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Genetically predicted circulating serum homocysteine levels on osteoporosis: a two-sample mendelian randomization study

To investigate the causal relationship between circulating serum homocysteine (Hcy) levels and osteoporosis (OP). Using public datasets gathered from independently published genome-wide association studies (GWAS), Mendelian randomization (MR) analysis was done to investigate the causal influence of...

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Autores principales: Wang, ChenYu, Zhang, Xiang, Qiu, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239750/
https://www.ncbi.nlm.nih.gov/pubmed/37271768
http://dx.doi.org/10.1038/s41598-023-35472-2
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author Wang, ChenYu
Zhang, Xiang
Qiu, Bo
author_facet Wang, ChenYu
Zhang, Xiang
Qiu, Bo
author_sort Wang, ChenYu
collection PubMed
description To investigate the causal relationship between circulating serum homocysteine (Hcy) levels and osteoporosis (OP). Using public datasets gathered from independently published genome-wide association studies (GWAS), Mendelian randomization (MR) analysis was done to investigate the causal influence of Hcy on OP. SNPs were selected from a meta-analysis of GWAS on Hcy concentrations in 44,147 individuals of European ancestry. Meanwhile, SNPs of individuals of European descent for OP were extracted from the Genetic Factors of Osteoporosis Consortium (GEFOS) UK Biobank. The odds ratio (OR) of inverse variance weighted (IVW) approaches was established as the primary outcome. Moreover, weighted median (WM) and MR-Egger regressions were included in the sensitivity analysis. There were no causal effects of Hcy on forearm bone mineral density and lumbar bone mineral density according to IVW, MR-Egger, and WM analyses (all p > 0.05). In the IVW, we discovered the causality between genetically predicted Hcy and heel bone mineral density (H-BMD) with an OR of 0.96 [95% confidence interval (CI) = 0.927–0.990, p = 0.011]. In the additional sensitivity analysis, WM regression (OR = 0.97, 95% CI = 0.995–1.076, p = 0.084) and MR-Egger regression (OR = 0.98, 95% CI = 0.918–1.049, p = 0.609) yielded values that were comparable in direction but less precise. The MR-Egger intercept, funnel plot, and IVW all indicate the absence of any discernible directional pleiotropy. The leave-one-out analysis revealed that a single SNP did not influence the results of the MR analysis. In conclusion, our MR investigation revealed evidence of a causal relationship between circulating serum Hcy levels and H-BMD, but not OP in the European population. However, larger sample sizes are needed in the future to get more reliable conclusions.
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spelling pubmed-102397502023-06-06 Genetically predicted circulating serum homocysteine levels on osteoporosis: a two-sample mendelian randomization study Wang, ChenYu Zhang, Xiang Qiu, Bo Sci Rep Article To investigate the causal relationship between circulating serum homocysteine (Hcy) levels and osteoporosis (OP). Using public datasets gathered from independently published genome-wide association studies (GWAS), Mendelian randomization (MR) analysis was done to investigate the causal influence of Hcy on OP. SNPs were selected from a meta-analysis of GWAS on Hcy concentrations in 44,147 individuals of European ancestry. Meanwhile, SNPs of individuals of European descent for OP were extracted from the Genetic Factors of Osteoporosis Consortium (GEFOS) UK Biobank. The odds ratio (OR) of inverse variance weighted (IVW) approaches was established as the primary outcome. Moreover, weighted median (WM) and MR-Egger regressions were included in the sensitivity analysis. There were no causal effects of Hcy on forearm bone mineral density and lumbar bone mineral density according to IVW, MR-Egger, and WM analyses (all p > 0.05). In the IVW, we discovered the causality between genetically predicted Hcy and heel bone mineral density (H-BMD) with an OR of 0.96 [95% confidence interval (CI) = 0.927–0.990, p = 0.011]. In the additional sensitivity analysis, WM regression (OR = 0.97, 95% CI = 0.995–1.076, p = 0.084) and MR-Egger regression (OR = 0.98, 95% CI = 0.918–1.049, p = 0.609) yielded values that were comparable in direction but less precise. The MR-Egger intercept, funnel plot, and IVW all indicate the absence of any discernible directional pleiotropy. The leave-one-out analysis revealed that a single SNP did not influence the results of the MR analysis. In conclusion, our MR investigation revealed evidence of a causal relationship between circulating serum Hcy levels and H-BMD, but not OP in the European population. However, larger sample sizes are needed in the future to get more reliable conclusions. Nature Publishing Group UK 2023-06-04 /pmc/articles/PMC10239750/ /pubmed/37271768 http://dx.doi.org/10.1038/s41598-023-35472-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wang, ChenYu
Zhang, Xiang
Qiu, Bo
Genetically predicted circulating serum homocysteine levels on osteoporosis: a two-sample mendelian randomization study
title Genetically predicted circulating serum homocysteine levels on osteoporosis: a two-sample mendelian randomization study
title_full Genetically predicted circulating serum homocysteine levels on osteoporosis: a two-sample mendelian randomization study
title_fullStr Genetically predicted circulating serum homocysteine levels on osteoporosis: a two-sample mendelian randomization study
title_full_unstemmed Genetically predicted circulating serum homocysteine levels on osteoporosis: a two-sample mendelian randomization study
title_short Genetically predicted circulating serum homocysteine levels on osteoporosis: a two-sample mendelian randomization study
title_sort genetically predicted circulating serum homocysteine levels on osteoporosis: a two-sample mendelian randomization study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239750/
https://www.ncbi.nlm.nih.gov/pubmed/37271768
http://dx.doi.org/10.1038/s41598-023-35472-2
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