Fig. 4. Drug target MR pipeline to identify plasma proteins associating with CMR traits and cardiac outcomes.

Plasma proteins were associated with CMR traits through cis-MR leveraging genetic variants (pQTLs) associated with the protein of interest. Multiplicity-corrected results were prioritized by identifying 4 sets of proteins: (i) whether the protein was targeted by an approved drug ('drugged proteins' set), (ii) whether the protein was targeted by a developmental drug compound ('druggable proteins' set), (iii) whether the protein showed a directionally concordant (table S1) effect on at least three CMR traits ('concordant proteins' set), and (iv) for the directionally concordant proteins we additionally identified their nearest druggable protein through protein-protein data from IntAct and included proteins with pQTLs available in the three available datasets (SCALLOP, Framingham, INTERVAL) ('nearest druggable proteins' set). These 72 proteins were finally prioritized on an MR association with HF, DCM, CM, and/or AF.