Identification of potential causal-genes-relevant blood pressure: a mitochondria-related genome-wide Mendelian...

Hypertension (HTN) is a mitochondrial and metabolic disease. However, cause-effect connections between mitochondrial dysfunction and HTN remains uncharted. we focused on mitochondria-related genes, identifying potential causal-genes-relevant blood pressure (BP) using mitochondria-related genome-wide Mendelian randomization (MR). Through the summary statistics from cis-expression quantitative trait loci (cis-eQTL) datasets (human blood and artery), mitochondrial transcription factor A (TFAM), and genome-wide association studies (GWAS) datasets of BP indices (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], and mean arterial pressure [MAP]) and HTN. we conducted a MR analysis to explore the potential causal relationship between mitochondrial-related genes and the BP indices, HTN. Sensitivity analysis and Bayesian colocalization were employed to validate this causal relationship. In aorta, HIBCH expression was negatively associated with SBP; OCIAD1 expression was positively associated with MAP. In tibial artery, HIBCH expression was negatively associated with SBP; OCIAD1 expression was positively associated with SBP, PP, and MAP; SLC25A37 was positively associated with MAP. In blood, LACTB expression was negatively associated with SBP, PP, and MAP; OCIAD1 expression was negatively associated with SBP and PP; and MTX1 expression was negatively associated with MAP. HARS2 expression was positively associated with SBP and PP; RAB24 and PRELID1 expression was positively associated with DBP; and NME6 expression was positively associated with SBP and DBP. In conclusion, the regulation of blood pressure correlates with mitochondria-related genes (HIBCH, SLC25A37 and OCIAD1 in artery; LACTB, OCIAD1, MTX1, HARS2, RAB24, PRELID1 and NME6 in blood). This study provides scientific evidence for specifically regulating BP phenotypes.