Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data

Mette Soerensen, Serena Dato, Kaare Christensen, Matt McGue, Tinna Stevnsner, Vilhelm A. Bohr, Lene Christiansen

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

Abstract

Genetic variation in FOXO3A has previously been associated with human longevity. Studies published so far have been case-control studies and hence vulnerable to bias introduced by cohort effects. In this study we extended the previous findings in the cohorts of oldest old Danes (the Danish 1905 cohort, N-=-1089) and middle-aged Danes (N-=-736), applying a longitudinal study design as well as the case-control study design. Fifteen SNPs were chosen in order to cover the known common variation in FOXO3A. Comparing SNP frequencies in the oldest old with middle-aged individuals, we found association (after correction for multiple testing) of eight SNPs; 4 (rs13217795, rs2764264, rs479744, and rs9400239) previously reported to be associated with longevity and four novel SNPs (rs12206094, rs13220810, rs7762395, and rs9486902 (corrected P-values 0.001-0.044). Moreover, we found association of the haplotypes TAC and CAC of rs9486902, rs10499051, and rs12206094 (corrected P-values: 0.01-0.03) with longevity. Finally, we here present data applying a longitudinal study design; when using follow-up survival data on the oldest old in a longitudinal analysis, we found no SNPs to remain significant after the correction for multiple testing (Bonferroni correction). Hence, our results support and extent the proposed role of FOXO3A as a candidate longevity gene for survival from younger ages to old age, yet not during old age.

Original languageEnglish (US)
Pages (from-to)1010-1017
Number of pages8
JournalAging cell
Volume9
Issue number6
DOIs
StatePublished - Dec 2010

Bibliographical note

Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.

Keywords

  • Association study
  • Case-control and longitudinal data
  • Forkhead box O3A (FOXO3A)
  • Human longevity

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