A 1-SD increase in the polygenic score for major depression was significantly associated with incident AF (HR 1.04), CAD (HR 1.07), and HF (HR 1.09) in females, but not in males.
Cohort (n=394,226)
Yes
Does genetic predisposition to psychiatric disorders increase the risk of cardiovascular diseases differently in females compared to males?
Genetic predisposition to major depression confers a greater risk of cardiovascular diseases in females compared to males, independent of clinical depression diagnosis or traditional risk factors.
Effect estimate: HR 1.04 (AF), HR 1.07 (CAD), HR 1.09 (HF) (95% CI 1.02-1.06 (AF), 1.04-1.11 (CAD), 1.06-1.13 (HF))
p-value: p=1.5x10^-4 (AF), 2.6x10^-6 (CAD), 9.7x10^-10 (HF)
BACKGROUND: Though epidemiological studies show increased cardiovascular disease (CVD) risks among 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 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. RESULTS: In the UK Biobank, a 1-SD increase in PGS MD 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 ; HR CAD-female =1.07 95% CI, 1.04–1.11; P =2.6×10 − 6 ; and HR HF-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 PGS MD 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 PGS MD 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 PGS MD with CAD risk was replicated in BioVU. 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, especially in women.
Jiang et al. (Fri,) conducted a cohort in Cardiovascular diseases and psychiatric disorders (n=394,226). Polygenic score for major depression vs. Males was evaluated on Incident atrial fibrillation (AF), coronary artery disease (CAD), and heart failure (HF) (HR 1.04 (AF), HR 1.07 (CAD), HR 1.09 (HF), 95% CI 1.02-1.06 (AF), 1.04-1.11 (CAD), 1.06-1.13 (HF), p=1.5x10^-4 (AF), 2.6x10^-6 (CAD), 9.7x10^-10 (HF)). A 1-SD increase in the polygenic score for major depression was significantly associated with incident AF (HR 1.04), CAD (HR 1.07), and HF (HR 1.09) in females, but not in males.