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2021-04-22Zeitschriftenartikel
Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease
dc.contributor.authorZheng, Tenghao
dc.contributor.authorEllinghaus, David
dc.contributor.authorJuzenas, Simonas
dc.contributor.authorCossais, François
dc.contributor.authorBurmeister, Greta
dc.contributor.authorMayr, Gabriele
dc.contributor.authorJørgensen, Isabella Friis
dc.contributor.authorTeder-Laving, Maris
dc.contributor.authorSkogholt, Anne Heidi
dc.contributor.authorChen, Sisi
dc.contributor.authorStrege, Peter R.
dc.contributor.authorIto, Go
dc.contributor.authorBanasik, Karina
dc.contributor.authorBecker, Thomas
dc.contributor.authorBokelmann, Frank
dc.contributor.authorBrunak, Søren
dc.contributor.authorBuch, Stephan
dc.contributor.authorClausnitzer, Hartmut
dc.contributor.authorDatz, Christian
dc.contributor.authorDBDS Consortium
dc.contributor.authorDegenhardt, Frauke
dc.contributor.authorDoniec, Marek
dc.contributor.authorErikstrup, Christian
dc.contributor.authorEsko, Tõnu
dc.contributor.authorForster, Michael
dc.contributor.authorFrey, Norbert
dc.contributor.authorFritsche, Lars G.
dc.contributor.authorElvestad Gabrielsen, Maiken
dc.contributor.authorGräßle, Tobias
dc.contributor.authorGsur, Andrea
dc.contributor.authorGross, Justus
dc.contributor.authorHampe, Jochen
dc.contributor.authorHendricks, Alexander
dc.contributor.authorHinz, Sebastian
dc.contributor.authorHveem, Kristian
dc.contributor.authorJongen, Johannes
dc.contributor.authorJunker, Ralf
dc.contributor.authorKarlsen, Tom Hemming
dc.contributor.authorHemmrich-Stanisak, Georg
dc.contributor.authorKruis, Wolfgang
dc.contributor.authorKupcinskas, Jouzas
dc.contributor.authorLaubert, Tilman
dc.contributor.authorRosenstiel, Philip C.
dc.contributor.authorRöcken, Christoph
dc.contributor.authorLaudes, Matthias
dc.contributor.authorLeendertz, Fabian H.
dc.contributor.authorLieb, Wolfgang
dc.contributor.authorLimperger, Verena
dc.contributor.authorMargetis, Nikolaos
dc.contributor.authorMätz-Rensing, Kerstin
dc.contributor.authorNémeth, Christopher Georg
dc.contributor.authorNess-Jensen, Eivind
dc.contributor.authorNowak-Göttl, Ulrike
dc.contributor.authorPandit, Anita
dc.contributor.authorBirger Pedersen, Ole
dc.contributor.authorPeleikis, Hans Günter
dc.contributor.authorPeuker, Kenneth
dc.contributor.authorRodriguez, Cristina Leal
dc.contributor.authorRühlemann, Malte Christoph
dc.contributor.authorSchniewind, Bodo
dc.contributor.authorSchulzky, Martin
dc.contributor.authorSkieceviciene, Jurgita
dc.contributor.authorTepel, Jürgen
dc.contributor.authorThomas, Laurent
dc.contributor.authorUellendahl-Werth, Florian
dc.contributor.authorUllum, Henrik
dc.contributor.authorVogel, Ilka
dc.contributor.authorVolzke, Henry
dc.contributor.authorvon Fersen, Lorenzo
dc.contributor.authorvon Schönfels, Witigo
dc.contributor.authorVanderwerff, Brett
dc.contributor.authorWilking, Julia
dc.contributor.authorWittig, Michael
dc.contributor.authorZeissig, Sebastian
dc.contributor.authorZobel, Myrko
dc.contributor.authorZawistowski, Matthew
dc.contributor.authorVacic, Vladimir
dc.contributor.authorSazonova, Olga
dc.contributor.authorNoblin, Elizabeth S.
dc.contributor.authorThe 23andMe Research Team
dc.contributor.authorFarrugia, Gianrico
dc.contributor.authorBeyder, Arthur
dc.contributor.authorWedel, Thilo
dc.contributor.authorKahlke, Volker
dc.contributor.authorSchafmayer, Clemens
dc.contributor.authorD'Amato, Mauro
dc.contributor.authorFranke, Andre
dc.date.accessioned2024-07-26T13:15:04Z
dc.date.available2024-07-26T13:15:04Z
dc.date.issued2021-04-22none
dc.identifier.other10.1136/gutjnl-2020-323868
dc.identifier.urihttp://edoc.rki.de/176904/11861
dc.description.abstractObjective 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.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY 3.0 DE) Namensnennung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/de/
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleGenome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal diseasenone
dc.typearticle
dc.identifier.urnurn:nbn:de:0257-176904/11861-7
dc.type.versionpublishedVersionnone
local.edoc.container-titleGutnone
local.edoc.container-issn1468-3288none
local.edoc.pages12none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://gut.bmj.com/none
local.edoc.container-publisher-nameBMJ Publishing Groupnone
local.edoc.container-volume70none
local.edoc.container-reportyear2021none
local.edoc.container-firstpage1538none
local.edoc.container-lastpage1549none
dc.description.versionPeer Reviewednone

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