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S‐GMAS: Genome‐Wide Mediation Analysis With Brain Subcortical Shape Mediators
Mediation analysis is widely utilized in neuroscience to investigate the role of brain image phenotypes in the neurological pathways from genetic exposures to clinical outcomes. However, it is still difficult to conduct mediation analyses with whole genome‐wide exposures and brain subcortical shape mediators due to several challenges including (i) large‐scale genetic exposures, that is, millions of single‐nucleotide polymorphisms (SNPs); (ii) nonlinear Hilbert space for shape mediators; and (iii) statistical inference on the direct and indirect effects. To tackle these challenges, this paper proposes a genome‐wide mediation analysis framework with brain subcortical shape mediators. First, to address the issue caused by the high dimensionality in genetic exposures, a fast genome‐wide association analysis is conducted to discover potential genetic variants with significant genetic effects on the clinical outcome. Second, the square‐root velocity function representations are extracted from the brain subcortical shapes, which fall in an unconstrained linear Hilbert subspace. Third, to identify the underlying causal pathways from the detected SNPs to the clinical outcome implicitly through the shape mediators, we utilize a shape mediation analysis framework consisting of a shape‐on‐scalar model and a scalar‐on‐shape model. Furthermore, the bootstrap resampling approach is adopted to investigate both global and spatial significant mediation effects. Finally, our framework is applied to the corpus callosum shape data from the Alzheimer's Disease Neuroimaging Initiative. Using the ADNI Corpus Callosum (CC) shape data, we proposed a genome‐wide mediation analysis framework involving high‐dimensional genetic exposures and shape mediators and successfully identified distinct genetic‐to‐clinical outcome pathways mediated through the CC in Alzheimer's Disease, revealing varying spatial causal effect patterns for different clinical outcomes.
Journal Article
The impact of caregiver burden on quality of life in family caregivers of patients with advanced cancer: a moderated mediation analysis of the role of psychological distress and family resilience
Background
The caregiver burden frequently experienced by family members tending to advanced cancer patients significantly impacts their psychological well-being and quality of life (QoL). Although family resilience might function as a mitigating factor in this relationship, its specific role remains to be elucidated. This study aims to probe the mediating effect of psychological distress on the relationship between caregiver burden and QoL, as well as the moderating effect of family resilience.
Methods
A cross-sectional study was conducted between June 2020 and March 2021 in five tertiary hospitals in China. Data were collected on caregiver burden, family resilience, psychological distress (including anxiety and depression), and QoL. Moderated mediation analysis was performed.
Results
Data analysis included 290 caregivers. It confirmed the mediating role of psychological distress in the caregiver burden-QoL relationship (
P
< 0.001). Both overall family resilience and the specific dimension of family communication and problem-solving (FCPS) demonstrated significant moderating effects on the “psychological distress/anxiety—QoL” paths (
P
< 0.05). The utilization of social and economic resources (USER) significantly moderated the association between depression and QoL (
P
< 0.05).
Conclusions
The study corroborates psychological distress's mediation between caregiver burden and QoL and family resilience's moderation between psychological distress and QoL. It underscores the need for minimizing psychological distress and bolstering family resilience among caregivers of advanced cancer patients. Accordingly, interventions should be tailored, inclusive of psychological assistance and promotion of family resilience, particularly focusing on FCPS and USER, to augment the caregivers' well-being and QoL.
Journal Article
Introduction to statistical mediation analysis
This volume introduces the statistical, methodological, and conceptual aspects of mediation analysis. Applications from health, social, and developmental psychology, sociology, communication, exercise science, and epidemiology are emphasized throughout. Single-mediator, multilevel, and longitudinal models are reviewed. The author's goal is to help the reader apply mediation analysis to their own data and understand its limitations. Each chapter features an overview, numerous worked examples, a summary, and exercises (with answers to the odd numbered questions). The accompanying CD contains outputs described in the book from SAS, SPSS, LISREL, EQS, MPLUS, and CALIS, and a program to simulate the model. The notation used is consistent with existing literature on mediation in psychology. The book opens with a review of the types of research questions the mediation model addresses. Part II describes the estimation of mediation effects including assumptions, statistical tests, and the construction of confidence limits. Advanced models including mediation in path analysis, longitudinal models, multilevel data, categorical variables, and mediation in the context of moderation are then described. The book closes with a discussion of the limits of mediation analysis, additional approaches to identifying mediating variables, and future directions. (DIPF/Verlag).
eBook
Causal mediation analysis for stochastic interventions
Mediation analysis in causal inference has traditionally focused on binary exposures and deterministic interventions, and a decomposition of the average treatment effect in terms of direct and indirect effects.We present an analogous decomposition of the population intervention effect, defined through stochastic interventions on the exposure. Population intervention effects provide a generalized framework in which a variety of interesting causal contrasts can be defined, including effects for continuous and categorical exposures. We show that identification of direct and indirect effects for the population intervention effect requires weaker assumptions than its average treatment effect counterpart, under the assumption of no mediator–outcome confounders affected by exposure. In particular, identification of direct effects is guaranteed in experiments that randomize the exposure and the mediator.We propose various estimators of the direct and indirect effects, including substitution, reweighted and efficient estimators based on flexible regression techniques, allowing for multivariate mediators. Our efficient estimator is asymptotically linear under a condition requiring n
1/4-consistency of certain regression functions. We perform a simulation study in which we assess the finite sample properties of our proposed estimators.We present the results of an illustrative study where we assess the effect of participation in a sports team on the body mass index among children, using mediators such as exercise habits, daily consumption of snacks and overweight status.
Journal Article
A Multi- Mediation Analysis on the Impact of Social Media and Internet Addiction on University and High School Students’ Mental Health Through Social Capital and Mindfulness
Introduction: Social media addiction (SMA) and internet addiction (IA) are increasingly prevalent, impacting mental health (MH) globally. This study investigates the mediating roles of mindfulness and social capital (SC) in the relationship between SMA, IA, and MH among Ethiopian high school and university students, contributing to the Sustainable Development Goal (SDG) 3 of good health and well-being. Methods: A cross-sectional study was conducted with 1160 university and 1473 high school students in Dessie, Ethiopia. Participants completed validated questionnaires assessing SMA, IA, mindfulness, SC, and MH. Structural Equation Modeling (SEM) with a multi- mediation Model (SMM) was used to examine the hypothesized relationships. Results: SEM revealed that both SMA and IA had a direct negative effect on mindfulness, SC, and MH in in both high school and university students. Notably, mindfulness and SC significantly and positively predicted MH, indicating their protective role against the negative effects of SMA and IA. Furthermore, both mindfulness or SC fully or partially mediated the relationship between SMA, IA, and MH, highlighting their crucial role in explaining the association. Conclusions: This study provides evidence for the crucial roles of mindfulness and SC in buffering the negative effects of SMA and IA on MH among Ethiopian students. The findings highlight the need for educational and health interventions that foster mindfulness and SC to enhance student mental health and promote a healthy digital environment. These results offer valuable insights for educators, health professionals, and policymakers in Ethiopia and other developing countries facing similar challenges.
Journal Article
A Parallel Mediation Analysis on the Effects of Pandemic Accentuated Occupational Stress on Hospitality Industry Staff Turnover Intentions in COVID-19 Context
The purpose of this research was to analyze how different effects of the COVID pandemic, expressed through pandemic accentuated occupational stress, perceived job insecurity, occupational safety and health perception and perceived organizational effectiveness, may impact turnover intentions of the personnel in the hospitality industry. Our research team designed an online questionnaire which was analyzed with network analysis to depict the relationship between factors, and, then, a confirmatory factor analysis was employed to confirm the distribution of the items to the envisaged five factors. Based on a sample of 324 randomized Romanian hospitality industry staff, the results of our cross-sectional study revealed that occupational safety and health perception, perceived organizational effectiveness and perceived job insecurity in the pandemic accentuated occupational stress to indirectly and significantly impact hospitality industry staff turnover intentions (TI). The results indicated that, while the total effect of PAOS on TI was significant, the direct effect was still significant, while all three mediators remained significant predictors. Overall, mediators partially mediated the relationship between PAOS and TI, indicating that employees with low scores on occupational safety and health perception (OSHP), and perceived organizational effectiveness (POE) and high scores on perceived job insecurity (PJI) were more likely to have higher levels of TI turnover intentions.
Journal Article
Association between Bullying Victimization and Symptoms of Depression among Adolescents: A Moderated Mediation Analysis
Background: Bullying victimization and its effect on symptoms of depression have received attention from researchers, but few studies have considered the potential mechanism. The aim of this study was to examine a moderated mediation model for the association between bullying victimization and depressive symptoms in terms of it being mediated by social anxiety, and investigated whether sleep duration would show moderating effects in this relationship. Methods: In this study, there were 2956 students, who completed three questionnaires, including a bullying victimization scale, as well as a social anxiety and epidemiologic studies depression scale. Results: Bullying victimization’s effects on depressive symptoms were mediated by social anxiety. Furthermore, sleep duration moderated the relationship between bullying victimization and depressive symptoms. Conclusions: The research contributes by clarifying the mechanisms underlying the relationship between bullying victimization and depressive symptoms.
Journal Article
The mediating roles of anxiety, loneliness, stress, and depression in the relationship between cyberbullying and non-suicidal self-injury: propensity score matching and causal mediation analysis
Background
Non-suicidal self-injury (NSSI) not only causes direct physical harm but also severely impacts mental health, increasing the risks of psychological disorders, behavioral issues, and suicidal tendencies. With the widespread use of the internet and electronic communication tools on smartphones, such as social media and instant messaging applications, cyberbullying has become increasingly prevalent. However, research on the relationship between cyberbullying and NSSI remains relatively limited at present.
Methods
This research was conducted in Nantong City, Jiangsu Province, from July to September 2024, utilizing a convenience sampling method with 1,751 participants. Propensity Score Matching (PSM) was employed to control for confounding factors, while causal mediation analysis was used to assess the mediating effects of anxiety, depression, stress, and loneliness between cyberbullying and NSSI.
Results
In this study, 557 participants (31.8%) reported having experienced cyberbullying, Cyberbullying significantly increases NSSI odds through direct and indirect effects, mediated by anxiety (ACME = 0.08, ADE = 0.22, mediated proportion = 0.28), loneliness (ACME = 0.04, ADE = 0.26, mediated proportion = 0.14), stress (ACME = 0.05, ADE = 0.24, mediated proportion = 0.18), and depression (ACME = 0.06, ADE = 0.24, mediated proportion = 0.19).
Conclusion
This study explores the relationship between cyberbullying, mental health issues (depression, anxiety, stress, loneliness), and NSSI. Findings show cyberbullying directly and indirectly increases NSSI risk, with loneliness as a key mediator. Despite insights, the study has limitations, suggesting a need for more rigorous designs and comprehensive data.
Journal Article
The role of leukocytes in cognitive impairment due to long‐term exposure to fine particulate matter: A large population‐based mediation analysis
INTRODUCTION Our understanding of how fine particulate matter (PM2.5) impacts cognitive functioning is limited. Systemic inflammation processes may play a role in mediating this effect. METHODS This prospective cohort study used data from 66,254 participants aged 18+ between 2006 and 2015 from the Dutch Lifelines Cohort Study and Biobank. Causal mediation analysis was conducted to examine the impact of ambient PM2.5 exposure on cognitive processing time (CPT), using the change in white blood cell (WBC) count and its subtypes as potential mediators. RESULTS Heightened PM2.5 exposure was associated with slower CPT (total effect = 81.76 × 10−3, 95% confidence interval [CI] 59.51 × 10−3–105.31 × 10−3). The effect was partially mediated via increased WBC count (indirect effect [IE] = 0.42 × 10−3, 95% CI 0.07 × 10−3–0.90 × 10−3), particularly driven by an increase in monocytes (IE = 0.73 × 10−3, 95% CI 0.24 × 10−3–1.31 × 10−3). DISCUSSION Systemic inflammation processes may partially explain the harmful effects of PM2.5 on cognitive functioning, why lower levels of systemic inflammation may help contain its neurotoxic effects. Highlights The pathways leading to the neurotoxic effects of fine particulate matter (PM2.5) are poorly understood. We analyzed data from over 66,000 participants using causal pathway analysis. Increased white blood cell (WBC) count mediates the effect of PM2.5 on cognitive functioning. Monocyte count played a crucial role in this low‐pollution setting. Systemic inflammation may contribute to the neurotoxic effects of PM2.5.
Journal Article