Association of Autism Spectrum Disorder, Neuroticism, and Subjective Well-Being With Cardiovascular Diseases: A Two-Sample Mendelian Randomization Study

Xingang Sun; Lu Chen; Zhen Wang; Yunlong Lu; Miao Chen; Yuxian He; Hongfei Xu; Liangrong Zheng

doi:10.3389/fcvm.2021.676030

Association of Autism Spectrum Disorder, Neuroticism, and Subjective Well-Being With Cardiovascular Diseases: A Two-Sample Mendelian Randomization Study

Front Cardiovasc Med. 2021 Jun 11:8:676030. doi: 10.3389/fcvm.2021.676030. eCollection 2021.

Authors

Xingang Sun¹, Lu Chen¹, Zhen Wang¹, Yunlong Lu¹, Miao Chen¹, Yuxian He¹, Hongfei Xu², Liangrong Zheng¹

Affiliations

¹ Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
² Department of Cardiothoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Abstract

Background: Previous observational studies have reported an association between psychiatric traits and cardiovascular diseases (CVDs). In this two-sample Mendelian randomization (MR) study, we aimed to investigate the causality between psychiatric traits and CVDs. Methods: Single-nucleotide polymorphisms (SNPs) associated with autism spectrum disorder (ASD), neuroticism, and subjective well-being at genome-wide significance (P < 1 × 10^-8) were identified from genome-wide association studies. Summary-level data of the outcomes, including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF), were obtained from several largest datasets. The inverse-variance weighted (IVW) method was used as our main analyses to conduct this MR study. Sensitivity analyses included the weighted median, the MR-robust adjusted profile score (MR-RAPS), and the MR pleiotropy residual sum and outlier (MR-PRESSO) method. Repeated MR analyses using a more relaxed threshold (P < 1 × 10^-6) for instruments selection and multivariable MR analyses were also applied to evaluate the robustness of results. Results: The MR analyses showed that genetic predisposition to ASD was associated with a higher risk of AF [odds ratio (OR), 1.109; 95% confidence interval (CI), 1.023-1.201; P = 0.011] and HF (OR, 1.138; 95% CI, 1.036-1.251; P = 0.007). Neuroticism was casually associated with an increased risk of AF (OR, 1.201; 95% CI, 1.037-1.392; P = 0.015), whereas subjective well-being had a protective effect on HF (OR, 0.732; 95% CI, 0.574-0.933; P = 0.012). No other causal association between psychiatric traits and CVDs was observed. Consistent results were obtained in sensitivity analyses. Conclusion: This study provided evidence of causal associations of ASD with a higher risk of AF and HF. Besides, neuroticism was casually associated with an increased risk of AF, and subjective well-being was associated with a decreased risk of HF.

Keywords: autism spectrum disorder; causality; mendelian randomization; neuroticism; subjective well-being.