Birth weight, childhood obesity and risk of hypertension: a Mendelian randomization study

Purposes: Observational studies indicate that birth weight and childhood obesity are associated with essential hypertension, but their causal effect on essential hypertension remains unclear. The aim of our study is to elucidate the causal relationship between birth weight, childhood obesity, and essential hypertension by Mendelian randomization (MR) with genetic variants as instrumental variables (IVs). Methods: We identified IVs based on single nucleotide polymorphisms (SNPs) associated with birth weight (n = 160 295) and childhood obesity (n = 6889, 1509 cases and 5380 controls) from the meta-analysis of a genome-wide association study. Summary level data from the UK Biobank essential hypertension consortium (n = 463 010, 54 358 cases and 408 652 controls) was used to analyze the relationship between IVs and essential hypertension. Two MR analysis methods, two threshold values of selecting IVs, and leave-one-out analysis were used to ensure the robustness of the results. Results: Genetic predisposition to higher birth weight did not increase the risk of essential hypertension. In contrast, per one standard deviation increase in childhood body mass index was significantly associated with an increased risk of essential hypertension (odds ratio = 1.0075, 95% confidence interval: 1.0035-1.0116) when using seven SNPs that achieved genome-wide significance (P< 5 x 10(-8)). Sensitivity analysis and MR-Egger regression indicated that the results were robust and not influenced by pleiotropy. Conclusions: No evidence of an association between birth weight and essential hypertension was found. Childhood obesity, however, showed a causal relationship with the risk of essential hypertension, which was helpful to understand the mechanisms of essential hypertension and develop strategies for its prevention.