Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F24%3A00582779" target="_blank" >RIV/68378041:_____/24:00582779 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/24:10476157 RIV/00216208:11120/24:43926624 RIV/00216208:11140/24:10476157 RIV/61989592:15110/24:73628355 RIV/00064173:_____/24:43926624
Result on the web
<a href="https://humgenomics.biomedcentral.com/articles/10.1186/s40246-024-00576-x" target="_blank" >https://humgenomics.biomedcentral.com/articles/10.1186/s40246-024-00576-x</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1186/s40246-024-00576-x" target="_blank" >10.1186/s40246-024-00576-x</a>
Alternative languages
Result language
angličtina
Original language name
Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk
Original language description
Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 x 10-8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 x 10-7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 x 10-6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 x 10-5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
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
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Human Genomics
ISSN
1473-9542
e-ISSN
1479-7364
Volume of the periodical
18
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
12
UT code for WoS article
001157071900001
EID of the result in the Scopus database
2-s2.0-85183753590