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

Neurol Genet 2020 Apr 3;6(2):e404. Epub 2020 Mar 3.

John P. Hussman Institute for Human Genomics (P.L.B., F.R., A.G., D.A.D., P.W., L.D.A., P.R.M., M.C., G.W.B., M.A.P.-V., J.I.Y., J.M.V.), Miller School of Medicine, University of Miami; Dr. John T. MacDonald Foundation Department of Human Genetics (A.G., M.C., G.W.B., M.A.P.-V., J.I.Y., J.M.V.), Miller School of Medicine, University of Miami; Department of Population and Quantitative Health Sciences (J.L.H.), Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH; and Wake Forest School of Medicine (G.S.B.), Bowman Gray Center for Medical Education, Winston-Salem, NC.

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.

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Source
http://dx.doi.org/10.1212/NXG.0000000000000404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164968PMC
April 2020

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