Mendelian randomization as an approach to assess causal effects of inflammatory bowel disease on atrial fibrillation

Chen, LaiTe; Fu, Guosheng; Jiang, Chenyang

doi:10.18632/aging.202906

Cited by 5 publications

(6 citation statements)

References 49 publications

(56 reference statements)

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“…Thus, we speculated that IBD patients have increased levels of traditional cardiovascular risk factors, resulting in an increased incidence of CVD in observational studies. Recent MR studies showed a lack of genetic causality between IBD and atrial fibrillation (42), which was consistent with our results. Although pleiotropy may cause the bias of the results in MR analysis, there is little possibility in our study (43).…”

Section: Discussionsupporting

confidence: 93%

Inflammatory bowel disease and cardiovascular disease: A two-sample Mendelian randomization analysis

Liu

et al. 2022

Front. Cardiovasc. Med.

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BackgroundAlthough epidemiological studies have shown a positive relationship between inflammatory bowel disease (IBD) and risk of cardiovascular disease (CVD) outcomes, a solid causal relationship has not been established. Thus, a two-sample Mendelian randomization (MR) study was conducted to explore the potential causal effect between IBD and CVD outcomes.MethodsWe performed a two-sample MR analysis to analyze the causal effect of the IBD on CVD outcome by using summary-level genome-wide association studies of European descent. The inverse-variance weighted (IVW) method was used as the main MR analysis, with complementary analyses of MR Egger, maximum likelihood, weighted median, penalized weighted media, simple mode, weighted mode, and MR-PRESSO methods. Multiple sensitivity analyses were used to evaluate the robustness of our results.ResultsAll P-values were greater than 0.05 in the IVW method, showing no evidence of a causal association between circulating IBD and CVD. Similar results were observed by using other MR methods. No evidence of heterogeneity, pleiotropy, or outlier single-nucleotide polymorphisms was detected. Sensitivity analyses demonstrated the robustness of the results.ConclusionThe findings of this study provided no evidence to support that IBD has a large effect on risk of CVD outcomes, which is in contrast to many previous observational reports. Further studies are needed to determine the potential mechanism of association identified in observational studies.

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Section: Discussionsupporting

confidence: 93%

Inflammatory bowel disease and cardiovascular disease: A two-sample Mendelian randomization analysis

Liu

et al. 2022

Front. Cardiovasc. Med.

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“…In the present study, we concentrated on the interactive effects between the gut microbiome and GD through bidirectional MR analysis, which we also used to detect the causal effect between the gut microbiome and GD. Compared with traditional clinical trials, MR analysis allows the identification of sequential relationships as the exposure is defined before the outcome through IVs in the design of the MR analysis, and IVs are less prone to influence by potential confounders ( 49 ). The present study utilized F -statistics and horizontal pleiotropy, which overcame weak biases and showed a direct association between SNPs and the outcome.…”

Section: Discussionmentioning

confidence: 99%

A cause–effect relationship between Graves’ disease and the gut microbiome contributes to the thyroid–gut axis: A bidirectional two-sample Mendelian randomization study

et al. 2023

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BackgroundAn association between Graves’ disease (GD) and the gut microbiome has been identified, but the causal effect between them remains unclear.MethodsBidirectional two-sample Mendelian randomization (MR) analysis was used to detect the causal effect between GD and the gut microbiome. Gut microbiome data were derived from samples from a range of different ethnicities (18,340 samples) and data on GD were obtained from samples of Asian ethnicity (212,453 samples). Single nucleotide polymorphisms (SNPs) were selected as instrumental variables according to different criteria. They were used to evaluate the causal effect between exposures and outcomes through inverse-variance weighting (IVW), weighted median, weighted mode, MR-Egger, and simple mode methods. F-statistics and sensitivity analyses were performed to evaluate bias and reliability.ResultsIn total, 1,560 instrumental variables were extracted from the gut microbiome data (p< 1 × 105). The classes Deltaproteobacteria [odds ratio (OR) = 3.603] and Mollicutes, as well as the genera Ruminococcus torques group, Oxalobacter, and Ruminococcaceae UCG 011 were identified as risk factors for GD. The family Peptococcaceae and the genus Anaerostipes (OR = 0.489) were protective factors for GD. In addition, 13 instrumental variables were extracted from GD (p< 1 × 10–8), causing one family and eight genera to be regulated. The genus Clostridium innocuum group (p = 0.024, OR = 0.918) and Anaerofilum (p = 0.049, OR = 1.584) had the greatest probability of being regulated. Significant bias, heterogeneity, and horizontal pleiotropy were not detected.ConclusionA causal effect relationship exists between GD and the gut microbiome, demonstrating regulatory activity and interactions, and thus providing evidence supporting the involvement of a thyroid–gut axis.

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“…in PA and minimizing sedentary time are linked to decreased weight gain and body fat, while overweight is associated with an increased risk of frailty and falls. [53][54][55] Given that body fat is likely involved in the causal pathway linking PA, sedentary behavior, and frailty and falling, it is challenging to disentangle independent effects of PA and sedentary behavior on the development of frailty and falling from adiposity. The close association between adiposity, PA, and sedentary behavior could be attributed to the fact that certain genetic instruments used to measure PA and LST have also demonstrated associations with genotypes associated with body fat.…”

Section: Discussionmentioning

confidence: 99%

“…Engaging in PA and minimizing sedentary time are linked to decreased weight gain and body fat, while overweight is associated with an increased risk of frailty and falls 53–55 . Given that body fat is likely involved in the causal pathway linking PA, sedentary behavior, and frailty and falling, it is challenging to disentangle independent effects of PA and sedentary behavior on the development of frailty and falling from adiposity.…”

Section: Discussionmentioning

confidence: 99%

Physical activity, sedentary behavior, and the risk of frailty and falling: A Mendelian randomization study

Zhou,

Zhu,

Huang

et al. 2024

Scandinavian Med Sci Sports

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BackgroundDue to inconclusive evidence from observational studies regarding the impact of physical activity (PA) and sedentary behavior on frailty and falling risk, we conducted a two‐sample Mendelian randomization analysis to investigate the causal associations between PA, sedentary behavior, and frailty and falls.MethodsWe extracted summary data from genome‐wide association studies conducted among individuals of European ancestry, encompassing PA (n = 90 667–608 595), sedentary behavior (n = 372 609‐526 725), frailty index (n = 175 226), and falling risk (n = 451 179). Single nucleotide polymorphisms associated with accelerometer assessed fraction >425 milligravities, self‐reported vigorous activity, moderate to vigorous physical acticity (MVPA), leisure screen time (LST), and sedentary behavior at work were taken as instrumental variables. The causal effects were primarily estimated using inverse variance weighted methods, complemented by several sensitivity and validation analyses.ResultsGenetically predicted higher levels of PA were significantly associated with a reduction in the frailty index (accelerometer assessed fraction >425 milligravities: β = −0.25, 95% CI = −0.36 to −0.14, p = 1.27 × 10−5; self‐reported vigorous activity: β = −0.13, 95% CI = −0.20 to −0.05, p = 7.9 × 10−4; MVPA: β = −0.28, 95% CI = −0.40 to −0.16, p = 9.9 × 10−6). Besides, LST was significantly associated with higher frailty index (β = 0.18, 95% CI = 0.14–0.22, p = 5.2 × 10−20) and higher odds of falling (OR = 1.13, CI = 1.07–1.19, p = 6.9 × 10−6). These findings remained consistent throughout sensitivity and validation analyses.ConclusionsOur study offers evidence supporting a causal relationship between PA and a reduced risk of frailty. Furthermore, it underscores the association between prolonged LST and an elevated risk of frailty and falls. Therefore, promoting PA and reducing sedentary behavior may be an effective strategy in primary frailty and falls prevention.

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Mendelian randomization as an approach to assess causal effects of inflammatory bowel disease on atrial fibrillation

Cited by 5 publications

References 49 publications

Inflammatory bowel disease and cardiovascular disease: A two-sample Mendelian randomization analysis

Inflammatory bowel disease and cardiovascular disease: A two-sample Mendelian randomization analysis

A cause–effect relationship between Graves’ disease and the gut microbiome contributes to the thyroid–gut axis: A bidirectional two-sample Mendelian randomization study

Physical activity, sedentary behavior, and the risk of frailty and falling: A Mendelian randomization study

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