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object 'alz14061-supitem-0002' cannot be found ID: PDF-HUL-122 Offset: 2273628 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'alz14061-supitem-0001' cannot be found ID: PDF-HUL-122 Offset: 2273628 MIMEtype: application/pdf Profile: Linearized PDF PDFMetadata: Objects: 725 FreeObjects: 1 IncrementalUpdates: 1 DocumentCatalog: PageLayout: SinglePage PageMode: UseOutlines Outlines: Item: Title: Blood-based multivariate methylation risk score for cognitive impairment and dementia Destination: chapter..1 Children: Item: Title: Abstract Destination: section*.2 Item: Title: 1 | BACKGROUND Destination: section..1.1 Item: Title: 2 | METHODS Destination: section..1.2 Children: Item: Title: 2.1 | Study design Destination: subsection..1.2.1 Item: Title: 2.2 | Study cohorts Destination: subsection..1.2.2 Children: Item: Title: 2.2.1 | The EXTEND cohort Destination: subsubsection..1.2.2.1 Item: Title: 2.2.2 | The EMIF-AD MBD study Destination: subsubsection..1.2.2.2 Item: Title: 2.2.3 | The ADNI cohort Destination: subsubsection..1.2.2.3 Item: Title: 2.2.4 | The PPMI cohort Destination: subsubsection..1.2.2.4 Item: Title: 2.2.5 | The BASE-II cohort Destination: subsubsection..1.2.2.5 Item: Title: 2.3 | Data pre-processing Destination: subsection..1.2.3 Children: Item: Title: 2.3.1 | Clinical outcomes Destination: subsubsection..1.2.3.1 Item: Title: 2.3.2 | Dementia risk factors Destination: subsubsection..1.2.3.2 Item: Title: 2.3.3 | Cerebral spinal fluid biomarkers Destination: subsubsection..1.2.3.3 Item: Title: 2.3.4 | Whole blood DNA methylation profiling Destination: subsubsection..1.2.3.4 Item: Title: 2.3.5 | Polygenic score generation Destination: subsubsection..1.2.3.5 Item: Title: 2.4 | Model generation Destination: subsection..1.2.4 Children: Item: Title: 2.4.1 | Approach 1: Generation of methylation risk scores for CAIDE and LIBRA Destination: subsubsection..1.2.4.1 Item: Title: 2.4.2 | Approach 2: Generation of MMRS Destination: subsubsection..1.2.4.2 Item: Title: 2.5 | Model validation Destination: subsection..1.2.5 Children: Item: Title: 2.5.1 | Validation in ADNI Destination: subsubsection..1.2.5.1 Item: Title: 2.5.2 | Validation in PPMI Destination: subsubsection..1.2.5.2 Item: Title: 2.5.3 | Validation in BASE-II Destination: subsubsection..1.2.5.3 Item: Title: 2.6 | Model interpretation Destination: subsection..1.2.6 Children: Item: Title: 2.6.1 | Variable importance Destination: subsubsection..1.2.6.1 Item: Title: 2.6.2 | GO overrepresentation analysis Destination: subsubsection..1.2.6.2 Item: Title: 2.6.3 | Influence of genetic variation Destination: subsubsection..1.2.6.3 Item: Title: 2.7 | Model extension Destination: subsection..1.2.7 Item: Title: 3 | RESULTS Destination: section..1.3 Children: Item: Title: 3.1 | Generation and validation of the epi-CAIDE and epi-LIBRA scores Destination: subsection..1.3.1 Item: Title: 3.2 | Generation and validation of MMRS models Destination: subsection..1.3.2 Item: Title: 3.3 | Validation in independent dementia cohorts Destination: subsection..1.3.3 Children: Item: Title: 3.3.1 | Validation in the PPMI cohort Destination: subsubsection..1.3.3.1 Item: Title: 3.3.2 | Validation in the ADNI cohort Destination: subsubsection..1.3.3.2 Item: Title: 3.3.3 | Validation in the BASE-II cohort Destination: subsubsection..1.3.3.3 Item: Title: 3.4 | Model interpretation Destination: subsection..1.3.4 Item: Title: 3.5 | Model extension Destination: subsection..1.3.5 Item: Title: 4 | DISCUSSION Destination: section..1.4 Item: Title: AFFILIATIONS Destination: section*.4 Item: Title: ACKNOWLEDGMENTS Destination: section*.6 Item: Title: CONFLICT OF INTEREST STATEMENT Destination: section*.8 Item: Title: CONSENT STATEMENT Destination: section*.10 Item: Title: ORCID Destination: section*.12 Item: Title: REFERENCES Destination: section*.14 Item: Title: SUPPORTING INFORMATION Destination: section*.16 Item: Title: APPENDIX 1: 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