Sökning: onr:"swepub:oai:DiVA.org:su-171174" > Genome-wide associa...
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000 | 05945naa a2201081 4500 | |
001 | oai:DiVA.org:su-171174 | |
003 | SwePub | |
008 | 190815s2019 | |||||||||||000 ||eng| | |
009 | oai:prod.swepub.kib.ki.se:141197628 | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1711742 URI |
024 | 7 | a https://doi.org/10.1136/gutjnl-2018-3176192 DOI |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1411976282 URI |
040 | a (SwePub)sud (SwePub)ki | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Schafmayer, Clemens4 aut |
245 | 1 0 | a Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms |
264 | c 2019-01-19 | |
264 | 1 | b BMJ,c 2019 |
338 | a print2 rdacarrier | |
520 | a Objective Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. Design Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. Results We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p< 0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3x10-10 and 0.002 (OR allelic = 1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). Conclusion I n silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng |
700 | 1 | a Harrison, James William4 aut |
700 | 1 | a Buch, Stephan4 aut |
700 | 1 | a Lange, Christinau Karolinska Institutet4 aut |
700 | 1 | a Reichert, Matthias C.4 aut |
700 | 1 | a Hofer, Philipp4 aut |
700 | 1 | a Cossais, François4 aut |
700 | 1 | a Kupcinskas, Juozas4 aut |
700 | 1 | a von Schönfels, Witigo4 aut |
700 | 1 | a Schniewind, Bodo4 aut |
700 | 1 | a Kruis, Wolfgang4 aut |
700 | 1 | a Tepel, Jürgen4 aut |
700 | 1 | a Zobel, Myrko4 aut |
700 | 1 | a Rosendahl, Jonas4 aut |
700 | 1 | a Jacobi, Thorsten4 aut |
700 | 1 | a Walther-Berends, Andreas4 aut |
700 | 1 | a Schroeder, Michael4 aut |
700 | 1 | a Vogel, Ilka4 aut |
700 | 1 | a Sergeev, Petr4 aut |
700 | 1 | a Boedeker, Hans4 aut |
700 | 1 | a Hinrichsen, Holger4 aut |
700 | 1 | a Volk, Andreas4 aut |
700 | 1 | a Erk, Jens-Uwe4 aut |
700 | 1 | a Burmeister, Greta4 aut |
700 | 1 | a Hendricks, Alexander4 aut |
700 | 1 | a Hinz, Sebastian4 aut |
700 | 1 | a Wolff, Sebastian4 aut |
700 | 1 | a Böttner, Martina4 aut |
700 | 1 | a Wood, Andrew R.4 aut |
700 | 1 | a Tyrrell, Jessica4 aut |
700 | 1 | a Beaumont, Robin N.4 aut |
700 | 1 | a Langheinrich, Melanie4 aut |
700 | 1 | a Kucharzik, Torsten4 aut |
700 | 1 | a Brezina, Stefanie4 aut |
700 | 1 | a Huber-Schönauer, Ursula4 aut |
700 | 1 | a Pietsch, Leonora4 aut |
700 | 1 | a Noack, Laura Sophie4 aut |
700 | 1 | a Brosch, Mario4 aut |
700 | 1 | a Herrmann, Alexander4 aut |
700 | 1 | a Thangapandi, Raghavan Veera4 aut |
700 | 1 | a Schimming, Hans Wolfgang4 aut |
700 | 1 | a Zeissig, Sebastian4 aut |
700 | 1 | a Palm, Stefan4 aut |
700 | 1 | a Focke, Gerd4 aut |
700 | 1 | a Andreasson, Annau Stockholms universitet,Stressforskningsinstitutet,Karolinska Institutet, Sweden4 aut0 (Swepub:su)anan6088 |
700 | 1 | a Schmidt, Peter T.u Karolinska Institutet4 aut |
700 | 1 | a Weitz, Juergen4 aut |
700 | 1 | a Krawczak, Michael4 aut |
700 | 1 | a Völzke, Henry4 aut |
700 | 1 | a Leeb, Gernot4 aut |
700 | 1 | a Michl, Patrick4 aut |
700 | 1 | a Lieb, Wolfgang4 aut |
700 | 1 | a Grützmann, Robert4 aut |
700 | 1 | a Franke, Andre4 aut |
700 | 1 | a Lammert, Frank4 aut |
700 | 1 | a Becker, Thomas4 aut |
700 | 1 | a Kupcinskas, Limas4 aut |
700 | 1 | a D'Amato, Maurou Karolinska Institutet4 aut |
700 | 1 | a Wedel, Thilo4 aut |
700 | 1 | a Datz, Christian4 aut |
700 | 1 | a Gsur, Andrea4 aut |
700 | 1 | a Weedon, Michael N.4 aut |
700 | 1 | a Hampe, Jochen4 aut |
710 | 2 | a Karolinska Institutetb Stressforskningsinstitutet4 org |
773 | 0 | t Gutd : BMJg 68:5, s. 854-865q 68:5<854-865x 0017-5749x 1468-3288 |
856 | 4 | u https://ore.exeter.ac.uk/repository/bitstream/10871/35810/1/Manuscript_Diverticular_disease_GUT.pdf |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-171174 |
856 | 4 8 | u https://doi.org/10.1136/gutjnl-2018-317619 |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:141197628 |
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