{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang L"],"funding":["Deutsche Forschungsgemeinschaft","Gemeinnützige Hertie-Stiftung","Deutsche Forschungsgemeinschaft (German Research Foundation)","The Munich Cluster for Systems Neurolog","Fritz Thyssen Stiftung","Gemeinnützige Hertie-Stiftung (Hertie Foundation)","Fritz Thyssen Stiftung (Fritz Thyssen Foundation)"],"pagination":["1172-1186"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12436178"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["4(9)"],"pubmed_abstract":["Human genetics supports a causal involvement of IL-6 signaling in atherosclerotic cardiovascular disease, prompting the clinical development of anti-IL-6 therapies. Genetic evidence has historically focused on IL6R missense variants, but emerging cardiovascular treatments target IL-6, not its receptor, questioning the translatability of genetic findings. Here we develop a genetic instrument for IL-6 signaling downregulation comprising IL6 locus variants that mimic the effects of the anti-IL-6 antibody ziltivekimab and use it to predict the effects of IL-6 inhibition on cardiometabolic and safety endpoints. Similar to IL6R, we found that genetically downregulated IL-6 signaling via IL6 perturbation is associated with lower lifetime risks of coronary artery disease, peripheral artery disease"],"journal":["Nature cardiovascular research"],"pubmed_title":["IL6 genetic perturbation mimicking IL-6 inhibition is associated with lower cardiometabolic risk."],"pmcid":["PMC12436178"],"funding_grant_id":["10.22.2.024MN","512461526","ID P1239935"],"pubmed_authors":["Xu L","deGoma E","Omarov M","Zhang L","Georgakis MK","Natarajan P"],"additional_accession":[]},"is_claimable":false,"name":"IL6 genetic perturbation mimicking IL-6 inhibition is associated with lower cardiometabolic risk.","description":"Human genetics supports a causal involvement of IL-6 signaling in atherosclerotic cardiovascular disease, prompting the clinical development of anti-IL-6 therapies. Genetic evidence has historically focused on IL6R missense variants, but emerging cardiovascular treatments target IL-6, not its receptor, questioning the translatability of genetic findings. Here we develop a genetic instrument for IL-6 signaling downregulation comprising IL6 locus variants that mimic the effects of the anti-IL-6 antibody ziltivekimab and use it to predict the effects of IL-6 inhibition on cardiometabolic and safety endpoints. Similar to IL6R, we found that genetically downregulated IL-6 signaling via IL6 perturbation is associated with lower lifetime risks of coronary artery disease, peripheral artery disease","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-02T05:52:52.446Z","creation":"2026-04-14T03:14:16.203Z"},"accession":"S-EPMC12436178","cross_references":{"pubmed":["40858837"],"doi":["10.1038/s44161-025-00700-7"]}}