DataSheet_7_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：衰弱与精神疾病（MI）之间的关联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）分析评估衰弱与MI之间的双向因果关系。方法：为了探究三者之间的因果关系，本研究纳入了衰弱指数（FI）的汇总统计数据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）。该MR分析采用逆方差加权（IVW）、MR-Egger回归和加权中位数方法进行。结果：FI的遗传易感性显著增加了焦虑（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，本研究未发现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IVW结果提示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，但我们所采用的三个方法得出的方向最终显示出不一致性。因此，结果必须谨慎解读。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之间存在显著的因果关系。然而，我们的研究结果并未支持躁狂（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风险增加之间的联系。结论：MR结果表明，FI与焦虑、抑郁和情感障碍之间存在潜在的双向因果关系。精神分裂症被发现与FI风险增加相关。关于FI与其他MI之间的因果关系，证据不足。这些发现为开发针对衰弱与MI的有效管理策略提供了新的洞见。