Zheng, Tenghao ORCID: 0000-0003-1587-7481, Ellinghaus, David, Juzenas, Simonas ORCID: 0000-0001-9293-0691, Cossais, Francois, Burmeister, Greta, Mayr, Gabriele, Jorgensen, Isabella Friis ORCID: 0000-0001-5694-4332, Teder-Laving, Maris, Skogholt, Anne Heidi, Chen, Sisi, Strege, Peter R., Ito, Go, Banasik, Karina ORCID: 0000-0003-2489-2499, Becker, Thomas, Bokelmann, Frank, Brunak, Soren, Buch, Stephan, Clausnitzer, Hartmut, Datz, Christian, Degenhardt, Frauke ORCID: 0000-0001-7516-3179, Doniec, Marek, Erikstrup, Christian ORCID: 0000-0001-6551-6647, Esko, Tonu, Forster, Michael ORCID: 0000-0001-9927-5124, Frey, Norbert ORCID: 0000-0001-7611-378X, Fritsche, Lars G., Gabrielsen, Maiken Elvestad, Grassle, Tobias, Gsur, Andrea, Gross, Justus, Hampe, Jochen, Hendricks, Alexander, Hinz, Sebastian, Hveem, Kristian, Jongen, Johannes, Junker, Ralf, Karlsen, Tom Hemming, Hemmrich-Stanisak, Georg, Kruis, Wolfgang, Kupcinskas, Juozas, Laubert, Tilman, Rosenstiel, Philip C., Roecken, Christoph, Laudes, Matthias, Leendertz, Fabian H., Lieb, Wolfgang, Limperger, Verena, Margetis, Nikolaos, Matz-Rensing, Kerstin, Nemeth, Christopher Georg, Ness-Jensen, Eivind, Nowak-Gottl, Ulrike, Pandit, Anita, Pedersen, Ole Birger ORCID: 0000-0003-2312-5976, Peleikis, Hans Gunter, Peuker, Kenneth, Rodriguez, Cristina Leal, Ruehlemann, Malte Christoph, Schniewind, Bodo, Schulzky, Martin, Skieceviciene, Jurgita, Tepel, Jurgen, Thomas, Laurent ORCID: 0000-0003-0548-2486, Uellendahl-Werth, Florian, Ullum, Henrik ORCID: 0000-0001-7306-9058, Vogel, Ilka, Volzke, Henry, von Fersen, Lorenzo ORCID: 0000-0002-3451-0530, von Schonfels, Witigo, Vanderwerff, Brett, Wilking, Julia, Wittig, Michael, Zeissig, Sebastian ORCID: 0000-0001-5124-0897, Zobel, Myrko, Zawistowski, Matthew, Vacic, Vladimir, Sazonova, Olga, Noblin, Elizabeth S., Farrugia, Gianrico, Beyder, Arthur, Wedel, Thilo, Kahlke, Volker, Schafmayer, Clemens, D'Amato, Mauro ORCID: 0000-0003-2743-5197 and Franke, Andre ORCID: 0000-0003-1530-5811 (2021). Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease. Gut, 70 (8). S. 1538 - 1550. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-3288

Full text not available from this repository.

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Zheng, TenghaoUNSPECIFIEDorcid.org/0000-0003-1587-7481UNSPECIFIED
Ellinghaus, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Juzenas, SimonasUNSPECIFIEDorcid.org/0000-0001-9293-0691UNSPECIFIED
Cossais, FrancoisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burmeister, GretaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayr, GabrieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jorgensen, Isabella FriisUNSPECIFIEDorcid.org/0000-0001-5694-4332UNSPECIFIED
Teder-Laving, MarisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Skogholt, Anne HeidiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, SisiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strege, Peter R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ito, GoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Banasik, KarinaUNSPECIFIEDorcid.org/0000-0003-2489-2499UNSPECIFIED
Becker, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bokelmann, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brunak, SorenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buch, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clausnitzer, HartmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Datz, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Degenhardt, FraukeUNSPECIFIEDorcid.org/0000-0001-7516-3179UNSPECIFIED
Doniec, MarekUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erikstrup, ChristianUNSPECIFIEDorcid.org/0000-0001-6551-6647UNSPECIFIED
Esko, TonuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Forster, MichaelUNSPECIFIEDorcid.org/0000-0001-9927-5124UNSPECIFIED
Frey, NorbertUNSPECIFIEDorcid.org/0000-0001-7611-378XUNSPECIFIED
Fritsche, Lars G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gabrielsen, Maiken ElvestadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grassle, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gsur, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gross, JustusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hampe, JochenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hendricks, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hinz, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hveem, KristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jongen, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Junker, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karlsen, Tom HemmingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hemmrich-Stanisak, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kruis, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kupcinskas, JuozasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laubert, TilmanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenstiel, Philip C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roecken, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laudes, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leendertz, Fabian H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lieb, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Limperger, VerenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Margetis, NikolaosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Matz-Rensing, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nemeth, Christopher GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ness-Jensen, EivindUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nowak-Gottl, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pandit, AnitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pedersen, Ole BirgerUNSPECIFIEDorcid.org/0000-0003-2312-5976UNSPECIFIED
Peleikis, Hans GunterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peuker, KennethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodriguez, Cristina LealUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruehlemann, Malte ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schniewind, BodoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulzky, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Skieceviciene, JurgitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tepel, JurgenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, LaurentUNSPECIFIEDorcid.org/0000-0003-0548-2486UNSPECIFIED
Uellendahl-Werth, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ullum, HenrikUNSPECIFIEDorcid.org/0000-0001-7306-9058UNSPECIFIED
Vogel, IlkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Volzke, HenryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Fersen, LorenzoUNSPECIFIEDorcid.org/0000-0002-3451-0530UNSPECIFIED
von Schonfels, WitigoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vanderwerff, BrettUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wilking, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wittig, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zeissig, SebastianUNSPECIFIEDorcid.org/0000-0001-5124-0897UNSPECIFIED
Zobel, MyrkoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zawistowski, MatthewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vacic, VladimirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sazonova, OlgaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noblin, Elizabeth S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Farrugia, GianricoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beyder, ArthurUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wedel, ThiloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kahlke, VolkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schafmayer, ClemensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
D'Amato, MauroUNSPECIFIEDorcid.org/0000-0003-2743-5197UNSPECIFIED
Franke, AndreUNSPECIFIEDorcid.org/0000-0003-1530-5811UNSPECIFIED
URN: urn:nbn:de:hbz:38-607875
DOI: 10.1136/gutjnl-2020-323868
Journal or Publication Title: Gut
Volume: 70
Number: 8
Page Range: S. 1538 - 1550
Date: 2021
Publisher: BMJ PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1468-3288
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BLOOD-GROUP; ACETYLCHOLINESTERASE; HEALTH; CELLSMultiple languages
Gastroenterology & HepatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60787

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