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

Authors: Soerensen M; Dato S; Christensen K; McGue M; Stevnsner T; Bohr VA; Christiansen L

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.

Keywords: Aged, 80 and over; Case-Control Studies; Forkhead Transcription Factors/*genetics/metabolism; Gene Frequency; Genetic Variation/*genetics; Genotype; Haplotypes; Humans; Longevity/*genetics; Longitudinal Studies; Male; Polymorphism, Single Nucleotide
Journal: Aging cell
Volume: 9
Issue: 6
Pages: 1010-7
Date: Sept. 21, 2010
PMID: 20849522
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Citation:

Soerensen M, Dato S, Christensen K, McGue M, Stevnsner T, Bohr VA, Christiansen L (2010) Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data. Aging cell 9: 1010-7.


Longevity Variant Associations (p-value):
  • rs9486902 (0.0118)
  • rs12206094 (0.0076)
  • rs2802292 (0.0078)
  • rs13220810 (0.0223)
  • rs2764264 (0.05)
  • rs7762395 (0.05)
  • rs13217795 (0.05)
  • rs9400239 (0.05)
  • rs9398172 (0.05)
  • rs3800231 (0.0495)
  • rs479744 (0.05)

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