Transcriptome-wide Mendelian randomization exploring dynamic CD4+ T cell gene expression in colorectal cancer development
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F25%3A00639029" target="_blank" >RIV/68378041:_____/25:00639029 - isvavai.cz</a>
Result on the web
<a href="https://academic.oup.com/jleukbio/advance-article/doi/10.1093/jleuko/qiaf131/8257067?searchresult=1" target="_blank" >https://academic.oup.com/jleukbio/advance-article/doi/10.1093/jleuko/qiaf131/8257067?searchresult=1</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/jleuko/qiaf131" target="_blank" >10.1093/jleuko/qiaf131</a>
Alternative languages
Result language
angličtina
Original language name
Transcriptome-wide Mendelian randomization exploring dynamic CD4+ T cell gene expression in colorectal cancer development
Original language description
Recent research suggests higher circulating lymphocyte counts may protect against colorectal cancer (CRC). However, the role of specific lymphocyte subtypes and activation states remain unclear. CD4+ T cells – a highly dynamic lymphocyte subtype – undergo gene expression changes upon activation that are critical to their effector function. Previous studies using bulk tissue have limited our understanding of their role in CRC risk to static associations. We applied Mendelian randomization (MR) and genetic colocalisation to evaluate causal relationships of gene expression on CRC risk across multiple CD4+ T cell subtypes and activation states. Genetic proxies were obtained from single-cell transcriptomic data, allowing us to investigate the causal effect of expression of 1,805 genes across CD4+ T cell activation states on CRC risk (78,473 cases, 107,143 controls). Analyses were stratified by CRC anatomical subsites and sex, with sensitivity analyses assessing whether the observed effect estimates were likely to be CD4+ T cell-specific. We identified six genes – FADS2, FHL3, HLA-DRB1, HLA-DRB5, RPL28, and TMEM258 – with strong evidence for a causal role in CRC development (FDR-P<0.05, colocalisation H4>0.8). Causal estimates varied by CD4+ T cell subtype, activation state, CRC subsite and sex. However, many of genetic proxies used to instrument gene expression in CD4+ T cells also act as eQTLs in other tissues, highlighting the challenges of using genetic proxies to instrument tissue-specific expression changes. We demonstrate the importance of capturing the dynamic nature of CD4+ T cells in understanding CRC risk, and prioritize genes for further investigation in cancer prevention.
Czech name
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Czech description
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Classification
Type
J<sub>ost</sub> - Miscellaneous article in a specialist periodical
CEP classification
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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
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Leukocyte Biology
ISSN
0741-5400
e-ISSN
1938-3673
Volume of the periodical
117
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
37
Pages from-to
giaf131
UT code for WoS article
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EID of the result in the Scopus database
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