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

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.

The influence of personality on the risk of myocardial infarction in UK Biobank cohort

“…In studies using non-fatal myocardial infarction (MI) as an endpoint, neuroticism was the only trait significantly associated with the incidence of MI 22 . On the other hand, a recent Mendelian randomization study found casual associations between neuroticism and the prevalence of atrial fibrillation, while no significant associations were detected with other CVDs such as myocardial infarction (MI) or coronary artery disease 23 . Thus, larger population-based studies are needed to clarify the mediating role of personality in development and progression of specific CVDs.…”

Attention‐deficit/hyperactivity disorder as a risk factor for cardiovascular diseases: a nationwide population‐based cohort study

“…Prospective studies have previously demonstrated that several psychiatric conditions (e.g., depression 7,8 , schizophrenia 9 , bipolar disorder 10 , and anxiety disorders 11 ) as well as neurodevelopmental disorders (e.g., autism 12,13 , intellectual disabilities 12 , and conduct disorder 12 ) are associated with a higher risk for cardiovascular diseases, the leading cause of mortality worldwide 14 . The mechanisms linking psychiatric illness to cardiovascular diseases are complex, but risky health behaviours (e.g., smoking, drinking alcohol, substance abuse, and sedentary lifestyles) 15 and prolonged use of psychotropic medications 16 have been proposed as potential contributors to the risk.…”

Association of mental health with the risk of coronary artery disease in patients with diabetes: A mendelian randomization study

“…Recently, a two-sample MR study suggested depression was associated with increased CAD risk. [18], and another MR study showed that neuroticism was casually associated with a higher risk of atrial fibrillation [19]. However, no MR studies have explored the causality between mental health and CAD in patients with diabetes.…”