biostudies-literatureLundin JINCATS NIH HHSNIDDK NIH HHSNIA NIH HHSNHLBI NIH HHSNHGRI NIH HHSNIH HHSWHI NIH HHS120219https://www.ebi.ac.uk/biostudies/studies/S-EPMC12276907biostudies-literatureUnknown407<h4>Background and aims</h4>Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality worldwide, yet the underlying molecular mechanisms remain less understood. Chronic low-grade inflammation is a complex immune response contributing to the pathophysiology of cardiovascular disease. This response is signaled in part by interleukin-6 (IL-6), a pleiotropic, pro-inflammatory cytokine. Phenotypic variance in circulating IL-6 level may be explained in part by DNA methylation which is increasingly being associated with cardiovascular effects.<h4>Methods</h4>In this study we evaluated methylated DNA (CpG sites) associated with blood IL-6 levels across ∼4,400 ancestrally diverse individuals (81 % self-reported White; 9 % Black or African American, 8 % Hispanic or Latino/AtherosclerosisEpigenetic mechanisms underlying variation of IL-6, a well-established inflammation biomarker and risk factor for cardiovascular disease.PMC12276907N01 HC085083N01 HC085082N01 HC085081N01 HC085086UL1 TR001881N01 HC095166N01 HC095165N01 HC095168N01 HC095167N01 HC085080N01 HC095169N01 HC095160R01 AG023629N01 HC095162N01 HC095161N01 HC095164N01 HC095163UL1 TR000040HHSN268201500001C75N92021D0000175N92021D0000275N92021D00003UL1 TR00012475N92021D0000475N92021D00005U54 HG00306775N92021D00006R01 HL120393R01 HL116747R01 HL076784HHSN268200800007CR01 HL092577N01 HC055222HHSN268201800001CP30 DK063491HHSN268201500001IUL1 TR001420R01 HG010297U01 HL080295R01 HL117626R01 HL111089U01 HL120393N01 HC02519575N92020D00007HHSN268201200036C75N92020D0000175N92019D00031S10 OD02868575N92020D0000275N92020D0000575N92020D0000675N92020D0000375N92020D00004R01 HL087652R01 AG028321HHSN268201500003CUL1 TR001079N01 HC095159K08 HL116640R01 HL092111R01 HL103612N01 HC085079R01 HL105756HHSN268201500003IU01 HL130114Kasela SRotter JIVan den Berg DHu YGuo XZhao WMatise TYe TRich SSSotoodehnia NLoos RJFHaessler JLiu YPeters ULappalainen TJoehanes RSmith JALundin JIBenjamin EJPark SLPAGE StudyCushman MHaiman CReiner ARaffield LMKenny EGignoux CRatliff SMBis JCTracy RAmmous FBrody JALevy DKooperberg CLiu CFuller HNorth KEfalseEpigenetic mechanisms underlying variation of IL-6, a well-established inflammation biomarker and risk factor for cardiovascular disease.<h4>Background and aims</h4>Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality worldwide, yet the underlying molecular mechanisms remain less understood. Chronic low-grade inflammation is a complex immune response contributing to the pathophysiology of cardiovascular disease. This response is signaled in part by interleukin-6 (IL-6), a pleiotropic, pro-inflammatory cytokine. Phenotypic variance in circulating IL-6 level may be explained in part by DNA methylation which is increasingly being associated with cardiovascular effects.<h4>Methods</h4>In this study we evaluated methylated DNA (CpG sites) associated with blood IL-6 levels across ∼4,400 ancestrally diverse individuals (81 % self-reported White; 9 % Black or African American, 8 % Hispanic or Latino/2025-01-01T00:00:00Z2025 Aug2026-07-15T08:57:13.051Z2025-08-23T03:09:09.254ZS-EPMC122769074048002010.1016/j.atherosclerosis.2025.120219