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

TitleUse of local genetic ancestry to assess -523' and risk for Alzheimer disease.
Publication TypeJournal Article
Year of Publication2020
AuthorsBussies PL, Rajabli F, Griswold A, Dorfsman DA, Whitehead P, Adams LD, Mena PR, Cuccaro M, Haines JL, Byrd GS, Beecham GW, Pericak-Vance MA, Young JI, Vance JM
JournalNeurol Genet
Date Published2020 Apr

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.

Pubmed Link
Alternate JournalNeurol Genet
PubMed ID32337333
PubMed Central IDPMC7164968
Grant ListRF1 AG059018 / AG / NIA NIH HHS / United States

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