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The mediating role of atrial fibrillation in causal associations between risk factors and stroke: a Mendelian randomization study
Shanmei Qin, Mengmeng Wang, Dipender Gill, Zhizhong Zhang, Xinfeng Liu
Epidemiol Health. 2024;46:e2024005.   Published online December 6, 2023
DOI: https://doi.org/10.4178/epih.e2024005
  • 4,293 View
  • 92 Download
AbstractAbstract AbstractSummary PDFSupplementary Material
Abstract
OBJECTIVES
Atrial fibrillation (AF) contributes to stroke development and progression. We aimed to quantify the mediating role of AF in the causal associations between a wide range of risk factors and stroke via a Mendelian randomization (MR) framework.
METHODS
We assessed the associations of 108 traits with stroke and its subtypes in a 2-sample univariable MR approach, then conducted a bidirectional MR analysis between these 108 traits and AF to evaluate the presence and direction of their causal associations. Finally, to further investigate the extent to which AF mediated the effects of eligible traits on stroke, we applied multivariable and 2-step MR techniques in a mediation analysis where outcomes were restricted to stroke types causally affected by AF (any stroke [AS], any ischemic stroke [AIS], and cardioembolic stroke [CES]).
RESULTS
Among 108 traits, 42 were putatively causal for at least 1 stroke type; of these 42 traits, 20 that had no bidirectional relationship with AF were retained. Finally, 33 associations of 15 eligible traits were examined in the mediation analysis. The mediation analyses for AS, AIS, and CES each included 11 eligible traits. After AF adjustment, the direct effects of all traits on CES were attenuated to null (all p>0.05), while the associations with AS and AIS persisted for most traits (AF-mediated proportion: from 6.6% [95% confidence interval, 2.7 to 0.6] to 52.0% [95% confidence interval, 39.8 to 64.3]).
CONCLUSIONS
The causal associations between all eligible traits and CES were largely mediated through AF, while most traits affected AS and AIS independently of AF.
Summary
Key Message
Previous studies have not systematically detected and quantified the mediating role of AF in causal associations between a wide range of risk factors and stroke types. This study, using several MR approaches, found that the causal associations between risk factors and stroke, and the role of AF in mediating these associations, varied across stroke types. Although AF largely mediated the trait-CES associations, most traits affected AS and AIS independently of AF, highlighting the need for accurate disease classification in clinical practice and trials.
Mediation analysis of leisure activities on the association between cognitive function and mortality: a longitudinal study of 42,942 Chinese adults 65 years and older
Xingxing Chen, Wenfan Wu, Xian Zhang, Tingxi Long, Wenyu Zhu, Rundong Hu, Xurui Jin, Lijing L. Yan, Yao Yao
Epidemiol Health. 2022;44:e2022112.   Published online November 27, 2022
DOI: https://doi.org/10.4178/epih.e2022112
  • 7,008 View
  • 268 Download
  • 5 Web of Science
  • 4 Crossref
AbstractAbstract AbstractSummary PDFSupplementary Material
Abstract
OBJECTIVES
Previous studies have established associations of cognitive function and leisure activities with mortality. This study aimed to evaluate whether leisure activities causally mediate these associations.
METHODS
This longitudinal study included 42,246 participants aged over 65 years from the Chinese Longitudinal Healthy Longevity Survey. The Mini-Mental State Examination and a self-reported scale were used to measure cognitive status and leisure activities, respectively. We examined the associations of cognitive function and leisure activities with mortality using Cox proportional hazards models. Causal mediation analysis was used to assess whether leisure activities mediated the association between cognitive function and mortality.
RESULTS
Cognitive function and leisure activities were inversely associated with mortality. Leisure activities accounted for 28.3% (95% confidence interval [CI], 25.6 to 31.1) of the total effect of cognitive function and mortality. A higher mediated proportion (PM) was observed for physical leisure activities (PM, 20.1%; 95% CI, 18.0 to 22.3) than for social leisure activities (PM, 17.7%; 95% CI, 15.7 to 19.7). The mediating effect was higher among participants at younger ages (PM, 41.5%; 95% CI, 21.3 to 65.4), those with higher education levels (PM, 30.5%; 95% CI, 25.3 to 36.2), and residents of rural China (PM, 42.5%; 95% CI, 25.4 to 62.5).
CONCLUSIONS
Cognitive function was associated with inverse mortality. Leisure activities significantly mediated this association. Participation in leisure activities at the early stages of mild cognitive impairment could reduce the risk of mortality, which has a major impact on interventional strategies for healthy aging.
Summary
Key Message
Both cognitive function and leisure activities were associated with inverse mortality. Leisure activities were an important mediator of the association between cognitive function and mortality. A planned intervention for leisure activities, at an early stage of mild cognitive impairment, could promote health outcomes and optimally reduce the risk of mortality.

Citations

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The association between aggression and risk of Internet gaming disorder in Korean adolescents: the mediation effect of father-adolescent communication style
Eunjin Kim, Hyeon Woo Yim, Hyunsuk Jeong, Sun-Jin Jo, Hae Kook Lee, Hye Jung Son, Hyun-ho Han
Epidemiol Health. 2018;40:e2018039.   Published online August 8, 2018
DOI: https://doi.org/10.4178/epih.e2018039
  • 18,742 View
  • 390 Download
  • 43 Web of Science
  • 42 Crossref
AbstractAbstract AbstractSummary PDFSupplementary Material
Abstract
OBJECTIVES
Open and supportive communication between parents and children is known to reduce adolescents’ delinquent behavior. Recently, the risk of Internet gaming disorder (IGD) has been increasing in adolescents. The purpose of this study was to investigate the mediating effects of parent-child communication styles on the relationship between adolescent aggressiveness and risk of IGD.
METHODS
Participants in this study were 402 first-year students from 4 middle schools in Seoul who enrolled in the Internet user Cohort for Unbiased Recognition of gaming disorder in Early adolescence (iCURE) and completed baseline assessment in 2016. The structural equation model was constructed based on an aggression questionnaire, the Internet game use-elicited symptom screen, a mother-child communication inventory, and a father-child communication inventory.
RESULTS
Adolescents’ aggressiveness was found to be related to their risk of IGD. The father-child communication style mediated the relationship between aggression and risk of IGD. However, the mother-child communication style had no mediating effect.
CONCLUSIONS
Our findings suggest that fathers should make an effort to improve open and positive communication skills with their children, because the father-child communication style plays an important role in the relationship between adolescent aggressiveness and risk of IGD.
Summary
Korean summary
본 연구는 청소년기의 공격성과 인터넷 게임장애 위험과의 연관성에서 부모와의 의사소통 방식의 매개효과를 알아보고자 하였다. 연구대상자는 인터넷 사용자 코호트 연구(the Internet user Cohort for Unbiased Recognition of gaming disorder in Early Adolescence, iCURE)에 등록된 중학교 1학년 402명을 대상으로 단면조사 연구를 실시하여 구조방정식 모형분석을 하였다. 청소년 시기의 공격성은 인터넷 게임중독과 연관성이 있었고, 이러한 연관성은 아버지와 자녀간의 의사소통을 통해 매개되고 있었다. 아버지가 청소년과 개방적이고 긍정적 의사소통을 하는 경우 청소년의 공격성과 인터넷 게임장애 위험의 연관성을 낮추는 매개효과가 있었다.

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Review
Applied mediation analyses: a review and tutorial
Theis Lange, Kim Wadt Hansen, Rikke Sørensen, Søren Galatius
Epidemiol Health. 2017;39:e2017035.   Published online August 6, 2017
DOI: https://doi.org/10.4178/epih.e2017035
  • 26,864 View
  • 1,036 Download
  • 88 Web of Science
  • 89 Crossref
AbstractAbstract PDF
Abstract
In recent years, mediation analysis has emerged as a powerful tool to disentangle causal pathways from an exposure/treatment to clinically relevant outcomes. Mediation analysis has been applied in scientific fields as diverse as labour market relations and randomized clinical trials of heart disease treatments. In parallel to these applications, the underlying mathematical theory and computer tools have been refined. This combined review and tutorial will introduce the reader to modern mediation analysis including: the mathematical framework; required assumptions; and software implementation in the R package medflex. All results are illustrated using a recent study on the causal pathways stemming from the early invasive treatment of acute coronary syndrome, for which the rich Danish population registers allow us to follow patients’ medication use and more after being discharged from hospital.
Summary

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