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Principal Investigator  
Principal Investigator's Name: Lars Bertram
Institution: University of Luebeck
Department: Section of Medicine
Proposed Analysis: Background: In order to find new novel, noninvasive genetic markers to better diagnose Alzheimer’s disease at an early stage, we performed genome-wide association studies (GWAS) of various phenotypes ascertained in the European Medical Information Framework for Alzheimer’s Disease (EMIF-AD) study. Our phenotypes include: 1) case-control status (AD and MCI vs. controls) 2) various CSF markers; 3) visual ratings and volumetric measures assessed by MRI; 4) various measures of cognitive function and the rate of their declines. Plan/Proposed Analyses: Using the available phenotype outcome data, we have both validated findings (SNPs in APOE and surrounding region) for AD versus control GWAS results, and identified interesting new findings (SNPs and genes) located in other genomic regions for some of the available CSF and cognitive measurements. In order to replicate and validate our results, we apply for access to equivalent ADNI genotype and phenotype data. For the GWAS analysis, we plan to: 1) assess whether our top SNPs and genes are also associated with equivalent outcomes in ADNI. 2) perform a meta-analysis of results from both ADNI and our EMIF data set. In addition, we would like to validate in ADNI the results from polygenic scores (PGS) constructed from the EMIF-AD data. To match up both ADNI and EMIF-AD data sets, we apply for ADNI-1 genotype data derived from WGS as well as ADNI clinical data (including recruitment, demographics, physical examinations and cognitive assessments), post-processed numeric data of measurement for each MRI exam, CSF and plasma tau and Aβ40 and Aβ42 concentrations.
Additional Investigators  
Investigator's Name: Shengjun Hong
Proposed Analysis: Dr. Hong will perform all analyses specified in the proposal for this application.
Investigator's Name: Yasmine Sommerer
Proposed Analysis: Mrs. Sommerer will be in charge of all DNA methylation analyses to be performed in ADNI EPIC data.