The mediating role of atrial fibrillation in causal associations between risk factors and stroke: a Mendelian randomization study

• 영문명: The mediating role of atrial fibrillation in causal associations between risk factors and stroke: a Mendelian randomization study
• 발행기관: 한국역학회
• 저자명: Shanmei Qin Mengmeng Wang Dipender Gill Zhizhong Zhang Xinfeng Liu
• 간행물 정보: 『Epidemiology and Health』46, 1~10쪽, 전체 10쪽
• 주제분류: 의약학 > 면역학
• 파일형태: PDF
• 발행일자: 2024.01.31

영문 초록

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.

목차

INTRODUCTION

MATERIALS AND METHODS

RESULTS

DISCUSSION

NOTES

REFERENCES

키워드

Stroke Mediation Mendelian randomization Atrial fibrillation