Association between frailty and depression: A bidirectional Mendelian randomization study
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ABSTRACT:
SUBMITTER: Deng M
PROVIDER: S-EPMC10511184 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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Project description:BackgroundObservational studies have demonstrated a strong bidirectional association between frailty and depression, but it remains unclear whether this association reflects causality. This study aimed to examine the bidirectional causal relationship between frailty and depression.MethodsUsing genome-wide association study summary data, two-sample Mendelian randomization was performed to test for the potential bidirectional causality between frailty, as defined by both the frailty index and the frailty phenotype, and depression. Several frailty-related traits were additionally investigated, including weaker hand grip strength, slower walking pace and physical inactivity. Findings were replicated using an independent depression data source and verified using multiple sensitivity analyses.ResultsGenetically predicted higher frailty index (odds ratio [OR], 1.86; P < 0.001), higher frailty phenotype score (OR, 2.79; P < 0.001), lower grip strength (OR, 1.23; P = 0.003), slower walking pace (OR, 1.55; P = 0.027) and physical inactivity (OR, 1.44; P = 0.003) all were associated with a higher risk of depression. As for the reverse direction, genetic liability to depression showed consistent associations with a higher frailty index (beta, 0.167; P < 0.001) and a higher frailty phenotype score (beta, 0.067; P = 0.001), but not with other frailty-related traits that were investigated. The results were stable across sensitivity analyses and across depression datasets.ConclusionsOur findings add novel evidence supporting the bidirectional causal association between frailty and depression. Improving balance and muscle strength and increasing physical activity may be beneficial in both depression and frailty.
| S-EPMC10570069 | biostudies-literature
Project description:BackgroundThe causality between frailty and gestational diabetes mellitus (GDM) has not yet been fully explored. A potential bidirectional causality was also needed to be confirmed.MethodsA bidirectional two-sample Mendelian randomization (MR) was conducted, with frailty-related data was collected from UK Biobank and TwinGen and GDM-related data was collected from the FinnGen consortium. We performed univariable and multivariable-adjusted MR with adjustments for body mass index (BMI). Several methodologies of MR were conducted to confirm the robustness of results.ResultsFrailty was significantly associated with elevated risks of GDM (OR, 3.563; 95% CI, 1.737 to 7.309; P< 0.001) and GDM was also significantly associated with elevated risks of frailty ( β , 0.087; 95% CI, 0.040 to 0.133; P< 0.001). There is no evidence demonstrating the existence of horizontal pleiotropy and heterogeneity. This association was robust after adjustments for BMI. The sensitivity analyses with Weighted median, Maximum likelihood, Penalised weighted median, MR Egger and MR PRESSO methods indicated consistent results.ConclusionOur study provides evidence of the bidirectional causal association between frailty and GDM from genetic perspectives, signaling that the identification and assessment of frailty should become a standard strategy during the early stages and care of gestational diabetes.
| S-EPMC11236542 | biostudies-literature
Project description:BackgroundNumerous observational studies have suggested a correlation between sarcopenia and depression, but the nature of this relationship requires further investigation.MethodsThis study employed bidirectional Mendelian randomization to explore this connection. Data from genome-wide association studies were used, encompassing measures of sarcopenia and mental factors, including depression and emotional states. The initial analysis concentrated on the impact of depression on sarcopenia, and then it examined the reverse relationship. The same methodology was applied to emotional data for validation.ResultsThe results indicated a reciprocal causation between sarcopenia and depression, even when emotional state data were considered. Various emotions can impact sarcopenia, and in turn, sarcopenia can affect emotions, except subjective well-being. These findings highlight a cyclic deterioration between sarcopenia and depression, with a link to negative emotions and a partially ameliorative effect of subjective well-being on sarcopenia.ConclusionsIn summary, this study sheds light on the interplay between psychiatric factors and sarcopenia, offering insights into intervention and prevention strategies.
| S-EPMC11319753 | biostudies-literature
Project description:BackgroundWhile previous observational studies have suggested a link between frailty and acute respiratory distress syndrome (ARDS), the causality of this connection remains unclear. The objective of this study was to explore the potential bidirectional causal links between frailty and ARDS.MethodsA two-sample univariable Mendelian randomization (MR) was performed to assess the causal relationship between frailty, as defined by frailty index (FI, n = 175,226) and fried frailty score (FFS, n = 386,565), and ARDS. The genome-wide association study (GWAS) data of frailty was from the UK Biobank and the ARDS data was from the FinnGen Database. Univariable MR analyses were conducted using inverse-variance weighted (IVW), weighted median, MR-Egger regression, and robust adjusted profile score (MR. RAPS). We also performed multivariable Mendelian randomization (MVMR) analysis including smoking initiation, alcohol consumption, body mass index (BMI), and cognitive performance.ResultsThis bidirectional MR analysis demonstrated no causal effect of FI (OR = 0.96, 95% CI 0.14-6.88) and FFS (OR = 1.95, 95%CI 0.14-28.16) on increased susceptibility of ARDS. Also, no evidence was found for an effect of ARDS on the risk of frailty. The MVMR analysis indicated higher BMI and poorer cognitive performance were associated with increased risk of ARDS.ConclusionsThe outcomes of our analysis imply a probable absence of a direct causal relationship between frailty and susceptibility to ARDS. To reinforce and expand upon these preliminary findings, it is imperative to conduct larger-scale genome-wide association studies.
| S-EPMC11605894 | biostudies-literature
Project description:ObjectiveThe bidirectional correlation between low bone mineral density (BMD) and frailty, despite its extensive documentation, still lacks a conclusive understanding. The objective of this Mendelian randomization (MR) study is to investigate the bidirectional causal relationship between BMD and frailty.MethodsWe utilized summary statistics data for BMD at different skeletal sites-including heel BMD (e-BMD, N = 40,613), forearm BMD (FA-BMD, N = 8,143), femoral neck BMD (FN-BMD, N = 32,735), and lumbar spine BMD (LS-BMD, N = 28,489), alongside frailty index (FI, N = 175,226) data in participants of European ancestry. MR analysis in our study was conducted using well-established analytical methods, including inverse variance weighted (IVW), weighted median (WM), and MR-Egger approaches.ResultsWe observed negative causal estimates between genetically predicted e-BMD (IVW β = - 0.020, 95% confidence interval (CI) = - 0.038, - 0.002, P = 0.029) and FA-BMD (IVW β = -0.035, 95% CI = -0.066, -0.004, P = 0.028) with FI. However, the results did not reach statistical significance after applying the Bonferroni correction, with a significance threshold set at P < 0.0125 (0.05/4). There was no causal effect of FN-BMD (IVW β = - 0.024, 95% CI = -0.052, 0.004, P = 0.088) and LS-BMD (IVW β = - 0.005, 95% CI = -0.034, 0.024, P = 0.749) on FI. In the reverse Mendelian randomization (MR) analysis, we observed no causal effect of FI on BMD at various skeletal sites.ConclusionOur study provides support for the hypothesis that low BMD may be a potential causal risk factor for frailty, but further research is needed to confirm this relationship. However, our findings did not confirm reverse causality.
| S-EPMC10810463 | biostudies-literature
Project description:BackgroundFrailty has been associated with mental illness (MI) observational studies, but the causal relationship between these factors remains uncertain. We aimed to assess the bidirectional causality between frailty and MI by two-sample Mendelian randomization (MR) analyses.MethodsTo investigate the causal relationship among them, summary statistics of frailty index (FI) and six types of MI: anxiety, depression, affective disorder, mania, schizophrenia, and obsessive-compulsive disorder (OCD) were included in this MR study. This MR analysis was performed using inverse variance weighting (IVW), MR-Egger regression, and weighted median. The stability of the results was evaluated using Cochran's Q test, MR-Egger intercept test, Funnel Plots, and leave-one-out analysis.ResultsGenetic predisposition to FI was significantly associated with increased anxiety (odds ratio [OR] = 1.62, 95% confidence interval [CI] 1.13-2.33, P = 8.18E-03), depression (OR = 1.88, 95% CI 1.30-2.71, P = 8.21E-04), affective disorder (OR = 1.70, 95% CI 1.28-2.27, P = 2.57E-04). However, our study findings do not demonstrate a causal relationship between FI and mania (OR = 1.02, 95% CI 0.99-1.06, P = 2.20E-01), schizophrenia (OR = 1.02, 95% CI 0.07-0.86, P = 9.28E-01). In particular, although the IVW results suggest a potential causal relationship between FI and OCD (OR = 0.64, 95% CI 0.07-0.86, P = 2.85E-02), the directions obtained from the three methods we employed ultimately show inconsistency. Therefore, the result must be interpreted with caution. The results of the reverse MR analysis indicated a statistically significant and causal relationship between anxiety (OR = 1.06, 95% CI 1.01-1.11, P = 2.00E-02), depression (OR = 1.14, 95% CI 1.04-1.26, P = 7.99E-03), affective disorder (OR = 1.15, 95% CI 1.09-1.21, P = 3.39E-07), and schizophrenia (OR = 1.02, 95% CI 1.01-1.04, P = 1.70E-03) with FI. However, our findings do not provide support for a link between mania (OR = 1.46, 95% CI 0.79-2.72, P = 2.27E-01), OCD (OR = 1.01, 95% CI 1.00-1.02, P = 2.11E-01) and an increased risk of FI.ConclusionThe MR results suggest a potential bidirectional causal relationship between FI and anxiety, depression, and affective disorder. Schizophrenia was found to be associated with a higher risk of FI. The evidence was insufficient to support a causal relationship between Fl and other Ml. These findings offer new insights into the development of effective management strategies for frailty and MI.
| S-EPMC11190300 | biostudies-literature
Project description:Observational studies suggested a bidirectional correlation between depression and metabolic syndrome (MetS) and its components. However, the causal associations between them remained unclear. We aimed to investigate whether genetically predicted depression is related to the risk of MetS and its components, and vice versa. We performed a bidirectional two-sample Mendelian randomization (MR) study using summary-level data from the most comprehensive genome-wide association studies (GWAS) of depression (n = 2,113,907), MetS (n = 291,107), waist circumference (n = 462,166), hypertension (n = 463,010) fasting blood glucose (FBG, n = 281,416), triglycerides (n = 441,016), high-density lipoprotein cholesterol (HDL-C, n = 403,943). The random-effects inverse-variance weighted (IVW) method was applied as the primary method. The results identified that genetically predicted depression was significantly positive associated with risk of MetS (OR: 1.224, 95% CI: 1.091-1.374, p = 5.58 × 10-4), waist circumference (OR: 1.083, 95% CI: 1.027-1.143, p = 0.003), hypertension (OR: 1.028, 95% CI: 1.016-1.039, p = 1.34 × 10-6) and triglycerides (OR: 1.111, 95% CI: 1.060-1.163, p = 9.35 × 10-6) while negative associated with HDL-C (OR: 0.932, 95% CI: 0.885-0.981, p = 0.007) but not FBG (OR: 1.010, 95% CI: 0.986-1.034, p = 1.34). No causal relationships were identified for MetS and its components on depression risk. The present MR analysis strength the evidence that depression is a risk factor for MetS and its components (waist circumference, hypertension, FBG, triglycerides, and HDL-C). Early diagnosis and prevention of depression are crucial in the management of MetS and its components.
| S-EPMC8668963 | biostudies-literature
Project description:BackgroundAccumulating evidence of clinical and neuroimaging studies indicated that migraine is related to brain structural alterations. However, it is still not clear whether the associations of brain structural alterations with migraine are likely to be causal, or could be explained by reverse causality confounding.MethodsWe carried on a bidirectional Mendelian randomization analysis in order to identify the causal relationship between brain structures and migraine risk. Summary-level data and independent variants used as instruments came from large genome-wide association studies of total surface area and average thickness of cortex (33,992 participants), gray matter volume (8,428 participants), white matter hyperintensities (50,970 participants), hippocampal volume (33,536 participants), and migraine (102,084 cases and 771,257 controls).ResultsWe identified suggestive associations of the decreased surface area (OR = 0.85; 95% CI, 0.75-0.96; P = 0.007), and decreased hippocampal volume (OR = 0.74; 95% CI, 0.55-1.00; P = 0.047) with higher migraine risk. We did not find any significant association of gray matter volume, cortical thickness, or white matter hyperintensities with migraine. No evidence supporting the significant association was found in the reverse MR analysis.ConclusionWe provided suggestive evidence that surface area and hippocampal volume are causally associated with migraine risk.
| S-EPMC10020331 | biostudies-literature
Project description:Urticaria is characterized by transient itchy symptoms on the skin, usually accompanied by swelling, which is caused by mast cell activation leading to increased vascular permeability and dilation of the dermis. Urticaria involves recurrent activation of mast cells, T cells, eosinophils, and other immune cells around lesioned venules, with complex regulatory systems affecting mast cell functions, potentially contributing to urticaria pathogenesis. The direct causal relationship between immune cells and urticaria is currently unclear. To address this, our study utilized a bidirectional Mendelian randomization analysis, employing instrumental variables (IVs) associated with immune cells and urticaria, to investigate this causal relationship. First, by utilizing Genome-wide Association Study (GWAS) data, we identified 31 immunophenotypes associated with urticaria risk, with 18 increasing and 13 decreasing the risk. Through rigorous criteria, we identified 4 immunophenotypes that have a strong causal relationship with urticaria. Notably, HLA DR+ CD4+AC, CD45 on CD8br, and HLA DR on plasmacytoid dendritic cells were associated with an increased risk, while CD8dim NKT %lymphocyte was identified as a protective factor. Sensitivity analyses, including the MR-Egger intercept test, scatter plots, funnel plots, and leave-one-out analysis, supported the robustness of the findings. Reverse MR analysis suggested an inverse causal effect of urticaria on CD8dim NKT %lymphocyte, reinforcing the potential bidirectional nature of the relationship between urticaria and immune cell phenotypes. Our research substantiates the bidirectional causal relationship between immune cells and urticaria, thus benefiting for urticaria-targeted therapy development.
| S-EPMC11599194 | biostudies-literature
Project description:BackgroundPrevious epidemiological studies have reported associations between vitamin D and postpartum depression (PPD); however, the findings are inconsistent. This study employs bidirectional Mendelian Randomization (MR) to investigate the causal link between serum 25-hydroxyvitamin D [25(OH)D] levels and PPD. By utilizing genetic data from cohorts, this research aims to provide a more robust understanding of the potential relationship between vitamin D and PPD, addressing a critical gap in the current literature.MethodsA bidirectional MR analysis was conducted to investigate the genetic association between serum 25(OH)D and PPD using summary statistics extracted from GWAS datasets. The study included data from 15,668 patients with PPD and 376,755 healthy controls of European ancestry. The GWAS data for 25(OH)D were obtained from two studies within the UK Biobank, encompassing 496,946 and 79,366 participants. The primary analysis employed the inverse-variance weighted (IVW) method, while supplementary MR estimates were derived through the MR-Egger and weighted median (WME) methods. Furthermore, sensitivity analyses were implemented to ensure robustness and reliability, including Cochran's Q test, MR-PRESSO, MR-Egger intercept test, and the leave-one-out test.ResultsThe MR study revealed no substantial genetic correlation between serum 25(OH)D levels and PPD (OR = 1.065, 95%CI = 0.878-1.293, P = 0.522 for set A; OR = 0.978, 95 % CI = 0.669-1.430, P = 0.910 for set B). Additionally, in the reverse analysis, we did not observe a significant causal impact of PPD on serum 25(OH)D (OR = 1.001, 95%CI = 0.974-1.028, P = 0.951 for set A; OR = 1.011, 95%CI = 0.992-1.031, P = 0.261 for set B). The results obtained from MR-Egger and WME analyses concord with those derived from the IVW method. Conducting leave-one-out tests did not identify any single nucleotide polymorphism that might have influenced the MR results, confirming the robustness and reliability of the findings.ConclusionsThe results suggest the absence of a causal link between vitamin D concentrations and PPD. Inconsistent observations in previous observational studies may be attributed to residual confounding.
| S-EPMC11255668 | biostudies-literature