Systematic comparison of observational and Mendelian Randomization estimates for cardiometabolic proteomic signatures.

ABSTRACT: Proteomic Mendelian randomization (MR) studies have gained widespread interest due to their potential to reveal novel therapeutic targets. Discrepancies are often reported between observational and genetic estimates of protein-trait associations, but the factors influencing directional agreement remain poorly understood. We systematically evaluated overlaps and directional agreement between observational associations and bi-directional two-sample MR estimates for 7,288 serum protein measurements across 25 cardiometabolic traits in the AGES-RS cohort (n = 5,364). Overall, our findings demonstrate that the proteomic signatures of cardiometabolic traits appear to be predominantly shaped by reverse causation, as observational associations significantly overlapped with those from the reverse (p

SUBMITTER: Jonmundsson T 

PROVIDER: S-EPMC12704627 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature