Using MR-PheWAS framework to investigate mediating roles of metabolomic and other circulating biomarkers in the pathway between early life exposures and adulthood health outcomes
Accumulating evidence suggests causal relationships between early life exposures or developments and a wide range of adulthood health outcomes such as cardiometabolic outcomes, reproductive outcomes, cognitive outcomes and cancer outcomes. However, the mediating roles of metabolomic biomarkers and other circulating biomarkers (e.g., apolipoprotein, c-reactive protein, testosterone and SHBG) in the above causal pathway and underlying biological mechanism still remain unclear. We will utilize UK biobank resources including the newly released metabolomic biomarker data under the state-of-the-art causal inference framework the Mendelian randomisation phenome-wide association study (MR-PheWAS) approach and Bayesian colocalization to systematically identify novel mediating metabolomic and other circulating biomarkers lying on the pathway between early life exposures/developments (including birth weight, breastfed as a child, maternal smoking around birth, and comparative body size, etc) and multiple adulthood health outcomes (cardiometabolic outcomes, reproductive outcomes, and cognitive outcomes, etc). The research will provide a better understanding of the genetic regulation of these traits and new insights into the underlying biological mechanisms. The research will help efforts to identify new targets for future potential precision intervention or prevention. We will include the full cohort in our analysis.