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Causal association of NAFLD with osteoporosis, fracture and falling risk: a bidirectional Mendelian randomization study

INTRODUCTION: The causal association between non-alcoholic fatty liver disease (NAFLD) and osteoporosis remains controversial in previous epidemiological studies. We employed a bidirectional two-sample Mendelian analysis to explore the causal relationship between NAFLD and osteoporosis. METHOD: The...

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Autores principales: Cui, Aiyong, Xiao, Peilun, Fan, Zhiqiang, Lei, Jinlai, Han, Shuang, Zhang, Danlong, Wei, Xing, Wang, Pengfei, Zhuang, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10446969/
https://www.ncbi.nlm.nih.gov/pubmed/37621646
http://dx.doi.org/10.3389/fendo.2023.1215790
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author Cui, Aiyong
Xiao, Peilun
Fan, Zhiqiang
Lei, Jinlai
Han, Shuang
Zhang, Danlong
Wei, Xing
Wang, Pengfei
Zhuang, Yan
author_facet Cui, Aiyong
Xiao, Peilun
Fan, Zhiqiang
Lei, Jinlai
Han, Shuang
Zhang, Danlong
Wei, Xing
Wang, Pengfei
Zhuang, Yan
author_sort Cui, Aiyong
collection PubMed
description INTRODUCTION: The causal association between non-alcoholic fatty liver disease (NAFLD) and osteoporosis remains controversial in previous epidemiological studies. We employed a bidirectional two-sample Mendelian analysis to explore the causal relationship between NAFLD and osteoporosis. METHOD: The NAFLD instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Two-sample Mendelian randomization (MR) analyses were used to estimate the causal effect of NAFLD on osteoporosis, fracture, and fall. Reverse Mendelian randomization analysis was conducted to estimate the causal effect of osteoporosis on NAFLD. The inverse-variance weighted (IVW) method was the primary analysis in this analysis. We used the MR-Egger method to determine horizontal pleiotropic. The heterogeneity effect of IVs was detected by MR-Egger and IVW analyses. RESULTS: Five SNPs (rs2980854, rs429358, rs1040196, rs738409, and rs5764430) were chosen as IVs for NAFLD. In forward MR analysis, the IVW-random effect indicated the causal effect of NAFLD on osteoporosis (OR= 1.0021, 95% CI: 1.0006-1.0037, P= 0.007) but not on fracture (OR= 1.0016, 95% CI: 0.998-1.0053, P= 0.389) and fall (OR= 0.9912, 95% CI: 0.9412-1.0440, P= 0.740). Furthermore, the reverse Mendelian randomization did not support a causal effect of osteoporosis on NAFLD (OR= 1.0002, 95% CI: 0.9997-1.0007, P= 0.231). No horizontal pleiotropic was detected in all MR analyses. CONCLUSIONS: The results of this study indicate a causal association between NAFLD and osteoporosis. NAFLD patients have a higher risk of osteoporosis but not fracture and falling risk. In addition, our results do not support a causal effect of osteoporosis on NAFLD.
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spelling pubmed-104469692023-08-24 Causal association of NAFLD with osteoporosis, fracture and falling risk: a bidirectional Mendelian randomization study Cui, Aiyong Xiao, Peilun Fan, Zhiqiang Lei, Jinlai Han, Shuang Zhang, Danlong Wei, Xing Wang, Pengfei Zhuang, Yan Front Endocrinol (Lausanne) Endocrinology INTRODUCTION: The causal association between non-alcoholic fatty liver disease (NAFLD) and osteoporosis remains controversial in previous epidemiological studies. We employed a bidirectional two-sample Mendelian analysis to explore the causal relationship between NAFLD and osteoporosis. METHOD: The NAFLD instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Two-sample Mendelian randomization (MR) analyses were used to estimate the causal effect of NAFLD on osteoporosis, fracture, and fall. Reverse Mendelian randomization analysis was conducted to estimate the causal effect of osteoporosis on NAFLD. The inverse-variance weighted (IVW) method was the primary analysis in this analysis. We used the MR-Egger method to determine horizontal pleiotropic. The heterogeneity effect of IVs was detected by MR-Egger and IVW analyses. RESULTS: Five SNPs (rs2980854, rs429358, rs1040196, rs738409, and rs5764430) were chosen as IVs for NAFLD. In forward MR analysis, the IVW-random effect indicated the causal effect of NAFLD on osteoporosis (OR= 1.0021, 95% CI: 1.0006-1.0037, P= 0.007) but not on fracture (OR= 1.0016, 95% CI: 0.998-1.0053, P= 0.389) and fall (OR= 0.9912, 95% CI: 0.9412-1.0440, P= 0.740). Furthermore, the reverse Mendelian randomization did not support a causal effect of osteoporosis on NAFLD (OR= 1.0002, 95% CI: 0.9997-1.0007, P= 0.231). No horizontal pleiotropic was detected in all MR analyses. CONCLUSIONS: The results of this study indicate a causal association between NAFLD and osteoporosis. NAFLD patients have a higher risk of osteoporosis but not fracture and falling risk. In addition, our results do not support a causal effect of osteoporosis on NAFLD. Frontiers Media S.A. 2023-08-09 /pmc/articles/PMC10446969/ /pubmed/37621646 http://dx.doi.org/10.3389/fendo.2023.1215790 Text en Copyright © 2023 Cui, Xiao, Fan, Lei, Han, Zhang, Wei, Wang and Zhuang 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 Endocrinology
Cui, Aiyong
Xiao, Peilun
Fan, Zhiqiang
Lei, Jinlai
Han, Shuang
Zhang, Danlong
Wei, Xing
Wang, Pengfei
Zhuang, Yan
Causal association of NAFLD with osteoporosis, fracture and falling risk: a bidirectional Mendelian randomization study
title Causal association of NAFLD with osteoporosis, fracture and falling risk: a bidirectional Mendelian randomization study
title_full Causal association of NAFLD with osteoporosis, fracture and falling risk: a bidirectional Mendelian randomization study
title_fullStr Causal association of NAFLD with osteoporosis, fracture and falling risk: a bidirectional Mendelian randomization study
title_full_unstemmed Causal association of NAFLD with osteoporosis, fracture and falling risk: a bidirectional Mendelian randomization study
title_short Causal association of NAFLD with osteoporosis, fracture and falling risk: a bidirectional Mendelian randomization study
title_sort causal association of nafld with osteoporosis, fracture and falling risk: a bidirectional mendelian randomization study
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10446969/
https://www.ncbi.nlm.nih.gov/pubmed/37621646
http://dx.doi.org/10.3389/fendo.2023.1215790
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