Sex-Specific Association Between Genetic Risk of Psychiatric Disorders and Cardiovascular Diseases
Year: 2024
Type: article
Study design: Observational Study
Abstract: Background The lack of research on female-specific risk factors for cardiovascular diseases (CVD) has led to sex-based disparities in cardiovascular health. Though epidemiological studies show increased CVD risks amongst individuals with psychiatric disorders, findings on sex differences in comorbidity have been inconsistent. Methods This genetic epidemiology study examined the sex-specific association between the genetic risk of three psychiatric disorders [major depression (MD), schizophrenia and bipolar disorder], estimated using polygenic scores (PGS), and risks of three CVDs [atrial fibrillation (AF), coronary artery disease (CAD) and heart failure (HF)] in 345,169 European-ancestry individuals (UK Biobank), with analyses replicated in an independent BioVU cohort (N=49,057). Mediation analysis was conducted to determine whether traditional CVD risk factors could explain any observed sex difference. Results In UK Biobank, PGS MD was significantly associated with the incident risks of all three CVDs in females after multiple testing correction [hazard ratio (HR) AF-female =1.04 (95% CI: 1.02-1.06; p=0.00015); HR CAD-female =1.07 (1.04-1.11; p=2.6E-06); HR HF-female =1.09 (1.06-1.13; p=9.7E-10)], but not in males. These female-specific associations remained even in the absence of any psychiatric disorder diagnosis or psychiatric medication use. Although mediation analysis demonstrated that the association between PGS MD and CVDs in females was partly mediated by baseline BMI, hypercholesterolemia, hypertension and smoking, these risk factors did not explain the higher risk compared to males. The association between PGS MD and CAD was consistent between females who were pre-menopausal and post-menopausal at baseline (mean baseline age of 44.9 and 60.8 years, respectively), while the association with AF and HF was only observed in the baseline post-menopausal cohort. No significant association with CVD risks was observed for the PGS of schizophrenia or bipolar disorder. The positive association of PGS MD with CAD and HF risk in females was replicated in BioVU, where the corresponding associations in males also reached nominal significance. Conclusions Genetic predisposition to MD confers a greater risk of CVDs in females versus males, even in the absence of any depression diagnosis. This study warrants further investigation into whether genetic predisposition to depression could be useful for improving cardiovascular risk prediction even in the absence of a depression diagnosis, especially in women.
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Funders: American Heart Association, Vanderbilt University, Vanderbilt University Medical Center, Georgia Clinical and Translational Science Alliance, National Institutes of Health, Medical Research Council, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Human Genome Research Institute, NIH Office of the Director, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, Office of Research on Women's Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Pharmacogenomics of Arrhythmia Therapy, G1531600799, G1766209448, G2103760183, Understanding the genetic risk underlying racial disparities in uterine fibroids, G2615776415, G2683268942, Improving Prediction of Drug Action, G3395468139, Mental health and chronic disease: A psycheMERGE investigation into the shared biology underlying psychiatric disorders and their physical comorbidities, G3619590958, G364208108, G3791753988, G3938985443, G4049315607, Automated Storage and Retrieval of Biological Systems, G4395870004, G4410787187, Overall: Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at Vanderbilt, G560889077, G5679716143, G5689014751, G5717004637, G5850737185, Genetic Epidemiology of Multiple Sclerosis, Elucidating the phenome-wide impact of sex and gender on disease, G6589054092, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, VESPA: Vanderbilt Electronic Systems for Pharmacogenomic Assessment, G7163342664, The Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt Genome Electronic Records Project, G8098630230, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), G8332127685, Vanderbilt Institute for Clinical and Translational Research (VICTR), 1/7-PsycheMERGE: Advancing Precision Psychiatry, Investigating the Biological Relationship between CAD and Depression
OpenAlex ID: W4404861935