DataSheet_6_Bidirectional causal relational between frailty and mental illness: a two-sample Mendelian randomization study.csv

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.

背景：脆性（BackgroundFrailty）与精神疾病（MI）之间的关系已在观察性研究中得到证实，但二者之间的因果关系尚不明确。本研究旨在通过双样本孟德尔随机化（MR）分析评估脆性与精神疾病之间的双向因果关系。方法：为了探究三者之间的因果关系，本研究纳入了脆性指数（FI）的汇总统计以及六种类型的精神疾病：焦虑、抑郁、情感障碍、躁狂、精神分裂症和强迫症（OCD）。本研究采用逆方差加权（IVW）、MR-Egger回归和加权中位数进行MR分析。结果：FI的遗传易感性显著增加焦虑（优势比[OR] = 1.62，95%置信区间[CI] 1.13-2.33，P = 8.18E-03）、抑郁（OR = 1.88，95% CI 1.30-2.71，P = 8.21E-04）和情感障碍（OR = 1.70，95% CI 1.28-2.27，P = 2.57E-04）的风险。然而，本研究结果未显示FI与躁狂（OR = 1.02，95% CI 0.99-1.06，P = 2.20E-01）、精神分裂症（OR = 1.02，95% CI 0.07-0.86，P = 9.28E-01）之间存在因果关系。特别是，尽管逆方差加权（IVW）的结果暗示FI与OCD（OR = 0.64，95% CI 0.07-0.86，P = 2.85E-02）之间可能存在因果关系，但我们采用的三个方法获得的结论最终显示不一致。因此，结果需谨慎解读。反向MR分析的结果表明，焦虑（OR = 1.06，95% CI 1.01-1.11，P = 2.00E-02）、抑郁（OR = 1.14，95% CI 1.04-1.26，P = 7.99E-03）、情感障碍（OR = 1.15，95% CI 1.09-1.21，P = 3.39E-07）和精神分裂症（OR = 1.02，95% CI 1.01-1.04，P = 1.70E-03）与FI之间存在显著且因果的关系。然而，我们的发现不支持躁狂（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）与FI风险增加之间存在联系。结论：MR结果表明，FI与焦虑、抑郁和情感障碍之间可能存在双向因果关系。精神分裂症被发现与FI的高风险相关。对于FI与其他精神疾病之间的因果关系，证据不足。这些发现为脆性及精神疾病的有效管理策略的发展提供了新的见解。