Summary: A large genetic study of more than 300,000 people found that women with a high genetic risk for depression are also more likely to develop cardiovascular disease, even if they have never been diagnosed with depression. This association did not appear in men, revealing important sex-specific differences. Researchers stress the need to screen and manage heart disease risk in women with depression or a genetic predisposition to depression, regardless of menopausal status.
The results highlight gaps in cardiovascular research and clinical practice where women have often been underrepresented. Because heart disease remains the leading cause of death for women worldwide, these findings underscore the importance of targeted heart-health monitoring and prevention strategies for women at elevated genetic risk for depression.
Key Facts:
- Women with a genetic predisposition to major depression face higher risks of developing heart disease.
- This increased cardiovascular risk was found even in women without a formal depression diagnosis or psychiatric treatment history.
- Traditional risk factors such as BMI, smoking, high blood pressure and high cholesterol did not fully explain the observed sex differences.
Source: University of Queensland
Women with higher genetic risk for depression show greater likelihood of heart disease, UQ study finds
Researchers at the University of Queensland’s Institute for Molecular Bioscience analyzed genetic and health records from over 300,000 individuals to investigate whether polygenic risk for psychiatric conditions relates to cardiovascular disease risk. The team, led by Dr Sonia Shah and Dr Clara Jiang, found a clear association in women between genetic risk of major depression and subsequent cardiovascular conditions, even among those without any recorded diagnosis or treatment for depression.
Dr Shah explained that the link between genetic risk for depression and cardiovascular disease was consistently observed in women but not in men, despite more men overall developing heart disease. Importantly, this sex-specific association remained after accounting for common cardiovascular risk factors.
“Our findings indicate a distinct relationship between genetic liability to depression and cardiovascular outcomes in females,” Dr Shah said. “This pattern was evident even among women who had not been diagnosed with depression or prescribed psychiatric medications. It signals the need to consider cardiovascular screening and prevention in women with elevated genetic risk or a history of depressive illness.”
Dr Jiang added that women have historically been underrepresented in cardiovascular studies and clinical trials, which has contributed to gaps in diagnosis and treatment for female patients. She emphasized that improving representation and developing sex-specific clinical guidance are critical for reducing missed diagnoses and improving outcomes for women.
The study also assessed whether menopausal status changed the pattern of association. While the elevated risk of coronary artery disease linked to depression genetic risk was present in women both before and after menopause, associations with atrial fibrillation and heart failure were stronger in women who were postmenopausal at baseline. Overall, the findings support routine heart-health monitoring for women with depression or a high genetic predisposition to depression, irrespective of their menopausal stage.
Genetic predictors used in the study were derived from large-scale genomic datasets, including consortia and biobanks that aggregate genetic, health and lifestyle information. Analyses were conducted primarily in the UK Biobank cohort and replicated in an independent cohort to validate results.
Funding: Dr Shah received funding support from the Heart Foundation.
About this genetics and depression research news
Author: IMB Communications
Source: University of Queensland
Contact: IMB Communications – University of Queensland
Image: Image credit to Neuroscience News
Original Research: The study, titled “Sex-Specific Association Between Genetic Risk of Psychiatric Disorders and Cardiovascular Diseases” by Sonia Shah et al., is published open access in Circulation: Genomic and Precision Medicine.
Abstract
Sex-Specific Association Between Genetic Risk of Psychiatric Disorders and Cardiovascular Diseases
Background:
Epidemiological research has linked psychiatric disorders to increased cardiovascular disease (CVD) risk, but evidence about sex differences has been inconsistent. This study explores whether genetic predisposition to psychiatric conditions shows sex-specific relationships with major cardiovascular outcomes.
Methods:
The investigation used polygenic scores (PGSs) to estimate genetic risk for three psychiatric disorders—major depression (MD), schizophrenia, and bipolar disorder—and tested associations with incident atrial fibrillation (AF), coronary artery disease (CAD), and heart failure (HF). Primary analyses involved 345,169 individuals of European ancestry from the UK Biobank, with replication in an independent cohort (BioVU, n=49,057). Mediation analyses evaluated the role of traditional CVD risk factors in any observed sex differences.
Results:
In the UK Biobank, each one standard-deviation increase in the polygenic score for major depression (PGS_MD) was significantly associated with higher incident risk of AF, CAD and HF in females after correction for multiple testing (AF: HR=1.04; CAD: HR=1.07; HF: HR=1.09), but these associations were not observed in males. The female-specific associations persisted even when excluding participants with recorded psychiatric diagnoses or psychiatric medication use.
Mediation analyses showed that baseline body mass index, hypercholesterolemia, hypertension, and smoking partly mediated the relationship between PGS_MD and CVD in women, but these factors did not fully account for the greater risk seen in females compared to males. The association between PGS_MD and CAD was similar in premenopausal and postmenopausal women, whereas associations with AF and HF were primarily observed in women who were postmenopausal at baseline. No significant CVD associations were found for polygenic scores of schizophrenia or bipolar disorder. The positive link between PGS_MD and CAD in females was replicated in the BioVU cohort.
Conclusions:
A genetic predisposition to major depression confers higher cardiovascular risk in females than in males, even when no clinical diagnosis of depression is present. These findings suggest genetic risk for depression could contribute to improved cardiovascular risk prediction and emphasize the need for sex-specific approaches to prevention and screening, particularly for women.