Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
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.
Methods
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.
Results
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.
Conclusions
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 language | English |
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Journal | British Journal of Cancer |
Early online date | 15 Dec 2021 |
DOIs | |
Publication status | E-pub ahead of print - 15 Dec 2021 |