Phenome-wide association study (PheWAS) of colorectal cancer risk SNP effects on health outcomes in UK Biobank

Xiaomeng Zhang, Xue Li, Yazhou He, Phillip Law, Susan M Farrington, Harry Campbell, Ian P.M. Tomlinson, Richard S Houlston, Malcolm G Dunlop, Maria Timofeeva*, Evropi Theodoratou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Associations between colorectal cancer (CRC) and other health outcomes have been reported, but these may be subject to biases, or due to limitations of observational studies.

We set out to determine whether geneticpredisposition to CRC is also associated with the risk of other phenotypes. Under the phenome-wide association study (PheWAS) and treestructured phenotypic model (TreeWAS), we studied 334,385 unrelated White British individuals (excluding CRC patients) from the UK Biobank cohort. We generated a polygenic risk score (PRS) from CRC genome-wide association studies as a measure of CRC risk. We performed sensitivity analyses to test the robustness of the results and searched the Danish Disease Trajectory Browser (DTB) to replicate the observed associations.

Eight PheWAS phenotypes and 21 TreeWAS nodes were associated with CRC genetic predisposition by PheWAS and TreeWAS respectively. The PheWAS detected associations were from neoplasms and digestive system disease group (e.g., benign neoplasm of colon, anal and rectal polyp, and diverticular disease). The results from the TreeWAS corroborated the results from the PheWAS. These results were replicated in the observational data within the DTB.

We show that benign colorectal neoplasms share genetic aetiology with CRC using PheWAS and TreeWAS methods. Additionally, CRC genetic predisposition is associated with diverticular disease.
Original languageEnglish
JournalBritish Journal of Cancer
Early online date15 Dec 2021
Publication statusE-pub ahead of print - 15 Dec 2021


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