Varying Effects of APOE Alleles on Extreme Longevity in European Ethnicities

Anastasia Gurinovich, Stacy L. Andersen, Annibale Puca, Gil Atzmon, Nir Barzilai, Paola Sebastiani

Research output: Contribution to journalArticlepeer-review


APOE is a well-studied gene with multiple effects on aging and longevity. The gene has three alleles: e2, e3, and e4, whose frequencies vary by ethnicity. While the e2 is associated with healthy cognitive aging, the e4 allele is associated with Alzheimer's disease and early mortality and therefore its prevalence among people with extreme longevity (EL) is low. Using the PopCluster algorithm, we identified several ethnically different clusters in which the effect of the e2 and e4 alleles on EL changed substantially. For example, PopCluster discovered a large group of 1,309 subjects enriched of Southern Italian genetic ancestry with weaker protective effect of e2 (odds ratio [OR] = 1.27, p =. 14) and weaker damaging effect of e4 (OR = 0.82, p =. 31) on the phenotype of EL compared to other European ethnicities. Further analysis of this cluster suggests that the odds for EL in carriers of the e4 allele with Southern Italian genetic ancestry differ depending on whether they live in the United States (OR = 0.29, p =. 009) or Italy (OR = 1.21, p =. 38). PopCluster also found clusters enriched of subjects with Danish ancestry with varying effect of e2 on EL. The country of residence (Denmark or United States) appears to change the odds for EL in the e2 carriers.

Original languageEnglish
Pages (from-to)S45-S51
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
StatePublished - 13 Nov 2019

Bibliographical note

Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.


  • APOE
  • Bioinformatics
  • Human genetics
  • Longevity

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Aging


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