide, Reproducibility of Results, International IBD Genetics Consortium, General Science & Technology
Abstract

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

Published
2012

45. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

Author

Anderson, Carl A, Boucher, Gabrielle, Lees, Charlie W, Franke, Andre, D'Amato, Mauro, Taylor, Kent D, Lee, James C, Goyette, Philippe, Imielinski, Marcin, Latiano, Anna, Lagacé, Caroline, Scott, Regan, Amininejad, Leila, Bumpstead, Suzannah, Baidoo, Leonard, Baldassano, Robert N, Barclay, Murray, Bayless, Theodore M, Brand, Stephan, Büning, Carsten, Colombel, Jean-Frédéric, Denson, Lee A, De Vos, Martine, Dubinsky, Marla, Edwards, Cathryn, Ellinghaus, David, Fehrmann, Rudolf SN, Floyd, James AB, Florin, Timothy, Franchimont, Denis, Franke, Lude, Georges, Michel, Glas, Jürgen, Glazer, Nicole L, Guthery, Stephen L, Haritunians, Talin, Hayward, Nicholas K, Hugot, Jean-Pierre, Jobin, Gilles, Laukens, Debby, Lawrance, Ian, Lémann, Marc, Levine, Arie, Libioulle, Cecile, Louis, Edouard, McGovern, Dermot P, Milla, Monica, Montgomery, Grant W, Morley, Katherine I, Mowat, Craig, Ng, Aylwin, Newman, William, Ophoff, Roel A, Papi, Laura, Palmieri, Orazio, Peyrin-Biroulet, Laurent, Panés, Julián, Phillips, Anne, Prescott, Natalie J, Proctor, Deborah D, Roberts, Rebecca, Russell, Richard, Rutgeerts, Paul, Sanderson, Jeremy, Sans, Miquel, Schumm, Philip, Seibold, Frank, Sharma, Yashoda, Simms, Lisa A, Seielstad, Mark, Steinhart, A Hillary, Targan, Stephan R, van den Berg, Leonard H, Vatn, Morten, Verspaget, Hein, Walters, Thomas, Wijmenga, Cisca, Wilson, David C, Westra, Harm-Jan, Xavier, Ramnik J, Zhao, Zhen Z, Ponsioen, Cyriel Y, Andersen, Vibeke, Torkvist, Leif, Gazouli, Maria, Anagnou, Nicholas P, Karlsen, Tom H, Kupcinskas, Limas, Sventoraityte, Jurgita, Mansfield, John C, Kugathasan, Subra, Silverberg, Mark S, Halfvarson, Jonas, Rotter, Jerome I, Mathew, Christopher G, Griffiths, Anne M, Gearry, Richard, Ahmad, Tariq, Brant, Steven R, and Chamaillard, Mathias

Subjects
Biological Sciences, Genetics, Autoimmune Disease, Human Genome, Crohn's Disease, Digestive Diseases, Nutrition, Inflammatory Bowel Disease, Prevention, Oral and gastrointestinal, Colitis, Ulcerative, Crohn Disease, Genome-Wide Association Study, Humans, Risk, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.

Published
2011

47. Gut Microbiome Composition Is Associated With Future Onset of Crohn’s Disease in Healthy First-Degree Relatives

Author

Raygoza Garay, Juan Antonio, primary, Turpin, Williams, additional, Lee, Sun-Ho, additional, Smith, Michelle I., additional, Goethel, Ashleigh, additional, Griffiths, Anne M., additional, Moayyedi, Paul, additional, Espin-Garcia, Osvaldo, additional, Abreu, Maria, additional, Aumais, Guy L., additional, Bernstein, Charles N., additional, Biron, Irit A., additional, Cino, Maria, additional, Deslandres, Colette, additional, Dotan, Iris, additional, El-Matary, Wael, additional, Feagan, Brian, additional, Guttman, David S., additional, Huynh, Hien, additional, Dieleman, Levinus A., additional, Hyams, Jeffrey S., additional, Jacobson, Kevan, additional, Mack, David, additional, Marshall, John K., additional, Otley, Anthony, additional, Panaccione, Remo, additional, Ropeleski, Mark, additional, Silverberg, Mark S., additional, Steinhart, A. Hillary, additional, Turner, Dan, additional, Yerushalmi, Baruch, additional, Paterson, Andrew D., additional, Xu, Wei, additional, Croitoru, Kenneth, additional, Beck, Paul, additional, Bernstein, Charles, additional, Griffiths, Anne, additional, Guttman, David, additional, Kaplan, Gilaad, additional, Krause, Denis O., additional, Madsen, Karen, additional, Marshall, John, additional, Seidman, Ernest, additional, Silverberg, Mark, additional, Snapper, Scott, additional, Stadnyk, Andy, additional, Steinhart, Hillary, additional, Surette, Michael, additional, Walters, Thomas, additional, Vallance, Bruce, additional, Aumais, Guy, additional, Bitton, Alain, additional, Critch, Jeff, additional, Denson, Lee, additional, Herfarth, Hans, additional, Higgins, Peter, additional, McGrath, Jerry, additional, and Panancionne, Remo, additional

Published
2023
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48. The chromatin and single-cell transcriptional landscapes of CD4 T cells in inflammatory bowel disease link risk loci with a proinflammatory Th17 cell population

Author

Medina, Tiago S., primary, Murison, Alex, additional, Smith, Michelle, additional, Kinker, Gabriela S., additional, Chakravarthy, Ankur, additional, Vitiello, Glauco A. F., additional, Turpin, Williams, additional, Shen, Shu Yi, additional, Yau, Helen L., additional, Sarmento, Olga F., additional, Faubion, William, additional, Lupien, Mathieu, additional, Silverberg, Mark S., additional, Arrowsmith, Cheryl H., additional, and De Carvalho, Daniel D., additional

Published
2023
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49. Ulcerative colitis–risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study

Author

Silverberg, Mark S, Cho, Judy H, Rioux, John D, McGovern, Dermot PB, Wu, Jing, Annese, Vito, Achkar, Jean-Paul, Goyette, Philippe, Scott, Regan, Xu, Wei, Barmada, M Michael, Klei, Lambertus, Daly, Mark J, Abraham, Clara, Bayless, Theodore M, Bossa, Fabrizio, Griffiths, Anne M, Ippoliti, Andrew F, Lahaie, Raymond G, Latiano, Anna, Paré, Pierre, Proctor, Deborah D, Regueiro, Miguel D, Steinhart, A Hillary, Targan, Stephan R, Schumm, L Philip, Kistner, Emily O, Lee, Annette T, Gregersen, Peter K, Rotter, Jerome I, Brant, Steven R, Taylor, Kent D, Roeder, Kathryn, and Duerr, Richard H

Subjects
Biological Sciences, Genetics, Butyrophilins, Case-Control Studies, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 6, Colitis, Ulcerative, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, HLA-DQ Antigens, HLA-DQ beta-Chains, Humans, Male, Membrane Glycoproteins, Polymorphism, Single Nucleotide, Receptors, Interleukin, Recombination, Genetic, Risk Factors, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29).

Published
2009

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