Maternal and fetal origins of offspring blood pressure: statistical analysis using genetic correlation and genetic risk score-based Mendelian randomization.

This article focuses on investigating the genetic and causal relationship between birthweight and blood pressure, distinguishing maternal-specific and fetal-specific genetic effects. Using large-scale genome-wide association study (GWAS) summary statistics and individual-level data from the UK Biobank, the study found a significant inverse genetic correlation between fetal-specific birthweight and blood pressure traits—systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP)—and identified numerous pleiotropic genes shared between these traits. Mendelian randomization analysis using maternal-specific genetic risk scores (GRS) in mother-offspring pairs revealed a causal negative association of maternal birthweight effects with offspring SBP and PP, supporting the developmental origins of health and disease (DOHaD) hypothesis, while no such causal effect was observed in father-offspring pairs. These findings highlight common genetic components underlying birthweight and blood pressure and provide insights into the early prevention of hypertension.