@article{3030541,
    title = "Genome-wide analysis of 944 133 individuals provides insights into the
etiology of haemorrhoidal disease",
    author = "Zheng, Tenghao and Ellinghaus, David and Juzenas, Simonas and Cossais, and Francois and Burmeister, Greta and Mayr, Gabriele and Jorgensen, and Isabella Friis and Teder-Laving, Maris and Skogholt, Anne Heidi and and Chen, Sisi and Strege, Peter R. and Ito, Go and Banasik, Karina and and Becker, Thomas and Bokelmann, Frank and Brunak, Soren and Buch, Stephan and and Clausnitzer, Hartmut and Datz, Christian and Degenhardt, Frauke and and Doniec, Marek and Erikstrup, Christian and Esko, Tonu and Forster, and Michael and Frey, Norbert and Fritsche, Lars G. and Gabrielsen, Maiken and Elvestad and Grassle, Tobias and Gsur, Andrea and Gross, Justus and and Hampe, Jochen and Hendricks, Alexander and Hinz, Sebastian and Hveem, and Kristian and Jongen, Johannes and Junker, Ralf and Karlsen, Tom Hemming and and Hemmrich-Stanisak, Georg and Kruis, Wolfgang and Kupcinskas, Juozas and and Laubert, Tilman and Rosenstiel, Philip C. and Roecken, Christoph and and Laudes, Matthias and Leendertz, Fabian H. and Lieb, Wolfgang and and Limperger, Verena and Margetis, Nikolaos and Matz-Rensing, Kerstin and and Nemeth, Christopher Georg and Ness-Jensen, Eivind and Nowak-Gottl, and Ulrike and Pandit, Anita and Pedersen, Ole Birger and Peleikis, Hans and Gunter and Peuker, Kenneth and Rodriguez, Cristina Leal and Ruehlemann, and Malte Christoph and Schniewind, Bodo and Schulzky, Martin and and Skieceviciene, Jurgita and Tepel, Jurgen and Thomas, Laurent and and Uellendahl-Werth, Florian and Ullum, Henrik and Vogel, Ilka and Volzke, and Henry and von Fersen, Lorenzo and von Schonfels, Witigo and Vanderwerff, and Brett and Wilking, Julia and Wittig, Michael and Zeissig, Sebastian and and Zobel, Myrko and Zawistowski, Matthew and Vacic, Vladimir and Sazonova, and Olga and Noblin, Elizabeth S. and Farrugia, Gianrico and Beyder, Arthur and and Wedel, Thilo and Kahlke, Volker and Schafmayer, Clemens and D'Amato, and Mauro and Franke, Andre and DBDS Consortium and The 23andMe Res Team",
    journal = "Gut Pathogens",
    year = "2021",
    volume = "70",
    number = "8",
    pages = "1538-1549",
    publisher = "BMJ Publishing Group",
    issn = "1757-4749",
    doi = "10.1136/gutjnl-2020-323868",
    keywords = "anorectal disorders; genetics; anal canal histopathology",
    abstract = "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."
}