title: Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data.
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.
authors.affiliation: The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, Odense C, Denmark. msoerensen@health.sdu.dk
authors.forename: Mette
authors.initials: M
authors.lastname: Soerensen
authors.forename: Serena
authors.initials: S
authors.lastname: Dato
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.forename: Matt
authors.initials: M
authors.lastname: McGue
authors.forename: Tinna
authors.initials: T
authors.lastname: Stevnsner
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
mesh_terms: D000369:Aged, 80 and over; D016022:Case-Control Studies; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors