Assessment of the bidirectional causal association between frailty and depression: A Mendelian randomization study

Zhu, Jiahao; Zhou, Dan; Nie, Yaoyao; Wang, Jing; Yang, Ye; Chen, Dingwan; Yu, Min; Li, Yingjun

doi:10.1002/jcsm.13319

Cited by 23 publications

(9 citation statements)

References 36 publications

(73 reference statements)

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“…A series of sensitivity analyses was subsequently conducted. The MR-Egger intercept test and Cochran's Q statistic were employed to assess the presence of horizontal pleiotropy and heterogeneity, respectively [20,21]. Additionally, a leave-one-out analysis was employed to assess the in uence of individual SNPs on the overall estimates.…”

Section: Discussionmentioning

confidence: 99%

Causal Associations between frailty and low back pain: a bidirectional two-sample Mendelian randomization study

Liu,

Fan,

et al. 2024

Preprint

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Background Previous observational studies have revealed a potentially robust reciprocal bidirectional relationship between frailty and low back pain (LBP). However, the precise causal relationship remains unclear. Methods To examine the potential causal association between frailty and low back pain, we conducted bidirectional two-sample Mendelian randomization analysis (MR) study. Genetic data on frailty index (FI) and LBP were acquired from publicly available genome-wide association studies (GWAS). Various MR methodologies were utilized, such as random effects inverse variance weighting (IVW), weighted median, and MR-Egger, to evaluate causality. Additionally, sensitivity analyses were conducted to evaluate the robustness of the findings. Results Genetically predicted higher frailty index (IVW, odds ratio [OR] = 1.66, 95% CI 1.17–2.36, p = 4.92E-03) was associated with a higher risk of low back pain. As for the reverse direction, genetic liability to low back pain showed consistent associations with a higher frailty index (IVW, OR = 1.13, 95% CI 1.07–1.19, p = 2.68E-05). The outcomes from various MR techniques and sensitivity analyses indicate the robustness of our findings. Conclusion Our research findings provide additional evidence bolstering the bidirectional causal relationship between frailty and LBP.

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Section: Discussionmentioning

confidence: 99%

Causal Associations between frailty and low back pain: a bidirectional two-sample Mendelian randomization study

Liu,

Fan,

et al. 2024

Preprint

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“…In contrast, schizophrenia was associated with higher FI, and there was no reliable evidence to support genetically predicted effects of manic and OCD on FI. Although several previous MR studies have explored the causal relationship between frailty and some MI ( 17 , 28 – 31 ), our study possesses several strengths worth noting. First, this study is the first to explore the causal relationship between FI and affective disorders, mania, and OCD through MR. Secondly, our data were sourced from the latest version of the database and enhancing the reliability of our results and updating for previous findings.…”

Section: Discussionmentioning

confidence: 99%

Bidirectional causal relational between frailty and mental illness: a two-sample Mendelian randomization study

Ma,

Liu,

et al. 2024

Front. Psychiatry

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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.

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“…The severity of frailty is related to the number of frailty phenotypes that a person possesses. In general, individuals are considered frail when they exhibit three or more of the aforementioned indicators of frailty ( Zhu et al, 2023 ). As there is no broad consensus on the definition of frailty, we relied on the prevailing definition of frailty in the existing literature to align with the GWAS data on frailty in UK Biobank ( Supplementary Material a ).…”

Section: Methodsmentioning

confidence: 99%

Association between physical frailty and cortical structure in middle-aged and elderly people: a Mendelian randomization study

Zhang,

Wang,

Zou

et al. 2024

Front. Aging Neurosci.

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IntroductionPhysical weakness is associated with cortical structures, but the exact causes remain to be investigated. Therefore, we utilized Mendelian randomization (MR) analysis to uncover the underlying connection between frailty and cortical structures.MethodsThe Genome-Wide Association Study (GWAS) on frailty pooled data from publicly available sources such as the UK Biobank and included five indicators of frailty: weakness, walking speed, weight loss, physical activity, and exhaustion. GWAS data on cerebral cortical structure were obtained from the ENIGMA consortium, and we assessed the causal relationship between hereditary frailty and cortical surface area (SA) or cortical thickness (TH). Inverse variance weighting (IVW) was used as the primary estimate, and heterogeneity and multidimensionality were monitored by MR-PRESSO to detect outliers. Additionally, MR-Egger, Cochran’s Q test, and weighted median were employed.ResultsAt the aggregate level, there was no causal relationship between frailty and cortical thickness or surface area. At the regional level, frailty was associated with the thickness of the middle temporal lobe, parahippocampus, rostral middle frontal lobe, lower parietal lobe, anterior cingulate gyrus, upper temporal lobe, lateral orbital frontal cortex, pericardial surface area, rostral middle frontal lobe, upper temporal lobe, rostral anterior cingulate gyrus, lower parietal lobe, and upper parietal lobe. These results were nominally significant, and sensitivity analyses did not detect any multidirectionality or heterogeneity, suggesting that the results of our analyses are reliable.DiscussionThe results of our analyses suggest a potential causal relationship between somatic weakness and multiple regions of cortical structure. However, the specific mechanisms of influence remain to be investigated. Preliminary results from our analysis suggest that the effects of physical frailty on cortical structures are influenced by various factors related to frailty exposure. This relationship has been documented, and it is therefore both feasible and meaningful to build on existing research to explore the clinical significance of the relationship.

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Assessment of the bidirectional causal association between frailty and depression: A Mendelian randomization study

Cited by 23 publications

References 36 publications

Causal Associations between frailty and low back pain: a bidirectional two-sample Mendelian randomization study

Causal Associations between frailty and low back pain: a bidirectional two-sample Mendelian randomization study

Bidirectional causal relational between frailty and mental illness: a two-sample Mendelian randomization study

Association between physical frailty and cortical structure in middle-aged and elderly people: a Mendelian randomization study

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