Major Depressive Disorder Impacts Peripheral Artery Disease Risk Through Intermediary Risk Factors

Abstract

Background Major depressive disorder (MDD) has been identified as a causal risk factor for multiple forms of cardiovascular disease. Although observational evidence has linked MDD to peripheral artery disease (PAD), causal evidence of this relationship is lacking. Methods and Results Inverse variance weighted 2‐sample Mendelian randomization was used to test the association the between genetic liability for MDD and genetic liability for PAD. Genetic liability for MDD was associated with increased genetic liability for PAD (odds ratio [OR], 1.17 [95% CI, 1.06–1.29]; P =2.6×10 −3 ). Genetic liability for MDD was also associated with increased genetically determined lifetime smoking ( β =0.11 [95% CI, 0.078–0.14]; P =1.2×10 −12 ), decreased alcohol intake ( β =−0.078 [95% CI, −0.15 to 0]; P =0.043), and increased body mass index ( β =0.10 [95% CI, 0.02–0.19]; P =1.8×10 −2 ), which in turn were associated with genetic liability for PAD (smoking: OR, 2.81 [95% CI, 2.28–3.47], P =9.8×10 −22 ; alcohol: OR, 0.77 [95% CI, 0.66–0.88]; P =1.8×10 −4 ; body mass index: OR, 1.61 [95% CI, 1.52–1.7]; P =1.3×10 −57 ). Controlling for lifetime smoking index, alcohol intake, and body mass index with multivariable Mendelian randomization completely attenuated the association between genetic liability for MDD with genetic liability for PAD. Conclusions This work provides evidence for a possible causal association between MDD and PAD that is dependent on intermediate risk factors, adding to the growing body of evidence suggesting that effective management and treatment of cardiovascular diseases may require a composite of physical and mental health interventions.

Exploring the mediating role of calcium homeostasis in the association between diabetes mellitus, glycemic traits, and vascular and valvular calcifications: a comprehensive Mendelian randomization analysis

“…Stage 2: Two-sample two-step MR analyses were carried out to identify potential intermediaries in the pathway linking DM and glycemic traits to vascular and valvular calcifications. We quantified the proportion of the mediating effect of DM and glycemic traits on these calcifications through calcium homeostasis, calculated as (β1 * β2)/β0 [ 13 ].…”

“…For MR analyses to yield valid results, three critical assumptions must be satisfied: (1) the SNPs are associated with the exposure; (2) the SNPs are independent of confounders of the exposure-outcome relationship (the independence assumption); and (3) the SNPs affect the outcome only through the exposure. Informed consent and ethics approval were obtained for each of the original studies [ 13 ].…”