Integrative multi-omic analyses identify candidate targets for celiac disease involving tissue-specific regulation DOI Creative Commons
Jiazheng Sun, Yulan Zeng

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Abstract Introduction: Celiac disease (CeD) is an autoimmune condition characterized by a reversible inflammatory reaction in the mucous membrane of small intestine. Nevertheless, there limited availability efficient control approaches. Prior research has demonstrated that pharmacological targets supported genetic evidence can greatly enhance efficacy drug development. Hence, study aims to integrate transcriptomic and proteomic information identify candidate for CeD. Methods The employed proteome-wide Mendelian randomization (MR) analysis circulating plasma proteins investigate their causal association with CeD were further assessed employing colocalization analysis, transcriptome-wide summary-data-based (SMR) multimarker genomic annotation (MAGMA) gene-based bulk RNAseq-based differential expression analysis. For identified, extended Phenome-wide studies (PheWAS) conducted assess side-effect profiles, while DGIdb database provided on approved or investigated drugs targets. Results Systematic MR identified 22 Among analyzed, BTN2A1 passed all subsequent verification analyses. Additionally, three proteins, including CatH, IL-18R1, PTPRC, majority other 18 also (Trehalase, CD226, SH2B3, ICOSLG, ULK3, Park7, ALDH2, RABEP1, TNFRSF9, COL11A2, GNPDA1, IL-1RL1, B3galt6, TNFSF11, CCL21, BTN3A3, OLFM2 Colipase). Conclusions combination human information, several analytical methods. As result, divided into four tiers, as prospective therapeutic

Язык: Английский

Cathepsin in Alzheimer's Disease, Parkinson's Disease and Dementia with Lewy Bodies: Mendelian Randomization Study DOI Creative Commons
Wenjuan Song,

Junqin Zhang,

Guixiang Ruan

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Фев. 28, 2024

Abstract Background Observational studies indicate a strong association between most neurodegenerative disorders and cathepsin, although the causative link remains unclear. Methods This research utilized Mendelian Randomization (MR) with genetic markers linked to cathepsins as instrumental variables, analyzed public Genome-Wide Association Studies (GWASs) summary data of individuals European ancestry for Alzheimer's disease (AD), Parkinson's (PD), dementia Lewy bodies (DLB) outcomes. The study applied inverse variance-weighted (IVW) method assess causal effects on AD, PD, DLB. Several sensitivity analyses heterogeneity test were conducted evaluate effectiveness results. Confounding variables accounted using multivariable MR (MVMR). Additionally, reverse was done improve forward analysis. Lastly, we utilize Bayesian Weighted (BWMR) further validate robustness Results investigation found an cathepsin H AD DLB risk. However, there negative correlation PD risk B levels. Effect estimates in MVMR BWMR remained constant. According analysis, decreased levels, negatively correlated Z no relationship cathepsins. Conclusion While higher levels associated risk, bidirectional B. By studying how influences development advancement DLB, novel methods diagnosis treatment might be investigated.

Язык: Английский

Процитировано

0
Causality between cathepsins and idiopathic pulmonary fibrosis: a Mendelian randomization study DOI Creative Commons

Zhuen Zhong,

Ruochen Xu, Changhao Xu

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Апрель 5, 2024

Abstract Background The pathogenesis of idiopathic pulmonary fibrosis (IPF) is complex and difficult to diagnose treat clinically. Cathepsins are involved in various physiological pathological processes, observational studies have shown an association between cathepsins IPF. However, the causal relationship them remains uncertain. Our aim was assess Methods Protein quantitative trait loci (pQTL) data for were obtained from INTERVAL studies, summary statistics IPF genome-wide (GWAS) FinnGen R10 study. Univariable Mendelian randomization (UVMR), multivariable (MVMR), data-based (SMR) Bayesian colocalization analysis conducted this Results UVMR indicated that elevated cathepsin H levels reduced overall risk (OR = 0.885,95%CI 0.827 ~ 0.947, P 3.86×10 − 4). MVMR showed effect on still present after adjusting interaction 0.895,95%CI 0.834 0.961, 0.002). In addition, SMR also suggested a 0.800,95%CI 0.699 0.916, 0.001). Finally, we validated results using UK Biobank Pharma Proteomics Project (UKB-PPP) dataset 0.897,95%CI 0.836 0.963, 0.003). Conclusions This study suggests has protective may serve as potential therapeutic target IPF, providing inspiration guidance diagnosis treatment

Язык: Английский

Процитировано

0
Genetic insights into serum cathepsins as diagnostic and therapeutic targets in knee and hip osteoarthritis DOI Creative Commons
Zhiqiang Shao, Hua Gao,

Qinyi Han

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июль 30, 2024

Osteoarthritis (OA) is a chronic disease due to the deterioration of cartilage structure and function, involving progressive degradation extracellular matrix. Cathepsins, lysosomal cysteine proteases, play pivotal roles in various biological pathological processes, particularly protein degradation. Excess cathepsins levels are reported contribute development OA. However, causal relationship between cathepsin family knee hip OA remains uncertain. Therefore, this study utilized bidirectional Mendelian Randomization (MR) analyses explore association. Our results indicated that elevated serum O increase overall risk OA, while increased H enhance Conversely, reverse MR did not reveal them. In summary, different anatomical locations may genetically result from elevations isoforms, which could be as diagnostic therapeutic targets clinical practice.

Язык: Английский

Процитировано

0
Mendelian randomisation analysis to explore the association between cathepsins and bipolar disorder DOI Creative Commons
Chuanhui Dong,

Yajing Han,

Siqiao Chen

и другие.

BMC Psychiatry, Год журнала: 2024, Номер 24(1)

Опубликована: Окт. 31, 2024

Bipolar disorder is a psychiatric condition characterized by the coexistence of depression and mania. Diagnosis this can be challenging due to limited pathologic experimental tools. Treatment compliance often poor medication side effects. Although cathepsin known play significant role in diseases such as tumors osteoporosis, its disorders not yet fully understood.

Язык: Английский

Процитировано

0
Integrative multi-omic analyses identify candidate targets for celiac disease involving tissue-specific regulation DOI Creative Commons
Jiazheng Sun, Yulan Zeng

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Abstract Introduction: Celiac disease (CeD) is an autoimmune condition characterized by a reversible inflammatory reaction in the mucous membrane of small intestine. Nevertheless, there limited availability efficient control approaches. Prior research has demonstrated that pharmacological targets supported genetic evidence can greatly enhance efficacy drug development. Hence, study aims to integrate transcriptomic and proteomic information identify candidate for CeD. Methods The employed proteome-wide Mendelian randomization (MR) analysis circulating plasma proteins investigate their causal association with CeD were further assessed employing colocalization analysis, transcriptome-wide summary-data-based (SMR) multimarker genomic annotation (MAGMA) gene-based bulk RNAseq-based differential expression analysis. For identified, extended Phenome-wide studies (PheWAS) conducted assess side-effect profiles, while DGIdb database provided on approved or investigated drugs targets. Results Systematic MR identified 22 Among analyzed, BTN2A1 passed all subsequent verification analyses. Additionally, three proteins, including CatH, IL-18R1, PTPRC, majority other 18 also (Trehalase, CD226, SH2B3, ICOSLG, ULK3, Park7, ALDH2, RABEP1, TNFRSF9, COL11A2, GNPDA1, IL-1RL1, B3galt6, TNFSF11, CCL21, BTN3A3, OLFM2 Colipase). Conclusions combination human information, several analytical methods. As result, divided into four tiers, as prospective therapeutic

Язык: Английский

Процитировано

0