Tobacco and alcohol consumption and the risk of frailty and falling: a Mendelian randomisation study

Guo, Xiaoqiang; Tang, Peng; Zhang, Lina; Li, Rui

doi:10.1136/jech-2022-219855

Cited by 10 publications

(6 citation statements)

References 39 publications

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“…Our study population consisted of ambulatory participants, excluding those with a life expectancy of less than 3 years, which could have influenced the observed association between the CCI and frailty [15]. Furthermore, our findings surprisingly suggest that alcohol consumption is inversely related to frailty, echoing results from limited studies, although this may be confounded by factors such as healthier individuals’ alcohol use or survivor bias [60,61].…”

Section: Discussionsupporting

confidence: 51%

The association between anticholinergic/sedative burden and physical frailty in people aging with HIV

Michael,

Brouillette,

Tamblyn

et al. 2023

Aids

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Objective: This study aimed to estimate the strength of the association between anticholinergic/sedative burden and concurrent physical frailty in people aging with HIV. Design: This cross-sectional analysis examined baseline data from 824 adults with a mean age of 53 enrolled in the Positive Brain Health Now study. Methods: Anticholinergic medications were identified using four methods: Anticholinergic Cognitive Burden (ACB) scale, Anticholinergic Risk Scale (ARS), Anticholinergic Drug Scale (ADS), and the anticholinergic list of the Anticholinergic and Sedative Burden Catalog (ACSBC). Sedatives were identified using the Sedative Load Model (SLM) and the sedative list of the ACSBC. Physical frailty was assessed using a modified Fried Frailty Phenotype based on self-report items. Multivariable logistic regression models, adjusted for sociodemographic factors, lifestyle considerations, HIV-related variables, comorbidities, and co-medication use, were used to estimate odds ratios (ORs). Results: Anticholinergic burden demonstrated associations with frailty across various methods: total anticholinergic burden (OR range: 1.22–1.32; 95% CI range: 1.03–1.66), sedative burden (OR range: 1.18–1.24; 95% CI range: 1.02–1.45), high anticholinergic burden (OR range: 2.12–2.74; 95% CI range: 1.03–6.19), and high sedative burden (OR range: 1.94–2.18; 95% CI: 1.01–4.34). Conclusion: The anticholinergic and sedative burdens may represent modifiable risk factors for frailty in people aging with HIV. Future studies should evaluate the effects of reducing anticholinergic and sedative burdens on frailty outcomes and explore the prognostic value of diverse scoring methods.

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Section: Discussionsupporting

confidence: 51%

The association between anticholinergic/sedative burden and physical frailty in people aging with HIV

Michael,

Brouillette,

Tamblyn

et al. 2023

Aids

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“…The independent assumption in MR stipulates that the selected SNPs are not correlated with confounding factors linked to both lung function and frailty. Although SNPs associated with previously reported confounding factors [ 21 , 42 ], such as smoking, alcohol consumption, body mass index, cancer, diabetes, coronary artery disease, inflammatory bowel disease, have been removed using the PhenoScanner V2 [ 19 ], we cannot completely rule out the influence of other undetermined potential confounding factors. This MR study exhibited robust statistical power for the causal effect of FEV1, FEV1/FVC, and PEF on frailty (> 99%), suggesting a good reliability of our findings.…”

Section: Discussionmentioning

confidence: 99%

“…An F -statistic greater than 10 indicates a strong IV, enabling the exclusion of weak IV biases. Subsequently, those IV with linkage disequilibrium (LD, r 2 < 0.001 within 10,000 kb) was clumped [ 21 ]. Finally, SNPs potentially associated with the corresponding outcome were also removed from the IV.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, we also employed MR-Egger and weighted median methods as sensitivity analyses to validate the stability of the estimates. The MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test was further used to identify outliers and exclude any peripheral SNPs that might influence the results, and the MR-Egger intercept test was conducted to assess the horizontal pleiotropy [ 21 , 24 ]. Additionally, to ensure the accuracy and credibility of MR analysis results, we conducted the Cochran's Q -statistic test to assess the heterogeneity of the IV.…”

Section: Mendelian Randomization Analysismentioning

confidence: 99%

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Lung function and the risk of frailty in the European population: a mendelian randomization study

Zhou,

Tian,

Guo

et al. 2024

Eur J Med Res

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Background Epidemiological evidence has suggested a relationship between lung function and frailty, but the precise nature of the causality remains unclear. In this study, we applied a two-sample Mendelian randomization (MR) analysis to determine the causal effects of lung function on frailty. Methods Single nucleotide polymorphisms (SNPs) independently related (P ≤ 5E−08) to lung function, as identified by genome-wide association study (GWAS), were applied as instrumental variables (IV). The association with frailty index (FI) was investigated using summary-level data from the latest GWAS on FI (n = 175,226). Different statistical methods were employed to evaluate the causal estimates between lung function and FI. The pleiotropy, heterogeneity, and leave-one-out analysis were applied to confirm the stability of the MR estimates. Results Using the random-effect inverse-variance weighted approach, genetically proxied forced expiratory volume in the first second (FEV1), ratio of FEV1 on forced vital capacity (FVC) [FEV1/FVC], and peak expiratory flow (PEF) were significantly and inversely associated with FI (FEV1, β = −0.08, P = 2.03E−05; FEV1/FVC, β = −0.06, P = 9.51E−06; PEF, β = −0.07, P = 4.09E−04) with good statistical power (99.7–100%). However, no significant association was observed between FVC and FI (β = −0.01, P = 0.681). Leave-one-out analysis showed that there was no single SNP driving the bias of the estimates. There was potential heterogeneity, but no obvious pleiotropy was founded in this MR study. Conclusions Our findings indicate that impaired pulmonary function is closely related to the risk of frailty. Enhancing lung function in the elderly population may contribute to the prevention of frailty to a certain extent.

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“…Previous studies have affirmed significantly correlation between genetically determined body mass index (BMI) and the initiation of smoking (whether an individual had ever smoked regularly) with the risk of falls [ 27 , 28 ]. BMI and smoking initiation are modifiable factors in daily life.…”

Section: Methodsmentioning

confidence: 99%

Causal associations between genetically determined common psychiatric disorders and the risk of falls: evidence from Mendelian randomization

Zhang,

Xu,

Yuan

et al. 2023

Eur J Med Res

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Background The causal associations between psychiatric disorders and falls risk remains uncertain. Consequently, this study aimed to explore the causal relationship between genetically determined three common psychiatric disorders and the risk of falls based on Mendelian randomization (MR). Methods The genome-wide association study (GWAS) data for schizophrenia (SCZ) (N = 320,404), major depressive disorder (MDD) (N = 480,359), and Alzheimer's disease (AD) (N = 63,926) were obtained as exposures. The GWAS data for falls risk (N = 451,179) was obtained as outcome. Univariate Mendelian randomization (UVMR) was used to evaluate the direct causal relationship between SCZ, MDD, AD, and risk of falls. Inverse variance weighting (IVW) was used as the primary analysis method. Sensitivity analysis was performed to assess the validity of the casualty. Multivariate Mendelian randomization (MVMR) analysis was conducted after adjusting body mass index and smoking initiation. Mediating MR was conducted to calculate the mediating effects of potential intermediaries. Results UVMR analysis showed that SCZ (OR 1.02, 95% CI 1.01–1.04, p = 8.03E−03) and MDD (OR 1.15, 95% CI 1.08–1.22, p = 1.38E−05) were positively associated with the risk of falls. Sensitivity analysis results were reliable and robust. MVMR results indicated that the relationship between MDD and SCZ and falls risk remained significant. Mediating MR results demonstrated that smoking initiation mediated partial causal effect of SCZ (0.65%, P = 0.03) and MDD (14.82%, P = 2.02E−03) on risk of falls. Conclusions This study provides genetic evidence for a causal relationship of individuals with SCZ and MDD on an increased risk of falls. Healthcare providers should be aware of the risk of falls in MDD and SCZ patients and develop strategies accordingly.

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Tobacco and alcohol consumption and the risk of frailty and falling: a Mendelian randomisation study

Cited by 10 publications

References 39 publications

The association between anticholinergic/sedative burden and physical frailty in people aging with HIV

The association between anticholinergic/sedative burden and physical frailty in people aging with HIV

Lung function and the risk of frailty in the European population: a mendelian randomization study

Causal associations between genetically determined common psychiatric disorders and the risk of falls: evidence from Mendelian randomization

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