Possible linking and treatment between Parkinson’s disease and inflammatory bowel disease: a study of Mendelian randomization based on gut–brain axis DOI Creative Commons
Beiming Wang, Xiaoyin Bai,

Yingmai Yang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 11, 2025

Mounting evidence suggests that Parkinson's disease (PD) and inflammatory bowel (IBD) are closely associated becoming global health burdens. However, the causal relationships common pathogeneses between them uncertain. Furthermore, they uncurable. Thus, we aimed to identify novel therapeutic targets shared based on their pathophysiological mechanisms in gut–brain-axis (GBA). A meta-analysis bidirectional Mendelian randomization (MR) utilizing various datasets was performed estimate relationship. Then, pleiotropic analysis under composite null hypothesis (PLACO) with functional mapping combined annotation of genetic associations (FUMA) were conducted genes. Next, blood, brain intestine expression quantitative trait locus (eQTL) taken perform drug-target MR finding genes two diseases. Colocalization ensured eQTLs corresponding gene colocalized disease. Enrichment protein‒protein interaction (PPI) network done explore pathogenesis pathways. Genes passed all regarded as drug targets. Our revealed relationship diseases, ORs for PD IBD, CD, UC (1.050 [95% CI 1.014–1.086], 1.044 0.995–1.095], 1.063 1.016–1.120]); (1.003 0.973–1.034], 1.035 1.004–1.067], 1.008 0.977–1.040]). Overall, 277, 216 201 identified UC. Total 733 classified tier 3 (found only one tissue) druggable targets, 57 2 tissues, 51 protein-coding genes) 9 three tissues). Among 60 over 2, 18 overlapped enriched mitochondria, antigen presentation, processing immune cell regulation Three (LRRK2, RAB29 HLA-DQA2) colocalization analysis. LRRK2 reported be genes, HLA-DQA2 first time potential This study established a reliable relationship, possible pathways which had important implications intervention treatment diseases simultaneously.

Language: Английский

Possible linking and treatment between Parkinson’s disease and inflammatory bowel disease: a study of Mendelian randomization based on gut–brain axis DOI Creative Commons
Beiming Wang, Xiaoyin Bai,

Yingmai Yang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 11, 2025

Mounting evidence suggests that Parkinson's disease (PD) and inflammatory bowel (IBD) are closely associated becoming global health burdens. However, the causal relationships common pathogeneses between them uncertain. Furthermore, they uncurable. Thus, we aimed to identify novel therapeutic targets shared based on their pathophysiological mechanisms in gut–brain-axis (GBA). A meta-analysis bidirectional Mendelian randomization (MR) utilizing various datasets was performed estimate relationship. Then, pleiotropic analysis under composite null hypothesis (PLACO) with functional mapping combined annotation of genetic associations (FUMA) were conducted genes. Next, blood, brain intestine expression quantitative trait locus (eQTL) taken perform drug-target MR finding genes two diseases. Colocalization ensured eQTLs corresponding gene colocalized disease. Enrichment protein‒protein interaction (PPI) network done explore pathogenesis pathways. Genes passed all regarded as drug targets. Our revealed relationship diseases, ORs for PD IBD, CD, UC (1.050 [95% CI 1.014–1.086], 1.044 0.995–1.095], 1.063 1.016–1.120]); (1.003 0.973–1.034], 1.035 1.004–1.067], 1.008 0.977–1.040]). Overall, 277, 216 201 identified UC. Total 733 classified tier 3 (found only one tissue) druggable targets, 57 2 tissues, 51 protein-coding genes) 9 three tissues). Among 60 over 2, 18 overlapped enriched mitochondria, antigen presentation, processing immune cell regulation Three (LRRK2, RAB29 HLA-DQA2) colocalization analysis. LRRK2 reported be genes, HLA-DQA2 first time potential This study established a reliable relationship, possible pathways which had important implications intervention treatment diseases simultaneously.

Language: Английский

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