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Mendelian Randomization and Colocalization Analysis Reveal New Drug Targets for Oral Ulcer: A Mendelian Randomization
Xiaoyu Zhang1, Hui Fan1, Xiaoguang Zhang1
1Department of Respiratory and Critical Care Medicine Renmin Hospital of Wuhan University Wuhan Hubei China.
Background And Aims:
Oral ulcer (OU) is a complex issue with limited effective treatments. This study uses multi-omics data through summary Mendelian randomization (SMR) and colocalization analysis to identify specific gene associations with OU, aiming to find new therapeutic targets, repurpose existing drugs, and develop new treatment options.
Methods:
Our study consists of two phases: first, extracting data from Genome-Wide Association Studies and using blood mQTL, eQTL, and pQTL data as exposure factors, then integrating these with OU gene data through SMR analysis. Then, we validate the results with UK Biobank data and perform colocalization analysis to confirm shared genetic variants.
Results:
Genetically predicted levels of four circulating proteins are associated with OU. Under strong supportive evidence from mQTL, eQTL, and pQTL, genetically predicted levels of NFKB1 are negatively correlated with the risk of OU. With moderate supportive evidence from mQTL and pQTL, genetically predicted levels of FAIM3 are negatively correlated with the risk of OU. Meanwhile, under low supportive evidence from eQTL and pQTL, higher genetically predicted levels of JUND and lower levels of IL12β are associated with a higher risk of OU.
Conclusion:
SMR approach employed in this study has pinpointed several proteins with tangible associations to the risk of OU. NFKB1, FAIM3, JUND, and IL12β stand out as promising therapeutic targets for OU, beckoning further exploration and research.
Insights
This study identifies four proteins, including NFKB1 and FAIM3, linked to oral ulcer (OU) risk. These findings offer potential new therapeutic targets for developing effective oral ulcer treatments.
Area of Science:
- Genetics
- Molecular Biology
- Immunology
Background:
- Oral ulcer (OU) presents a significant clinical challenge with limited therapeutic options.
- Identifying genetic associations can reveal novel pathways and drug targets for OU.
Purpose of the Study:
- To identify specific gene associations with oral ulcer (OU) using multi-omics data.
- To discover potential therapeutic targets and inform drug repurposing for OU treatment.
Main Methods:
- Employed summary Mendelian randomization (SMR) and colocalization analysis on multi-omics data.
- Utilized Genome-Wide Association Studies (GWAS) data, including blood molecular, expression, and protein quantitative trait loci (mQTL, eQTL, pQTL).
- Validated findings using UK Biobank data.
Main Results:
- Four circulating proteins showed significant genetic associations with OU risk.
- NFKB1 and FAIM3 levels were negatively correlated with OU risk.
- JUND and IL12β levels were positively correlated with OU risk.
Conclusions:
- The study identified NFKB1, FAIM3, JUND, and IL12β as promising protein targets for OU.
- These findings warrant further investigation for developing new OU therapies.
