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

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 V.

AU - Bohr, Vilhelm A

AU - Christiansen, Lene

N1 - © 2010 The Authors. Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

PY - 2010/12/1

Y1 - 2010/12/1

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 - Aged, 80 and over

KW - Case-Control Studies

KW - Forkhead Transcription Factors

KW - Gene Frequency

KW - Genetic Variation

KW - Genotype

KW - Haplotypes

KW - Humans

KW - Longevity

KW - Longitudinal Studies

KW - Male

KW - Polymorphism, Single Nucleotide

U2 - 10.1111/j.1474-9726.2010.00627.x

DO - 10.1111/j.1474-9726.2010.00627.x

M3 - Journal article

C2 - 20849522

SN - 1474-9718

VL - 9

SP - 1010

EP - 1017

JO - Aging Cell

JF - Aging Cell

IS - 6

ER -