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@ARTICLE{Zhang:132877,
      author       = {Y. Zhang$^*$ and K.-U. Saum$^*$ and B. Schöttker$^*$ and
                      B. Holleczek and H. Brenner$^*$},
      title        = {{M}ethylomic survival predictors, frailty, and mortality.},
      journal      = {Aging},
      volume       = {10},
      number       = {3},
      issn         = {1945-4589},
      address      = {[S.l.]},
      publisher    = {Impact Journals, LLC},
      reportid     = {DKFZ-2018-00519},
      pages        = {339-357},
      year         = {2018},
      abstract     = {Survival predictors are of potential use for informing on
                      biological age and targeting prevention of aging-related
                      morbidity. We assessed associations of 2 novel methylomic
                      survival indicators, a methylation-based mortality risk
                      score (MRscore) and the epigenetic clock-derived age
                      acceleration (AA), with a well-known survival predictor,
                      frailty index (FI), and compared the 3 indicators in
                      mortality prediction. In a large population-based cohort
                      with 14-year follow-up, we found both MRscore and AA to be
                      independently associated with FI, but the association was
                      much stronger for MRscore than for AA. Although all 3
                      indicators were individually associated with all-cause
                      mortality, robust associations only persisted for MRscore
                      and FI when simultaneously including the 3 indicators in
                      regression models, with hazard ratios $(95\%$ CI) of 1.91
                      (1.63-2.22), 1.37 (1.25-1.51), and 1.05 (0.90-1.22),
                      respectively, per standard deviation increase of MRscore,
                      FI, and AA. Prediction error curves, Harrell's C-statistics,
                      and time-dependent AUCs all showed higher predictive
                      accuracy for MRscore than for FI and AA. These findings were
                      validated in independent samples. Our study demonstrates the
                      ability of the MRscore to strongly enhance survival
                      prediction beyond established markers of biological age,
                      such as FI and AA, and it thus bears potential of a
                      surrogate endpoint for clinical research and intervention.},
      cin          = {C070 / G110 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)G110-20160331 /
                      I:(DE-He78)L101-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29514134},
      pmc          = {pmc:PMC5892685},
      doi          = {10.18632/aging.101392},
      url          = {https://inrepo02.dkfz.de/record/132877},
}