Assessing the Causal Impact of Social Isolation on Angina Risk: Evidence from a Two-Sample Mendelian Randomization Study

Shenghua Yan,1,&ast; Feifei Gu,2,&ast; Bei Tian1,2 1Shanghai University of Traditional Chinese Medicine (SHUTCM), Shanghai, 201203, People’s Republic of China; 2Department of Nursing, Shanghai Pudong New Area Zhoupu Hospital (Shanghai Health Medical College Affiliated Zhoupu Hospital), Shanghai, 201318, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bei Tian, Department of Nursing, Shanghai Pudong New Area Zhoupu Hospital (Shanghai Health Medical College Affiliated Zhoupu Hospital), No. 1500 Zhou Yuan Road, Pudong New District, Shanghai, 201318, People’s Republic of China, Tel +86-18121216302, Email [email protected]: Previous observational studies have indicated an association between social isolation and an increased risk of cardiovascular diseases such as angina, but various factors may confound these studies. This study employs Mendelian randomization to investigate the causal relationship between social isolation and angina, minimizing potential confounding effects.Methods: We conducted a two-sample Mendelian randomization analysis using genetic variants as instrumental variables for social isolation. Genetic data for social isolation was sourced from a large-scale genome-wide association study (GWAS), while outcome data for angina came from an independent GWAS dataset.Results: Our findings suggest that a higher genetic predisposition to social isolation and loneliness is significantly associated with an increased risk of developing angina (Odds Ratio [OR] = 1.07, 95% confidence interval [Cl]: 1.03– 1.11, P< 0.01). The analysis did not provide strong evidence of horizontal pleiotropy affecting the results. This supports the hypothesis that social isolation may causally contribute to the risk of angina.Conclusion: Our study demonstrates the hypothesis that social isolation causally influences the risk of angina and emphasizes the importance of interventions targeting social isolation and loneliness as social factors in the prevention and management of cardiovascular diseases.Keywords: angina, genome-wide association study, Mendelian randomization