Major depressive disorder increased the risk of hypertension: A Mendelian randomization study

Despite the high prevalence of comorbid hypertension in patients with major depressive disorder (MDD), the relationship between the two diseases has received little attention. Previous observational studies have descripted the association between MDD and hypertension, the causality from MDD on hypertension remained unknown. The present Mendelian randomization (MR) study aimed to assess the causal effect of MDD on hypertension.

A set of genetics instrument was used for analysis, derived from publicly available genetic meta-analysis data. A total of 44 single-nucleotide polymorphisms (SNPs) associated with MDD. The largest genome-wide association study (GWAS) for hypertension (54,358 cases and 408,652 controls) was used to assess the effect of MDD on hypertension. Inverse variance weighted method (IVW), weighted median method (WM), and MR-Egger regression were used for MR analyses. The MR-Egger_intercept test and Cochran's Q statistic were used to determine the pleiotropy and the heterogeneity, respectively.

A total of 28 independent and effective MDD genetic instrumental variables were extracted from the hypertension GWAS summary statistics. Pleiotropy analysis suggested no significant pleiotropic variant among the 28 selected MDD genetic instrument variants in hypertension GWAS datasets. As MDD based on genetic changes increased, the risk of hypertension increased using MR-Egger (OR = 1.004436, 95%CI 0.9884666-1.020663, P = 0.5932928), WM (OR = 1.000499, 95%CI 1.0000188-1.000980, P = 0.0416871), and IVW (OR = 1.000573, 95%CI 1.0000732-1.001074, P = 0.0246392). Our results were robust, with no obvious bias based on investigating the single MDD SNP on hypertension.

Our result suggested a causal associated between genetically increased MDD and increased hypertension risk in European population.