Use of local genetic ancestry to assess -523' and risk for Alzheimer disease.

Objective: Here, we re-examine -523' as a race/ethnicity-specific risk modifier for late-onset Alzheimer disease (LOAD) with adjustment for local genomic ancestry (LGA) in (4 haplotypes.
Methods: The -523' size was determined by fragment analysis and whole genome sequencing in homozygous 3 and 4 haplotypes of African (AF) or European (EUR) ancestry. The risk for LOAD was assessed within groups by allele size.
Results: The -523' length did not modify risk for LOAD in haplotypes with EUR or AF LGA. Increasing length of -523' was associated with a significantly reduced risk for LOAD in EUR ε3 haplotypes.
Conclusions: Adjustment for LGA confirms that -523' cannot explain the strong differential risk for LOAD between ε4 with EUR and AF LGA. Our study does confirm previous reports that increasing allele length of the repeat is associated with decreased risk for LOAD in carriers of homozygous ε3 alleles and demonstrates that this effect is occurring in those individuals with the EUR LGA ε3 allele haplotype.