Association of Loneliness and Social Isolation with Ischemic Heart Disease: A Bidirectional and Network Mendelian Randomization Study.

Shu Yao SU; Wan Yue WANG; Chen Xi YUAN; Zhen Nan LIN; Xiang Feng LU; Fang Chao LIU

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Association of Loneliness and Social Isolation with Ischemic Heart Disease: A Bidirectional and Network Mendelian Randomization Study.

Author: Shu Yao SU ¹ ; Wan Yue WANG ¹ ; Chen Xi YUAN ² ; Zhen Nan LIN ¹ ; Xiang Feng LU ¹ ; Fang Chao LIU ²
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1. Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China;Key Laboratory of Cardiovascular Epidemiology, Chinese Academy of Medical Sciences, Beijing 100037, China.
2. Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China;Key Laboratory of Cardiovascular Epidemiology, Chinese Academy of Medical Sciences, Beijing 100037, China;Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China.
Publication Type:Journal Article
Keywords: Ischemic heart disease; Loneliness; Mediation analyses; Mendelian randomization; Social isolation
MeSH: Loneliness/psychology*; Humans; Mendelian Randomization Analysis; Social Isolation; Myocardial Ischemia/etiology*; Male; Female; Middle Aged; Genome-Wide Association Study; Risk Factors; Aged
From: Biomedical and Environmental Sciences 2025;38(3):351-364
CountryChina
Language:English
Abstract: OBJECTIVE:Observational studies have shown inconsistent associations of loneliness or social isolation (SI) with ischemic heart disease (IHD), with unknown mediators.
METHODS:Using data from genome-wide association studies of predominantly European ancestry, we performed a bidirectional two-sample Mendelian Randomization (MR) study to estimate causal effects of loneliness ( N = 487,647) and SI traits on IHD ( N = 184,305). SI traits included whether individuals lived alone, participated in various types of social activities, and how often they had contact with friends or family ( N = 459,830 to 461,369). A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators, including metabolic, behavioral and psychological factors.
RESULTS:Loneliness increased IHD risk ( OR= 2.129; 95% confidence interval [ CI]: 1.380 to 3.285), mediated by body fat percentage, waist-hip ratio, total cholesterol, and low-density lipoprotein cholesterol. For SI traits, only fewer social activities increased IHD risk ( OR= 1.815; 95% CI: 1.189 to 2.772), mediated by hypertension, high-density lipoprotein cholesterol, triglycerides, fasting insulin, and smoking cessation. No reverse causality of IHD with loneliness and SI was found.
CONCLUSION:These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD, with several mediators as prioritized targets for intervention.