Approved research

Identification of Genetic Risk Factors for Colonic Diverticular Disease

Lay summary

Diverticular disease (DD) refers to the presence of outpouchings of the colonic wall. DD becomes a health risk due to its potentially life-threatening complications: diverticulitis, bleeding, perforation and abscess. DD is the most common gastrointestinal condition in Western countries and accounts for ~100,000 hospitalizations annually in the UK, which likely will increase with an ageing population. The project will use UK Biobank GWAS data resource for the discovery of disease genes for DD. Given the firmly established heritable component of DD and the lack of previous GWAS for the phenotype, chances for robust gene discoveries are very high. The UK Biobank GWAS data provide a unique opportunity to efficiently perform the first large-scale GWAS analysis in DD. It offers a unique chance for a better understanding of its etiology and pathophysiology and will lay a basis for future gene × environment interaction studies. A better pathogenesis understanding will help to develop new prevention strategies and treatment options for DD. It could offer the potential for targeted preventive and therapeutic interventions for groups with high genetic risk likely to develop severe disease complications. Genetic risk factors could be used to help determine optimal timing for surgery before complications ensue. The project will use the GWAS resource with approximately 22,500 registered diagnoses of DD for the discovery of DD risk genes. We will evaluate genetic risk factors for the presence of diverticula and for diverticulitis, a severe complication. The PI leads a German/Austrian consortium that has recruited over 2000 patients with a focus on high risk DD patients and is funded by the German and Austrian research councils. A key asset of the proposed project is the large replication cohort (1,000 diverticulosis patients/1,000 diverticulitis patients/2,000 controls), allowing for the confirmation of gene discoveries. Association analyses will be performed in the full cohort, for maximizing statistical power, and furthermore, in a subset of participants that all received diagnostic colonoscopy (count 44983) to ensure for a diverticula-free control cohort.