A higher genetic risk for depression is a greater risk factor for cardiovascular disease in women

Abstract

AbstractBackgroundEpidemiological studies show increased cardiovascular disease (CVD) risk amongst individuals with psychiatric disorders; however, sex differences in comorbidity have been inconsistent. This study examined the sex-specific association between higher genetic risk of three psychiatric disorders [major depression (MD), schizophrenia and bipolar disorder] and the risk of three CVDs [coronary artery disease (CAD), heart failure (HF) and atrial fibrillation].Methods and FindingsSex-specific association between polygenic scores (PGS) for psychiatric disorders and CVD outcomes was assessed in 345,201 European-ancestry individuals (UK Biobank) using logistic regression, with analyses replicated in an independent BioVU cohort (N = 62,641).In the UK Biobank cohort, a 1-standard-deviation increase in PGSMDwas associated with a 1.11- (95% CI: 1.06 - 1.16; p = 5E-06) and 1.09-fold (95% CI: 1.04 - 1.14; p = 0.00038) higher risk of incident CAD and HF in females respectively, but only with a 1.04-fold (95% CI: 1.02 - 1.07; p = 0.0016) increased risk of incident CAD in males. These associations remained even in the absence of any psychiatric disorder diagnosis. The higher risk in females may potentially be mediated by greater BMI increase in females. The risk increase of HF was consistent between females who were pre-menopausal at baseline (mean age = 44.9 years) and post-menopausal at baseline (mean age = 60.8 years), while the risk increase of CAD was only observed in the baseline post- menopausal cohort. No significant association with CVD risks was observed for the genetic risk of schizophrenia or bipolar disorder. The greater increase in CAD risk in females was replicated in the BioVU cohort.ConclusionsGenetic predisposition to MD confers a greater risk of CAD and HF in females compared to males, even in the absence of any depression diagnosis. In addition to depression diagnosis, this study highlights the importance of considering predisposition to depression in heart health checks, especially in women.