The study investigated how genetic predisposition to psychiatric disorders, especially major depression (MD), is related to the risk of cardiovascular diseases (CVDs) in men and women. The results showed that women with a higher genetic predisposition to DM have a significantly higher risk of developing atrial fibrillation, coronary artery disease and heart failure, even without a clinical diagnosis of depression. This increased risk was not observed in men.
Studies have shown that people with psychiatric disorders face a higher risk of developing cardiovascular diseases (CVDs), such as atrial fibrillation (AF), coronary artery disease (CAD) and heart failure (HF).
However, the differences in risk between men and women have generated inconsistent results, raising questions about the factors that may influence this relationship.
This study, conducted at The University of Queensland, Australia, investigated how genetic predisposition to three psychiatric disorders, major depression (MD), schizophrenia and bipolar disorder, is associated with the risk of cardiovascular disease, considering possible gender differences.
The researchers analyzed data from 345,169 people of European ancestry from the UK Biobank, supplemented by an independent cohort of 49,057 individuals from the BioVU database.
To estimate the genetic risk of each psychiatric disorder, polygenic risk scores (PGSs), which reflect genetic predisposition based on known genetic variants, were used.
The researchers examined how these risks were associated with the development of CVDs in men and women. In addition, they sought to determine whether traditional cardiovascular risk factors, such as hypertension, obesity and smoking, could explain the observed differences.
The results showed that women with a higher genetic predisposition for major depression had significantly increased risks for all three CVDs analyzed: atrial fibrillation, coronary artery disease, and heart failure.
For example, an increase in the gene for major depression was associated with a 4% increase in the risk of atrial fibrillation, 7% in the risk of coronary artery disease, and 9% in the risk of heart failure in women. Interestingly, this association was not observed in men.
These female-specific associations remained evident even when individuals diagnosed with depression or taking psychiatric medications were excluded, suggesting that the increased risk was driven by genetic predisposition rather than external factors such as the manifestation of the disorder.
Furthermore, although factors such as obesity, hypertension, high cholesterol, and smoking were identified as partial mediators, they did not fully explain why women with a genetic predisposition for DM were at higher risk compared to men.
The analysis also revealed differences associated with menopause. While the risk of CAD was consistent in pre- and postmenopausal women, the risk of atrial fibrillation and heart failure was observed only in postmenopausal women.
In contrast, genetic scores for schizophrenia and bipolar disorder did not show significant associations with CVD risk, indicating that the observed relationship was specific to the genetic predisposition to major depression.
The findings suggest that genetic predisposition to major depression is a stronger risk factor for CVD in women than in men, regardless of whether or not they have developed clinical depression.
This reinforces the need to include genetic assessment and gender differences in planning strategies for the prevention and treatment of CVD.
Furthermore, investigating whether this genetic predisposition can improve cardiovascular risk prediction in women is an important next step towards personalized and preventive medicine.
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Sex-Specific Association Between Genetic Risk of Psychiatric Disorders and Cardiovascular Diseases
Jiayue-Clara Jiang, Kritika Singh, Rachana Nitin, Lea K. Davis, Naomi R. Wray, and Sonia Shah
Circulation: Genomic and Precision Medicine. Originally Published 29 November 2024
Abstract:
Though epidemiological studies show increased cardiovascular disease (CVD) risks among individuals with psychiatric disorders, findings on sex differences in comorbidity have been inconsistent. This genetic epidemiology study examined the sex-specific association between the genetic risk of 3 psychiatric disorders (major depression [MD], schizophrenia, and bipolar disorder), estimated using polygenic scores (PGSs), and risks of 3 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. In the UK Biobank, a 1-SD increase in PGSMD was significantly associated with the incident risks of all 3 CVDs in females after multiple testing corrections (hazard ratio [HR]AF-female=1.04 [95% CI, 1.02–1.06]; P=1.5×10−4; HRCAD-female=1.07 [95% CI, 1.04–1.11]; P=2.6×10−6; and HRHF-female=1.09 [95% CI, 1.06–1.13]; P=9.7×10−10), 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 PGSMD and CVDs in females was partly mediated by baseline body mass index, hypercholesterolemia, hypertension, and smoking, these risk factors did not explain the higher risk compared with males. The association between PGSMD and CAD was consistent between females who were premenopausal and postmenopausal at baseline, while the association with AF and HF was only observed in the baseline postmenopausal cohort. No significant association with CVD risks was observed for the PGS of schizophrenia or bipolar disorder. The female-specific positive association of PGSMD with CAD risk was replicated in BioVU. 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, especially in women.
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