Causal effects of various types of physical activities on psychiatric disorders: a Mendelian randomization study

BackgroundPsychiatric disorders (PD) pose a significant burden, with vast prevalence and mortality, inflicting substantial costs on individuals and society. Despite its widespread prevalence, the complex pathogenesis of PD remains elusive, leading to limited and challenging therapeutic development. An emerging risk factor for chronic diseases, prolonged sedentary behavior, contrasts with the therapeutic potential of exercise, regardless of its intensity, for various ailments, including PD. Yet, the diversity in exercise modalities and intensities may offer varied impacts on health. This study, leveraging Mendelian Randomization (MR), seeks to investigate the causal relationship between exercise and PD, aiming to elucidate the optimal exercise modality and intensity for PD mitigation while addressing potential confounders.MethodsThis study employed a Mendelian randomization analysis using the genome-wide association study (GWAS) database to investigate the causal relationship between types of physical activity and psychiatric disorders. Sensitivity analysis was conducted to demonstrate the reliability and robustness of the results.ResultsIn the past 4 weeks, engaging in a substantial amount of DIY physical activity was found to have a causal relationship with psychiatric disorders (IVW: OR = 0.228, 95% CI: 0.113–0.461, P = 0.000038). As for the types of exercises, there may be a potential causal association between aerobic training (including swimming, cycling, fitness, and bowling) and psychiatric disorders (IVW: OR = 0.322, 95% CI = 0.148–0.704, P = 0.004). However, there was no causal relationship found between mild DIY physical activity and psychiatric disorders (IVW: OR = 0.918, 95% CI = 0.417–2.021, P = 0.831). Furthermore, it seems that there is no causal relationship between vigorous exercise and psychiatric disorders (IVW: OR = 2.705, 95% CI = 0.081–3.419, P = 0.578).ConclusionOur study confirms that only a certain level of training activity can have a protective effect on psychiatric disorders, while mild physical activity or vigorous training does not have an impact on psychiatric disorders

DomainRBF: a Bayesian regression approach to the prioritization of candidate domains for complex diseases

BACKGROUND: Domains are basic units of proteins, and thus exploring associations between protein domains and human inherited diseases will greatly improve our understanding of the pathogenesis of human complex diseases and further benefit the medical prevention, diagnosis and treatment of these diseases. Within a given domain-domain interaction network, we make the assumption that similarities of disease phenotypes can be explained using proximities of domains associated with such diseases. Based on this assumption, we propose a Bayesian regression approach named domainRBF (domain Rank with Bayes Factor) to prioritize candidate domains for human complex diseases. RESULTS: Using a compiled dataset containing 1,614 associations between 671 domains and 1,145 disease phenotypes, we demonstrate the effectiveness of the proposed approach through three large-scale leave-one-out cross-validation experiments (random control, simulated linkage interval, and genome-wide scan), and we do so in terms of three criteria (precision, mean rank ratio, and AUC score). We further show that the proposed approach is robust to the parameters involved and the underlying domain-domain interaction network through a series of permutation tests. Once having assessed the validity of this approach, we show the possibility of ab initio inference of domain-disease associations and gene-disease associations, and we illustrate the strong agreement between our inferences and the evidences from genome-wide association studies for four common diseases (type 1 diabetes, type 2 diabetes, Crohn\u27s disease, and breast cancer). Finally, we provide a pre-calculated genome-wide landscape of associations between 5,490 protein domains and 5,080 human diseases and offer free access to this resource. CONCLUSIONS: The proposed approach effectively ranks susceptible domains among the top of the candidates, and it is robust to the parameters involved. The ab initio inference of domain-disease associations shows strong agreement with the evidence provided by genome-wide association studies. The predicted landscape provides a comprehensive understanding of associations between domains and human diseases

Functional analysis and binding affinity of tomato ethylene response factors provide insight on the molecular bases of plant differential responses to ethylene

Background : The phytohormone ethylene is involved in a wide range of developmental processes and in mediating plant responses to biotic and abiotic stresses. Ethylene signalling acts via a linear transduction pathway leading to the activation of Ethylene Response Factor genes (ERF)which represent one of the largest gene families of plant transcription factors. How an apparently simple signalling pathway can account for the complex and widely diverse plant responses to ethylene remains yet an unanswered question. Building on the recent release of the complete tomato genome sequence, the present study aims at gaining better insight on distinctive features among ERF proteins. Results : A set of 28 cDNA clones encoding ERFs in the tomato (Solanum lycopersicon) were isolated and shown to fall into nine distinct subclasses characterised by specific conserved motifs most of which with unknown function. In addition of being able to regulate the transcriptional activity of GCC-box containing promoters, tomato ERFs are also shown to be active on promoters lacking this canonical ethylene-responsive-element. Moreover, the data reveal that ERF affinity to the GCC-box depends on the nucleotide environment surrounding this cis-acting element. Site-directed mutagenesis revealed that the nature of the flanking nucleotides can either enhance or reduce the binding affinity, thus conferring the binding specificity of various ERFs to target promoters. Based on their expression pattern, ERF genes can be clustered in two main clades given their preferential expression in reproductive or vegetative tissues. The regulation of several tomato ERF genes by both ethylene and auxin, suggests their potential contribution to the convergence mechanism between the signalling pathways of the two hormones. Conclusions : The data reveal that regions flanking the core GCC-box sequence are part of the discrimination mechanism by which ERFs selectively bind to their target promoters. ERF tissue-specific expression combined to their responsiveness to both ethylene and auxin bring some insight on the complexity and fine regulation mechanisms involving these transcriptional mediators. All together the data support the hypothesis that ERFs are the main component enabling ethylene to regulate a wide range of physiological processes in a highly specific and coordinated manner

Identification and expression pattern analysis of the OsSnRK2 gene family in rice

Sucrose non-fermenting-1-related protein kinase 2 (SnRK2) is a class of plant-specific serine/threonine (Ser/Thr) protein kinase that plays an important role in rice stress tolerance, growth and development. However, systematic bioinformatics and expression pattern analysis have not been reported. In the current study, ten OsSnRK2 genes were identified in the rice genome and located on 7 chromosomes, which can be classified into three subfamilies (I, II, and III). Many cis-regulatory elements were identified in the promoter region of OsSnRK2 genes, including hormone response elements, defense and stress responsive elements, indicating that the OsSnRK2 family may play a crucial role in response to hormonal and abiotic stress. Quantitative tissue analysis showed that OsSnRK2 genes expressed in all tissues of rice, but the expression abundance varied from different tissues and showed varietal variability. In addition, expression pattern of OsSnRK2 were analyzed under abiotic stress (salt, drought, salt and drought) and showed obvious difference in diverse abiotic stress. In general, these results provide useful information for understanding the OsSnRK2 gene family and analyzing its functions in rice in response to ABA, salt and drought stress, especially salt-drought combined stress

Integrating multiple protein-protein interaction networks to prioritize disease genes: a Bayesian regression approach

Abstract Background The identification of genes responsible for human inherited diseases is one of the most challenging tasks in human genetics. Recent studies based on phenotype similarity and gene proximity have demonstrated great success in prioritizing candidate genes for human diseases. However, most of these methods rely on a single protein-protein interaction (PPI) network to calculate similarities between genes, and thus greatly restrict the scope of application of such methods. Meanwhile, independently constructed and maintained PPI networks are usually quite diverse in coverage and quality, making the selection of a suitable PPI network inevitable but difficult. Methods We adopt a linear model to explain similarities between disease phenotypes using gene proximities that are quantified by diffusion kernels of one or more PPI networks. We solve this model via a Bayesian approach, and we derive an analytic form for Bayes factor that naturally measures the strength of association between a query disease and a candidate gene and thus can be used as a score to prioritize candidate genes. This method is intrinsically capable of integrating multiple PPI networks. Results We show that gene proximities calculated from PPI networks imply phenotype similarities. We demonstrate the effectiveness of the Bayesian regression approach on five PPI networks via large scale leave-one-out cross-validation experiments and summarize the results in terms of the mean rank ratio of known disease genes and the area under the receiver operating characteristic curve (AUC). We further show the capability of our approach in integrating multiple PPI networks. Conclusions The Bayesian regression approach can achieve much higher performance than the existing CIPHER approach and the ordinary linear regression method. The integration of multiple PPI networks can greatly improve the scope of application of the proposed method in the inference of disease genes.</p

Table1_Causal effects of various types of physical activities on psychiatric disorders: a Mendelian randomization study.xls

BackgroundPsychiatric disorders (PD) pose a significant burden, with vast prevalence and mortality, inflicting substantial costs on individuals and society. Despite its widespread prevalence, the complex pathogenesis of PD remains elusive, leading to limited and challenging therapeutic development. An emerging risk factor for chronic diseases, prolonged sedentary behavior, contrasts with the therapeutic potential of exercise, regardless of its intensity, for various ailments, including PD. Yet, the diversity in exercise modalities and intensities may offer varied impacts on health. This study, leveraging Mendelian Randomization (MR), seeks to investigate the causal relationship between exercise and PD, aiming to elucidate the optimal exercise modality and intensity for PD mitigation while addressing potential confounders.MethodsThis study employed a Mendelian randomization analysis using the genome-wide association study (GWAS) database to investigate the causal relationship between types of physical activity and psychiatric disorders. Sensitivity analysis was conducted to demonstrate the reliability and robustness of the results.ResultsIn the past 4 weeks, engaging in a substantial amount of DIY physical activity was found to have a causal relationship with psychiatric disorders (IVW: OR = 0.228, 95% CI: 0.113–0.461, P = 0.000038). As for the types of exercises, there may be a potential causal association between aerobic training (including swimming, cycling, fitness, and bowling) and psychiatric disorders (IVW: OR = 0.322, 95% CI = 0.148–0.704, P = 0.004). However, there was no causal relationship found between mild DIY physical activity and psychiatric disorders (IVW: OR = 0.918, 95% CI = 0.417–2.021, P = 0.831). Furthermore, it seems that there is no causal relationship between vigorous exercise and psychiatric disorders (IVW: OR = 2.705, 95% CI = 0.081–3.419, P = 0.578).ConclusionOur study confirms that only a certain level of training activity can have a protective effect on psychiatric disorders, while mild physical activity or vigorous training does not have an impact on psychiatric disorders.</p

The PUMCH Conservative Classification System for Young Idiopathic Scoliosis Patients

Objective  To establish a new method of scoliosis specific exercise(SSE) classification foryoung idiopathic scoliosis(IS) patients and evaluate its clinical practicability.  Methods  This study consists of two parts, the first part, a retrospective analysis, aimed at establishing Peking Union Medical College Hospital(PUMCH) conservative classification system for young IS patients and evaluating its reliability and repeatability. The research subjects were young IS patients in PUMCH from January 2013 to June 2020. The standing X-ray(A-P and lateral) and clinical appearance (bending and standing) were analyzed. The PUMCH conservative classification system was established based on PUMC surgical classification system, and the consistency test was conducted for the inter group reliability and intra group repeatability of the observers. The second part, an ambispective cohort study, aimed at verifying the role of PUMCH conservative classification system in guiding clinical treatment and evaluating its clinical practicability. The research subjects were young IS patients(4 to 17 years old) who received conservative treatment in PUMCH from July 2020 to August 2020. According to the wishes of patients and their families, they were divided into training group and control group. The control group only had regular reexamination without clinical intervention, while the training group conducted SSE based on PUMCH conservative classification system (continuous treatment for 1 year). Cobb angle difference and patient satisfaction were compared between the two groups after 1 year.  Results  (1) A total of 899 young IS patients who met the inclusion and exclusion criteria were selected for the retrospective study. PUMCH conservative classification system finally included 4 types and 9 subtypes after revising the single-curve(type Ⅰ), double-curve(type Ⅱ) and triple-curve(type Ⅲ) in PUMC surgical classification, and adding a micro-curve (type 0). The mean inter-observer reliability was 88.23%, with Kappa coefficient 0.862, while mean intra-observer repeatability was 92.78%, with Kappa coefficient 0.908. (2) Ambispective cohort study included 90 young IS patients who met the inclusion and exclusion criteria. There were 51 cases in the training group and 39 cases in the control group. The Cobb angle of the training group decreased from (16.61±2.88)°to (12.16±9.97)° after 1 year of treatment(P=0.002), while the Cobb angle of the control group increased from (15.74±2.75)° to (17.64±5.60)° after 1 year(P=0.014). There was clinical significance between the two groups(Cobb angle difference≥5°). After 1 year, the satisfaction score of the training group increased from 3(3, 3) to 5(3, 5)(P≤0.001), while that of the control group decreased from 3(3, 3) to 3(1, 3) (P=0.004).  Conclusions  A new conservative classification system for young IS patients is established. The PUMCH conservative classification system not only has good reliability and repeatability, but also has clinical practicability in guiding SSE