Mendelian Randomization Study of Lipid Metabolites Reveals Causal Associations with Heel Bone Mineral Density.
Mendelian Randomization Study of Lipid Metabolites Reveals Causal Associations with Heel Bone Mineral Density.
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DOI：
10.3390/nu15194160
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发表时间：
2023-09-27
期刊：
影响因子：
5.9
通讯作者：
Zhou H
中科院分区：
文献类型：
--
作者：
Wu M;Du Y;Zhang C;Li Z;Li Q;Qi E;Ruan W;Feng S;Zhou H
背景：骨质疏松症是一种以骨密度低和骨折风险增加为特征的骨骼疾病。足跟骨矿物质密度通常用作总体骨矿物质密度的代表性测量。脂质代谢包括脂肪酸代谢、甘油代谢、肌醇代谢、胆汁酸代谢、肉毒碱代谢、酮体代谢、甾醇和类固醇代谢等过程，可能会影响骨密度的变化。虽然一些研究已经报道了脂质代谢和足跟骨矿物质密度之间的相关性，但代谢物和足跟骨矿物质密度之间的总体因果关系仍不清楚。目的：采用双样本孟德尔随机化分析方法，探讨脂质代谢产物与跟骨骨密度之间的因果关系。研究方法：从大规模全基因组关联研究中提取汇总水平数据，以识别与脂质代谢物水平相关的遗传变异。这些遗传变异随后被用作孟德尔随机化分析中的工具变量，以估计每种脂质代谢物对足跟骨矿物质密度的因果影响。此外，从KEGG和WikiPathways数据库中提取了可能受到与骨密度因果关系影响的代谢物。然后检查这些下游代谢物和足跟骨矿物质密度之间的因果关系。最后，进行了敏感性分析，以评价结果的稳健性并解决潜在偏倚来源。结果如下：共分析了130种脂质代谢物，发现乙酰肉碱、丙酰肉碱、十六烷二酸、十四烷二酸、肌醇、1-花生四烯酸甘油磷、1-亚油酰甘油磷酸乙醇胺和硫酸表雄酮与跟骨骨密度有因果关系（p <0.05）。此外，我们的研究结果还表明，与KEGG和WikiPathways数据库中确定的上述代谢物相关的下游代谢物与足跟骨矿物质密度之间不存在因果关系。结论：这项工作支持的假设，脂质代谢物对骨骼健康的影响，通过证明特定的脂质代谢物和足跟骨矿物质密度之间的因果关系。本研究对骨质疏松症防治新策略的开发具有重要意义。
Background: Osteoporosis, which is a bone disease, is characterized by low bone mineral density and an increased risk of fractures. The heel bone mineral density is often used as a representative measure of overall bone mineral density. Lipid metabolism, which includes processes such as fatty acid metabolism, glycerol metabolism, inositol metabolism, bile acid metabolism, carnitine metabolism, ketone body metabolism, sterol and steroid metabolism, etc., may have an impact on changes in bone mineral density. While some studies have reported correlations between lipid metabolism and heel bone mineral density, the overall causal relationship between metabolites and heel bone mineral density remains unclear. Objective: to investigate the causal relationship between lipid metabolites and heel bone mineral density using two-sample Mendelian randomization analysis. Methods: Summary-level data from large-scale genome-wide association studies were extracted to identify genetic variants linked to lipid metabolite levels. These genetic variants were subsequently employed as instrumental variables in Mendelian randomization analysis to estimate the causal effects of each lipid metabolite on heel bone mineral density. Furthermore, metabolites that could potentially be influenced by causal relationships with bone mineral density were extracted from the KEGG and WikiPathways databases. The causal associations between these downstream metabolites and heel bone mineral density were then examined. Lastly, a sensitivity analysis was conducted to evaluate the robustness of the results and address potential sources of bias. Results: A total of 130 lipid metabolites were analyzed, and it was found that acetylcarnitine, propionylcarnitine, hexadecanedioate, tetradecanedioate, myo-inositol, 1-arachidonoylglycerophosphorine, 1-linoleoylglycerophoethanolamine, and epiandrosterone sulfate had a causal relationship with heel bone mineral density (p < 0.05). Furthermore, our findings also indicate an absence of causal association between the downstream metabolites associated with the aforementioned metabolites identified in the KEGG and WikiPathways databases and heel bone mineral density. Conclusion: This work supports the hypothesis that lipid metabolites have an impact on bone health through demonstrating a causal relationship between specific lipid metabolites and heel bone mineral density. This study has significant implications for the development of new strategies to osteoporosis prevention and treatment.
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影响因子：
7.7
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan NA;Thompson JR
通讯作者：
Thompson JR
影响因子：
6
作者：
Bispo, Daniela S. C.;Michalkova, Lenka;Correia, Marlene;Jesus, Catarina S. H.;Duarte, Iola F.;Goodfellow, Brian J.;Oliveira, Mariana B.;Mano, Joao F.;Gil, Ana M.
通讯作者：
Gil, Ana M.
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
4.6
作者：
Irie A;Yamamoto K;Miki Y;Murakami M
通讯作者：
Murakami M
影响因子：
4.8
作者：
Di Pietro, Giulia;Capuani, Silvia;Tarantino, Umberto
通讯作者：
Tarantino, Umberto