Background The 2019 coronavirus disease pandemic (COVID-19) poses an enormous threat to public health worldwide, and the ensuing management of social isolation has greatly decreased opportunities for physical activity (PA) and increased opportunities for leisure sedentary behaviors (LSB). Given that both PA and LSB have been established as major influencing factors for obesity, diabetes and cardiometabolic syndrome, whether PA/LSB in turn affects the susceptibility to COVID-19 by disrupting metabolic homeostasis remains to be explored. In this study, we aimed to systematically evaluate the causal relationship between PA/LSB and COVID-19 susceptibility, hospitalization and severity using a Mendelian randomization study. Methods Data were obtained from a large-scale PA dataset (N = 377,000), LSB dataset (N = 422,218) and COVID-19 Host Genetics Initiative (N = 2,586,691). The causal effects were estimated with inverse variance weighted, MR-Egger, weighted median and MR-PRESSO. Sensitivity analyses were implemented with Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis and the funnel plot. Risk factor analyses were further conducted to investigate the potential mediators. Results Genetically predicted accelerometer-assessed PA decreased the risk for COVID-19 hospitalization (OR = 0.93, 95% CI 0.88–0.97; P = 0.002), while leisure television watching significantly increased the risk of COVID-19 hospitalization (OR = 1.55, 95% CI 1.29–1.88; P = 4.68 × 10–6) and disease severity (OR = 1.85, 95% CI 1.33–2.56; P = 0.0002) after Bonferroni correction. No causal effects of self-reported moderate to vigorous physical activity (MVPA), accelerometer fraction of accelerations > 425 milligravities, computer use or driving on COVID-19 progression were observed. Risk factor analyses indicated that the above causal associations might be mediated by several metabolic risk factors, including smoking, high body mass index, elevated serum triglyceride levels, insulin resistance and the occurrence of type 2 diabetes. Conclusion Our findings supported a causal effect of accelerometer-assessed PA on the reduced risk of COVID-19 hospitalization as well as television watching on the increased risk of COVID-19 hospitalization and severity, which was potentially mediated by smoking, obesity and type 2 diabetes-related phenotypes. Particular attention should be given to reducing leisure sedentary behaviors and encouraging proper exercise during isolation and quarantine for COVID-19.

BackgroundPrevious studies have reported that gut microbiota is associated with an increased risk of chronic kidney disease (CKD) progression. However, whether gut microbiota has a causal effect on the development of CKD has not been revealed. Thus, we aimed to analyze the potential causal effect of gut microbiota on the risk of CKD using mendelian randomization (MR) study.Materials and MethodsIndependent single nucleotide polymorphisms closely associated with 196 gut bacterial taxa (N = 18340) were identified as instrumental variables. Two-sample MR was performed to evaluate the causal effect of gut microbiota on CKD (N = 480698), including inverse-variance-weighted (IVW) method, weighted median method, MR-Egger, mode-based estimation and MR-PRESSO. The robustness of the estimation was tested by a series of sensitivity analyses including Cochran’s Q test, MR-Egger intercept analysis, leave-one-out analysis and funnel plot. Statistical powers were also calculated.ResultsThe genetically predicted higher abundance of order Desulfovibrionales was causally associated with an increased risk of CKD (odds ratio = 1.15, 95% confidence interval: 1.05-1.26; p = 0.0026). Besides, we also detected potential causalities between nine other taxa (Eubacterium eligens group, Desulfovibrionaceae, Ruminococcaceae UCG-002, Deltaproteobacteria, Lachnospiraceae UCG-010, Senegalimassilia, Peptostreptococcaceae, Alcaligenaceae and Ruminococcus torques group) and CKD (p < 0.05). No heterogeneity or pleiotropy was detected for significant estimates.ConclusionWe found that Desulfovibrionales and nine other taxa are associated with CKD, thus confirming that gut microbiota plays an important role in the pathogenesis of CKD. Our work also provides new potential indicators and targets for screening and prevention of CKD.

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ObjectivesAdiponectin is closely related to glucose metabolism and traditional diabetes risk factors (obesity, hypertension and dyslipidaemia). We aimed to explore the association between adiponectin levels and newly diagnosed type 2 diabetes mellitus (T2DM) and pre-diabetes in subgroups classified according to T2DM risk factors.SettingSun Yat-sen Memorial Hospital of Sun Yat-sen University.Participants3680 individuals (1753 men and 1927 women) aged 18–70 years from Guangzhou and Dongguan, China, were enrolled from December 2018 to October 2019.Primary and secondary outcome measuresT2DM was defined as fasting plasma glucose (FPG)≥7.0 mmol/L or HbA1c≥6.5%, and pre-diabetes was defined as 6.1 mmol/L≤FPG<7.0 mmol/L or 5.7≤HbA1c<6.5%.ResultsWith the increasing number of T2DM risk factors, the proportion of the population with high-quartile adiponectin levels gradually decreased (p<0.001). A low level of adiponectin was significantly associated with diabetes and pre-diabetes in a population with ≥1 T2DM risk factor, whereas its association was not consistently significant in the population with all three T2DM risk factors. For instance, participants were more likely to have diabetes or prediabetes with low levels of adiponectin when they had ≥ one T2DM risk factor (quartile 2 vs. 1: OR 0.71 [95%CI: 0.56–0.89]; P=0.003; quartile 3 vs. 1: OR 0.57 [95%CIs: 0.44–0.72]; P<0.001; and quartile 4 vs. 1: OR 0.52 [95%CIs: 0.40–0.67]; P<0.001).ConclusionAdiponectin was negatively associated with diabetes and pre-diabetes in a population with few T2DM risk factors, while their relationship gradually attenuated with the accumulation of T2DM risk factors, especially in a population with coexisting diseases such as obesity, hypertension and dyslipidaemia.

Background It has been observed that cancer and venous thromboembolism (VTE) are associated, but anticancer therapy may violate the causality. Therefore, this study aimed to elucidate the causal relationship of various cancers to VTE using Mendelian randomization (MR). Methods Three MR methods were used to estimate causal effects: Inverse variance weighted (IVW), MR‐Egger and weighted median. Sensitivity analyses included Cochran's Q‐test, MR‐Egger intercept test and MR‐PRESSO. Gene ontology enrichment analysis was performed to elucidate the underlying mechanisms of VTE development in cancer patients. Results The primary IVW approach showed that non‐Hodgkin's lymphoma (NHL) might increase the risk of VTE (odds ratio [OR]: 1.20, 95% confidence interval [95% CI]: 1.00–1.44, p = 0.045), while melanoma possibly reduced the risk of VTE (OR: 0.89, 95% CI: 0.82–0.97, p = 0.006), although there was no significance after adjustment for multiple testing. No association was observed between VTE risk and other site‐specific cancers. Gene ontology enrichment analysis revealed that vitamin D played an important role in the development of VTE in cancer patients. Conclusions Our findings suggested that genetically predicted NHL was associated with higher VTE risk, whereas melanoma had lower VTE risk compared with other site‐specific cancers. Moreover, this study suggested that anticancer therapy and increased extensive examination might play a more important role in VTE development than the nature of cancer.