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A, Measured by cerebrospinal fluid samples. B, Measured by positron emission tomography imaging. Box plot error bars show the 95th-percentile range. Gray circles indicate values outside of the 95th percentile range. Admixture plots for A the five major super populations and B three major sub-European populations across all 22 case-control cohorts. First three principal components of the genetic population structure in Northwestern European subjects across all 22 case-control cohorts.

Case-control sample sizes per cohort after sequential quality control and filtering steps detailed in the titles above each column. Sample sizes per conversion risk cohort after sequential quality control and filtering steps. JAMA Neurol.

Importance Identification of genetic factors that interact with the apolipoprotein e4 APOE4 allele to reduce risk for Alzheimer disease AD would accelerate the search for new AD drug targets. Design, Setting, and Participants This study combined 25 independent case-control, family-based, and longitudinal AD cohorts that recruited referred and volunteer participants and made data available through public repositories.

Analyses were stratified by APOE4 status. Genetic data were available from high-density single-nucleotide variant microarrays. All data were collected between September and September and analyzed between April and December Main Outcomes and Measures The risk of AD was evaluated through logistic regression analyses under a case-control design.