Discovery of risk factors for haemorrhoids

• Applicants: Professor Dr. Andre Franke; Professor Dr. Clemens Schafmayer
• Subject Area: General and Visceral Surgery
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 410561950

Haemorrhoids are normal anal vascular cushions of tissue filled with blood vessels at the junction of the rectum and the anus. Haemorrhoids become a disease when pathological changes occur in the anal cushions causing the development of symptomatic haemorrhoids. Different grades of the disease can be specified based on the extent of a possible prolapse and reduction of the haemorrhoids. Grade I haemorrhoids do not prolapse, grade II haemorrhoids prolapse but reduce spontaneously, grade III haemorrhoids only reduce by manual replacement and grade IV haemorrhoids are irreducible. Haemorrhoids most often develop between 45 and 65 years of age. Men and women are equally often affected. In 2002, 3.1 million medications for haemorrhoids were prescribed in Germany alone. Haemorrhoids represent one of the most common disorders among populations of Western countries. The actual prevalence of symptomatic haemorrhoids in general population remains unknown. Studies have reported a prevalence rate ranging from 4.4% to 86%. the exact pathophysiology of haemorrhoids remains unknown and apart from pregnancy, the reported risk factors are inconsistently reported and based on small sample sizes. No genome-wide significant and robust genetic associations have been described so far. Therefore, this common disease is grossly understudied.We have gained exclusive access to summary statistics data of a case-control analysis for haemorrhoids. The data set comprises 174,785 patients with self-reported haemorrhoids (Grades I-IV) and 228,060 matched controls that reported not to have haemorrhoids. The preliminary analysis of the data yielded multiple genome-wide significant findings that implicate a genetic component in the disease etiology and therefore, further validation studies should be carried out with cohorts for which better clinical data exists. In this application, we apply for funding to carry out a genome-wide association study (GWAS) in a clinically well-characterized German cohort of more than 2,000 patients with Grade III-IV hemorrhoids. The results of this GWAS together with the results of additional data sets for the same disease will likely yield the first disease genes and the causative disturbed pathways in disease etiology. We will further study whether the genetic risk maps of connective tissue weaknesses in general, such as diverticulitis and chronic venous disease, are similar to the map we derived for hemorrhoids.

• DFG Programme: Research Grants