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@ARTICLE{OchoaRosales:153653,
      author       = {C. Ochoa-Rosales and E. Portilla-Fernandez and J. Nano and
                      R. Wilson and B. Lehne and P. P. Mishra and X. Gao and M.
                      Ghanbari and O. L. Rueda-Ochoa and D. Juvinao-Quintero and
                      M. Loh and W. Zhang and J. S. Kooner and H. J. Grabe and S.
                      B. Felix and B. Schöttker$^*$ and Y. Zhang$^*$ and C.
                      Gieger and M. Müller-Nurasyid and M. Heier and A. Peters
                      and T. Lehtimäki and A. Teumer and H. Brenner$^*$ and M.
                      Waldenberger and M. A. Ikram and J. B. J. van Meurs and O.
                      H. Franco and T. Voortman and J. Chambers and B. H. Stricker
                      and T. Muka},
      title        = {{E}pigenetic {L}ink {B}etween {S}tatin {T}herapy and {T}ype
                      2 {D}iabetes.},
      journal      = {Diabetes care},
      volume       = {43},
      number       = {4},
      issn         = {1935-5548},
      address      = {Alexandria, Va.},
      publisher    = {Assoc.},
      reportid     = {DKFZ-2020-00376},
      pages        = {875-884},
      year         = {2020},
      note         = {2020 Apr;43(4):875-884},
      abstract     = {To investigate the role of epigenetics in statins'
                      diabetogenic effect comparing DNA methylation (DNAm) between
                      statin users and nonusers in an epigenome-wide association
                      study in blood.Five cohort studies' participants (n = 8,270)
                      were classified as statin users when they were on statin
                      therapy at the time of DNAm assessment with Illumina 450K or
                      EPIC array or noncurrent users otherwise. Associations of
                      DNAm with various outcomes like incident type 2 diabetes,
                      plasma glucose, insulin, and insulin resistance (HOMA of
                      insulin resistance [HOMA-IR]) as well as with gene
                      expression were investigated.Discovery (n = 6,820) and
                      replication (n = 1,450) phases associated five DNAm sites
                      with statin use: cg17901584 (1.12 × 10-25 [DHCR24]),
                      cg10177197 (3.94 × 10-08 [DHCR24]), cg06500161 (2.67 ×
                      10-23 [ABCG1]), cg27243685 (6.01 × 10-09 [ABCG1]), and
                      cg05119988 (7.26 × 10-12 [SC4MOL]). Two sites were
                      associated with at least one glycemic trait or type 2
                      diabetes. Higher cg06500161 methylation was associated with
                      higher fasting glucose, insulin, HOMA-IR, and type 2
                      diabetes (odds ratio 1.34 $[95\%$ CI 1.22, 1.47]). Mediation
                      analyses suggested that ABCG1 methylation partially mediates
                      the effect of statins on high insulin and HOMA-IR. Gene
                      expression analyses showed that statin exposure and ABCG1
                      methylation were associated with ABCG1 downregulation,
                      suggesting epigenetic regulations of ABCG1 expression.
                      Further, outcomes insulin and HOMA-IR were significantly
                      associated with ABCG1 expression.This study sheds light on
                      potential mechanisms linking statins with type 2 diabetes
                      risk, providing evidence on DNAm partially mediating
                      statins' effects on insulin traits. Further efforts shall
                      disentangle the molecular mechanisms through which statins
                      may induce DNAm changes, potentially leading to ABCG1
                      epigenetic regulation.},
      cin          = {C070},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32033992},
      doi          = {10.2337/dc19-1828},
      url          = {https://inrepo02.dkfz.de/record/153653},
}