Novel insights into genetic susceptibility for colorectal cancer from transcriptome-wide association and functional investigation
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F24%3A00580791" target="_blank" >RIV/68378041:_____/24:00580791 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/24:10473900 RIV/00216208:11140/24:10473900
Result on the web
<a href="https://academic.oup.com/jnci/article/116/1/127/7252238?login=true" target="_blank" >https://academic.oup.com/jnci/article/116/1/127/7252238?login=true</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/jnci/djad178" target="_blank" >10.1093/jnci/djad178</a>
Alternative languages
Result language
angličtina
Original language name
Novel insights into genetic susceptibility for colorectal cancer from transcriptome-wide association and functional investigation
Original language description
Background: Transcriptome-wide association studies have been successful in identifying candidate susceptibility genes for colorectal cancer (CRC). To strengthen susceptibility gene discovery, we conducted a large transcriptome-wide association study and an alternative splicing transcriptome-wide association study in CRC using improved genetic prediction models and performed in-depth functional investigations. Methods: We analyzed RNA-sequencing data from normal colon tissues and genotype data from 423 European descendants to build genetic prediction models of gene expression and alternative splicing and evaluated model performance using independent RNA-sequencing data from normal colon tissues of the Genotype-Tissue Expression Project. We applied the verified models to genome-wide association studies (GWAS) summary statistics among 58 131 CRC cases and 67 347 controls of European ancestry to evaluate associations of genetically predicted gene expression and alternative splicing with CRC risk. We performed invitro functional assays for 3 selected genes in multiple CRC cell lines. Results: We identified 57 putative CRC susceptibility genes, which included the 48 genes from transcriptome-wide association studies and 15 genes from splicing transcriptome-wide association studies, at a Bonferroni-corrected P value less than .05. Of these, 16 genes were not previously implicated in CRC susceptibility, including a gene PDE7B (6q23.3) at locus previously not reported by CRC GWAS. Gene knockdown experiments confirmed the oncogenic roles for 2 unreported genes, TRPS1 and METRNL, and a recently reported gene, C14orf166. Conclusion: This study discovered new putative susceptibility genes of CRC and provided novel insights into the biological mechanisms underlying CRC development.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30204 - Oncology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
JNCI-Journal of the National Cancer Institute
ISSN
0027-8874
e-ISSN
1460-2105
Volume of the periodical
116
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
127-137
UT code for WoS article
001072729300001
EID of the result in the Scopus database
2-s2.0-85182091185