Genome-wide analysis of 944,133 individuals provides insights into the etiology of hemorrhoidal disease Article Swipe

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Tenghao Zheng , David Ellinghaus , Simonas Juzėnas , François Cossais , Greta Burmeister , Gabriele Mayr , Isabella Friis Jørgensen , Maris Teder‐Laving , Anne Heidi Skogholt , Karina Banasik , Thomas Becker , Frank Bokelmann , Søren Brunak , Stephan Buch , Hartmut Clausnizer , Christian Datz , Frauke Degenhardt , Marek J. Doniec , Christian Erikstrup , Tõnu Esko , Michael Förster , Norbert Frey , Lars G. Fritsche , Maiken E. Gabrielsen , Tobias Gräßle , Andrea Gsur , Justus Groß , Jochen Hampe , Alexander Hendricks , Sebastian Hinz , Kristian Hveem , Johannes Jongen , Ralf Junker , Tom H. Karlsen , Georg Hemmrich‐Stanisak , Wolfgang Kruis , Juozas Kupčinskas , Tilman Laubert , Matthias Laudes , Fabian H. Leendertz , Wolfgang Lieb , Verena Limperger , Nikolaos Margetis , Kerstin Mätz‐Rensing , Christopher Georg Németh , Eivind Ness‐Jensen , Ulrike Nowak‐Göttl , Anita Pandit , Ole Birger Pedersen , H.-G. Peleikis , Kenneth Peuker , Cristina Leal Rodríguez , Malte Rühlemann , Bodo Schniewind , Martin Schulzky , Jurgita Skiecevičienė , Jürgen Tepel , Laurent F. Thomas , Florian Uellendahl-Werth , Henrik Ullum , Ilka Vogel , Henry Völzke , Lorenzo von Fersen , Witigo von Schoenfels , Brett Vanderwerff , Julia Wilking , Michael Wittig , Sebastian Zeißig , Myrko Zobel , Matthew Zawistowski , Vladimir Vacic , Olga V. Sazonova , Elizabeth S. Noblin , Thilo Wedel , Volker Kahlke , Clemens Schafmayer , Mauro D’Amato , André Franke ·

YOU? · · 2020 · Open Access · · DOI: https://doi.org/10.1101/2020.12.03.20242776

Hemorrhoidal disease (HEM) affects a large fraction of the population but its etiology including suspected genetic predisposition is poorly understood. We conducted a GWAS meta-analysis of 218,920 HEM patients and 725,213 controls of European ancestry, demonstrating modest heritability and genetic correlation with several other diseases from the gastrointestinal, neuroaffective and cardiovascular domains. HEM polygenic risk scores 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 harboring genes whose expression is enriched in blood vessels and gastrointestinal tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses of affected tissue from HEM patients highlighted HEM gene co-expression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organization of the extracellular matrix. We conclude HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.

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Genome-Wide Association Study

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Etiology Genome-wide association study Heritability Biology Disease Transcriptome Extracellular matrix Population Genetic architecture Genetics Genetic association Genetic predisposition Bioinformatics Gene Pathology Quantitative trait locus Medicine Gene expression Single-nucleotide polymorphism Genotype Environmental health

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1101/2020.12.03.20242776
PDF: https://www.medrxiv.org/content/medrxiv/early/2020/12/04/2020.12.03.20242776.full.pdf
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References: 63
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DOI: https://doi.org/10.1101/2020.12.03.20242776

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Title: Genome-wide analysis of 944,133 individuals provides insights into the etiology of hemorrhoidal disease

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Type: preprint

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Language: en

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Publication year: 2020

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Publication date: 2020-12-04

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Authors: Tenghao Zheng, David Ellinghaus, Simonas Juzėnas, François Cossais, Greta Burmeister, Gabriele Mayr, Isabella Friis Jørgensen, Maris Teder‐Laving, Anne Heidi Skogholt, Karina Banasik, Thomas Becker, Frank Bokelmann, Søren Brunak, Stephan Buch, Hartmut Clausnizer, Christian Datz, Frauke Degenhardt, Marek J. Doniec, Christian Erikstrup, Tõnu Esko, Michael Förster, Norbert Frey, Lars G. Fritsche, Maiken E. Gabrielsen, Tobias Gräßle, Andrea Gsur, Justus Groß, Jochen Hampe, Alexander Hendricks, Sebastian Hinz, Kristian Hveem, Johannes Jongen, Ralf Junker, Tom H. Karlsen, Georg Hemmrich‐Stanisak, Wolfgang Kruis, Juozas Kupčinskas, Tilman Laubert, Matthias Laudes, Fabian H. Leendertz, Wolfgang Lieb, Verena Limperger, Nikolaos Margetis, Kerstin Mätz‐Rensing, Christopher Georg Németh, Eivind Ness‐Jensen, Ulrike Nowak‐Göttl, Anita Pandit, Ole Birger Pedersen, H.-G. Peleikis, Kenneth Peuker, Cristina Leal Rodríguez, Malte Rühlemann, Bodo Schniewind, Martin Schulzky, Jurgita Skiecevičienė, Jürgen Tepel, Laurent F. Thomas, Florian Uellendahl-Werth, Henrik Ullum, Ilka Vogel, Henry Völzke, Lorenzo von Fersen, Witigo von Schoenfels, Brett Vanderwerff, Julia Wilking, Michael Wittig, Sebastian Zeißig, Myrko Zobel, Matthew Zawistowski, Vladimir Vacic, Olga V. Sazonova, Elizabeth S. Noblin, Thilo Wedel, Volker Kahlke, Clemens Schafmayer, Mauro D’Amato, André Franke

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Concepts: Etiology, Genome-wide association study, Heritability, Biology, Disease, Transcriptome, Extracellular matrix, Population, Genetic architecture, Genetics, Genetic association, Genetic predisposition, Bioinformatics, Gene, Pathology, Quantitative trait locus, Medicine, Gene expression, Single-nucleotide polymorphism, Genotype, Environmental health

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