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Mendelian Randomization Study of Lipid Metabolites Reveals Causal Associations with Heel Bone Mineral Density
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 m...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10574167/ https://www.ncbi.nlm.nih.gov/pubmed/37836445 http://dx.doi.org/10.3390/nu15194160 |
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author | Wu, Mingxin Du, Yufei Zhang, Chi Li, Zhen Li, Qingyang Qi, Enlin Ruan, Wendong Feng, Shiqing Zhou, Hengxing |
author_facet | Wu, Mingxin Du, Yufei Zhang, Chi Li, Zhen Li, Qingyang Qi, Enlin Ruan, Wendong Feng, Shiqing Zhou, Hengxing |
author_sort | Wu, Mingxin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10574167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105741672023-10-14 Mendelian Randomization Study of Lipid Metabolites Reveals Causal Associations with Heel Bone Mineral Density Wu, Mingxin Du, Yufei Zhang, Chi Li, Zhen Li, Qingyang Qi, Enlin Ruan, Wendong Feng, Shiqing Zhou, Hengxing Nutrients Article 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. MDPI 2023-09-27 /pmc/articles/PMC10574167/ /pubmed/37836445 http://dx.doi.org/10.3390/nu15194160 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wu, Mingxin Du, Yufei Zhang, Chi Li, Zhen Li, Qingyang Qi, Enlin Ruan, Wendong Feng, Shiqing Zhou, Hengxing Mendelian Randomization Study of Lipid Metabolites Reveals Causal Associations with Heel Bone Mineral Density |
title | Mendelian Randomization Study of Lipid Metabolites Reveals Causal Associations with Heel Bone Mineral Density |
title_full | Mendelian Randomization Study of Lipid Metabolites Reveals Causal Associations with Heel Bone Mineral Density |
title_fullStr | Mendelian Randomization Study of Lipid Metabolites Reveals Causal Associations with Heel Bone Mineral Density |
title_full_unstemmed | Mendelian Randomization Study of Lipid Metabolites Reveals Causal Associations with Heel Bone Mineral Density |
title_short | Mendelian Randomization Study of Lipid Metabolites Reveals Causal Associations with Heel Bone Mineral Density |
title_sort | mendelian randomization study of lipid metabolites reveals causal associations with heel bone mineral density |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10574167/ https://www.ncbi.nlm.nih.gov/pubmed/37836445 http://dx.doi.org/10.3390/nu15194160 |
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