TY - JOUR
T1 - Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data
AU - Soerensen, Mette
AU - Dato, Serena
AU - Christensen, Kaare
AU - McGue, Matt
AU - Stevnsner, Tinna
AU - Bohr, Vilhelm A.
AU - Christiansen, Lene
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
KW - Association study
KW - Case-control and longitudinal data
KW - Forkhead box O3A (FOXO3A)
KW - Human longevity
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U2 - 10.1111/j.1474-9726.2010.00627.x
DO - 10.1111/j.1474-9726.2010.00627.x
M3 - Article
C2 - 20849522
AN - SCOPUS:78249280592
SN - 1474-9718
VL - 9
SP - 1010
EP - 1017
JO - Aging cell
JF - Aging cell
IS - 6
ER -