Dissecting Causal Relationships Between Plasma Metabolites and Osteoporosis: A Bidirectional Mendelian Randomization Study

Lv Hao; Zhang Ge; Hu Zhi-Mu; Chu Qing-Song; Wang Jiu-Xiang; Jiang Ting

doi:10.24920/004356

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Dissecting Causal Relationships Between Plasma Metabolites and Osteoporosis: A Bidirectional Mendelian Randomization Study

中国医学科学杂志（英文）;Chinese Medical Sciences Journal Vol. 39, Issue 3, Pages: 182-188(2024)

Research Articles | Updated：2025-01-08

- Dissecting Causal Relationships Between Plasma Metabolites and Osteoporosis: A Bidirectional Mendelian Randomization Study
- Affiliations：
  
  1.Department of Orthopaedics, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei230031, China
  2.Graduate School of Anhui University of Chinese Medicine, Hefei230012, China
  3.Department of Geriatrics, The Third People's Hospital of Hefei, Hefei230041, China
  4.Experimental Center of Clinical Research, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei230031, China
- Author bio：
- Funds：
- DOI：10.24920/004356
  CLC：
- Published：30 September 2024，
  
  Published Online：14 September 2024，
  
  Received：07 March 2024，
  
  Accepted：2024-08-22
- Accepted：
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.Dissecting Causal Relationships Between Plasma Metabolites and Osteoporosis: A Bidirectional Mendelian Randomization Study[J]. 中国医学科学杂志（英文）,2024,39(03):182-188.

LV HAO, ZHANG GE, HU ZHI-MU, et al. Dissecting Causal Relationships Between Plasma Metabolites and Osteoporosis: A Bidirectional Mendelian Randomization Study. [J]. 中国医学科学杂志（英文）;chinese medical sciences journal, 2024, 39(3): 182-188.
.Dissecting Causal Relationships Between Plasma Metabolites and Osteoporosis: A Bidirectional Mendelian Randomization Study[J]. 中国医学科学杂志（英文）,2024,39(03):182-188. DOI： 10.24920/004356.

LV HAO, ZHANG GE, HU ZHI-MU, et al. Dissecting Causal Relationships Between Plasma Metabolites and Osteoporosis: A Bidirectional Mendelian Randomization Study. [J]. 中国医学科学杂志（英文）;chinese medical sciences journal, 2024, 39(3): 182-188. DOI： 10.24920/004356.

摘要

目的

采用孟德尔随机化分析研究血浆代谢物与骨质疏松症之间的因果关系。

方法

采用双向孟德尔随机化方法分析不同全基因组关联研究的汇总数据

研究血浆代谢物与骨质疏松症之间的因果关系。首先

采用逆方差加权法评估血浆代谢物对骨质疏松症的因果效应

从而从不同来源的骨质疏松症相关全基因组关联研究汇总数据中获得具有统计学意义的代谢物交集

并对这些代谢物进行敏感性分析。接着

采用Cochran's Q检验评估单核苷酸多态性之间的异质性。最后

应用MR-Egger截距法和MR-PRESSO法评估水平多效性。同样采用逆方差加权法评估骨质疏松症对血浆代谢物的因果效应。此外

采用通路分析以确定参与骨质疏松症调节的潜在代谢通路。

结果

经过初步分析和敏感性分析

从GCST90038656和GCST90044600数据集的全基因组关联研究数据中

我们分别鉴别出77个和61个血浆代谢物与骨质疏松症有因果关系。通过交集确定了5个共同的代谢物。X-13684水平、葡萄糖与麦芽糖比值同骨质疏松症呈负相关

而甘氨脱氧胆酸水平、花生四烯酰肉碱(C20)水平与骨质疏松症呈正相关(P < 0.05)。X-11299水平与骨质疏松症的关系表现出矛盾的结果。通路分析表明:甘氨酸、丝氨酸和苏氨酸代谢

缬氨酸、亮氨酸和异亮氨酸生物合成

半乳糖代谢

精氨酸生物合成以及淀粉和蔗糖代谢通路参与了骨质疏松症的发展。

结论

我们发现血浆代谢物与骨质疏松症之间存在因果关系。这些结果为骨质疏松症治疗中针对代谢物的靶向干预提供了新的视角。

Abstract

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 MR-PRESSO 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

0.05). The relationship between

X-11299 levels and osteoporosis showed contradictory results (all

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.

关键词

骨质疏松症血浆代谢物孟德尔随机化双向分析

Keywords

osteoporosisplasma metabolitesMendelian randomizationbidirectional analysis

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