Increased effect of the ApoE gene on survival at advanced age in healthy and long-lived Danes: two nationwide cohort studies.
Abstract
Studies of Nordic twins suggest an increased genetic influence on mortality with age.
Contrary to this, the heterogeneity hypothesis predicts that the mortality of individuals
carrying a 'frail' or 'risky' genotype in a population will approach that of noncarriers
with age because of selection pressure. The ApoE ε4 allele is associated with an increased
mortality risk, and its effect has been suggested to decrease with age. Here, we investigated
the effect of ApoE ε4 allele on survival in a sample of the healthiest and long-lived
Danes. The study population comprised Danes born in 1905 and a replicate sample of
the 1895 cohort. For the 1905 cohort, a total of 350 carriers and 1256 noncarriers
of the ApoE ε4 allele were followed from 1998 until death or end of follow-up. Cox
regression models were used for the analysis. Of the 1606 persons with known ApoE
ε4 status in 1998, 1546 had died at the end of the 10-year follow-up. Carriers of
the ApoE ε4 allele had an increased mortality compared to noncarriers, and the influence
of ApoE status on mortality increased in the age interval 92-103. For the covariates
sex and independency status, the difference in relative risk of death between groups
decreased with advancing age. Our findings of increasing influence of ApoE ε4 allele
on mortality with age do not support previous findings of decreased influence ApoE
ε4 allele on mortality with age, and alternative models such as the multifactorial
threshold models should be considered for understanding the genetic effects on mortality
at advanced age.
Type
Journal articleSubject
AgingAlleles
Apolipoprotein E4
Cohort Studies
Denmark
Female
Humans
Longevity
Longitudinal Studies
Male
Survival Analysis
Permalink
https://hdl.handle.net/10161/14788Published Version (Please cite this version)
10.1111/j.1474-9726.2010.00626.xPublication Info
Jacobsen, Rune; Martinussen, Torben; Christiansen, Lene; Jeune, Bernard; Andersen-Ranberg,
Karen; Vaupel, James W; & Christensen, Kaare (2010). Increased effect of the ApoE gene on survival at advanced age in healthy and long-lived
Danes: two nationwide cohort studies. Aging Cell, 9(6). pp. 1004-1009. 10.1111/j.1474-9726.2010.00626.x. Retrieved from https://hdl.handle.net/10161/14788.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
James Walton Vaupel
Research Professor Emeritus in the Sanford School of Public Policy
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info