Citations 2
Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease
Zheng, Tenghao , Ellinghaus, David , Juzėnas, Simonas , Cossais, François , Burmeister, Greta , Mayr, Gabriele , Jørgensen, Isabella Friis , Teder‐Laving, Maris , Skogholt, Anne Heidi , Chen, Sisi , Strege, Peter R. , Ito, Go , Banasik, Karina , Bokelmann, Frank, Buch, Stephan , Clausnitzer, Hartmut, Degenhardt, Frauke , Doniec, Marek J., Erikstrup, Christian , Förster, Michael , Frey, Norbert , Fritsche, Lars G. , Gabrielsen, Maiken E. , Gräßle, Tobias , Gsur, Andrea , Hampe, Jochen , Hendricks, Alexander , Hinz, Sebastian , Jongen, Johannes , Junker, Ralf, Karlsen, Tom H. , Hemmrich‐Stanisak, Georg , Kruis, Wolfgang , Kupčinskas, Juozas , Laubert, Tilman , Rosenstiel, Philip , Röcken, Christoph , Laudes, Matthias , Leendertz, Fabian H. , Limperger, Verena , Margetis, Nikolaos, Mätz‐Rensing, Kerstin, Németh, Christopher Georg , Ness‐Jensen, Eivind , Nowak‐Göttl, Ulrike, Pandit, Anita , Pedersen, Ole Birger , Peleikis, H.-G., Peuker, Kenneth , Rodríguez, Cristina Leal , Schniewind, Bodo, Schulzky, Martin, Skiecevičienė, Jurgita , Tepel, Jürgen, Thomas, Laurent F. , Uellendahl-Werth, Florian , Ullum, Henrik , Vogel, Ilka, Völzke, Henry , Schönfels, Witigo von , Vanderwerff, Brett , Wilking, Julia, Wittig, Michael , Zeißig, Sebastian , Zobel, Myrko, Zawistowski, Matthew , Vacic, Vladimir, Sazonova, Olga V. , Noblin, Elizabeth S., Farrugia, Gianrico , Kahlke, Volker, Schafmayer, Clemens , D’Amato, Mauro , Datz, Christian , Forster, Michael , Gsur, Andrea , Hampe, Jochen , Röcken, Christoph , Ness-Jensen, Eivind , Rühlemann, Malte Christoph , Farrugia, Gianrico , D'Amato, Mauro , Franke, André , Ellinghaus, David , Zheng, Tenghao , Strege, Peter R , Erikstrup, Christian , Kupcinskas, Juozas , Becker, Thomas S , Brunak, Søren , Esko, Tõnu , Groß, Justus , Hveem, Kristian , Lieb, Wolfgang , Fersen, Lorenzo von , Sazonova, Olga, Beyder, Arthur , Wedel, Thilo
Gut | April 22, 2021 | Volume: 70 | Issue: 8 | Pages: 1538-1549
Objective Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date. Design We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry. Results We demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix. Conclusion HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.
Development of an index to define overall disease severity in IBD
Whitman, Cynthia B. , Spiegel, Brennan , Feagan, Brian G. , Loftus, Edward V. , D’Haens, Geert , Bernstein, Çharles N. , Gearry, Richard B. , Mantzaris, Gerassimos J. , Sartor, Balfour R., Silverberg, Mark S. , Riddell, Robert H. , O’Morain, Colm, Lakatos, Péter L. , Halfvarson, Jonas , Reinisch, Walter, Rogler, Gerhard , Kruis, Wolfgang , Tysk, Curt , Danese, Silvio , Sandborn, William J. , Gasché, Christoph , Pallone, Francesco, Travis, Simon , Peyrin‐Biroulet, Laurent , Siegel, Corey A , Sands, Bruce E , Panaccione, Remo , Bernstein, Charles Noah , Ng, Siew C. , Κoutroubakis, Ioannis E. , McGovern, Dermot , Halfvarson, Jonas , Schreiber, Stefan , Griffiths, Anne Marie , Moum, Bjørn Allan , Panés, Julián , Colombel, Jean‐Frédéric , Hanauer, Stephen B. , Loftus, Edward V , Danese, Silvio , Peyrin-Biroulet, Laurent , Spiegel, Brennan , Lakatos, Peter L
Gut | October 25, 2016 | Volume: 67 | Issue: 2 | Pages: 244-254
Background and aim Disease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC. Methods Using a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute. Results For CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities. Conclusions Based on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD.