Understanding Your APOE Status. Why Two SNPs Are Required
Your APOE genotype cannot be determined from a single genetic position. It requires reading two SNPs together: rs429358 (codon 112) and rs7412 (codon 158). The combination of your alleles at both positions determines which APOE isoforms you carry. Varia reads both positions from your raw file and resolves your complete APOE diplotype.
The APOE Isoform Table
| rs429358 | rs7412 | APOE Diplotype | Alzheimer's Risk | Notes |
|---|---|---|---|---|
| T,T | T,T | ε2/ε2 | Below average | Lowest AD risk; elevated Type III hyperlipoproteinemia risk |
| T,T | C,T | ε2/ε3 | Below average | Cardioprotective lipid profile |
| T,T | C,C | ε3/ε3 | Population average | Most common genotype globally |
| C,T | C,T | ε2/ε4 | Modestly elevated (~2-3x) | The ε4 allele drives the risk; the ε2 provides little offset |
| C,T | C,C | ε3/ε4 | ~3x elevated | ~25% of European-descent population |
| C,C | C,C | ε4/ε4 | ~12-15x elevated | ~2% (Northern European descent; lower in other populations) |
Risk figures are odds ratios for Alzheimer's diagnosis relative to the ε3/ε3 genotype, drawn from large APOE meta-analyses (APOE genotype and Alzheimer disease risk across age, sex, and population ancestry, JAMA Neurology 2023; foundational meta-analysis Farrer et al., JAMA 1997). They come largely from European-ancestry cohorts and vary by genetic ancestry: the association is strongest in East Asian populations and weaker in African-ancestry and Hispanic populations, so these multipliers do not transfer cleanly across ancestries. Frequencies are approximate and population-dependent.
What 23andMe's Authorized Report Covers
23andMe's FDA-authorized Genetic Health Risk reports (de novo authorization DEN160026, April 6, 2017) cover a defined list of reports, including a late-onset Alzheimer's report based on APOE e4 status. That authorization does not make Varia an FDA-authorized product, and it does not describe what Varia does. Varia is not FDA-authorized and performs no variant detection. Varia reads both rs429358 and rs7412 from a DNA file you already have and resolves the APOE diplotype as educational post-test interpretation. 23andMe's health interface shows the authorized report; the raw data file you download still contains both positions.
Why AncestryDNA Results May Be Unreliable for APOE
AncestryDNA chip files do not reliably report rs429358. Varia's scanner therefore does not treat that marker as determinable from an AncestryDNA file; it asks for a 23andMe v5 export or a sequencing file when APOE e4 status is needed. That guard is in the scanner, not a community anecdote. If you have only AncestryDNA data, do not read a missing or reference-looking rs429358 call as proof you lack e4.
How Varia Resolves Your APOE Diplotype
Varia reads both rs429358 and rs7412 from your raw file entirely within your browser. No upload, no server. For WGS VCF files from Sequencing.com or Dante Labs, both positions are present with high-confidence sequencing depth and are the most reliable source for APOE determination. For chip-based files, both positions are read and the AncestryDNA caveat is flagged explicitly in the Domain I results if an AncestryDNA file is detected.