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Investigation of the causal relationship between osteocalcin and dementia: A Mendelian randomization study

OBJECTIVE: Basic medical studies have reported an improved effect of osteocalcin on cognition. We explored the causal link between osteocalcin and dementia via the implementation of Mendelian randomization methodology. METHODS: Genome-wide association studies were employed to identify single nucleot...

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Detalles Bibliográficos
Autores principales: Liu, Wangmi, Hu, Qiang, Zhang, Feng, Shi, Kesi, Wu, Jiayan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616355/
https://www.ncbi.nlm.nih.gov/pubmed/37916108
http://dx.doi.org/10.1016/j.heliyon.2023.e21073
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author Liu, Wangmi
Hu, Qiang
Zhang, Feng
Shi, Kesi
Wu, Jiayan
author_facet Liu, Wangmi
Hu, Qiang
Zhang, Feng
Shi, Kesi
Wu, Jiayan
author_sort Liu, Wangmi
collection PubMed
description OBJECTIVE: Basic medical studies have reported an improved effect of osteocalcin on cognition. We explored the causal link between osteocalcin and dementia via the implementation of Mendelian randomization methodology. METHODS: Genome-wide association studies were employed to identify single nucleotide polymorphisms (SNPs) showing significant correlations with osteocalcin. Subsequently, A two-sample Mendelian randomization analysis was conducted utilizing the inverse-variance-weighted (IVW) technique to assess the causal relationship between osteocalcin and various types of dementia, including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), and vascular dementia (VD). This approach aimed to minimize potential sources of confounding bias and provide more robust results. Multivariable MR (MVMR) analysis was conducted to adjust for potential genetic pleiotropy. RESULTS: The study employed three SNPs, namely rs71631868, rs9271374, and rs116843408, as genetic tools to evaluate the causal association of osteocalcin with dementia. The IVW analysis indicated that osteocalcin may have a potential protective effect against AD with an odds ratio (OR) of 0.790 (95 % CI: 0.688–0.906; P < 0.001). However, no significant relationship was observed between osteocalcin and other types of dementia. Furthermore, the MVMR analysis indicated that the impact of osteocalcin on AD remained consistent even after adjusting for age-related macular degeneration and Type 2 diabetes with an OR of 0.856 (95 % CI: 0.744–0.985; P = 0.030). CONCLUSIONS: Our findings provide important insights into the role of osteocalcin in the pathogenesis of AD. Future research is required to clarify the underlying mechanisms and their clinical applications.
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spelling pubmed-106163552023-11-01 Investigation of the causal relationship between osteocalcin and dementia: A Mendelian randomization study Liu, Wangmi Hu, Qiang Zhang, Feng Shi, Kesi Wu, Jiayan Heliyon Research Article OBJECTIVE: Basic medical studies have reported an improved effect of osteocalcin on cognition. We explored the causal link between osteocalcin and dementia via the implementation of Mendelian randomization methodology. METHODS: Genome-wide association studies were employed to identify single nucleotide polymorphisms (SNPs) showing significant correlations with osteocalcin. Subsequently, A two-sample Mendelian randomization analysis was conducted utilizing the inverse-variance-weighted (IVW) technique to assess the causal relationship between osteocalcin and various types of dementia, including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), and vascular dementia (VD). This approach aimed to minimize potential sources of confounding bias and provide more robust results. Multivariable MR (MVMR) analysis was conducted to adjust for potential genetic pleiotropy. RESULTS: The study employed three SNPs, namely rs71631868, rs9271374, and rs116843408, as genetic tools to evaluate the causal association of osteocalcin with dementia. The IVW analysis indicated that osteocalcin may have a potential protective effect against AD with an odds ratio (OR) of 0.790 (95 % CI: 0.688–0.906; P < 0.001). However, no significant relationship was observed between osteocalcin and other types of dementia. Furthermore, the MVMR analysis indicated that the impact of osteocalcin on AD remained consistent even after adjusting for age-related macular degeneration and Type 2 diabetes with an OR of 0.856 (95 % CI: 0.744–0.985; P = 0.030). CONCLUSIONS: Our findings provide important insights into the role of osteocalcin in the pathogenesis of AD. Future research is required to clarify the underlying mechanisms and their clinical applications. Elsevier 2023-10-16 /pmc/articles/PMC10616355/ /pubmed/37916108 http://dx.doi.org/10.1016/j.heliyon.2023.e21073 Text en © 2023 The Authors. Published by Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Liu, Wangmi
Hu, Qiang
Zhang, Feng
Shi, Kesi
Wu, Jiayan
Investigation of the causal relationship between osteocalcin and dementia: A Mendelian randomization study
title Investigation of the causal relationship between osteocalcin and dementia: A Mendelian randomization study
title_full Investigation of the causal relationship between osteocalcin and dementia: A Mendelian randomization study
title_fullStr Investigation of the causal relationship between osteocalcin and dementia: A Mendelian randomization study
title_full_unstemmed Investigation of the causal relationship between osteocalcin and dementia: A Mendelian randomization study
title_short Investigation of the causal relationship between osteocalcin and dementia: A Mendelian randomization study
title_sort investigation of the causal relationship between osteocalcin and dementia: a mendelian randomization study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616355/
https://www.ncbi.nlm.nih.gov/pubmed/37916108
http://dx.doi.org/10.1016/j.heliyon.2023.e21073
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