Use of local genetic ancestry to assess TOMM40-523' and risk for Alzheimer disease

Parker L. Bussies, Farid Rajabli, Anthony Griswold, Daniel A. Dorfsman, Patrice Whitehead, Larry D. Adams, Pedro R. Mena, Michael Cuccaro, Jonathan L. Haines, Goldie S. Byrd, Gary W. Beecham, Margaret A. Pericak-Vance, Juan I. Young, Jeffery M. Vance

Research output: Contribution to journalArticle

Abstract

ObjectiveHere, we re-examine TOMM40-523' as a race/ethnicity-specific risk modifier for late-onset Alzheimer disease (LOAD) with adjustment for local genomic ancestry (LGA) in Apolipoprotein E (APOE) ?4 haplotypes.MethodsThe TOMM40-523' size was determined by fragment analysis and whole genome sequencing in homozygous APOE ?3 and APOE ?4 haplotypes of African (AF) or European (EUR) ancestry. The risk for LOAD was assessed within groups by allele size.ResultsThe TOMM40-523' length did not modify risk for LOAD in APOE ?4 haplotypes with EUR or AF LGA. Increasing length of TOMM40-523' was associated with a significantly reduced risk for LOAD in EUR APOE ?3 haplotypes.ConclusionsAdjustment for LGA confirms that TOMM40-523' cannot explain the strong differential risk for LOAD between APOE ?4 with EUR and AF LGA. Our study does confirm previous reports that increasing allele length of the TOMM40-523' repeat is associated with decreased risk for LOAD in carriers of homozygous APOE ?3 alleles and demonstrates that this effect is occurring in those individuals with the EUR LGA APOE ?3 allele haplotype.

Original languageEnglish (US)
Article numbere404
JournalNeurology: Genetics
Volume6
Issue number2
DOIs
StatePublished - 2020

ASJC Scopus subject areas

  • Clinical Neurology
  • Genetics(clinical)

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