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1. Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19

Author

Kotanidis, Christos P, Xie, Cheng, Alexander, Donna, Rodrigues, Jonathan C L, Burnham, Katie, Mentzer, Alexander, O’Connor, Daniel, Knight, Julian, Siddique, Muhammad, Lockstone, Helen, Thomas, Sheena, Kotronias, Rafail, Oikonomou, Evangelos K, Badi, Ileana, Lyasheva, Maria, Shirodaria, Cheerag, Lumley, Sheila F, Constantinides, Bede, Sanderson, Nicholas, Rodger, Gillian, Chau, Kevin K, Lodge, Archie, Tsakok, Maria, Gleeson, Fergus, Adlam, David, Rao, Praveen, Indrajeet, Das, Deshpande, Aparna, Bajaj, Amrita, Hudson, Benjamin J, Srivastava, Vivek, Farid, Shakil, Krasopoulos, George, Sayeed, Rana, Ho, Ling-Pei, Neubauer, Stefan, Newby, David E, Channon, Keith M, Deanfield, John, Antoniades, Charalambos, Ahern, David J, Ai, Zhichao, Ainsworth, Mark, Allan, Chris, Allcock, Alice, Angus, Brian, Ansari, M Azim, Arancibia-Cárcamo, Carolina, Aschenbrenner, Dominik, Attar, Moustafa, Baillie, J Kenneth, Barnes, Eleanor, Bashford-Rogers, Rachael, Bashyal, Archana, Beer, Sally, Berridge, Georgina, Beveridge, Amy, Bibi, Sagida, Bicanic, Tihana, Blackwell, Luke, Bowness, Paul, Brent, Andrew, Brown, Andrew, Broxholme, John, Buck, David, Burnham, Katie, Byrne, Helen, Camara, Susana, Ferreira, Ivan Candido, Charles, Philip, Chen, Wentao, Chen, Yi-Ling, Chong, Amanda, Clutterbuck, Elizabeth, Coles, Mark, Conlon, Christopher, Cornall, Richard, Cribbs, Adam, Curion, Fabiola, Davenport, Emma, Davidson, Neil, Davis, Simon, Dendrou, Calliope, Dequaire, Julie, Dib, Lea, Docker, James, Dold, Christina, Dong, Tao, Downes, Damien, Drakesmith, Hal, Dunachie, Susanna, Duncan, David, Eijsbouts, Chris, Esnouf, Robert, Espinosa, Alexis, Etherington, Rachel, Fairfax, Benjamin, Fairhead, Rory, Fang, Hai, Fassih, Shayan, Felle, Sally, Fernandez Mendoza, Maria, Ferreira, Ricardo, Fischer, Roman, Foord, Thomas, Forrow, Aden, Frater, John, Fries, Anastasia, Gallardo Sanchez, Veronica, Garner, Lucy, Geeves, Clementine, Georgiou, Dominique, Godfrey, Leila, Golubchik, Tanya, Gomez Vazquez, Maria, Green, Angie, Harper, Hong, Harrington, Heather, Heilig, Raphael, Hester, Svenja, Hill, Jennifer, Hinds, Charles, Hird, Clare, Ho, Ling-Pei, Hoekzema, Renee, Hollis, Benjamin, Hughes, Jim, Hutton, Paula, Jackson-Wood, Matthew, Jainarayanan, Ashwin, James-Bott, Anna, Jansen, Kathrin, Jeffery, Katie, Jones, Elizabeth, Jostins, Luke, Kerr, Georgina, Kim, David, Klenerman, Paul, Knight, Julian, Kumar, Vinod, Kumar Sharma, Piyush, Kurupati, Prathiba, Kwok, Andrew, Lee, Angela, Linder, Aline, Lockett, Teresa, Lonie, Lorne, Lopopolo, Maria, Lukoseviciute, Martyna, Luo, Jian, Marinou, Spyridoula, Marsden, Brian, Martinez, Jose, Matthews, Philippa, Mazurczyk, Michalina, McGowan, Simon, McKechnie, Stuart, Mead, Adam, Mentzer, Alexander, Mi, Yuxin, Monaco, Claudia, Montadon, Ruddy, Napolitani, Giorgio, Nassiri, Isar, Novak, Alex, O'Brien, Darragh, O'Connor, Daniel, O'Donnell, Denise, Ogg, Graham, Overend, Lauren, Park, Inhye, Pavord, Ian, Peng, Yanchun, Penkava, Frank, Pereira Pinho, Mariana, Perez, Elena, Pollard, Andrew, Powrie, Fiona, Psaila, Bethan, Quan, T Phuong, Repapi, Emmanouela, Revale, Santiago, Silva-Reyes, Laura, Richard, Jean-Baptiste, Rich-Griffin, Charlotte, Ritter, Thomas, Rollier, Christine, Rowland, Matthew, Ruehle, Fabian, Salio, Mariolina, Sansom, Stephen Nicholas, Sanches Peres, Raphael, Santos Delgado, Alberto, Sauka-Spengler, Tatjana, Schwessinger, Ron, Scozzafava, Giuseppe, Screaton, Gavin, Seigal, Anna, Semple, Malcolm, Sergeant, Martin, Simoglou Karali, Christina, Sims, David, Skelly, Donal, Slawinski, Hubert, Sobrinodiaz, Alberto, Sousos, Nikolaos, Stafford, Lizzie, Stockdale, Lisa, Strickland, Marie, Sumray, Otto, Sun, Bo, Taylor, Chelsea, Taylor, Stephen, Taylor, Adan, Thongjuea, Supat, Thraves, Hannah, Todd, John, Tomic, Adriana, Tong, Orion, Trebes, Amy, Trzupek, Dominik, Tucci, Felicia Anna, Turtle, Lance, Udalova, Irina, Uhlig, Holm, van Grinsven, Erinke, Vendrell, Iolanda, Verheul, Marije, Voda, Alexandru, Wang, Guanlin, Wang, Lihui, Wang, Dapeng, Watkinson, Peter, Watson, Robert, Weinberger, Michael, Whalley, Justin, Witty, Lorna, Wray, Katherine, Xue, Luzheng, Yuen Yeung, Hing, Yin, Zixi, Young, Rebecca, Youngs, Jonathan, Zhang, Ping, Zurke, Yasemin-Xiomara, Banning, Adrian, Antonopoulos, Alexios, Bajaj, Amrita, Kelion, Andrew, Deshpande, Aparna, Kardos, Attila, Hudson, Benjamin, Koo, Bon-Kwon, Shirodaria, Cheerag, Xie, Cheng, Kotanidis, Christos, Mahon, Ciara, Berry, Colin, Adlam, David, Newby, David, Connolly, Derek, Scaletta, Diane, Alexander, Donna, Nicol, Ed, McAlindon, Elisa, Oikonomou, Evangelos, Pugliese, Francesca, Pontone, Gianluca, Benedetti, Giulia, He, Guo-Wei, West, Henry, Kondo, Hidekazu, Benedek, Imre, Das, Intrajeet, Deanfield, John, Graby, John, Greenwood, John, Rodrigues, Jonathan, Ge, Junbo, Channon, Keith, Fabritz, Larissa, Fan, Li-Juan, Kingham, Lucy, Guglielmo, Marco, Lyasheva, Maria, Schmitt, Matthias, Beer, Meinrad, Anderson, Michelle, Desai, Milind, Marwan, Mohamed, Takahashi, Naohiko, Mehta, Nehal, Dai, Neng, Screaton, Nicholas, Sabharwal, Nikant, Maurovich-Horvat, Pál, Rao, Praveen, Kotronias, Rafail, Kharbanda, Rajesh, Preston, Rebecca, Wood, Richard, Blankstein, Ron, Rajani, Ronak, Mirsadraee, Saeed, Munir, Shahzad, Thomas, Sheena, Neubauer, Stefan, Klömpken, Steffen, Petersen, Steffen, Achenbach, Stephan, Anthony, Susan, Mak, Sze, Mittal, Tarun, Benedek, Theodora, Sharma, Vinoda, and Lin, Wen-Hua

Abstract

Direct evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven vascular inflammation from routine CT angiograms, and sought to validate its prognostic value in COVID-19.

Published
2022
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2. Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders

Author

Eijsbouts, Chris, Zheng, Tenghao, Kennedy, Nicholas A., Bonfiglio, Ferdinando, Anderson, Carl A., Moutsianas, Loukas, Holliday, Joanne, Shi, Jingchunzi, Shringarpure, Suyash, Voda, Alexandru-Ioan, Farrugia, Gianrico, Franke, Andre, Hübenthal, Matthias, Abecasis, Gonçalo, Zawistowski, Matthew, Skogholt, Anne Heidi, Ness-Jensen, Eivind, Hveem, Kristian, Esko, Tõnu, Teder-Laving, Maris, Zhernakova, Alexandra, Camilleri, Michael, Boeckxstaens, Guy, Whorwell, Peter J., Spiller, Robin, McVean, Gil, D’Amato, Mauro, Jostins, Luke, and Parkes, Miles

Abstract

Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg> 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS.

Published
2021
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3. Genomic profiling of T-cell activation suggests increased sensitivity of memory T cells to CD28 costimulation

Author

Glinos, Dafni A., Soskic, Blagoje, Williams, Cayman, Kennedy, Alan, Jostins, Luke, Sansom, David M., and Trynka, Gosia

Abstract

T-cell activation is a critical driver of immune responses. The CD28 costimulation is an essential regulator of CD4 T-cell responses, however, its relative importance in naive and memory T cells is not fully understood. Using different model systems, we observe that human memory T cells are more sensitive to CD28 costimulation than naive T cells. To deconvolute how the T-cell receptor (TCR) and CD28 orchestrate activation of human T cells, we stimulate cells using varying intensities of TCR and CD28 and profiled gene expression. We show that genes involved in cell cycle progression and division are CD28-driven in memory cells, but under TCR control in naive cells. We further demonstrate that T-helper differentiation and cytokine expression are controlled by CD28. Using chromatin accessibility profiling, we observe that AP1 transcriptional regulation is enriched when both TCR and CD28 are engaged, whereas open chromatin near CD28-sensitive genes is enriched for NF-kB motifs. Lastly, we show that CD28-sensitive genes are enriched in GWAS regions associated with immune diseases, implicating a role for CD28 in disease development. Our study provides important insights into the differential role of costimulation in naive and memory T-cell responses and disease susceptibility.

Published
2020
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4. Bayesian analysis of genetic association across tree-structured routine healthcare data in the UK Biobank

Author

Cortes, Adrian, Dendrou, Calliope A, Motyer, Allan, Jostins, Luke, Vukcevic, Damjan, Dilthey, Alexander, Donnelly, Peter, Leslie, Stephen, Fugger, Lars, and McVean, Gil

Abstract

Genetic discovery from the multitude of phenotypes extractable from routine healthcare data can transform understanding of the human phenome and accelerate progress toward precision medicine. However, a critical question when analyzing high-dimensional and heterogeneous data is how best to interrogate increasingly specific subphenotypes while retaining statistical power to detect genetic associations. Here we develop and employ a new Bayesian analysis framework that exploits the hierarchical structure of diagnosis classifications to analyze genetic variants against UK Biobank disease phenotypes derived from self-reporting and hospital episode statistics. Our method displays a more than 20% increase in power to detect genetic effects over other approaches and identifies new associations between classical human leukocyte antigen (HLA) alleles and common immune-mediated diseases (IMDs). By applying the approach to genetic risk scores (GRSs), we show the extent of genetic sharing among IMDs and expose differences in disease perception or diagnosis with potential clinical implications.

Published
2017
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5. Fine-mapping inflammatory bowel disease loci to single-variant resolution

Author

Huang, Hailiang, Fang, Ming, Jostins, Luke, Umićević Mirkov, Maša, Boucher, Gabrielle, Anderson, Carl A., Andersen, Vibeke, Cleynen, Isabelle, Cortes, Adrian, Crins, François, D’Amato, Mauro, Deffontaine, Valérie, Dmitrieva, Julia, Docampo, Elisa, Elansary, Mahmoud, Farh, Kyle Kai-How, Franke, Andre, Gori, Ann-Stephan, Goyette, Philippe, Halfvarson, Jonas, Haritunians, Talin, Knight, Jo, Lawrance, Ian C., Lees, Charlie W., Louis, Edouard, Mariman, Rob, Meuwissen, Theo, Mni, Myriam, Momozawa, Yukihide, Parkes, Miles, Spain, Sarah L., Théâtre, Emilie, Trynka, Gosia, Satsangi, Jack, van Sommeren, Suzanne, Vermeire, Severine, Xavier, Ramnik J., Weersma, Rinse K., Duerr, Richard H., Mathew, Christopher G., Rioux, John D., McGovern, Dermot P. B., Cho, Judy H., Georges, Michel, Daly, Mark J., and Barrett, Jeffrey C.

Abstract

Inflammatory bowel diseases are chronic gastrointestinal inflammatory disorders that affect millions of people worldwide. Genome-wide association studies have identified 200 inflammatory bowel disease-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals. We pinpoint 18 associations to a single causal variant with greater than 95% certainty, and an additional 27 associations to a single variant with greater than 50% certainty. These 45 variants are significantly enriched for protein-coding changes (n = 13), direct disruption of transcription-factor binding sites (n = 3), and tissue-specific epigenetic marks (n = 10), with the last category showing enrichment in specific immune cells among associations stronger in Crohn’s disease and in gut mucosa among associations stronger in ulcerative colitis. The results of this study suggest that high-resolution fine-mapping in large samples can convert many discoveries from genome-wide association studies into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms.

Published
2017
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6. Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn's disease

Author

Lee, James C, Biasci, Daniele, Roberts, Rebecca, Gearry, Richard B, Mansfield, John C, Ahmad, Tariq, Prescott, Natalie J, Satsangi, Jack, Wilson, David C, Jostins, Luke, Anderson, Carl A, Traherne, James A, Lyons, Paul A, Parkes, Miles, and Smith, Kenneth G C

Abstract

For most immune-mediated diseases, the main determinant of patient well-being is not the diagnosis itself but instead the course that the disease takes over time (prognosis). Prognosis may vary substantially between patients for reasons that are poorly understood. Familial studies support a genetic contribution to prognosis, but little evidence has been found for a proposed association between prognosis and the burden of susceptibility variants. To better characterize how genetic variation influences disease prognosis, we performed a within-cases genome-wide association study in two cohorts of patients with Crohn's disease. We identified four genome-wide significant loci, none of which showed any association with disease susceptibility. Conversely, the aggregated effect of all 170 disease susceptibility loci was not associated with disease prognosis. Together, these data suggest that the genetic contribution to prognosis in Crohn's disease is largely independent of the contribution to disease susceptibility and point to a biology of prognosis that could provide new therapeutic opportunities.

Published
2017
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7. Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7

Author

Luo, Yang, de Lange, Katrina M, Jostins, Luke, Moutsianas, Loukas, Randall, Joshua, Kennedy, Nicholas A, Lamb, Christopher A, McCarthy, Shane, Ahmad, Tariq, Edwards, Cathryn, Serra, Eva Goncalves, Hart, Ailsa, Hawkey, Chris, Mansfield, John C, Mowat, Craig, Newman, William G, Nichols, Sam, Pollard, Martin, Satsangi, Jack, Simmons, Alison, Tremelling, Mark, Uhlig, Holm, Wilson, David C, Lee, James C, Prescott, Natalie J, Lees, Charlie W, Mathew, Christopher G, Parkes, Miles, Barrett, Jeffrey C, and Anderson, Carl A

Abstract

To further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, we sequenced the whole genomes of 4,280 patients at low coverage and compared them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing genome-wide association study cohorts and tested for association at ∼12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles the risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants and found that such variants explained little heritability. We detected a burden of very rare, damaging missense variants in known Crohn's disease risk genes, suggesting that more comprehensive sequencing studies will continue to improve understanding of the biology of complex diseases.

Published
2017
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8. Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease

Author

Ji, Sun-Gou, Juran, Brian D, Mucha, Sören, Folseraas, Trine, Jostins, Luke, Melum, Espen, Kumasaka, Natsuhiko, Atkinson, Elizabeth J, Schlicht, Erik M, Liu, Jimmy Z, Shah, Tejas, Gutierrez-Achury, Javier, Boberg, Kirsten M, Bergquist, Annika, Vermeire, Severine, Eksteen, Bertus, Durie, Peter R, Farkkila, Martti, Müller, Tobias, Schramm, Christoph, Sterneck, Martina, Weismüller, Tobias J, Gotthardt, Daniel N, Ellinghaus, David, Braun, Felix, Teufel, Andreas, Laudes, Mattias, Lieb, Wolfgang, Jacobs, Gunnar, Beuers, Ulrich, Weersma, Rinse K, Wijmenga, Cisca, Marschall, Hanns-Ulrich, Milkiewicz, Piotr, Pares, Albert, Kontula, Kimmo, Chazouillères, Olivier, Invernizzi, Pietro, Goode, Elizabeth, Spiess, Kelly, Moore, Carmel, Sambrook, Jennifer, Ouwehand, Willem H, Roberts, David J, Danesh, John, Floreani, Annarosa, Gulamhusein, Aliya F, Eaton, John E, Schreiber, Stefan, Coltescu, Catalina, Bowlus, Christopher L, Luketic, Velimir A, Odin, Joseph A, Chopra, Kapil B, Kowdley, Kris V, Chalasani, Naga, Manns, Michael P, Srivastava, Brijesh, Mells, George, Sandford, Richard N, Alexander, Graeme, Gaffney, Daniel J, Chapman, Roger W, Hirschfield, Gideon M, de Andrade, Mariza, Rushbrook, Simon M, Franke, Andre, Karlsen, Tom H, Lazaridis, Konstantinos N, and Anderson, Carl A

Abstract

Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (rG) between PSC and ulcerative colitis (UC) (rG= 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (rG= 0.04) (P = 2.55 × 10−15). UC and CD were genetically more similar to each other (rG= 0.56) than either was to PSC (P < 1.0 × 10−15). Our study represents a substantial advance in understanding of the genetics of PSC.

Published
2017
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9. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease

Author

de Lange, Katrina M, Moutsianas, Loukas, Lee, James C, Lamb, Christopher A, Luo, Yang, Kennedy, Nicholas A, Jostins, Luke, Rice, Daniel L, Gutierrez-Achury, Javier, Ji, Sun-Gou, Heap, Graham, Nimmo, Elaine R, Edwards, Cathryn, Henderson, Paul, Mowat, Craig, Sanderson, Jeremy, Satsangi, Jack, Simmons, Alison, Wilson, David C, Tremelling, Mark, Hart, Ailsa, Mathew, Christopher G, Newman, William G, Parkes, Miles, Lees, Charlie W, Uhlig, Holm, Hawkey, Chris, Prescott, Natalie J, Ahmad, Tariq, Mansfield, John C, Anderson, Carl A, and Barrett, Jeffrey C

Abstract

Genetic association studies have identified 215 risk loci for inflammatory bowel disease, thereby uncovering fundamental aspects of its molecular biology. We performed a genome-wide association study of 25,305 individuals and conducted a meta-analysis with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new susceptibility loci, 3 of which contain integrin genes that encode proteins in pathways that have been identified as important therapeutic targets in inflammatory bowel disease. The associated variants are correlated with expression changes in response to immune stimulus at two of these genes (ITGA4 and ITGB8) and at previously implicated loci (ITGAL and ICAM1). In all four cases, the expression-increasing allele also increases disease risk. We also identified likely causal missense variants in a gene implicated in primary immune deficiency, PLCG2, and a negative regulator of inflammation, SLAMF8. Our results demonstrate that new associations at common variants continue to identify genes relevant to therapeutic target identification and prioritization.

Published
2017
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10. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci

Author

Ellinghaus, David, Jostins, Luke, Spain, Sarah L, Cortes, Adrian, Bethune, Jörn, Han, Buhm, Park, Yu Rang, Raychaudhuri, Soumya, Pouget, Jennie G, Hübenthal, Matthias, Folseraas, Trine, Wang, Yunpeng, Esko, Tonu, Metspalu, Andres, Westra, Harm-Jan, Franke, Lude, Pers, Tune H, Weersma, Rinse K, Collij, Valerie, D'Amato, Mauro, Halfvarson, Jonas, Jensen, Anders Boeck, Lieb, Wolfgang, Degenhardt, Franziska, Forstner, Andreas J, Hofmann, Andrea, Schreiber, Stefan, Mrowietz, Ulrich, Juran, Brian D, Lazaridis, Konstantinos N, Brunak, Søren, Dale, Anders M, Trembath, Richard C, Weidinger, Stephan, Weichenthal, Michael, Ellinghaus, Eva, Elder, James T, Barker, Jonathan N W N, Andreassen, Ole A, McGovern, Dermot P, Karlsen, Tom H, Barrett, Jeffrey C, Parkes, Miles, Brown, Matthew A, and Franke, Andre

Abstract

We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European ancestry, we identified 244 independent multidisease signals, including 27 new genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multidisease signals with expression data sets from human, rat and mouse together with epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases genetically identical to those with another disease, possibly owing to diagnostic misclassification, molecular subtypes or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes.

Published
2016
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11. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

Author

Cleynen, Isabelle, Boucher, Gabrielle, Jostins, Luke, Schumm, L Philip, Zeissig, Sebastian, Ahmad, Tariq, Andersen, Vibeke, Andrews, Jane M, Annese, Vito, Brand, Stephan, Brant, Steven R, Cho, Judy H, Daly, Mark J, Dubinsky, Marla, Duerr, Richard H, Ferguson, Lynnette R, Franke, Andre, Gearry, Richard B, Goyette, Philippe, Hakonarson, Hakon, Halfvarson, Jonas, Hov, Johannes R, Huang, Hailang, Kennedy, Nicholas A, Kupcinskas, Limas, Lawrance, Ian C, Lee, James C, Satsangi, Jack, Schreiber, Stephan, Théâtre, Emilie, van der Meulen-de Jong, Andrea E, Weersma, Rinse K, Wilson, David C, Parkes, Miles, Vermeire, Severine, Rioux, John D, Mansfield, John, Silverberg, Mark S, Radford-Smith, Graham, McGovern, Dermot P B, Barrett, Jeffrey C, and Lees, Charlie W

Abstract

Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases.

Published
2016
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13. Comparison of LABORAS with static incapacitance testing for assessing spontaneous pain behaviour in surgically-induced murine osteoarthritis

Author

von Loga, Isabell S., Miotla-Zarebska, Jadwiga, Huang, Yi-Shu, Williams, Richard, Jostins, Luke, and Vincent, Tonia L.

Abstract

Evoked responses following mechanical or thermal stimulation are typically used to assess pain behaviour in murine osteoarthritis (OA). However, there is no consensus on how best to measure spontaneous pain behaviour.

Published
2020
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14. Resolving TYK2locus genotype-to-phenotype differences in autoimmunity

Author

Dendrou, Calliope A., Cortes, Adrian, Shipman, Lydia, Evans, Hayley G., Attfield, Kathrine E., Jostins, Luke, Barber, Thomas, Kaur, Gurman, Kuttikkatte, Subita Balaram, Leach, Oliver A., Desel, Christiane, Faergeman, Soren L., Cheeseman, Jane, Neville, Matt J., Sawcer, Stephen, Compston, Alastair, Johnson, Adam R., Everett, Christine, Bell, John I., Karpe, Fredrik, Ultsch, Mark, Eigenbrot, Charles, McVean, Gil, and Fugger, Lars

Abstract

Resolving TYK2locus genotype-to-phenotype differences reveals an immune signaling optimum that may be exploited therapeutically for treating autoimmune diseases.

Published
2016
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