Identifying Potential Drug Targets for the Treatment of Ulcerative Colitis Using Mendelian Randomization Combined with Co-localization Analysis DOI Creative Commons
Tianyu Zhang

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 28, 2024

Abstract Purpose To identify potential therapeutic targets for ulcerative colitis by integrating Mendelian randomization (MR) and Bayesian colocalization analysis to pinpoint gene expression quantitative trait loci (eQTLs) associated with risk. Methods Leveraging peripheral blood eQTL data from the eQTLGen Consortium genome-wide association study (GWAS) summary statistics, we performed MR eQTLs significantly risk in discovery replication datasets. The identified were then subjected evaluate whether same single nucleotide polymorphisms (SNPs) influence both disease Finally, Drug Gene Interaction database (DGIdb) was queried known drugs targeting genes. Results 15 potentially positive eQTLs, of which 7 (CD300C, GPX1, LAMC3, RORC, SIGLEC6, SLC22A5, WFIKKN1) replicated be (Correction P -value < 0.005). Colocalization provided strong evidence that SNPs driving these also impact susceptibility. While LAMC3 have approved other indications, CD300C, WFIKKN1 represent novel drug targets. Conclusions By colocalization, this pinpointed colitis-associated genes genome, including 3 existing 4 new WFIKKN1), providing important leads development colitis.

Language: Английский

Sarcopenia and immune-mediated inflammatory diseases: Evaluating causality and exploring therapeutic targets for sarcopenia through Mendelian randomization DOI Creative Commons

Qijun Wang,

Xuan Zhao,

Shuai-Kang Wang

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 144, P. 113687 - 113687

Published: Nov. 26, 2024

Language: Английский

Citations

1
Identifying Potential Drug Targets for Varicose Veins through Integration of GWAS and eQTL Summary Data DOI Creative Commons
Yu Cui, Mengting Hu, He Zhou

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 29, 2024

Abstract Background Varicose veins (VV) is a common chronic venous disease that influenced by multiple factors. It affects the quality of life patients and imposes huge economic burden on healthcare system. This study aimed to use integrated analysis methods, including Mendelian randomization analysis, identify potential pathogenic genes drug targets for VV treatment. Methods conducted summary-data-based (SMR) colocalization data collected from genome-wide association studies (GWASs) cis-expression quantitative trait loci (cis-eQTL) databases. Only with PP. H4 > 0.7 were chosen significant SMR results. After above we screened 12 performed Randomization them. sensitivity identified four causal relationships VV. Finally, used transcriptome-wide (TWAS) The Drug-Gene Interaction Database (DGIdb, https://dgidb.org )data screen remaining treatment Results We significantly associated VV, namely KRTAP5-AS1 (OR = 1.08, 95% CI: 1.05−1.11, p 1.42e−10) PLEKHA5 1.13, 1.06-1.20, 6.90e−5), CBWD1 1.05, 1.01-1.11, 1.42e−2) CRIM1 0.87, 0.81-0.95, 3.67e−3). Increased expression three genes, , was increased risk disease, decreased disease. These could be targeted therapy. Conclusion results may contribute improving patients.

Language: Английский

Citations

0
Insight into telomere regulation: road to discovery and intervention in plasma drug-protein targets DOI Creative Commons
Kaixi Ding,

Juejue Zhangwang,

Ming Lei

et al.

BMC Genomics, Journal Year: 2024, Volume and Issue: 25(1)

Published: March 2, 2024

Background Telomere length is a critical metric linked to aging, health, and disease. Currently, the exploration of target proteins related telomere usually limited context aging specific diseases, which limits discovery more relevant drug targets. This study integrated large-scale plasma cis-pQTLs data GWAS datasets. We used Mendelian randomization(MR) identify for length, providing essential clues future precision therapy targeted development. Methods Using from previous (3,606 Pqtls associated with 2,656 proteins) dataset (sample size: 472,174; ID: ieu-b-4879) UK Biobank, using MR, external validation, reverse causality testing, we identified length. also performed co-localization, Phenome-wide association studies enrichment analysis, protein-protein interaction network construction, search existing intervening drugs, potential drug/compound prediction these targets strengthen expand our findings. Results After Bonferron correction ( p < 0.05/734), RPN1 (OR: 0.96; 95%CI: (0.95, 0.97)), GDI2 0.94; (0.92, 0.96)), NT5C 0.97; 0.98)) had significant negative causal length; TYRO3 1.11; (1.09, 1.15)) positive shared same genetic variants (coloc.abf-PPH 4 > 0.8). Conclusion Genetically determined RPN1, GDI2, NT5C, have effects on can potentially be Further role mechanism proteins/genes in regulating needed.

Language: Английский

Citations

0
Identifying therapeutic targets for rheumatoid arthritis by genomics-driven integrative approaches DOI Creative Commons
Jie Zhang, Xinyu Fang, Jingwei Wu

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 20, 2024

Summary Genomics-driven drug discovery framework holds promise in developing novel therapeutic targets. Here, we leveraged large-scale genomic data including genome-wide association studies (GWAS), rare variant burden tests exome sequencing (Exome), and protein quantitative trait loci (pQTL), to prioritize potential targets identify opportunities for repositioning rheumatoid arthritis (RA). We found that prioritized genes covering two approved RA treatment (IL6R CD86), five tested clinical trials RA. Eighteen proteins were identified as having causalities with risk, three out of them showed strong support colocalization. Bromodomain-containing 2 (BRD2) was nominated one the most promising candidates translation its wide expression joint synovial tissues validation observational analyses associating incidence. Collectively, our systematic screening candidate from different genetically informed approaches, provided a comprehensive insight into strategies

Language: Английский

Citations

0
Identifying Potential Drug Targets for the Treatment of Ulcerative Colitis Using Mendelian Randomization Combined with Co-localization Analysis DOI Creative Commons
Tianyu Zhang

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 28, 2024

Abstract Purpose To identify potential therapeutic targets for ulcerative colitis by integrating Mendelian randomization (MR) and Bayesian colocalization analysis to pinpoint gene expression quantitative trait loci (eQTLs) associated with risk. Methods Leveraging peripheral blood eQTL data from the eQTLGen Consortium genome-wide association study (GWAS) summary statistics, we performed MR eQTLs significantly risk in discovery replication datasets. The identified were then subjected evaluate whether same single nucleotide polymorphisms (SNPs) influence both disease Finally, Drug Gene Interaction database (DGIdb) was queried known drugs targeting genes. Results 15 potentially positive eQTLs, of which 7 (CD300C, GPX1, LAMC3, RORC, SIGLEC6, SLC22A5, WFIKKN1) replicated be (Correction P -value < 0.005). Colocalization provided strong evidence that SNPs driving these also impact susceptibility. While LAMC3 have approved other indications, CD300C, WFIKKN1 represent novel drug targets. Conclusions By colocalization, this pinpointed colitis-associated genes genome, including 3 existing 4 new WFIKKN1), providing important leads development colitis.

Language: Английский

Citations

0