Causal Associations Between Socioeconomic Status, Intelligence, Cognition and Atrial Fibrillation: Evidence From Mendelian Randomization

Wulamiding Kaisaier; Min Ye; Zexuan Wu; Chen Liu; Jiangui He; Gregory Y H Lip; Yili Chen; Wengen Zhu

doi:10.1016/j.jacasi.2025.04.008

Causal Associations Between Socioeconomic Status, Intelligence, Cognition and Atrial Fibrillation: Evidence From Mendelian Randomization

JACC Asia. 2025 Jun 2:S2772-3747(25)00265-0. doi: 10.1016/j.jacasi.2025.04.008. Online ahead of print.

Authors

Wulamiding Kaisaier¹, Min Ye², Zexuan Wu¹, Chen Liu¹, Jiangui He¹, Gregory Y H Lip³, Yili Chen⁴, Wengen Zhu⁵

Affiliations

¹ Department of Cardiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; The National Health Commission Key Laboratory of Assisted Circulation and Vascular Diseases Key Laboratory of Assisted Circulation and Vascular Diseases, Sun Yat-sen University, Guangzhou, China.
² Department of Cardiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; The National Health Commission Key Laboratory of Assisted Circulation and Vascular Diseases Key Laboratory of Assisted Circulation and Vascular Diseases, Sun Yat-sen University, Guangzhou, China; Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
³ Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom; Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
⁴ Department of Cardiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; The National Health Commission Key Laboratory of Assisted Circulation and Vascular Diseases Key Laboratory of Assisted Circulation and Vascular Diseases, Sun Yat-sen University, Guangzhou, China. Electronic address: chenyil7@mail.sysu.edu.cn.
⁵ Department of Cardiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; The National Health Commission Key Laboratory of Assisted Circulation and Vascular Diseases Key Laboratory of Assisted Circulation and Vascular Diseases, Sun Yat-sen University, Guangzhou, China. Electronic address: zhuwg6@mail.sysu.edu.cn.

PMID: 40560110
DOI: 10.1016/j.jacasi.2025.04.008

Abstract

Background: Lower socioeconomic status, intelligence, and cognition are linked to a higher likelihood of atrial fibrillation (AF). However, whether these factors directly cause AF or whether others mediate this relationship is unclear.

Objectives: Our study aimed to determine the causal link between lower socioeconomic status, intelligence, cognition, and AF, and identify mediators.

Methods: We conducted a 2-sample Mendelian randomization analysis with data from European ancestry genome-wide association studies. Genetic instruments for education, intelligence, cognition, income, and occupation (n = 248,847-1,131,881) evaluated their relationship with AF (FinnGen study: 50,743 cases and 210,652 control subjects; 6 European studies: 60,620 and 970,216).

Results: The pooled results from meta-analysis combining data from 2 studies indicated that education, intelligence, and cognition were causally associated with AF (P < 0.05). Genetically predicted, each 1-SD increase in educational attainment was associated with a 19% decreased risk of AF (OR: 0.81; 95% CI: 0.71-0.92), independent of intelligence and cognition. Among 44 candidate mediators, 8 factors were identified to mediate the education-AF association, including heart failure (mediation proportion: 95.35%), body fat mass (44.05%), waist circumference (42.93%), coronary heart disease (30.1%), body mass index (29.0%), myocardial infarction (28.8%), diastolic blood pressure (21.7%), and waist-to-hip ratio (14.3%).

Conclusions: Our study suggests that education exerts a causal and protective effect against AF, independent of intelligence and cognition. Heart failure, obesity, and ischemic heart disease serve as mediating factors in the pathway from education to AF, underscoring the importance of considering these conditions in preventing AF associated with education inequality.

Keywords: Mendelian randomization; atrial fibrillation; education; mediation analysis.