Dataset Information

No genetic causal association between Alzheimer's disease and osteoporosis: A bidirectional two-sample Mendelian randomization study.

ABSTRACT:

Objective

Many observational studies have found an association between Alzheimer's disease (AD) and osteoporosis. However, it is unclear whether there is causal genetic between osteoporosis and AD.

Methods

A two-sample Mendelian randomization (MR) study was used to investigate whether there is a causal relationship between osteoporosis and AD. Genes for osteoporosis and AD were obtained from published the genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) with significant genome-wide differences (p < 5 × 10^-8) and independent (r ² < 0.001) were selected, and SNPs with F ≥ 10 were further analyzed. Inverse variance weighted (IVW) was used to assess causality, and the results were reported as odds ratios (ORs). Subsequently, heterogeneity was tested using Cochran's Q test, pleiotropy was tested using the MR-Egger intercept, and leave-one-out sensitivity analysis was performed to assess the robustness of the results.

Results

Using the IVW method, MR Egger method, and median-weighted method, we found that the results showed no significant causal effect of osteoporosis at different sites and at different ages on AD, regardless of the removal of potentially pleiotropic SNPs. The results were similar for the opposite direction of causality. These results were confirmed to be reliable and stable by sensitivity analysis.

Conclusion

This study found that there is no bidirectional causal relationship between osteoporosis and AD. However, they share similar pathogenesis and pathways.

SUBMITTER: Hu H

PROVIDER: S-EPMC9905740 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

No genetic causal association between Alzheimer's disease and osteoporosis: A bidirectional two-sample Mendelian randomization study.

Hu Hongxin H Mei Jian J Cai Yuanqing Y Ding Haiqi H Niu Susheng S Zhang Wenming W Fang Xinyu X

Frontiers in aging neuroscience 20230125

<h4>Objective</h4>Many observational studies have found an association between Alzheimer's disease (AD) and osteoporosis. However, it is unclear whether there is causal genetic between osteoporosis and AD.<h4>Methods</h4>A two-sample Mendelian randomization (MR) study was used to investigate whether there is a causal relationship between osteoporosis and AD. Genes for osteoporosis and AD were obtained from published the genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNP ...[more]

PMID: 36761181

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Project description:Background: Traditional observational studies have demonstrated an association between heart failure and Alzheimer's disease. The strengths of observational studies lie in their speed of implementation, cost, and applicability to rare diseases. However, observational studies have several limitations, such as uncontrollable confounders. Therefore, we employed Mendelian randomization of genetic variants to evaluate the causal relationships existing between AD and HF, which can avoid these limitations. Materials and Methods: A two-sample bidirectional MR analysis was employed. All datasets were results from the UK's Medical Research Council Integrative Epidemiology Unit genome-wide association study database, and we conducted a series of control steps to select the most suitable single-nucleotide polymorphisms for MR analysis, for which five primary methods are offered. We reversed the functions of exposure and outcomes to explore the causal direction of HF and AD. Sensitivity analysis was used to conduct several tests to avoid heterogeneity and pleiotropic bias in the MR results. Results: Our MR studies did not support a meaningful causal relationship between AD on HF (MR-Egger, p = 0.634 > 0.05; weighted median (WM), p = 0.337 > 0.05; inverse variance weighted (IVW), p = 0.471 > 0.05; simple mode, p = 0.454 > 0.05; weighted mode, p = 0.401 > 0.05). At the same time, we did not find a significant causal relationship between HF and AD with four of the methods (MR-Egger, p = 0.195 > 0.05; IVW, p = 0.0879 > 0.05; simple mode, p = 0.170 > 0.05; weighted mode, p = 0.110 > 0.05), but the WM method indicated a significant effect of HF on AD (p = 0.025 < 0.05). Because the statistical powers of IVW and MR-Egger are more than that of WM, we think that there is no causal effect of HF on AD. Sensitivity analysis and horizontal pleiotropy were not detected in the MR analysis. Conclusion: Our results did not provide significant evidence indicating any causal relationships between HF and AD in the European population. Therefore, more large-scale datasets or datasets related to similar factors are expected for further MR analysis.

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Dataset Information

No genetic causal association between Alzheimer's disease and osteoporosis: A bidirectional two-sample Mendelian randomization study.

Objective

Methods

Results

Conclusion

Publications

No genetic causal association between Alzheimer's disease and osteoporosis: A bidirectional two-sample Mendelian randomization study.

Similar Datasets

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