LongevityMap Gene

Gene details

HGNC symbol
FOXO3 
Aliases
FOXO2; AF6q21; FKHRL1; FOXO3A; FKHRL1P2 
Common name
forkhead box O3 
Description
This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. This gene likely functions as a trigger for apoptosis through expression of genes necessary for cell death. Translocation of this gene with the MLL gene is associated with secondary acute leukemia. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]
Cytogenetic Location
6q21
UCSC Genome Browser
View 6q21 on the UCSC genome browser
OMIM
602681
Ensembl
ENSG00000118689
UniProt/Swiss-Prot
FOXO3_HUMAN
Entrez Gene
2309
UniGene
220950
1000 Genomes
1000 Genomes

Homologs in model organisms

Danio rerio
foxo3a
Mus musculus
Foxo3
Rattus norvegicus
Foxo3

In other databases

GenAge human genes
  • This gene is present as FOXO3
GenDR gene manipulations
  • A homolog of this gene for Mus musculus is present as Foxo3
CellAge
  • This gene is present as FOXO3

Studies (13)

Significant/Non-significant: 8/5

Study 1

Longevity Association
Significant
Population
German
Study Design
16 known FOXO3A SNPs were examined in 1,762 German centenarians/nonagenarians and younger controls
Conclusions
Polymorphisms in FOXO3A were associated with longevity. The FOXO3A association was considerably stronger in centenarians than in nonagenarians, highlighting the importance of centenarians for genetic longevity research. Replication in 535 French centenarians (mean age: 103.8 years) and 553 younger controls (aged 18–70 years) generated a trend that supported the results, although it was not statistically significant.
Indentifier
rs2802288
Reference

    Study 2

    Longevity Association
    Significant
    Population
    Italian (Southern)
    Study Design
    FOXO3A polymorphisms (rs2802292, rs2764264, and rs13217795) were analyzed for longevity associations in 281 long-lived men (age range 90-108 years) and 195 controls (age range 18-48 years) from the Southern Italian Centenarian Study.
    Conclusions
    rs2802288, a proxy of rs2802292, showed the best allelic association--minor allele frequency (MAF) = 0.49; p = 0.003; odds ratio (OR) = 1.51; 95% confidence interval (CI), 1.15-1.98).
    Indentifier
    rs2802292
    Reference

      Study 3

      Longevity Association
      Significant
      Population
      Chinese (Han)
      Study Design
      Six tagging SNPs from FOXO1A and FOXO3A were selected and genotyped in 1817 centenarians and younger individuals
      Conclusions
      All 3 SNPs of FOXO3A were associated with longevity in both genders (P = 0.005-0.001)
      Indentifier
      rs2253310
      Reference

        Study 4

        Longevity Association
        Significant
        Population
        American of Japanese origin
        Study Design
        Nested-case control study of 5 candidate longevity genes in 8006 Japanese American men from the Honolulu Heart Program and 3741 men part of the Honolulu Asia Aging Study
        Conclusions
        Genetic variation in the FOXO3A gene was associated with longevity
        Indentifier
        rs2764264
        Reference

          Study 5

          Longevity Association
          Non-significant
          Population
          American of Japanese origin
          Study Design
          85 multiethnic (Caucasian, Filipino, Japanese, Chinese, and mixed ethnicity; aged 10- 78 y) sequences were chosen to determine allele frequency. Then 282 Americans of Japanese ancestry were examined for the allele frequency. Furthermore, 675 Hawaii Lifespan Study case (>95 y, average 97.9 y)-control(< 81 y, average 78.5 y) study participants were examined for the allele frequency.
          Conclusions
          All 38 of the previously reported coding SNPs in FOXO3 are either invalid or too rare to be useful for phenotype–genotype association and other genetic mapping studies. These are likely not involved in longevity. A novel identified SNP (rs138174682) is prevalent in multiple ethnic groups but too rare for longevity analysis in Hawaii Lifespan Study.
          Indentifier
          rs111556510
          Reference

            Study 6

            Longevity Association
            Significant
            Population
            American (Caucasian)
            Study Design
            291 SNPs in 30 genes in the insulin/IGF1 signaling pathway were evaluated in 293 long-lived cases and 603 average-lifespan controls (all female), then replicated the candidate genes in two independent cohorts: 279 cases (47% male vs 797 controls(52.6% male) and 383 cases (25.2% male) vs 363 controls (42.7 % male)
            Conclusions
            The association of FOXO3A rs1935949 and rs4946935 with longevity in the meta-analysis have statistical significance (adjusted P values were 0.0093 and 0.019 respectively) in female samples
            Indentifier
            rs1935949
            Reference

              Study 7

              Longevity Association
              Non-significant
              Population
              German
              Study Design
              Genome-wide association study comparing 664,472 autosomal SNPs in 763 long-lived individuals (mean age: 99.7 years) and 1085 controls (mean age: 60.2 years). Top SNPs from the GWAS were further investigated in an independent German sample comprised of 754 long-lived individuals (mean age: 96.9 years) and 860 controls (mean age: 67.3 years).
              Conclusions
              FOXO3A and EXO1 were not significantly associated with longevity
              Indentifier
              FOXO3
              Reference

                Study 8

                Longevity Association
                Non-significant
                Population
                Dutch
                Study Design
                Genome-wide association study in 403 unrelated nonagenarians from long-living families and 1670 younger controls. Strongest candidates were then investigated in a meta-analysis of 4149 nonagenarian cases and 7582 younger controls.
                Conclusions
                No association with survival into old age was observed for SNPs in FOXO3A
                Indentifier
                rs9486902
                Reference

                  Study 9

                  Longevity Association
                  Significant
                  Population
                  Dutch
                  Study Design
                  1,018 SNPs within a 10-kb window around 40 mTOR signalling genes were studied for differences in variation between 417 unrelated nonagenarian participants and 476 younger controls
                  Conclusions
                  As a whole, there was a significant association of genetic variation in the mTOR pathway and familial longevity, though no individual gene was significant after correcting for multiple hypothesis testing
                  Indentifier
                  FOXO3
                  Reference

                    Study 10

                    Longevity Association
                    Significant
                    Population
                    Chinese (Han)
                    Study Design
                    Three SNPs in FOXO1A and three in FOXO3A were analyzed in a sample of 760 centenarians (578 female and 182 male) and 1060 middle-age controls (378 female and 682 male)
                    Conclusions
                    All three SNPs in FOXO3A were positively associated with longevity in both genders, even at ages 92-110 (odds ratio [OR] = 1.61–1.73, p = .0002–0.005; dominant model)
                    Indentifier
                    rs2253310
                    Reference

                      Study 11

                      Longevity Association
                      Non-significant
                      Population
                      Italian (Southern)
                      Study Design
                      A two-stage case-control study was performed to identify the association between longevity and variation of in homeostasis regulation pathway genes. 317 SNPs in 104 genes were analyzed in 78 cases (≥90 years, median age 98 years, 42 females) and 71 controls (<90 years, median age 67 years, 32 females) in stage 1. Then, 31 candidate SNPs identified in stage 1 (π markers = 0.1) were analyzed in an independent sample composed by 288 cases (≥90 years, median age 92 years, 163 females) and 554 controls (<90 years, median age 67 years, 277 females).
                      Conclusions
                      After adjustment for multiple testing, no significant association was identified between various SNPs and longevity.
                      Indentifier
                      rs2253310
                      Reference

                        Study 12

                        Longevity Association
                        Significant
                        Population
                        Danish
                        Study Design
                        15 SNPs that covered FOXO3A common variation were examined in 1089 oldest old and 736 middle-aged for longevity association by longitudinal study design as well as case-control study design
                        Conclusions
                        4 SNPs previously reported to be associated with longevity were verified in this study. 4 novel SNPs (rs12206094, rs13220810, rs7762395, and rs9486902 (corrected P-values 0.001–0.044)) and two haplotypes(corrected P-values: 0.01–0.03) associated with longevity were found in this study. FOXO3A was a candidate longevity gene for survival from younger ages to old age, yet not during old age.
                        Indentifier
                        rs13217795
                        Reference

                          Study 13

                          Longevity Association
                          Non-significant
                          Population
                          Danish
                          Study Design
                          15 SNPs that covered FOXO3A common variation were examined in 1089 oldest old and 736 middle-aged for longevity association by longitudinal study design as well as case-control study design
                          Conclusions
                          4 SNPs previously reported to be associated with longevity were verified in this study. 4 novel SNPs (rs12206094, rs13220810, rs7762395, and rs9486902 (corrected P-values 0.001–0.044)) and two haplotypes(corrected P-values: 0.01–0.03) associated with longevity were found in this study. FOXO3A was a candidate longevity gene for survival from younger ages to old age, yet not during old age.
                          Indentifier
                          rs2802292
                          Reference