目的通过孟德尔随机化(Mendelian randomization,MR)分析探究免疫细胞与慢性胰腺炎(chronic pancreatitis,CP)之间的因果关系。方法本研究的免疫细胞表型和CP的全基因组关联研究(genome-wide association studies,GWAS)数据来自公开数据...目的通过孟德尔随机化(Mendelian randomization,MR)分析探究免疫细胞与慢性胰腺炎(chronic pancreatitis,CP)之间的因果关系。方法本研究的免疫细胞表型和CP的全基因组关联研究(genome-wide association studies,GWAS)数据来自公开数据库,共纳入731种免疫细胞表型。采用双样本双向MR分析法探索免疫细胞与CP之间的因果关系,并使用多种敏感性分析方法对结果的异质性和水平多效性进行验证。结果共发现33个免疫细胞表型与CP存在因果关联,其中18个表现为抑制因素,调节性T细胞(Treg)细胞群中的CD25 on CD4^(+)表现出最显著的抑制作用;其余15个则表现为风险因素,成熟T细胞组的CD8 on TD CD8br、TBNK组的CD8br AC以及Treg组的CD39^(+)CD8br%T cell和CD28 on CD4^(+)表现出显著的促进作用。反向MR结果也进一步证明了因果关系的单向性。结论通过MR方法揭示了免疫细胞与CP之间的密切联系,凸显了免疫系统与CP之间复杂的相互作用模式。展开更多
Objective To investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization(MR) analysis.Methods Bidirectional MR was used to analyze pooled data from different genome-wid...Objective To investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization(MR) analysis.Methods Bidirectional MR was used to analyze pooled data from different genome-wide association studies(GWAS). The causal effect of plasma metabolites on osteoporosis was estimated using the inverse variance weighted method, intersections of statistically significant metabolites obtained from different sources of osteoporosis-related GWAS aggregated data was determined, and then sensitivity analysis was performed on these metabolites. Heterogeneity between single nucleotide polymorphisms was evaluated by Cochran's Q test. Horizontal pleiotropy was assessed through the application of the MR-Egger intercept method and the MRPRESSO method. The causal effect of osteoporosis on plasma metabolites was also evaluated using the inverse variance weighted method. Additionally, pathway analysis was conducted to identify potential metabolic pathways involved in the regulation of osteoporosis.Results Primary analysis and sensitivity analysis showed that 77 and 61 plasma metabolites had a causal relationship with osteoporosis from the GWAS data in the GCST90038656 and GCST90044600 datasets, respectively. Five common metabolites were identified via intersection. X-13684 levels and the glucose-to-maltose ratio were negatively associated with osteoporosis, whereas glycoursodeoxycholate levels and arachidoylcarnitine(C20) levels were positively associated with osteoporosis(all P < 0.05). The relationship between X-11299 levels and osteoporosis showed contradictory results(all P < 0.05). Pathway analysis indicated that glycine, serine, and threonine metabolism, valine, leucine, and isoleucine biosynthesis, galactose metabolism, arginine biosynthesis, and starch and sucrose metabolism pathways were participated in the development of osteoporosis.Conclusion We found a causal relationship between plasma metabolites and osteoporosis. These results offer novel perspectives with important implications for targeted metabolite-focused interventions in the management of osteoporosis.展开更多
文摘目的通过孟德尔随机化(Mendelian randomization,MR)分析探究免疫细胞与慢性胰腺炎(chronic pancreatitis,CP)之间的因果关系。方法本研究的免疫细胞表型和CP的全基因组关联研究(genome-wide association studies,GWAS)数据来自公开数据库,共纳入731种免疫细胞表型。采用双样本双向MR分析法探索免疫细胞与CP之间的因果关系,并使用多种敏感性分析方法对结果的异质性和水平多效性进行验证。结果共发现33个免疫细胞表型与CP存在因果关联,其中18个表现为抑制因素,调节性T细胞(Treg)细胞群中的CD25 on CD4^(+)表现出最显著的抑制作用;其余15个则表现为风险因素,成熟T细胞组的CD8 on TD CD8br、TBNK组的CD8br AC以及Treg组的CD39^(+)CD8br%T cell和CD28 on CD4^(+)表现出显著的促进作用。反向MR结果也进一步证明了因果关系的单向性。结论通过MR方法揭示了免疫细胞与CP之间的密切联系,凸显了免疫系统与CP之间复杂的相互作用模式。
文摘Objective To investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization(MR) analysis.Methods Bidirectional MR was used to analyze pooled data from different genome-wide association studies(GWAS). The causal effect of plasma metabolites on osteoporosis was estimated using the inverse variance weighted method, intersections of statistically significant metabolites obtained from different sources of osteoporosis-related GWAS aggregated data was determined, and then sensitivity analysis was performed on these metabolites. Heterogeneity between single nucleotide polymorphisms was evaluated by Cochran's Q test. Horizontal pleiotropy was assessed through the application of the MR-Egger intercept method and the MRPRESSO method. The causal effect of osteoporosis on plasma metabolites was also evaluated using the inverse variance weighted method. Additionally, pathway analysis was conducted to identify potential metabolic pathways involved in the regulation of osteoporosis.Results Primary analysis and sensitivity analysis showed that 77 and 61 plasma metabolites had a causal relationship with osteoporosis from the GWAS data in the GCST90038656 and GCST90044600 datasets, respectively. Five common metabolites were identified via intersection. X-13684 levels and the glucose-to-maltose ratio were negatively associated with osteoporosis, whereas glycoursodeoxycholate levels and arachidoylcarnitine(C20) levels were positively associated with osteoporosis(all P < 0.05). The relationship between X-11299 levels and osteoporosis showed contradictory results(all P < 0.05). Pathway analysis indicated that glycine, serine, and threonine metabolism, valine, leucine, and isoleucine biosynthesis, galactose metabolism, arginine biosynthesis, and starch and sucrose metabolism pathways were participated in the development of osteoporosis.Conclusion We found a causal relationship between plasma metabolites and osteoporosis. These results offer novel perspectives with important implications for targeted metabolite-focused interventions in the management of osteoporosis.
