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@ARTICLE{Stcker:156724,
      author       = {S. Stöcker$^*$ and L. Perna$^*$ and K. Weigl$^*$ and T.
                      Möllers$^*$ and B. Schöttker$^*$ and H. Thomsen and B.
                      Holleczek and D. Rujescu and H. Brenner$^*$},
      title        = {{P}rediction of clinical diagnosis of {A}lzheimer's
                      disease, vascular, mixed, and all-cause dementia by a
                      polygenic risk score and {APOE} status in a community-based
                      cohort prospectively followed over 17 years.},
      journal      = {Molecular psychiatry},
      volume       = {26},
      issn         = {1476-5578},
      address      = {London},
      publisher    = {Macmillan},
      reportid     = {DKFZ-2020-01062},
      pages        = {5812–5822},
      year         = {2021},
      note         = {26, pages 5812–5822 (2021) / #EA:C070#LA:C070#},
      abstract     = {The strongest genetic risk factor for Alzheimer's disease
                      (AD) is the ε4 allele of Apolipoprotein E (APOE) and recent
                      genome-wide association meta-analyses have confirmed
                      additional associated genetic loci with smaller effects. The
                      aim of this study was to investigate the ability of an AD
                      polygenic risk score (PRS) and APOE status to predict
                      clinical diagnosis of AD, vascular (VD), mixed (MD), and
                      all-cause dementia in a community-based cohort prospectively
                      followed over 17 years and secondarily across age, sex, and
                      education strata. A PRS encompassing genetic variants
                      reaching genome-wide significant associations to AD
                      (excluding APOE) from the most recent genome-wide
                      association meta-analysis data was calculated and APOE
                      status was determined in 5203 participants. During
                      follow-up, 103, 111, 58, and 359 participants were diagnosed
                      with AD, VD, MD, and all-cause dementia, respectively.
                      Prediction ability of AD, VD, MD, and all-cause dementia by
                      the PRS and APOE was assessed by multiple logistic
                      regression and receiver operating characteristic curve
                      analyses. The PRS per standard deviation increase in score
                      and APOE4 positivity (≥1 ε4 allele) were significantly
                      associated with greater odds of AD (OR, $95\%$ CI: PRS:
                      1.70, 1.45-1.99; APOE4: 3.34, 2.24-4.99) and AD prediction
                      accuracy was significantly improved when adding the PRS to a
                      base model of age, sex, and education (ASE) (c-statistics:
                      ASE, 0.772; ASE + PRS, 0.810). The PRS enriched the
                      ability of APOE to discern AD with stronger associations
                      than to VD, MD, or all-cause dementia in a prospective
                      community-based cohort.},
      cin          = {C070},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32404947},
      doi          = {10.1038/s41380-020-0764-y},
      url          = {https://inrepo02.dkfz.de/record/156724},
}