Poly-T TOMM40-523' variant size does not explain the large difference in risk of late-onset Alzheimer’s disease (LOAD) between patients with African or European local genomic ancestry (LGA) on the APOE ε4 haplotype.
Increasing TOMM40-523' repeat size is associated with decreased risk of LOAD in carriers of the homozygous APOE ε3 haplotype with European LGA.
Why this matters
The APOE ε4 allele in African and African Americans confers a lower risk of LOAD compared with Europeans, which may be attributable to LGA within the APOE haplotype. TOMM40-523' repeat size varies in length by individual and race, possibly influencing the transcription of APOE and affecting the risk of developing LOAD.
Previous studies have analyzed the relationship between TOMM40-523' length and LOAD framed in the context of global genetic ancestry, though this is the first to adjust for LGA and thus offer the most accurate insight into this relationship.