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@ARTICLE{Carbonneau:280965,
      author       = {Carbonneau, Madeleine and Li, Yi and Qu, Yishu and Zheng,
                      Yinan and Wood, Alexis C and Wang, Mengyao and Liu, Chunyu
                      and Huan, Tianxiao and Joehanes, Roby and Guo, Xiuqing and
                      Yao, Jie and Taylor, Kent D and Tracy, Russell P and Durda,
                      Peter and Liu, Yongmei and Johnson, W Craig and Post, Wendy
                      S and Blackwell, Tom and Rotter, Jerome I and Rich, Stephen
                      S and Redline, Susan and Fornage, Myriam and Wang, Jun and
                      Ning, Hongyan and Hou, Lifang and Lloyd-Jones, Donald and
                      Ferrier, Kendra and Min, Yuan-I and Carson, April P and
                      Raffield, Laura M and Teumer, Alexander and Grabe, Hans J
                      and Völzke, Henry and Nauck, Matthias and Dörr, Marcus and
                      Domingo-Relloso, Arce and Fretts, Amanda and Tellez-Plaza,
                      Maria and Cole, Shelley A and Navas-Acien, Ana and Wang,
                      Meng and Murabito, Joanne M and Heard-Costa, Nancy L and
                      Prescott, Brenton and Xanthakis, Vanessa and Mozaffarian,
                      Dariush and Levy, Daniel and Ma, Jiantao},
      title        = {{DNA} {M}ethylation {S}ignatures of {C}ardiovascular
                      {H}ealth {P}rovide {I}nsights {I}nto {D}iseases.},
      journal      = {Circulation},
      volume       = {152},
      number       = {7},
      issn         = {0009-7322},
      address      = {Philadelphia, Pa.},
      publisher    = {Lippincott, Williams $\&$ Wilkins},
      reportid     = {DZNE-2025-01047},
      pages        = {436 - 449},
      year         = {2025},
      abstract     = {The association of overall cardiovascular health (CVH) with
                      changes in DNA methylation (DNAm) has not been well
                      characterized.We calculated the American Heart Association's
                      Life's Essential 8 score to reflect CVH in 5 cohorts with
                      diverse backgrounds (mean age 54 years, $55\%$ women, and
                      enrollment year ranging from 1989 to 2012). Epigenome-wide
                      association studies (EWAS) for Life's Essential 8 score were
                      conducted, followed by bioinformatic analyses. DNAm loci
                      significantly associated with Life's Essential 8 score were
                      used to calculate a CVH DNAm score. We examined the
                      association of the CVH DNAm score with incident
                      cardiovascular disease (CVD), cardiovascular
                      disease-specific mortality, and all-cause mortality.We
                      identified 609 cytosine-phosphate-guanines (CpGs) associated
                      with Life's Essential 8 score at false discovery rate<0.05
                      in the discovery analysis and at Bonferroni-corrected P<0.05
                      in the multicohort replication stage. Most had low to
                      moderate heterogeneity (414 CpGs $[68.0\%]$ with
                      heterogeneity <0.2) in replication analysis. Pathway
                      enrichment analyses and a phenome-wide association study
                      search associated these CpGs with inflammatory or autoimmune
                      phenotypes. We observed enrichment for phenotypes in the
                      Epigenome-Wide Association Study Catalog, with 29-fold
                      enrichment for stroke (P=2.4e-15) and 21-fold for ischemic
                      heart disease (P=7.4e-38). Two-sample Mendelian
                      randomization (MR) analysis showed significant association
                      between 141 CpGs and ten phenotypes (261 CpG-phenotype
                      pairs) at false discovery rate<0.05. For example,
                      hypomethylation at cg20544516 (MIR33B [microRNA 33b] and
                      SREBF1 [sterol regulatory element-binding transcription
                      factor 1]) is associated with a lower risk of stroke
                      (P=8.1e-6). In multivariable prospective analyses, the CVH
                      DNAm score was consistently associated with clinical
                      outcomes across participating cohorts. Per SD increase in
                      the CVH DNAm score, the decrease in risk of incident
                      cardiovascular disease, cardiovascular disease mortality,
                      and all-cause mortality ranged from $19\%$ to $32\%,$ $28\%$
                      to $40\%,$ and $27\%$ to $45\%,$ respectively.We identified
                      new DNAm signatures for CVH across diverse cohorts. Our
                      analyses indicate that multiple biological pathways may be
                      relevant to the observed association between CVH and
                      clinical outcomes.},
      keywords     = {DNA methylation (Other) / Life’s Essential 8 (Other) /
                      all-cause mortality (Other) / cardiovascular diseases
                      (Other) / cardiovascular health (Other) / epigenome-wide
                      association study (Other)},
      cin          = {AG Grabe},
      ddc          = {610},
      cid          = {I:(DE-2719)5000001},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40654086},
      pmc          = {pmc:PMC12262172},
      doi          = {10.1161/CIRCULATIONAHA.124.073181},
      url          = {https://pub.dzne.de/record/280965},
}