Causal effects of genetically determined blood metabolites on asthma: a bidirectional Mendelian randomization study.

OBJECTIVE: The observational association between blood metabolites and asthma has been extensively studied. However, it is still unclear whether this association is causal. In this study, we aimed to investigate the causal relationship between blood metabolites and asthma using a bidirectional Mendelian randomization (MR) analysis. Additionally, we aimed to explore the potential mechanisms underlying this relationship. METHODS: The study design involved the use of genetic instruments as instrumental variables (IVs) to fulfill the assumptions of MR analysis. The data on 1,091 metabolites and 309 metabolite ratios were obtained from the Canadian Longitudinal Study on Aging (CLSA), while the data on asthma were obtained from the Integrative Epidemiology Unit (IEU) Open GWAS Project. Utilizing the inverse variance-weighted (IVW) method as the primary MR analysis approach, sensitivity tests were conducted to assess the reliability of the findings, which involved employing Cochran's Q and the MR-Egger intercept. Furthermore, Bayesian weighted MR was used to further test the robustness of the results. Additionally, pathway analysis was conducted to explore the metabolic explanations underlying asthma. RESULT: In our study, a comprehensive MR Analysis identified 10 metabolites and 6 metabolite ratios significantly associated with the development of asthma (FDR < 0.05). The metabolites included glycerophosphocholines(GPCs), glycerophosphoethanolamines(GPEs), and an unknown metabolite. Of these, 1-arachidonoyl-GPC, 1-myristoyl-2-arachidonoyl-GPC, 1-palmitoyl-2-arachidonoyl-GPC, and 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC were associated with an increased risk of asthma, whereas 1,2-dilinoleoyl-GPC, 1-palmitoyl-2-linoleoyl-GPC, 1,2-dilinoleoyl-GPE, 1 - oleoyl - 2 - linoleoyl - GPE, 1-palmitoyl-2-linoleoyl-GPE, and X-21470 were found to have a protective effect. No heterogeneity and pleiotropy were observed in the significant metabolites (p > 0.05), and each metabolite exhibited a consistent effect direction across all five methods. BWMR analysis results confirmed the significance and direction of effects across exposures, except for Cholesterol to linoleoyl-arachidonoyl-glycerol ratio(p = 0.673). Pathway analysis suggests that glycerophospholipid metabolism may potentially be a mechanism underlying the development of asthma. CONCLUSION: Our MR findings suggest that the identified metabolites and pathways can serve as biomarkers for clinical asthma screening and prevention, while also providing new insights for future mechanistic exploration and drug target selection.

Cathepsin-mediated regulation of alpha-synuclein in Parkinson's disease: a Mendelian randomization study.

Objective: The observational association between cathepsin and Parkinson's disease (PD) has been partially explored in previous research. However, the causal relationship remains unclear. In this study, our objective is to investigate the causal link between cathepsin and PD using Mendelian randomization (MR) analysis and elucidate the underlying mechanisms governing their interaction. Methods: Utilizing bidirectional two-sample MR and multivariable MR, we systematically investigates the causal relationship between nine cathepsins and PD. The data pertaining to cathepsins were obtained from the Integrative Epidemiology Unit (IEU) Open GWAS Project, while data related to PD were sourced from versions R9 and R10 of the FinnGen database. The primary analytical method utilized was the inverse variance weighted (IVW), with MR analysis initially conducted using PD data from R9, complemented by a series of sensitivity analyses. Subsequently, replication analysis was performed on the R10 dataset, and meta-analysis were employed to merge the findings from both datasets. To explore potential mechanisms by which Cathepsins may impact PD, MR analyses were performed on significant Cathepsins with alpha-synuclein. MR analysis and colocalization analysis were conducted on expression quantitative trait loci (eQTL) data of gene related to alpha-synuclein with PD data. Result: Forward MR analyses revealed more cathepsin B (CTSB) associated with less PD risk (OR = 0.898, 95%CI: 0.834-0.966, p = 0.004), while more cathepsin H (CTSH) (OR = 1.076, 95%CI: 1.007-1.149, p = 0.029) and more cathepsin S (CTSS) (OR = 1.076, 95%CI: 1.007-1.150, p = 0.030) associated with increasing PD risk. Meta-analyses validated these associations. Multivariate MR Results were consistent with those before adjustment. No significant results were observed in bidirectional MR analysis. In the investigation of the underlying mechanism, our findings demonstrate that CTSB significantly reduces the levels of alpha-synuclein (OR = 0.909, 95%CI: 0.841-0.983, p = 0.017). Concurrently, a genetically determined positive correlation between alpha-synuclein and PD is illuminated by both eQTL MR and colocalization analysis. Conclusion: In conclusion, this MR study yields robust evidence suggesting an association between elevated levels of CTSB and reduced PD risk, mediated by the downregulation of alpha-synuclein levels. Conversely, higher levels of CTSH and CTSS are associated with an increased risk of PD. These findings offer novel insights into the pathophysiological mechanisms of PD and identify potential drug targets for disease prevention and treatment warranting further clinical investigations.

Sleep problems in adolescents with depression: Role of childhood trauma, alexithymia, rumination, and self-esteem.

BACKGROUND: While sleep problems are common in adolescents with depression, the exact prevalence has not been reported. Although previous studies have shown that childhood trauma, alexithymia, rumination, and self-esteem are related to sleep problems, the interactions between these factors remain unclear. METHODS: This study, conducted from March 1, 2021 to January 20, 2022, employed a cross-sectional design. The participants were 2192 adolescents with depression with a mean age of 15 years. The Chinese version of the Pittsburgh Sleep Quality Index, Childhood Trauma Questionnaire, Toronto Alexithymia Scale-20, Ruminative Response Scale, and Rosenberg Self-Esteem Scale were used to measure sleep problems, childhood trauma, alexithymia, rumination, and self-esteem, respectively. We used PROCESS 3.3 for SPSS to determine the chain mediating effect of alexithymia and rumination and the moderating effect of self-esteem in the relationship between childhood trauma and sleep problems. RESULTS: Up to 70.71 % of adolescents with depression had sleep problems. Furthermore, alexithymia and rumination played a chain mediation role in the relationship between childhood trauma and sleep problems. Finally, self-esteem moderated the relationships between alexithymia and sleep problems and rumination and sleep problems. LIMITATIONS: Owing to the study design, we cannot derive causal relationships between variables. Further, the self-reported data may have been influenced by subjective participant factors. CONCLUSIONS: This study reveals potential ways of how childhood trauma influences sleep problems in adolescents with depression. These findings suggest that interventions targeting alexithymia, rumination, and self-esteem in adolescents with depression may be effective in reducing their sleep problems.

Parent-child relationship and smartphone addiction among Chinese adolescents: A longitudinal moderated mediation model.

Using a three-wave longitudinal design, we examined the relationship between early parent-child relationship and subsequent smartphone addiction (SA) and explored mediating and moderating mechanisms underlying this relation. A total of 527 Chinese adolescents (271 boys and 256 girls, mean age = 11.23 years) completed questionnaires regarding parent-child relationship, smartphone addiction, hope and life satisfaction. The results showed that: (1) parent-child relationship (T1) was positively associated with life satisfaction (T1) and hope (T2); parent-child relationship (T1), life satisfaction (T1), and hope (T2) were significantly negatively associated with SA (T3); (2) After controlling for age, gender, and SA (T1), hope (T2) completely mediated the relationship between parental-child relationship (T1) and adolescents' SA (T3); (3) life satisfaction (T1) moderated the association between parent-child relationship (T1) and hope (T2). Specifically, as life satisfaction (T1) increased, parent-child relationship (T1) was more likely to promote hope (T2). Moreover, the indirect negative links between parent-child relationship (T1) and SA (T3) via hope (T2) were stronger for adolescents with high level of life satisfaction (T1) than for adolescents with low level of life satisfaction (T1). The results reveal the mechanism of hope and life satisfaction in the effect of parent-child relationship on SA in adolescents, indicating that SA among adolescents can be weakened through the improvement of parent-child relationship, the rise in hope and the increase in life satisfaction.

Parental Warmth, Gratitude, and Prosocial Behavior among Chinese Adolescents: The Moderating Effect of School Climate.

Parental warmth plays an important role in the development of adolescents' physical and mental health. There are numerous empirical studies indicating a relationship between parental warmth and prosocial behavior among adolescents, although the underlying mechanisms of this association remain unclear. Adopting a longitudinal design across two time points, the present study proposes a moderated mediation model to explore the mediating role of gratitude and the moderating role of the school climate between parental warmth and prosocial behavior. The sample consisted of 943 participants (483 boys and 451 girls) who participated in the second assessment and completed questionnaires assessing gratitude, school climate, and prosocial behavior in April 2019. Their parents participated in the first assessment and completed a questionnaire pertaining to parental warmth in October 2018. After controlling for the gender and age of the adolescents, the results showed that the positive association between parental warmth and prosocial behavior is mediated by gratitude, and school climate does play a moderating role in the second half of the mediating path. Specifically, the school climate can play a protective role in adolescents with low levels of gratitude. For adolescents with less gratitude, a strong school climate can promote more prosocial behaviors and can effectively alleviate the negative prediction of low levels of gratitude. This study provides a theoretical explanation for the generation of adolescents' prosocial behavior and provides theoretical guidance for the interventions of schools and parents.

Social Exclusion and Impulsive Buying among Chinese College Students: The Mediating Role of Self-Esteem and the Moderating Role of Risk Preference.

With the development of science and technology, buying has become much easier. At the same time, however, impulsive buying has many negative consequences for college students, such as dissatisfaction and debt; the causes of impulsive buying should, therefore, be explored urgently. There are numerous empirical studies indicating that social exclusion may be a potential factor of impulsive buying, and the underlying mechanisms of this association remain unclear. In this study, we used the Social Exclusion Scale, Self-Esteem Scale, Risk Preference Scale, and Impulsive Buying Scale, as well as a cross-sectional design to investigate the roles of self-esteem and risk preference in the relationship between social exclusion and impulsive buying among 768 college students (387 were female, Mage = 20.25 years). The results were as follows: (1) when controlling for gender, age, family monthly income, and monthly living expenses, social exclusion significantly and positively predicted impulsive buying; (2) self-esteem played a mediating role between social exclusion and impulsive buying; (3) risk preference moderated the relationship between the second half of the mediating path and the direct path. These results reveal the mechanism underlying impulsive buying in college students, that is, social exclusion will predict the decrease in college students' self-esteem, and low self-esteem will further predict college students' impulsive buying, which is a way for them to gain a sense of self-worth. Relatively low risk preference can well alleviate the negative impact of social exclusion and low self-esteem on impulsive buying. What is more, these results have implications for impulsive buying interventions and preventions. Schools should aim to create a good peer atmosphere by implementing certain rules that help to reduce social exclusion, and parents and education departments should cultivate students' risk awareness to avoid risk behaviors in college students, such as impulsive buying behavior. This study fills the research gap regarding college students' impulsive buying and explores its internal psychological mechanism.