eAppendix. Additional acknowledgments eMethods. eFigure 1. Flowchart describing the number of individuals remaining at each filtering steps eFigure 2. V236E and R251G are associated with decreased AD risk across dataset in APOE-stratified sensitivity analyses eFigure 3. APOE ε3/ε3[V236E] individuals have a lower AD risk than APOE ε2/ε3 individuals and APOE ε3/ε4[R251G] have a risk equivalent to ε2/ε3 carriers despite carrying 1 ε4 allele, regardless of the EUR ancestry cutoff for admixed Europeans and Europeans eTable 1. Queried cohort overview to identify admixed and European ancestry individuals in the ADSP discovery and ADGC internal replication eTable 2. Overview of ADSP studies with whole-exome sequencing (WES) and/or whole-genome sequencing (WGS) available at NIAGADS DSS (NG00067) eTable 3. Demographic characteristics of the cohorts queried for discovery and internal replication samples eTable 4. Missense variants on the APOE canonical transcript reported in gnomADv.3.1 eTable 5. Demographic characteristics per cohort in ADSP discovery and ADGC internal replication after ancestry selection, quality control, and duplicates removal eTable 6. APOE missense variants rs769452-C (APOE[L28P]), rs199768005-A (APOE[V236E]), and rs267606661-G (APOE[R251G]) allelic breakdown by APOE main genotype eTable 7. V236E and R251G association in primary and secondary analyses, nonstratified and APOE stratified eTable 8. Nonstratified sensitivity analyses at various European ancestry cutoffs eTable 9. Sensitivity analysis, including all dementia in the CCHS and CGPS data set, slightly strengthens the V236E and R251G associations with decreased AD risk eTable 10. Sensitivity analysis, excluding the UK Biobank proxy-AD phenotype from the meta-analysis, results in slight worsening of the P values of the V236E and R251G associations with decreased AD risk eReferences. Supplemental Online Content: Nonauthor Collaborators.

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

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