Julián Albarrán-Juárez, Anton Markov, Anne Louise Jensen, Peter Möller, Anna Uryga, Djordje Djordjevic, Jakob Hansen, Lise Filt Jensen, Diana Sharysh, Charles Pyke, Jaime A. Moreno, Giulia Borghetti, Julian C. Bachmann, Kate M. Herum, Lisa Maria Røge, Matthew J. Traylor, Michael Nyberg, Mette Nyegaard, Jacob Fog Bentzon
perturbation experiments in SMCs driven toward plaque-relevant phenotypes. Although the genes encode diverse proteins, their perturbations converged on shared transcriptional programs regulating contractile machinery, cell-cycle progression, nuclear factor κB (NF-κB), and type I interferon signaling. Integrating GWAS effect-direction with cholesterol- and stretch-responsive gene modules suggest that cholesterol-induced signaling promotes pro-atherogenic SMC states and is differentially modulated by risk versus protective variants. These results delineate polygenic regulation of SMC disease mechanisms and show that GWAS effect-directionality can help prioritize cellular pathways for follow-up functional studies across genes and cell types.