rs429358 - APOE e4 - The Alzheimer's Risk Allele
Gene: APOE
rs429358 is one of two SNPs (along with rs7412) that define the APOE genotype. The C allele at this position (combined with C at rs7412) creates the e4 allele, the strongest common genetic risk factor for late-onset Alzheimer's disease.
Genotype Interpretations
APOE e3/e3 (most likely) - Average Alzheimer's risk. This is the most common genotype
Likely APOE e3/e4 - ~3x increased Alzheimer's risk. One copy of the risk allele
Likely APOE e4/e4 - ~12x increased Alzheimer's risk. Two copies. Important to discuss with a physician
Population Context
The e4 allele frequency is ~14% globally but varies: ~26% in African populations (where the Alzheimer's risk is lower per copy), ~14% European, ~9% East Asian. APOE e4 was likely the ancestral human allele.
Clinical Relevance
APOE e4 carriers benefit most from exercise (Raichlen 2016), MIND diet, cardiovascular risk management, and sleep optimization. 23andMe stopped reporting APOE due to anxiety concerns, but knowing your status enables proactive prevention.
Sources
- [1] Corder EH et al. (1993) Science 261:921-3
- [2] Lourida I et al. (2019) JAMA 322:430-7
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