What the genotype is
APOE status is determined by two SNPs read together: rs429358 and rs7412. The e4/e4 diplotype means you carry two copies of the e4 isoform at this locus. In Varia's catalog this is the highest common genetic risk configuration for late-onset Alzheimer's disease among people of European descent PMID 9343467.
What the literature reports
Meta-analytic data from clinic- and autopsy-based studies report an odds ratio of about 14.9 for Alzheimer disease in e4/e4 carriers compared with the e3/e3 reference genotype in Caucasian cohorts PMID 9343467. Earlier family-based work described a gene-dose relationship, with risk rising as e4 allele count increases PMID 8346443.
What Varia does with this variant
Varia reads both rs429358 and rs7412 from your raw DNA file and resolves your complete APOE diplotype locally. The result appears under Brain and Cognition with sourced effect language and linked citations from the curated catalog.
Questions and answers
Why do both SNPs matter?
Neither rs429358 nor rs7412 alone determines APOE isoform status. Varia requires both positions to resolve e2, e3, and e4 combinations correctly.
Does e4/e4 mean someone will develop Alzheimer's disease?
No. The e4/e4 genotype is associated with higher population-average risk in published studies, not certainty for any individual. Age, ancestry, and other factors also matter PMID 9343467.