Research Question:
What are the genetic risk factors for developing rectal prolapse?
Objectives:
1. To carry out a GWAS to identify significant loci associated with the clinical phenotype of rectal prolapse
2. To compare these findings with recent GWAS in patients with pelvic organ prolapse (i.e. genitourinary prolapse)
Scientific rationale:
Rectal prolapse is a debilitating condition which impacts a patient’s quality of life. A number of risk factors are established, including advanced age, constipation and high parity. However, a comprehensive understanding of the aetiology remains elusive. Rectal prolapse is rare and we believe the explanation as to why only a small proportion of at risk individuals develop the condition may be due to a genetic predisposition. Furthermore, a small but significant minority of patients develop rectal prolapse without these established risk factors, in whom a genetic predisposition is considered likely.
Joint hypermobility is common in patients with rectal prolapse. Approximately 70% of the risk for joint hypermobility can be attributed to genetic risk. The phenotype of hypermobility is varied however, and is feature in a number of connective tissue diseases, some of which are not defined at a molecular level.
The integrity of the pelvic floor is essential for the maintenance of the normal position of the pelvic organs, including the rectum. The connective tissues of the endopelvic fascia and lateral ligaments of the rectum are key components in maintaining its integrity.
We hypothesize that pathogenic mutations in genes which are vital for synthesising and maintaining healthy connective tissue may be implicated in the risk of developing rectal prolapse. This theory is supported by recent genome wide association studies which have identified a number of significant loci in candidate genes which are implicated in connective tissue architecture in patients with the related condition of pelvic organ prolapse.