Causal Relationships Between Osteoarthritis and Senile Central Nerve System Dysfunction: A Bidirectional Two-Sample Mendelian Randomization Study

Cai, Yuanqing; Zhang, Guangyang; Liang, Jialin; Jing, Zhaopu; Zhang, Rupeng; Lv, Leifeng; Dang, Xiaoqian

doi:10.3389/fnagi.2021.793023

Cited by 23 publications

(14 citation statements)

References 34 publications

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“…Observational epidemiological studies are prone to confounding factors, reverse causation and various biases and have generated findings that have proven to be unreliable indicators of causal effects (16). However, MR studies are free from the confounding factors (as in retrospective studies) and reverse causality of traditional epidemiological approaches (46). In addition, compared with observational epidemiological studies, MR analysis does not involve high measurement costs or a large number of appropriate biospecimens (16).…”

Section: Discussionmentioning

confidence: 99%

No genetic causal association between iron status and osteoporosis: A two-sample Mendelian randomization

Ma²,

Zhang³

et al. 2022

Front. Endocrinol.

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ObjectiveTo explore the genetic causal association between osteoporosis (OP) and iron status through Mendelian randomization (MR).MethodsPublicly available genome-wide association study (GWAS) summary data were used for MR analysis with four iron status-related indicators (ferritin, iron, total iron binding capacity, and transferrin saturation) as exposures and three different types of OP (OP, OP with pathological fracture, and postmenopausal OP with pathological fracture) as outcomes. The inverse-variance weighted (IVW) method was used to analyze the genetic causal association between the four indicators of iron status and OP. The heterogeneity of MR results was determined using IVW and MR–Egger methods. The pleiotropy of MR results was determined using MR–Egger regression. A leave-one-SNP-out test was performed to determine whether the MR results were affected by a single nucleotide polymorphism (SNP). The weighted median method was conducted to further validate our results.ResultsBased on IVW, MR–Egger and weighted median models, we found no causal association between iron status (ferritin, iron, total iron binding capacity, or transferrin saturation) and OP (Pbeta > 0.05 in all models). IVW and MR–Egger analysis of OP with pathological fracture and iron status indicators showed no potential genetic causal association (Pbeta> 0.05 in the two analyses). The results of the weighted median were consistent with those of IVW (Pbeta> 0.05 in all analyses). There was no potential genetic causal association between iron status and postmenopausal OP with pathological fracture based on serum iron (Pbeta>0.05 in all models). No heterogeneity or horizontal pleiotropy was found in any of the analyses. None of the leave-one-out tests in the analyses found any SNP that could affect the results of MR.ConclusionOur results demonstrate that there is no genetic causal association between OP and iron status, but the effects of other factors were not excluded.

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Section: Discussionmentioning

confidence: 99%

No genetic causal association between iron status and osteoporosis: A two-sample Mendelian randomization

Ma²,

Zhang³

et al. 2022

Front. Endocrinol.

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“…In addition, we used MR–Egger, the weighted median, and the weighted mode to assess the causal relationship between osteoporosis and AD. MR–Egger has low statistical power, so the focus is more on direction and effect ( Luo et al, 2020 ; Cai et al, 2021 ). The weighted median provided a reliable Mendelian evaluation when 50% of the instrumental variables (instrument variables) were not valid ( Wu et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

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

Mei

Cai

et al. 2023

Front. Aging Neurosci.

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ObjectiveMany 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.MethodsA 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 (r2 < 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.ResultsUsing 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.ConclusionThis study found that there is no bidirectional causal relationship between osteoporosis and AD. However, they share similar pathogenesis and pathways.

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“…In addition, we used MR−Egger, weighted median, sample mode, and weighted mode to assess the causal relationship between BMI and SSTIs. MR−Egger has low statistical power; thus, the focus is more on direction and effect ( 32 , 33 ). The weighted median provides a reliable Mendelian evaluation when 50% of the instrument variables are not valid ( 34 ).…”

Section: Methodsmentioning

confidence: 99%

The causal relationship between obesity and skin and soft tissue infections: A two-sample Mendelian randomization study

Mei

et al. 2022

Front. Endocrinol.

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ObjectiveMany observational studies have shown that obesity strongly affects skin and soft tissue infections (SSTIs). However, whether a causal genetic relationship exists between obesity and SSTIs is unclear.MethodsA two-sample Mendelian randomization (MR) study was used to explore whether obesity is causally associated with SSTIs using a publicly released genome-wide association study (GWAS). An inverse-variance weighted (IVW) analysis was used as the primary analysis, and the results are reported as the odds ratios (ORs). Heterogeneity was tested using Cochran’s Q test and the I2 statistic, and horizontal pleiotropy was tested using the MR−Egger intercept and MR pleiotropy residual sum and outlier (MR-PRESSO).ResultsThe results of the MR analysis showed a positive effect of BMI on SSTIs (OR 1.544, 95% CI 1.399-1.704, P= 5.86 × 10-18). After adjusting for the effect of type 2 diabetes (T2D) and peripheral vascular disease (PVD), the positive effect still existed. Then, we further assessed the effect of BMI on different types of SSTIs. The results showed that BMI caused an increased risk of impetigo, cutaneous abscess, furuncle and carbuncle, cellulitis, pilonidal cyst, and other local infections of skin and subcutaneous tissues, except for acute lymphadenitis. However, the associations disappeared after adjusting for the effect of T2D and PVD, and the associations between BMI and impetigo or cellulitis disappeared. Finally, we assessed the effects of several obesity-related characteristics on SSTIs. Waist circumference, hip circumference, body fat percentage, and whole-body fat mass, excluding waist-to-hip ratio, had a causal effect on an increased risk of SSTIs. However, the associations disappeared after adjusting for the effect of BMI.ConclusionThis study found that obesity had a positive causal effect on SSTIs. Reasonable weight control is a possible way to reduce the occurrence of SSTIs, especially in patients undergoing surgery.

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Causal Relationships Between Osteoarthritis and Senile Central Nerve System Dysfunction: A Bidirectional Two-Sample Mendelian Randomization Study

Cited by 23 publications

References 34 publications

No genetic causal association between iron status and osteoporosis: A two-sample Mendelian randomization

No genetic causal association between iron status and osteoporosis: A two-sample Mendelian randomization

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

The causal relationship between obesity and skin and soft tissue infections: A two-sample Mendelian randomization study

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