ArticleGut2021
Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease.
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In one paragraph
Article in Gut, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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24citing papers in PubMed, 1 pooled it
7.5field-weighted citation impact, top 2% of its field
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Pooled it
- Vaginal microbiomes and their pertinent social context: a microbial ecological review proffering AMR-STI acquisition and emergence.Biology of sex differences · 2026Review
- Causal associations between lifestyle factors and hemorrhoidal disease: Insights from Mendelian randomization analysis.Medicine · 2026Article
- The HUNT study identifies host genetic factors reproducibly associated with human gut microbiota composition.Nature genetics · 2026Article
- How Can Molecules Induce Hemorrhoids? The Role of Genetics and Epigenetics in Hemorrhoidal Disease.International journal of molecular sciences · 2025Review
- Role of glycolysis related genes in the pathogenesis of hemorrhoids and immune cell infiltration analysis.Scientific reports · 2025Article
- Medical Hemorrhoid Gel Ameliorates Croton Oil-Induced Hemorrhoids by Suppressing the NLRP3 Inflammasome Activation via NF-κB Signaling Pathway.Journal of inflammation research · 2025Article
- Inflammatory bowel disease and risk for hemorrhoids: a Mendelian randomization analysis.Scientific reports · 2024Article
- Article
- Hemorrhoidal disease and its genetic association with depression, bipolar disorder, anxiety disorders, and schizophrenia: a bidirectional mendelian randomization study.Human genomics · 2024Article
- Impact of insomnia upon inflammatory digestive diseases and biomarkers: a two-sample mendelian randomization research on Europeans.BMC gastroenterology · 2024Article
- Shared genetic architecture of psychiatric disorders and hemorrhoidal disease: a large-scale genome-wide cross-trait analysis.Frontiers in psychiatry · 2024Article
- Bowel Habits, Obesity, Intestinal Microbiota and Their Influence on Hemorrhoidal Disease: a Mendelian Randomization Study.Clinical and experimental gastroenterology · 2024Article
- Integrated genomic network analysis revealed potential of a druggable target for hemorrhoid treatment.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- Evaluation of Clinical Manifestations of Hemorrhoidal Disease, Carried Out Surgeries and Prolapsed Anorectal Tissues: Associations with ABO Blood Groups of Patients.Journal of clinical medicine · 2023Article
- 150 risk variants for diverticular disease of intestine prioritize cell types and enable polygenic prediction of disease susceptibility.Cell genomics · 2023Article
- Identification of the microRNA alterations in extracellular vesicles derived from human haemorrhoids.Experimental physiology · 2023Article
- CODA: a combo-Seq data analysis workflow.Briefings in bioinformatics · 2023Article
- InferringGenes · 2022Article
- Challenges and future directions for studying effects of host genetics on the gut microbiome.Nature genetics · 2022Review
Corrections and comments
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Authors and funding
87 authors at 20 institutions in 12 countries.
Tenghao Zheng *School of Biological Sciences, Monash University, Clayton, Victoria, Australia.ORCID http://orcid.org/0000-0003-1587-7481
David Ellinghaus *Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.ORCID http://orcid.org/0000-0002-4332-6110
Simonas Juzenas *Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.ORCID http://orcid.org/0000-0001-9293-0691
François CossaisInstitute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany.
Greta BurmeisterDepartment for General, Visceral, Vascular and Transplantation Surgery, University Medical Center Rostock, Rostock, Germany.
Gabriele MayrInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Isabella Friis JørgensenNovo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Maris Teder-LavingInstitute of Genomics, University of Tartu, Tartu, Estonia.
Anne Heidi SkogholtK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Sisi ChenEnteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Peter R StregeEnteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Go ItoInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Karina BanasikNovo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Thomas BeckerDepartment of General-, Visceral- Transplant-, Thoracic and Pediatric Surgery, Kiel University, Kiel, Germany.
Frank BokelmannMedical Office for Surgery Preetz, Preetz, Germany.
Søren BrunakNovo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Stephan BuchMedical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.
Hartmut ClausnitzerUniversity Hospital Schleswig-Holstein, Institute of Clinical Chemistry, Thrombosis & Hemostasis Treatment Center, Campus Kiel & Lübeck, Kiel, Germany.
Christian DatzDepartment of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Private Medical University of Salzburg, Oberndorf, Austria.ORCID http://orcid.org/0000-0001-7838-4532
DBDS Consortium
Frauke DegenhardtInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Marek DoniecMedical office for Colo-Proctology Kiel, Kiel, Germany.
Christian ErikstrupDepartment of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.
Tõnu EskoInstitute of Genomics, University of Tartu, Tartu, Estonia.
Michael ForsterInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.ORCID http://orcid.org/0000-0001-9927-5124
Norbert FreyDepartment of Internal Medicine III, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Lars G FritscheDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Maiken Elvestad GabrielsenK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Tobias GräßleEpidemiology of highly pathogenic microorganisms, Robert Koch-Institute, Berlin, Germany.
Andrea GsurDepartment of Medicine I, Institute of Cancer Research, Medical University Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0002-9795-1528
Justus GrossDepartment for General, Visceral, Vascular and Transplantation Surgery, University Medical Center Rostock, Rostock, Germany.
Jochen HampeMedical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.ORCID http://orcid.org/0000-0002-2421-6127
Alexander HendricksDepartment for General, Visceral, Vascular and Transplantation Surgery, University Medical Center Rostock, Rostock, Germany.
Sebastian HinzDepartment for General, Visceral, Vascular and Transplantation Surgery, University Medical Center Rostock, Rostock, Germany.
Kristian HveemK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Johannes JongenDepartment of Proctological Surgery Park Klinik Kiel, Kiel, Germany.
Ralf JunkerUniversity Hospital Schleswig-Holstein, Institute of Clinical Chemistry, Thrombosis & Hemostasis Treatment Center, Campus Kiel & Lübeck, Kiel, Germany.
Tom Hemming KarlsenResearch Institute for Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway.
Georg Hemmrich-StanisakInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Wolfgang KruisFaculty of Medicine, University of Cologne, Cologne, Germany.
Juozas KupcinskasDepartment of Gastroenterology, Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Tilman LaubertDepartment of Proctological Surgery Park Klinik Kiel, Kiel, Germany.
Philip C RosenstielInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Christoph RöckenDepartment of Pathology, University Medical Center Schleswig-Holstein, Kiel, Germany.ORCID http://orcid.org/0000-0002-6989-8002
Matthias LaudesDivision of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, University of Kiel, Kiel, Germany.
Fabian H LeendertzEpidemiology of highly pathogenic microorganisms, Robert Koch-Institute, Berlin, Germany.
Wolfgang LiebInstitute of Epidemiology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Verena LimpergerUniversity Hospital Schleswig-Holstein, Institute of Clinical Chemistry, Thrombosis & Hemostasis Treatment Center, Campus Kiel & Lübeck, Kiel, Germany.
Nikolaos MargetisUniversity of Athens, Athens Euroclinic, Athens, Greece.
Kerstin Mätz-RensingPathology Unit, German Primate Center, Leibniz Institute for Primatology, Göttingen, Germany.
Christopher Georg NémethDepartment of General-, Visceral- Transplant-, Thoracic and Pediatric Surgery, Kiel University, Kiel, Germany.
Eivind Ness-JensenK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.ORCID http://orcid.org/0000-0001-6005-0729
Ulrike Nowak-GöttlUniversity Hospital Schleswig-Holstein, Institute of Clinical Chemistry, Thrombosis & Hemostasis Treatment Center, Campus Kiel & Lübeck, Kiel, Germany.
Anita PanditDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Ole Birger PedersenDepartment of Clinical Immunology, Naestved Hospital, Naestved, Denmark.
Hans Günter PeleikisDepartment of Proctological Surgery Park Klinik Kiel, Kiel, Germany.
Kenneth PeukerMedical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.
Cristina Leal RodriguezNovo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Malte Christoph RühlemannInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.ORCID http://orcid.org/0000-0002-0685-0052
Bodo SchniewindGeneral Hospital Lüneburg, Lüneburg, Germany.
Martin SchulzkyInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Jurgita SkiecevicieneDepartment of Gastroenterology, Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Jürgen TepelDepartment of General and Thoracic Surgery, Hospital Osnabrück, Osnabrück, Germany.
Laurent ThomasK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Florian Uellendahl-WerthInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Henrik UllumDepartment of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark.
Ilka VogelDepartment of Surgery, Community Hospital Kiel, Kiel, Germany.
Henry VolzkeInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Lorenzo von FersenDepartment Research & Conservation, Zoo Nuremberg, Nuremberg, Germany.
Witigo von SchönfelsDepartment of General-, Visceral- Transplant-, Thoracic and Pediatric Surgery, Kiel University, Kiel, Germany.
Brett VanderwerffDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Julia WilkingDepartment for General, Visceral, Vascular and Transplantation Surgery, University Medical Center Rostock, Rostock, Germany.
Michael WittigInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Sebastian ZeissigMedical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.
Myrko ZobelDepartment of Gastroenterology, Helios Hospital Weißeritztal, Freital, Germany.
Matthew ZawistowskiDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Vladimir Vacic23andMe Inc, Sunnyvale, CA, USA.
Olga Sazonova23andMe Inc, Sunnyvale, CA, USA.
Elizabeth S Noblin23andMe Inc, Sunnyvale, CA, USA.
23andMe Research Team
Gianrico FarrugiaEnteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-3473-5235
Arthur BeyderEnteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Thilo WedelInstitute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany.
Volker KahlkeDepartment of Proctological Surgery Park Klinik Kiel, Kiel, Germany.
Clemens Schafmayer *Department for General, Visceral, Vascular and Transplantation Surgery, University Medical Center Rostock, Rostock, Germany.
Mauro D'Amato *School of Biological Sciences, Monash University, Clayton, Victoria, Australia mdamato@cicbiogune.es a.franke@mucosa.de.ORCID http://orcid.org/0000-0003-2743-5197
Andre Franke *Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany mdamato@cicbiogune.es a.franke@mucosa.de.ORCID http://orcid.org/0000-0003-1530-5811
Christian-Albrechts-Universität zu Kiel · DEUniversity of Rostock · DEClinical Research Center Kiel · DENorwegian University of Science and Technology · NOUniversity Hospital Schleswig-Holstein · DEUniversity of Copenhagen · DKMayo Clinic in Arizona · USTechnische Universität Dresden · DEUniversity of Michigan · US23andMe (United States) · USLithuanian University of Health Sciences · LTRobert Koch Institute · DEUniversity of Tartu · EEAarhus University Hospital · DKCopenhagen University Hospital · DKGerman Primate Center · DEGoethe University Frankfurt · DEHeidelberg University · DEHelios Hospital Schwerin · DEIkerbasque · ES
Funding
CALCIUM DYNAMICS IN INTERSTITIAL CELLS OF CAJALR01DK057061 · NIDDK · MAYO CLINIC ROCHESTER · PI GIANRICO FARRUGIA, Tamas Ordog · 2000 to 2026
$8.2MAustrian Science Fund FWF I 1542NIDDK NIH HHS R01 DK057061
Abstract
objectiveHaemorrhoidal 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.
designWe 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.
resultsWe 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.
conclusionHEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.
Indexed as
anal canal histopathologyanorectal disordersgenetics
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