Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease

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Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease. / Zheng, Tenghao; Ellinghaus, David; Juzenas, 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; Becker, Thomas; Bokelmann, Frank; Brunak, Søren; Buch, Stephan; Clausnitzer, Hartmut; Datz, Christian; Degenhardt, Frauke; Doniec, Marek; Erikstrup, Christian; Esko, Tõnu; Forster, Michael; Frey, Norbert; Fritsche, Lars G; Gabrielsen, Maiken Elvestad; Gräßle, 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; Röcken, Christoph; Laudes, Matthias; Leendertz, Fabian H; Lieb, Wolfgang; Limperger, Verena; Pedersen, Ole Birger; Rodriguez, Cristina Leal; Ullum, Henrik; DBDS Consortium.

In: Gut, Vol. 70, No. 8, 2021, p. 1538-1549.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Zheng, T, Ellinghaus, D, Juzenas, S, Cossais, F, Burmeister, G, Mayr, G, Jørgensen, IF, Teder-Laving, M, Skogholt, AH, Chen, S, Strege, PR, Ito, G, Banasik, K, Becker, T, Bokelmann, F, Brunak, S, Buch, S, Clausnitzer, H, Datz, C, Degenhardt, F, Doniec, M, Erikstrup, C, Esko, T, Forster, M, Frey, N, Fritsche, LG, Gabrielsen, ME, Gräßle, T, Gsur, A, Gross, J, Hampe, J, Hendricks, A, Hinz, S, Hveem, K, Jongen, J, Junker, R, Karlsen, TH, Hemmrich-Stanisak, G, Kruis, W, Kupcinskas, J, Laubert, T, Rosenstiel, PC, Röcken, C, Laudes, M, Leendertz, FH, Lieb, W, Limperger, V, Pedersen, OB, Rodriguez, CL, Ullum, H & DBDS Consortium 2021, 'Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease', Gut, vol. 70, no. 8, pp. 1538-1549. https://doi.org/10.1136/gutjnl-2020-323868

APA

Zheng, T., Ellinghaus, D., Juzenas, S., Cossais, F., Burmeister, G., Mayr, G., Jørgensen, I. F., Teder-Laving, M., Skogholt, A. H., Chen, S., Strege, P. R., Ito, G., Banasik, K., Becker, T., Bokelmann, F., Brunak, S., Buch, S., Clausnitzer, H., Datz, C., ... DBDS Consortium (2021). Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease. Gut, 70(8), 1538-1549. https://doi.org/10.1136/gutjnl-2020-323868

Vancouver

Zheng T, Ellinghaus D, Juzenas S, Cossais F, Burmeister G, Mayr G et al. Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease. Gut. 2021;70(8):1538-1549. https://doi.org/10.1136/gutjnl-2020-323868

Author

Zheng, Tenghao ; Ellinghaus, David ; Juzenas, 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 ; Becker, Thomas ; Bokelmann, Frank ; Brunak, Søren ; Buch, Stephan ; Clausnitzer, Hartmut ; Datz, Christian ; Degenhardt, Frauke ; Doniec, Marek ; Erikstrup, Christian ; Esko, Tõnu ; Forster, Michael ; Frey, Norbert ; Fritsche, Lars G ; Gabrielsen, Maiken Elvestad ; Gräßle, 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 ; Röcken, Christoph ; Laudes, Matthias ; Leendertz, Fabian H ; Lieb, Wolfgang ; Limperger, Verena ; Pedersen, Ole Birger ; Rodriguez, Cristina Leal ; Ullum, Henrik ; DBDS Consortium. / Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease. In: Gut. 2021 ; Vol. 70, No. 8. pp. 1538-1549.

Bibtex

@article{36ff4129dd6f439a90818eedd56a910c,
title = "Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease",
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.",
author = "Tenghao Zheng and David Ellinghaus and Simonas Juzenas and Fran{\c c}ois Cossais and Greta Burmeister and Gabriele Mayr and J{\o}rgensen, {Isabella Friis} and Maris Teder-Laving and Skogholt, {Anne Heidi} and Sisi Chen and Strege, {Peter R} and Go Ito and Karina Banasik and Thomas Becker and Frank Bokelmann and S{\o}ren Brunak and Stephan Buch and Hartmut Clausnitzer and Christian Datz and Frauke Degenhardt and Marek Doniec and Christian Erikstrup and T{\~o}nu Esko and Michael Forster and Norbert Frey and Fritsche, {Lars G} and Gabrielsen, {Maiken Elvestad} and Tobias Gr{\"a}{\ss}le and Andrea Gsur and Justus Gross and Jochen Hampe and Alexander Hendricks and Sebastian Hinz and Kristian Hveem and Johannes Jongen and Ralf Junker and Karlsen, {Tom Hemming} and Georg Hemmrich-Stanisak and Wolfgang Kruis and Juozas Kupcinskas and Tilman Laubert and Rosenstiel, {Philip C} and Christoph R{\"o}cken and Matthias Laudes and Leendertz, {Fabian H} and Wolfgang Lieb and Verena Limperger and Pedersen, {Ole Birger} and Rodriguez, {Cristina Leal} and Henrik Ullum and {DBDS Consortium}",
note = "{\textcopyright} Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",
year = "2021",
doi = "10.1136/gutjnl-2020-323868",
language = "English",
volume = "70",
pages = "1538--1549",
journal = "Gut",
issn = "0017-5749",
publisher = "B M J Group",
number = "8",

}

RIS

TY - JOUR

T1 - Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease

AU - Zheng, Tenghao

AU - Ellinghaus, David

AU - Juzenas, Simonas

AU - Cossais, François

AU - Burmeister, Greta

AU - Mayr, Gabriele

AU - Jørgensen, Isabella Friis

AU - Teder-Laving, Maris

AU - Skogholt, Anne Heidi

AU - Chen, Sisi

AU - Strege, Peter R

AU - Ito, Go

AU - Banasik, Karina

AU - Becker, Thomas

AU - Bokelmann, Frank

AU - Brunak, Søren

AU - Buch, Stephan

AU - Clausnitzer, Hartmut

AU - Datz, Christian

AU - Degenhardt, Frauke

AU - Doniec, Marek

AU - Erikstrup, Christian

AU - Esko, Tõnu

AU - Forster, Michael

AU - Frey, Norbert

AU - Fritsche, Lars G

AU - Gabrielsen, Maiken Elvestad

AU - Gräßle, Tobias

AU - Gsur, Andrea

AU - Gross, Justus

AU - Hampe, Jochen

AU - Hendricks, Alexander

AU - Hinz, Sebastian

AU - Hveem, Kristian

AU - Jongen, Johannes

AU - Junker, Ralf

AU - Karlsen, Tom Hemming

AU - Hemmrich-Stanisak, Georg

AU - Kruis, Wolfgang

AU - Kupcinskas, Juozas

AU - Laubert, Tilman

AU - Rosenstiel, Philip C

AU - Röcken, Christoph

AU - Laudes, Matthias

AU - Leendertz, Fabian H

AU - Lieb, Wolfgang

AU - Limperger, Verena

AU - Pedersen, Ole Birger

AU - Rodriguez, Cristina Leal

AU - Ullum, Henrik

AU - DBDS Consortium

N1 - © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1136/gutjnl-2020-323868

DO - 10.1136/gutjnl-2020-323868

M3 - Journal article

C2 - 33888516

VL - 70

SP - 1538

EP - 1549

JO - Gut

JF - Gut

SN - 0017-5749

IS - 8

ER -

ID: 262744847