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Matrix Metalloproteinases in Relation to Bone Mineral Density: A Two-Sample Mendelian Randomization Study

Background: We aimed at investigating causal associations between matrix metalloproteinases (MMPs) and bone mineral density (BMD) by the Mendelian randomization (MR) analysis. Methods: From genome-wide association studies of European ancestry, we selected instrumental variables for MMP-1, MMP-3, MMP...

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Autores principales: Lv, Xin, Wu, Pengfei, Xiao, Shipeng, Zhang, Wan, Li, Yawei, Ren, Bolin, Li, Zhihong, Xia, Kun, Wang, Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637623/
https://www.ncbi.nlm.nih.gov/pubmed/34868227
http://dx.doi.org/10.3389/fgene.2021.754795
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author Lv, Xin
Wu, Pengfei
Xiao, Shipeng
Zhang, Wan
Li, Yawei
Ren, Bolin
Li, Zhihong
Xia, Kun
Wang, Bing
author_facet Lv, Xin
Wu, Pengfei
Xiao, Shipeng
Zhang, Wan
Li, Yawei
Ren, Bolin
Li, Zhihong
Xia, Kun
Wang, Bing
author_sort Lv, Xin
collection PubMed
description Background: We aimed at investigating causal associations between matrix metalloproteinases (MMPs) and bone mineral density (BMD) by the Mendelian randomization (MR) analysis. Methods: From genome-wide association studies of European ancestry, we selected instrumental variables for MMP-1, MMP-3, MMP-7, MMP-8, MMP-10, and MMP-12. Accordingly, we retrieved summary statistics of three site-specific BMD, namely, forearm, femoral neck, and lumbar spine. We conducted an inverse variance weighted MR as the primary method to compute overall effects from multiple instruments, while additional MR approaches and sensitivity analyses were implemented. Bonferroni-adjusted significance threshold was set at p < 0.05/18 = 0.003. Results: Totally, there was no evidence for causal effects of genetically-predicted levels of MMPs on BMD measurement at three common sites. MR results indicated that there were no causal associations of circulating MMPs with forearm BMD (all p ≥ 0.023) by the inverse variance weighted method. Similarly, there were no causal effects of MMPs on femoral neck BMD (all p ≥ 0.120) and MR results did not support causal relationships between MMPs and lumbar spine BMD (all p ≥ 0.017). Multiple sensitivity analyses suggested the robustness of MR results, which were less likely to be biased by unbalanced pleiotropy or evident heterogeneity. Conclusion: We found no evidence for the causal relationship between MMPs and BMD in the European population.
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spelling pubmed-86376232021-12-03 Matrix Metalloproteinases in Relation to Bone Mineral Density: A Two-Sample Mendelian Randomization Study Lv, Xin Wu, Pengfei Xiao, Shipeng Zhang, Wan Li, Yawei Ren, Bolin Li, Zhihong Xia, Kun Wang, Bing Front Genet Genetics Background: We aimed at investigating causal associations between matrix metalloproteinases (MMPs) and bone mineral density (BMD) by the Mendelian randomization (MR) analysis. Methods: From genome-wide association studies of European ancestry, we selected instrumental variables for MMP-1, MMP-3, MMP-7, MMP-8, MMP-10, and MMP-12. Accordingly, we retrieved summary statistics of three site-specific BMD, namely, forearm, femoral neck, and lumbar spine. We conducted an inverse variance weighted MR as the primary method to compute overall effects from multiple instruments, while additional MR approaches and sensitivity analyses were implemented. Bonferroni-adjusted significance threshold was set at p < 0.05/18 = 0.003. Results: Totally, there was no evidence for causal effects of genetically-predicted levels of MMPs on BMD measurement at three common sites. MR results indicated that there were no causal associations of circulating MMPs with forearm BMD (all p ≥ 0.023) by the inverse variance weighted method. Similarly, there were no causal effects of MMPs on femoral neck BMD (all p ≥ 0.120) and MR results did not support causal relationships between MMPs and lumbar spine BMD (all p ≥ 0.017). Multiple sensitivity analyses suggested the robustness of MR results, which were less likely to be biased by unbalanced pleiotropy or evident heterogeneity. Conclusion: We found no evidence for the causal relationship between MMPs and BMD in the European population. Frontiers Media S.A. 2021-11-18 /pmc/articles/PMC8637623/ /pubmed/34868227 http://dx.doi.org/10.3389/fgene.2021.754795 Text en Copyright © 2021 Lv, Wu, Xiao, Zhang, Li, Ren, Li, Xia and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Lv, Xin
Wu, Pengfei
Xiao, Shipeng
Zhang, Wan
Li, Yawei
Ren, Bolin
Li, Zhihong
Xia, Kun
Wang, Bing
Matrix Metalloproteinases in Relation to Bone Mineral Density: A Two-Sample Mendelian Randomization Study
title Matrix Metalloproteinases in Relation to Bone Mineral Density: A Two-Sample Mendelian Randomization Study
title_full Matrix Metalloproteinases in Relation to Bone Mineral Density: A Two-Sample Mendelian Randomization Study
title_fullStr Matrix Metalloproteinases in Relation to Bone Mineral Density: A Two-Sample Mendelian Randomization Study
title_full_unstemmed Matrix Metalloproteinases in Relation to Bone Mineral Density: A Two-Sample Mendelian Randomization Study
title_short Matrix Metalloproteinases in Relation to Bone Mineral Density: A Two-Sample Mendelian Randomization Study
title_sort matrix metalloproteinases in relation to bone mineral density: a two-sample mendelian randomization study
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637623/
https://www.ncbi.nlm.nih.gov/pubmed/34868227
http://dx.doi.org/10.3389/fgene.2021.754795
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