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@ARTICLE{Perrier:143520,
      author       = {F. Perrier and V. Viallon and S. Ambatipudi and A. Ghantous
                      and C. Cuenin and H. Hernandez-Vargas and V. Chajès and L.
                      Baglietto and M. Matejcic and H. Moreno-Macias and T.
                      Kühn$^*$ and H. Boeing and A. Karakatsani and A. Kotanidou
                      and A. Trichopoulou and S. Sieri and S. Panico and F.
                      Fasanelli and M. Dolle and C. Onland-Moret and I. Sluijs and
                      E. Weiderpass and J. R. Quirós and A. Agudo and J. M.
                      Huerta and E. Ardanaz and M. Dorronsoro and T. Y. N. Tong
                      and K. Tsilidis and E. Riboli and M. J. Gunter and Z. Herceg
                      and P. Ferrari and I. Romieu},
      title        = {{A}ssociation of leukocyte {DNA} methylation changes with
                      dietary folate and alcohol intake in the {EPIC} study.},
      journal      = {Clinical epigenetics},
      volume       = {11},
      number       = {1},
      issn         = {1868-7083},
      address      = {[S.l.]},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2019-01104},
      pages        = {57},
      year         = {2019},
      abstract     = {There is increasing evidence that folate, an important
                      component of one-carbon metabolism, modulates the epigenome.
                      Alcohol, which can disrupt folate absorption, is also known
                      to affect the epigenome. We investigated the association of
                      dietary folate and alcohol intake on leukocyte DNA
                      methylation levels in the European Prospective Investigation
                      into Cancer and Nutrition (EPIC) study. Leukocyte
                      genome-wide DNA methylation profiles on approximately
                      450,000 CpG sites were acquired with Illumina
                      HumanMethylation 450K BeadChip measured among 450 women
                      control participants of a case-control study on breast
                      cancer nested within the EPIC cohort. After data
                      preprocessing using surrogate variable analysis to reduce
                      systematic variation, associations of DNA methylation with
                      dietary folate and alcohol intake, assessed with dietary
                      questionnaires, were investigated using CpG site-specific
                      linear models. Specific regions of the methylome were
                      explored using differentially methylated region (DMR)
                      analysis and fused lasso (FL) regressions. The DMR analysis
                      combined results from the feature-specific analysis for a
                      specific chromosome and using distances between features as
                      weights whereas FL regression combined two penalties to
                      encourage sparsity of single features and the difference
                      between two consecutive features.After correction for
                      multiple testing, intake of dietary folate was not
                      associated with methylation level at any DNA methylation
                      site, while weak associations were observed between alcohol
                      intake and methylation level at CpG sites cg03199996 and
                      cg07382687, with qval = 0.029 and qval = 0.048,
                      respectively. Interestingly, the DMR analysis revealed a
                      total of 24 and 90 regions associated with dietary folate
                      and alcohol, respectively. For alcohol intake, 6 of the 15
                      most significant DMRs were identified through FL.Alcohol
                      intake was associated with methylation levels at two CpG
                      sites. Evidence from DMR and FL analyses indicated that
                      dietary folate and alcohol intake may be associated with
                      genomic regions with tumor suppressor activity such as the
                      GSDMD and HOXA5 genes. These results were in line with the
                      hypothesis that epigenetic mechanisms play a role in the
                      association between folate and alcohol, although further
                      studies are warranted to clarify the importance of these
                      mechanisms in cancer.},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30940212},
      pmc          = {pmc:PMC6444439},
      doi          = {10.1186/s13148-019-0637-x},
      url          = {https://inrepo02.dkfz.de/record/143520},
}