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:	Xin Lv, Pengfei Wu, Shipeng Xiao, Wan Zhang, Yawei Li, Bolin Ren, Zhihong Li, Kun Xia, Bing Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	matrix metalloproteinase bone mineral density mendelian randomization genome-wide association study summary statistics causal inference Genetics QH426-470
Acceso en línea:	https://doaj.org/article/21dfca2486154126b3d3a12556791fde
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spelling	oai:doaj.org-article:21dfca2486154126b3d3a12556791fde2021-11-18T09:49:37ZMatrix Metalloproteinases in Relation to Bone Mineral Density: A Two-Sample Mendelian Randomization Study1664-802110.3389/fgene.2021.754795https://doaj.org/article/21dfca2486154126b3d3a12556791fde2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.754795/fullhttps://doaj.org/toc/1664-8021Background: 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.Xin LvPengfei WuPengfei WuShipeng XiaoWan ZhangYawei LiBolin RenBolin RenZhihong LiZhihong LiKun XiaKun XiaKun XiaBing WangFrontiers Media S.A.articlematrix metalloproteinasebone mineral densitymendelian randomizationgenome-wide association studysummary statisticscausal inferenceGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	matrix metalloproteinase bone mineral density mendelian randomization genome-wide association study summary statistics causal inference Genetics QH426-470
spellingShingle	matrix metalloproteinase bone mineral density mendelian randomization genome-wide association study summary statistics causal inference Genetics QH426-470 Xin Lv Pengfei Wu Pengfei Wu Shipeng Xiao Wan Zhang Yawei Li Bolin Ren Bolin Ren Zhihong Li Zhihong Li Kun Xia Kun Xia Kun Xia Bing Wang Matrix Metalloproteinases in Relation to Bone Mineral Density: A Two-Sample Mendelian Randomization Study
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.
format	article
author	Xin Lv Pengfei Wu Pengfei Wu Shipeng Xiao Wan Zhang Yawei Li Bolin Ren Bolin Ren Zhihong Li Zhihong Li Kun Xia Kun Xia Kun Xia Bing Wang
author_facet	Xin Lv Pengfei Wu Pengfei Wu Shipeng Xiao Wan Zhang Yawei Li Bolin Ren Bolin Ren Zhihong Li Zhihong Li Kun Xia Kun Xia Kun Xia Bing Wang
author_sort	Xin Lv
title	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_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_sort	matrix metalloproteinases in relation to bone mineral density: a two-sample mendelian randomization study
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/21dfca2486154126b3d3a12556791fde
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Matrix Metalloproteinases in Relation to Bone Mineral Density: A Two-Sample Mendelian Randomization Study

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