Investigation into the Effect of Brain Functional Circuits on Hypertensive Disorders in Pregnancy: A Mendelian Randomization Analysis

Background: Brain resting-state functional networks are extensively utilized in research on psychiatric disorders. Meanwhile, pregnancy promotes specific and substantial changes in neural structure and network integration, which are most prominent in the default mode network (DMN). Prior studies have established a relationship between hypertensive disorders in pregnancy (HDP) and mental disorders. Nevertheless, the causal influence of brain resting-state functional networks on HDP is poorly understood. Methods: A bidirectional two-sample Mendelian randomization (MR) framework was applied to estimate the causal effects of 191 resting-state functional magnetic resonance imaging (rsfMRI) phenotypes (sample size: 34,691) on five HDPs, and vice versa. The five HDP conditions were gestational hypertension (GH), pre-eclampsia (PE), eclampsia, chronic hypertension, and PE superimposed on chronic hypertension. Results: Forward MR estimates identified a potential causal relationship between one rsfMRI phenotype (attention, salience, and motor network) and chronic hypertension in pregnancy. The MR analysis of the reverse direction revealed that chronic hypertension in pregnancy may exert a causal influence on three rsfMRI phenotypes: the motor and subcortical-cerebellum network, the attention, salience, and motor network, and the subcortical–cerebellum and motor network. The causal relationship between the attention, salience, and the motor network and chronic hypertension in pregnancy was found to be bidirectional. Conclusions: Our findings reveal a potential causal relationship between altered patterns of intrinsic brain connectivity and chronic hypertension in pregnancy. These results provide crucial evidence for an association between chronic hypertension in pregnancy and alterations in functional brain networks.