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50 results on '"Clark S.K."'

6. Peutz-Jeghers syndrome: a systematic review and recommendations for management

Author

Beggs, A.D., Latchford, A.R., Vasen, H.F.A., Moslein, G., Alonso, A., Aretz, S., Bertario, L., Blanco, I., Bulow, S., Burn, J., Capella, G., Colas, C., Friedl, W., Moller, P., Hes, F.J., Jarvinen, H., Mecklin, J.-P., Nagengast, F.M., Parc, Y., Phillips, R.K.S., Hyer, W., Ponz de Leon, M., Renkonen-Sinisalo, L., Sampson, J.R., Stormorken, A., Tejpar, S., Thomas, H.J.W., Wijnen, J.T., Clark, S.K., and Hodgson, S.V.

Subjects
Peutz-Jeghers syndrome -- Diagnosis, Peutz-Jeghers syndrome -- Care and treatment, Peutz-Jeghers syndrome -- Development and progression, Peutz-Jeghers syndrome -- Risk factors, Medical literature -- Analysis, Health
Published
2010

7. Guidelines for the clinical management of familial adenomatous polyposis (FAP)

Author

Vasen, H.F.A., Moslein, G., Alonso, A., Aretz, S., Bernstein, I., Bertario, L., Blanco, I., Bulow, S., Burn, J., Capella, G., Colas, C., Engel, C., Frayling, I., Friedl, W., Hes, F.J., Hodgson, S., Jarvinen, H., Mecklin, J.-P., Moller, P., Myrhoi, T., Nagengast, F.M., Parc, Y., Phillips, R., Clark, S.K., Ponz de Leon, M., Renkonen-Sinisalo, L., Sampson, J.R., Stormorken, A., Tejpar, S., Thomas, H.J.W., and Wijnen, J.

Subjects
Polyposis, Familial -- Care and treatment, Practice guidelines (Medicine) -- Evaluation, Colorectal cancer -- Risk factors, Colorectal cancer -- Prevention, Health
Published
2008

9. Genome-wide study identifies association between HLA-B∗55:01 and Self-Reported Penicillin Allergy

Author

Krebs, K., Bovijn, J., Zheng, N., Lepamets, M., Censin, J.C., Jürgenson, T., Särg, D., Abner, E., Laisk, T., Luo, Y., Skotte, L., Geller, F., Feenstra, B., Wang, W., Auton, A., Raychaudhuri, S., Esko, T., Metspalu, A., Laur, S., Roden, D.M., Wei, W-Q, Holmes, M.V., Lindgren, C.M., Phillips, E.J., Mägi, R., Milani, L., Fadista, J., Agee, M., Aslibekyan, S., Bell, R.K., Bryc, K., Clark, S.K., Elson, S.L., Fletez-Brant, K., Fontanillas, P., Furlotte, N.A., Gandhi, P.M., Heilbron, K., Hicks, B., Hinds, D.A., Huber, K.E., Jewett, E.M., Jiang, Y., Kleinman, A., Lin, K-H, Litterman, N.K., Luff, M.K., McCreight, J.C., McIntyre, M.H., McManus, K.F., Mountain, J.L., Mozaffari, S.V., Nandakumar, P., Noblin, E.S., Northover, C.A.M., O’Connell, J., Petrakovitz, A.A., Pitts, S.J., Poznik, G.D., Sathirapongsasuti, J.F., Shastri, A.J., Shelton, J.F., Shringarpure, S., Tian, C., Tung, J.Y., Tunney, R.J., Vacic, V., Wang, X., Zare, A.S., Krebs, K., Bovijn, J., Zheng, N., Lepamets, M., Censin, J.C., Jürgenson, T., Särg, D., Abner, E., Laisk, T., Luo, Y., Skotte, L., Geller, F., Feenstra, B., Wang, W., Auton, A., Raychaudhuri, S., Esko, T., Metspalu, A., Laur, S., Roden, D.M., Wei, W-Q, Holmes, M.V., Lindgren, C.M., Phillips, E.J., Mägi, R., Milani, L., Fadista, J., Agee, M., Aslibekyan, S., Bell, R.K., Bryc, K., Clark, S.K., Elson, S.L., Fletez-Brant, K., Fontanillas, P., Furlotte, N.A., Gandhi, P.M., Heilbron, K., Hicks, B., Hinds, D.A., Huber, K.E., Jewett, E.M., Jiang, Y., Kleinman, A., Lin, K-H, Litterman, N.K., Luff, M.K., McCreight, J.C., McIntyre, M.H., McManus, K.F., Mountain, J.L., Mozaffari, S.V., Nandakumar, P., Noblin, E.S., Northover, C.A.M., O’Connell, J., Petrakovitz, A.A., Pitts, S.J., Poznik, G.D., Sathirapongsasuti, J.F., Shastri, A.J., Shelton, J.F., Shringarpure, S., Tian, C., Tung, J.Y., Tunney, R.J., Vacic, V., Wang, X., and Zare, A.S.

Abstract

Hypersensitivity reactions to drugs are often unpredictable and can be life threatening, underscoring a need for understanding their underlying mechanisms and risk factors. The extent to which germline genetic variation influences the risk of commonly reported drug allergies such as penicillin allergy remains largely unknown. We extracted data from the electronic health records of more than 600,000 participants from the UK, Estonian, and Vanderbilt University Medical Center’s BioVU biobanks to study the role of genetic variation in the occurrence of self-reported penicillin hypersensitivity reactions. We used imputed SNP to HLA typing data from these cohorts to further fine map the human leukocyte antigen (HLA) association and replicated our results in 23andMe’s research cohort involving a total of 1.12 million individuals. Genome-wide meta-analysis of penicillin allergy revealed two loci, including one located in the HLA region on chromosome 6. This signal was further fine-mapped to the HLA-B∗55:01 allele (OR 1.41 95% CI 1.33–1.49, p value 2.04 × 10−31) and confirmed by independent replication in 23andMe’s research cohort (OR 1.30 95% CI 1.25–1.34, p value 1.00 × 10−47). The lead SNP was also associated with lower lymphocyte counts and in silico follow-up suggests a potential effect on T-lymphocytes at HLA-B∗55:01. We also observed a significant hit in PTPN22 and the GWAS results correlated with the genetics of rheumatoid arthritis and psoriasis. We present robust evidence for the role of an allele of the major histocompatibility complex (MHC) I gene HLA-B in the occurrence of penicillin allergy.

Published
2020

13. Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis

Author

Ijspeert, J.E., Rana, S.A., Atkinson, N.S., Herwaarden, Y.J. van, Bastiaansen, B.A., Leerdam, M.E. van, Sanduleanu, S., Bisseling, T.M., Spaander, M.C., Clark, S.K., Meijer, G.A., Lelyveld, N. van, Koornstra, J.J., Nagtegaal, I.D., East, J.E., Latchford, A., Dekker, E., Ijspeert, J.E., Rana, S.A., Atkinson, N.S., Herwaarden, Y.J. van, Bastiaansen, B.A., Leerdam, M.E. van, Sanduleanu, S., Bisseling, T.M., Spaander, M.C., Clark, S.K., Meijer, G.A., Lelyveld, N. van, Koornstra, J.J., Nagtegaal, I.D., East, J.E., Latchford, A., and Dekker, E.

Abstract

Contains fulltext : 169924pub.pdf (publisher's version ) (Closed access), OBJECTIVE: Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. DESIGN: In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. RESULTS: In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis >/=1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), >/=1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). CONCLUSION: The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias.

Published
2017

14. A feasibility study of bezafibrate in mitochondrial myopathy

Author

Steele, H.E., primary, Newman, J., additional, Jakovljevic, D.G., additional, Scadeng, A.J., additional, Clark, S.K., additional, Jimenez-Moreno, A.C., additional, Trenell, M.I., additional, Parikh, J.D., additional, Hollingsworth, K.G., additional, Blamire, A.M., additional, Pitceathly, R.D.S., additional, Hanna, M.G., additional, Gorman, G.S., additional, McFarland, R., additional, Turnbull, D.M., additional, Taylor, R.W., additional, Horvath, R., additional, and Chinnery, P.F., additional

Published
2017
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18. Consensus statement on the multidisciplinary management of patients with recurrent and primary rectal cancer beyond total mesorectal excision planes

Author

Bhangu, A., Beynon, J., Brown, G., Chang, G., Das, P., Desai, A., Frizelle, F., Glynne-Jones, R., Goldin, R., Hawkins, M.A., Heriot, A., Laurberg, S., Mirnezami, A., Nicholls, R.J., Sagar, P., Tekkis, P., Vuong, T., Wilson, M., Ali, S.M., Antoniou, A., Bose, P., Boyle, K., Branagan, G., Burling, D., Clark, S.K., Colquhuon, P., Crane, C.H., Darzi, A., Davies, M., Delaney, C.P., Dietz, D., Dozois, E.J., Duff, M., Dziki, A., Faria, J., Fitzgerald, J.E., Georgiou, P., George, B., George, M.L., Gupta, A., Guy, R., Harji, D.P., Harris, D.A., Herzig, D., Holm, T., Hompes, R., Jeys, L., Jenkins, J.T., Kiran, R.P., Koh, C.E., Law, W.L., Liberman, A.S., Marshall, M., McArthur, D.R., Mortensen, N., Myers, E., O'Connell, P.R., O'Dwyer, S.T., Oliver, A., Pallan, A., Patel, P., Patel, U.B., Radley, S., Ramsey, K.W.D., Rasmussen, P.C., Richard, C., Rutten, H.J., Sebag-Montefiore, D., Solomon, M.J., Stocchi, L., Swallow, C.J., Tait, D.M., Tan, E.C.T.H., As, N. van, Wiggers, T., Wilt, J.H.W. de, Winter, D.C., Woodhouse, C., Bhangu, A., Beynon, J., Brown, G., Chang, G., Das, P., Desai, A., Frizelle, F., Glynne-Jones, R., Goldin, R., Hawkins, M.A., Heriot, A., Laurberg, S., Mirnezami, A., Nicholls, R.J., Sagar, P., Tekkis, P., Vuong, T., Wilson, M., Ali, S.M., Antoniou, A., Bose, P., Boyle, K., Branagan, G., Burling, D., Clark, S.K., Colquhuon, P., Crane, C.H., Darzi, A., Davies, M., Delaney, C.P., Dietz, D., Dozois, E.J., Duff, M., Dziki, A., Faria, J., Fitzgerald, J.E., Georgiou, P., George, B., George, M.L., Gupta, A., Guy, R., Harji, D.P., Harris, D.A., Herzig, D., Holm, T., Hompes, R., Jeys, L., Jenkins, J.T., Kiran, R.P., Koh, C.E., Law, W.L., Liberman, A.S., Marshall, M., McArthur, D.R., Mortensen, N., Myers, E., O'Connell, P.R., O'Dwyer, S.T., Oliver, A., Pallan, A., Patel, P., Patel, U.B., Radley, S., Ramsey, K.W.D., Rasmussen, P.C., Richard, C., Rutten, H.J., Sebag-Montefiore, D., Solomon, M.J., Stocchi, L., Swallow, C.J., Tait, D.M., Tan, E.C.T.H., As, N. van, Wiggers, T., Wilt, J.H.W. de, Winter, D.C., and Woodhouse, C.

Abstract

Item does not contain fulltext

Published
2013

20. Guidelines for the clinical management of familial adenomatous polyposis (FAP).

Author

Vasen, H.F., Moslein, G., Alonso, A., Aretz, S., Bernstein, I., Bertario, L., Blanco, I., Bulow, S., Burn, J., Capella, G., Colas, C., Engel, C., Frayling, I., Friedl, W., Hes, F.J., Hodgson, S., Jarvinen, H., Mecklin, J.P., Moller, P., Myrhoi, T., Nagengast, F.M., Parc, Y., Phillips, R., Clark, S.K., Leon, M.P. de, Renkonen-Sinisalo, L., Sampson, J.R., Stormorken, A., Tejpar, S., Thomas, H.J., Wijnen, J., Vasen, H.F., Moslein, G., Alonso, A., Aretz, S., Bernstein, I., Bertario, L., Blanco, I., Bulow, S., Burn, J., Capella, G., Colas, C., Engel, C., Frayling, I., Friedl, W., Hes, F.J., Hodgson, S., Jarvinen, H., Mecklin, J.P., Moller, P., Myrhoi, T., Nagengast, F.M., Parc, Y., Phillips, R., Clark, S.K., Leon, M.P. de, Renkonen-Sinisalo, L., Sampson, J.R., Stormorken, A., Tejpar, S., Thomas, H.J., and Wijnen, J.

Abstract

Item does not contain fulltext, BACKGROUND: Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, which is responsible for <1% of all colorectal cancer (CRC) cases. The syndrome is characterised by the development of hundreds to thousands of adenomas in the colorectum. Almost all patients will develop CRC if they are not identified and treated at an early stage. The syndrome is inherited as an autosomal dominant trait and caused by mutations in the APC gene. Recently, a second gene has been identified that also gives rise to colonic adenomatous polyposis, although the phenotype is less severe than typical FAP. The gene is the MUTYH gene and the inheritance is autosomal recessive. In April 2006 and February 2007, a workshop was organised in Mallorca by European experts on hereditary gastrointestinal cancer aiming to establish guidelines for the clinical management of FAP and to initiate collaborative studies. Thirty-one experts from nine European countries participated in these workshops. Prior to the meeting, various participants examined the most important management issues according to the latest publications. A systematic literature search using Pubmed and reference lists of retrieved articles, and manual searches of relevant articles, was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described herein may be helpful in the appropriate management of FAP families. In order to improve the care of these families further, prospective controlled studies should be undertaken.

Published
2008

22. P093 Dendritic cell characteristics in pouchitis

Author

Landy, J., primary, Ronde, E., additional, Omar Al-Hassi, H., additional, Mann, E., additional, Peake, S., additional, Ciclitira, P.J., additional, Nicholls, R.J., additional, Clark, S.K., additional, Knight, S., additional, and Hart, A.L., additional

Published
2013
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23. P012 The effects of faecal microbiota transplantation on the innate immune system and epithelial tight junction expression in chronic refractory pouchitis

Author

Landy, J., primary, Omar Al-Hassi, H., additional, Ronde, E., additional, Mann, E., additional, Peake, S., additional, McLaughlin, S., additional, Perry-Woodford, Z.L., additional, Ciclitira, P.J., additional, Nicholls, R.J., additional, Clark, S.K., additional, Knight, S., additional, and Hart, A.L., additional

Published
2013
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27. P071 Alterations in epithelial and dendritic cell tight junction proteins expression in the ileo-anal pouch following ileostomy closure

Author

Landy, J., primary, Al-Hassi, H.O., additional, Ronde, E., additional, Peake, S., additional, English, N., additional, Mann, E., additional, Bernardo, D., additional, Tee, C., additional, Ciclitira, P.J., additional, Nicholls, R.J., additional, Clark, S.K., additional, Knight, S., additional, and Hart, A.L., additional

Published
2012
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46. Etiology of pouchitis.

Author

Landy, J., Al-Hassi, H.O., McLaughlin, S.D., Knight, S.C., Ciclitira, P.J., Nicholls, R.J., Clark, S.K., and Hart, A.L.

Published
2012
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49. Short report Surveillance of individuals at intermediate risk of colorectal cancer – the impact of new guidelines.

Author

Clark, S.K., Carpenter, S., Broughton, C.I.M., and Marks, C.G.

Subjects
*COLON cancer, *COLONOSCOPY
Abstract

Individuals with two first degree relatives, or one diagnosed at age < 45 years, with colorectal cancer are at sufficient risk to merit surveillance. Most undergo colonoscopy four to five yearly, starting 10 years before the youngest case. The aim of this study was to assess the impact of a proposed new surveillance protocol. We identified individuals with these risk criteria seen in our clinic from 1989 to 2001 and reviewed their notes with respect to colonoscopy. Colonoscopy ( n = 295) was performed on 186 patients in accordance with current recommendations. Cancer was detected in three and adenoma in 21 individuals. Applying the proposed protocol, 123 (42%) fewer colonoscopies would have been performed. No cancers would have been missed, but in five cases a small adenoma would not have been detected. Proposed new guidelines for surveillance of those at intermediate risk reduce the burden of colonoscopy without compromising identification of significant neoplasia. [ABSTRACT FROM AUTHOR]

Published
2003
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50. 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, H��benthal, Matthias, Abecasis, Gon��alo, Zawistowski, Matthew, Skogholt, Anne Heidi, Ness-Jensen, Eivind, Hveem, Kristian, Esko, T��nu, Teder-Laving, Maris, Zhernakova, Alexandra, Camilleri, Michael, Boeckxstaens, Guy, Whorwell, Peter J., Spiller, Robin, McVean, Gil, D���Amato, Mauro, Jostins, Luke, Parkes, Miles, Agee, Michelle, Aslibekyan, Stella, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Clark, Sarah K., Elson, Sarah L., Fletez-Brant, Kipper, Fontanillas, Pierre, Furlotte, Nicholas A., Gandhi, Pooja M., Heilbron, Karl, Hicks, Barry, Hinds, David A., Huber, Karen E., Jewett, Ethan M., Jiang, Yunxuan, Kleinman, Aaron, Lin, Keng-Han, Litterman, Nadia K., Luff, Marie K., McCreight, Jey C., McIntyre, Matthew H., McManus, Kimberly F., Mountain, Joanna L., Mozaffari, Sahar V., Nandakumar, Priyanka, Noblin, Elizabeth S., Northover, Carrie A. M., O���Connell, Jared, Petrakovitz, Aaron A., Pitts, Steven J., Poznik, G. David, Sathirapongsasuti, J. Fah, Shastri, Anjali J., Shelton, Janie F., Tian, Chao, Tung, Joyce Y., Tunney, Robert J., Vacic, Vladimir, Wang, Xin, Zare, Amir S., Kashyap, Purna, Chang, Lin, Mayer, Emeran, Heitkemper, Margaret, Sayuk, Gregory S., Ringel-Kulka, Tamar, Ringel, Yehuda, Chey, William D., Eswaran, Shanti, Merchant, Juanita L., Shulman, Robert J., Bujanda, Luis, Garcia-Etxebarria, Koldo, Dlugosz, Aldona, Lindberg, Greger, Schmidt, Peter T., Karling, Pontus, Ohlsson, Bodil, Walter, Susanna, Faresj��, ��shild O., Simren, Magnus, Halfvarson, Jonas, Portincasa, Piero, Barbara, Giovanni, Usai-Satta, Paolo, Neri, Matteo, Nardone, Gerardo, Cuomo, Rosario, Galeazzi, Francesca, Bellini, Massimo, Latiano, Anna, Houghton, Lesley, Jonkers, Daisy, Kurilshikov, Alexander, Weersma, Rinse K., Netea, Mihai, Tesarz, Jonas, Gauss, Annika, Goebel-Stengel, Miriam, Andresen, Viola, Frieling, Thomas, Pehl, Christian, Schaefert, Rainer, Niesler, Beate, Lieb, Wolfgang, Hanevik, Kurt, Langeland, Nina, Wensaas, Knut-Arne, Litleskare, Sverre, Gabrielsen, Maiken E., Thomas, Laurent, Thijs, Vincent, Lemmens, Robin, Van Oudenhove, Lukas, Wouters, Mira, Eijsbouts C., Zheng T., Kennedy N.A., Bonfiglio F., Anderson C.A., Moutsianas L., Holliday J., Shi J., Shringarpure S., Agee M., Aslibekyan S., Auton A., Bell R.K., Bryc K., Clark S.K., Elson S.L., Fletez-Brant K., Fontanillas P., Furlotte N.A., Gandhi P.M., Heilbron K., Hicks B., Hinds D.A., Huber K.E., Jewett E.M., Jiang Y., Kleinman A., Lin K.-H., Litterman N.K., Luff M.K., McCreight J.C., McIntyre M.H., McManus K.F., Mountain J.L., Mozaffari S.V., Nandakumar P., Noblin E.S., Northover C.A.M., O'Connell J., Petrakovitz A.A., Pitts S.J., Poznik G.D., Sathirapongsasuti J.F., Shastri A.J., Shelton J.F., Tian C., Tung J.Y., Tunney R.J., Vacic V., Wang X., Zare A.S., Voda A.-I., Kashyap P., Chang L., Mayer E., Heitkemper M., Sayuk G.S., Ringel-Kulka T., Ringel Y., Chey W.D., Eswaran S., Merchant J.L., Shulman R.J., Bujanda L., Garcia-Etxebarria K., Dlugosz A., Lindberg G., Schmidt P.T., Karling P., Ohlsson B., Walter S., Faresjo A.O., Simren M., Halfvarson J., Portincasa P., Barbara G., Usai-Satta P., Neri M., Nardone G., Cuomo R., Galeazzi F., Bellini M., Latiano A., Houghton L., Jonkers D., Kurilshikov A., Weersma R.K., Netea M., Tesarz J., Gauss A., Goebel-Stengel M., Andresen V., Frieling T., Pehl C., Schaefert R., Niesler B., Lieb W., Hanevik K., Langeland N., Wensaas K.-A., Litleskare S., Gabrielsen M.E., Thomas L., Thijs V., Lemmens R., Van Oudenhove L., Wouters M., Farrugia G., Franke A., Hubenthal M., Abecasis G., Zawistowski M., Skogholt A.H., Ness-Jensen E., Hveem K., Esko T., Teder-Laving M., Zhernakova A., Camilleri M., Boeckxstaens G., Whorwell P.J., Spiller R., McVean G., D'Amato M., Jostins L., Parkes M., Eijsbouts, Chris [0000-0001-5179-0653], Anderson, Carl A. [0000-0003-1719-7009], Moutsianas, Loukas [0000-0001-5453-345X], Holliday, Joanne [0000-0003-4568-7320], Shringarpure, Suyash [0000-0001-6464-2668], Voda, Alexandru-Ioan [0000-0003-2974-6992], Farrugia, Gianrico [0000-0003-3473-5235], Hübenthal, Matthias [0000-0002-5956-3006], Abecasis, Gonçalo [0000-0003-1509-1825], Zawistowski, Matthew [0000-0002-3005-083X], Ness-Jensen, Eivind [0000-0001-6005-0729], Teder-Laving, Maris [0000-0002-5872-1850], Camilleri, Michael [0000-0001-6472-7514], Whorwell, Peter J. [0000-0002-5220-8474], Spiller, Robin [0000-0001-6371-4500], McVean, Gil [0000-0002-5012-4162], D’Amato, Mauro [0000-0003-2743-5197], Jostins, Luke [0000-0002-2475-3969], Parkes, Miles [0000-0002-6467-0631], Apollo - University of Cambridge Repository, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Eijsbouts, C., Zheng, T., Kennedy, N. A., Bonfiglio, F., Anderson, C. A., Moutsianas, L., Holliday, J., Shi, J., Shringarpure, S., Agee, M., Aslibekyan, S., Auton, A., Bell, R. K., Bryc, K., Clark, S. K., Elson, S. L., Fletez-Brant, K., Fontanillas, P., Furlotte, N. A., Gandhi, P. M., Heilbron, K., Hicks, B., Hinds, D. A., Huber, K. E., Jewett, E. M., Jiang, Y., Kleinman, A., Lin, K. -H., Litterman, N. K., Luff, M. K., Mccreight, J. C., Mcintyre, M. H., Mcmanus, K. F., Mountain, J. L., Mozaffari, S. V., Nandakumar, P., Noblin, E. S., Northover, C. A. M., O'Connell, J., Petrakovitz, A. A., Pitts, S. J., Poznik, G. D., Sathirapongsasuti, J. F., Shastri, A. J., Shelton, J. F., Tian, C., Tung, J. Y., Tunney, R. J., Vacic, V., Wang, X., Zare, A. S., Voda, A. -I., Kashyap, P., Chang, L., Mayer, E., Heitkemper, M., Sayuk, G. S., Ringel-Kulka, T., Ringel, Y., Chey, W. D., Eswaran, S., Merchant, J. L., Shulman, R. J., Bujanda, L., Garcia-Etxebarria, K., Dlugosz, A., Lindberg, G., Schmidt, P. T., Karling, P., Ohlsson, B., Walter, S., Faresjo, A. O., Simren, M., Halfvarson, J., Portincasa, P., Barbara, G., Usai-Satta, P., Neri, M., Nardone, G., Cuomo, R., Galeazzi, F., Bellini, M., Latiano, A., Houghton, L., Jonkers, D., Kurilshikov, A., Weersma, R. K., Netea, M., Tesarz, J., Gauss, A., Goebel-Stengel, M., Andresen, V., Frieling, T., Pehl, C., Schaefert, R., Niesler, B., Lieb, W., Hanevik, K., Langeland, N., Wensaas, K. -A., Litleskare, S., Gabrielsen, M. E., Thomas, L., Thijs, V., Lemmens, R., Van Oudenhove, L., Wouters, M., Farrugia, G., Franke, A., Hubenthal, M., Abecasis, G., Zawistowski, M., Skogholt, A. H., Ness-Jensen, E., Hveem, K., Esko, T., Teder-Laving, M., Zhernakova, A., Camilleri, M., Boeckxstaens, G., Whorwell, P. J., Spiller, R., Mcvean, G., D'Amato, M., Jostins, L., and Parkes, M.

Subjects
Male, Molecular Chaperone, Mood Disorder, 631/208/205/2138, Biology, 692/699/1503/1502/2071, Bioinformatics, Polymorphism, Single Nucleotide, Genetic pathways, 38/43, Irritable Bowel Syndrome, Cytoskeletal Protein, Genetics, medicine, Genetic predisposition, Aged, Anxiety Disorders, CD56 Antigen, Cell Adhesion Molecules, Cytoskeletal Proteins, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Guanine Nucleotide Exchange Factors, Homeodomain Proteins, Humans, Middle Aged, Molecular Chaperones, Mood Disorders, United Kingdom, Polymorphism, 692/699/476, Irritable bowel syndrome, Depression (differential diagnoses), article, Homeodomain Protein, Single Nucleotide, Guanine Nucleotide Exchange Factor, medicine.disease, Neuroticism, Biobank, Mood, Cell Adhesion Molecule, Anxiety, medicine.symptom, Anxiety Disorder, Human
Abstract

Funder: Kennedy Trust Rheumatology Research Prize Studentship, Funder: DFG Cluster of Excellence ���Precision Medicine in Chronic In-flammation��� (PMI; ID: EXC2167), Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: ���Ideas��� Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): 715772, Funder: NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and NWO Gravitation grant ExposomeNL, Funder: Li Ka Shing Foundation (Li Ka Shing Foundation Limited); doi: https://doi.org/10.13039/100007421, 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/TPTE2P3 and 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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