Network Mendelian randomization study: exploring the causal pathway from insomnia to type 2 diabetes.

INTRODUCTION: Insomnia is a novel pathogen for type 2 diabetes mellitus (T2DM). However, mechanisms linking insomnia and T2DM are poorly understood. In this study, we apply a network Mendelian randomization (MR) framework to determine the causal association between insomnia and T2DM and identify the potential mediators, including overweight (body mass index (BMI), waist-to-hip ratio, and body fat percentage) and glycometabolism (HbA1c, fasting blood glucose, and fasting blood insulin). RESEARCH DESIGN AND METHODS: We use the MR framework to detect effect estimates of the insomnia-T2DM, insomnia-mediator, and mediator-T2DM associations. A mediator between insomnia and T2DM is established if MR studies in all 3 steps prove causal associations. RESULTS: In the Inverse variance weighted method, the results show that insomnia will increase the T2DM risk (OR 1.142; 95% CI 1.072 to 1.216; p=0.000), without heterogeneity nor horizontal pleiotropy, strongly suggesting that genetically predicted insomnia has a causal association with T2DM. Besides, our MR analysis provides strong evidence that insomnia is causally associated with BMI and body fat percentage. There is also suggestive evidence of an association between insomnia and the waist-to-hip ratio. At the same time, our results indicate that insomnia is not causally associated with glycometabolism. Higher BMI, waist-to-hip ratio, and body fat percentage levels are strongly associated with increased risk of T2DM. CONCLUSIONS: Genetically predicted insomnia has a causal association with T2DM. Being overweight (especially BMI and body fat percentage) mediates the causal pathway from insomnia to T2DM.

Education and stroke: evidence from epidemiology and Mendelian randomization study.

We aim to characterize the association between education and incident stroke (including total stroke, ischemic stroke, and hemorrhagic stroke) and assess whether there is a causal relationship between them. The final sample size was 11,509 in this study from the Atherosclerosis Risk in Communities (ARIC) study. Cox hazard regression models were used to explore the association between education level and incident stroke. Two-sample Mendelian randomization (MR) was used to estimate the causality. During a median follow-up of 25.3 years, 915 cases (8.0%) of stroke occurred. Participants with advanced education level were associated with 25% (HR 0.75; 95% CI 0.62, 0.91) decreased the rate of incident total stroke. Hazard ratio of intermediate and advanced education level for ischemic stroke were 0.82 (0.69, 0.98) and 0.73 (0.60, 0.90) separately. In the MR analysis, we observed evidence that education was likely a negetive causal risk factor for ischemic stroke (OR 0.764, 95% CI 0.585-0.998, P = 0.048). Higher education level was associated with a decreased rate of total stroke and ischemic stroke incident, but not hemorrhagic stroke incident. There might be a protective causal association between education and ischemic stroke (but not total stroke nor hemorrhagic stroke).

High-frequency repetitive transcranial magnetic stimulation can relieve mild amnestic cognitive impairment / 中华物理医学与康复杂志

Objective:To investigate the therapeutic mechanism of high-frequency repetitive transcranial magnetic stimulation (rTMS) in treating mild amnestic cognitive impairment (aMCI).Methods:Twenty-five patients with aMCI were randomly divided into an observation group of 13 and a control group of 12. The observation group was given 10-Hz rTMS over the left dorsolateral prefrontal cortex at 80% of the motor threshold-400 pulses a day, 5 times a week for 4 consecutive weeks. The control group received sham stimulation on the same schedule. Before and after the experiment, both groups were evaluated using the Montreal cognitive assessment (MoCA) and received fMRI scans.Results:After the intervention, the average MoCA score of the observation group had improved significantly more compared with that of the control group and compared with before the intervention. According to the fMRI results, regional homogeneity in the right middle frontal gyrus of the observation group had increased significantly, while that of the control group both there and in the left precuneus had decreased significantly.Conclusions:High-frequency rTMS can effectively improve the cognitive function of patients with aMCI and synchronize neuron activity in cognition-related brain regions.