Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms

Journal article

Publication Details

Author(s): Schafmayer C, Harrison JW, Buch S, Lange C, Reichert MC, Hofer P, Cossais F, Kupcinskas J, von Schönfels W, Schniewind B, Kruis W, Tepel J, Zobel M, Rosendahl J, Jacobi T, Walther-Berends A, Schroeder M, Vogel I, Sergeev P, Boedeker H, Hinrichsen H, Volk A, Erk JU, Burmeister G, Hendricks A, Hinz S, Wolff S, Böttner M, Wood AR, Tyrrell J, Beaumont RN, Langheinrich M, Kucharzik T, Brezina S, Huber-Schönauer U, Pietsch L, Noack LS, Brosch M, Herrmann A, Thangapandi RV, Schimming HW, Zeissig S, Palm S, Focke G, Andreasson A, Schmidt PT, Weitz J, Krawczak M, Völzke H, Leeb G, Michl P, Lieb W, Grützmann R, Franke A, Lammert F, Becker T, Kupcinskas L, D'Amato M, Wedel T, Datz C, Gsur A, Weedon MN, Hampe J
Journal: Gut
Publication year: 2019
Volume: 68
Journal issue: 5
Pages range: 854-865
ISSN: 0017-5749
eISSN: 1468-3288


OBJECTIVE: Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. DESIGN: Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. RESULTS: We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p<0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3×10-10 and 0.002 (ORallelic=1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). CONCLUSION: In silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.

FAU Authors / FAU Editors

Grützmann, Robert Prof. Dr.
Chirurgische Klinik

External institutions with authors

Christian-Albrechts-Universität zu Kiel
Evangelisches Krankenhaus Kalk
HELIOS Kliniken
Karolinska Institute
Klinikum Osnabrück
KRAGES Burgenländische Krankenanstalten-Ges.m.b.H.
Krankenhaus Dresden-Friedrichstadt, Städtisches Klinikum
Kreiskrankenhaus Freiberg gGmbH
Lithuanian University of Health Sciences / Lietuvos sveikatos mokslų universitetas (LSMU)
Medizinische Universität Wien
Paracelsus Medizinische Privatuniversität
Städtisches Klinikum Lüneburg
Städtisches Krankenhaus Kiel
Technische Universität Dresden
Universitätsklinikum Carl Gustav Carus Dresden
Universitätsklinikum des Saarlandes
Universitätsklinikum Halle (Saale)
Universitätsmedizin Greifswald / Universitätsklinikum Greifswald
University of Exeter

How to cite

Schafmayer, C., Harrison, J.W., Buch, S., Lange, C., Reichert, M.C., Hofer, P.,... Hampe, J. (2019). Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms. Gut, 68(5), 854-865.

Schafmayer, Clemens, et al. "Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms." Gut 68.5 (2019): 854-865.


Last updated on 2019-27-05 at 13:48