Phenome-wide association study (PheWAS) of colorectal cancer risk SNP effects on health outcomes in UK Biobank.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
22
04
2021
accepted:
23
11
2021
revised:
12
11
2021
pubmed:
17
12
2021
medline:
11
3
2022
entrez:
16
12
2021
Statut:
ppublish
Résumé
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 genetic predisposition to CRC is also associated with the risk of other phenotypes. Under the phenome-wide association study (PheWAS) and tree-structured 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.
Sections du résumé
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 genetic predisposition to CRC is also associated with the risk of other phenotypes. Under the phenome-wide association study (PheWAS) and tree-structured 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.
Identifiants
pubmed: 34912076
doi: 10.1038/s41416-021-01655-9
pii: 10.1038/s41416-021-01655-9
pmc: PMC8888597
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
822-830Subventions
Organisme : Cancer Research UK
ID : 12076
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Cancer Research UK (CRUK)
ID : C348/A18927
Organisme : Cancer Research UK (CRUK)
ID : C1298/A25514
Organisme : Cancer Research UK (CRUK)
ID : C31250/A22804
Organisme : Medical Research Council
ID : MC_UU_00007/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_U127527198
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U127527198
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K018647/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 22804
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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