Open AccessVarying Effects of APOE Alleles on Extreme Longevity in European Ethnicities
Author(s) -
Anastasia Gurinovich,
Stacy Andersen,
Annibale Alessandro Puca,
Gil Atzmon,
Nir Barzilai,
Paola Sebastiani
Publication year - 2019
Publication title -
the journals of gerontology. series a, biological sciences and medical sciences
Language(s) - English
Resource type - Journals
eISSN - 1758-535X
pISSN - 1079-5006
DOI - 10.1093/gerona/glz179
Subject(s) - longevity , allele , apolipoprotein e , ethnic group , demography , odds ratio , danish , odds , genetics , residence , biology , disease , medicine , logistic regression , gene , sociology , linguistics , philosophy , anthropology
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.