Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, Mingxin, Du, Yufei, Zhang, Chi, Li, Zhen, Li, Qingyang, Qi, Enlin, Ruan, Wendong, Feng, Shiqing, Zhou, Hengxing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785120630853599232
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
work_keys_str_mv AT wumingxin mendelianrandomizationstudyoflipidmetabolitesrevealscausalassociationswithheelbonemineraldensity
AT duyufei mendelianrandomizationstudyoflipidmetabolitesrevealscausalassociationswithheelbonemineraldensity
AT zhangchi mendelianrandomizationstudyoflipidmetabolitesrevealscausalassociationswithheelbonemineraldensity
AT lizhen mendelianrandomizationstudyoflipidmetabolitesrevealscausalassociationswithheelbonemineraldensity
AT liqingyang mendelianrandomizationstudyoflipidmetabolitesrevealscausalassociationswithheelbonemineraldensity
AT qienlin mendelianrandomizationstudyoflipidmetabolitesrevealscausalassociationswithheelbonemineraldensity
AT ruanwendong mendelianrandomizationstudyoflipidmetabolitesrevealscausalassociationswithheelbonemineraldensity
AT fengshiqing mendelianrandomizationstudyoflipidmetabolitesrevealscausalassociationswithheelbonemineraldensity
AT zhouhengxing mendelianrandomizationstudyoflipidmetabolitesrevealscausalassociationswithheelbonemineraldensity