LongevityMap Gene

Gene details

HGNC symbol: FOXO1
Aliases: FKH1; FKHR; FOXO1A
Common name: forkhead box O1
Description: This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in myogenic growth and differentiation. Translocation of this gene with PAX3 has been associated with alveolar rhabdomyosarcoma. [provided by RefSeq, Jul 2008]
Cytogenetic Location: 13q14.11
UCSC Genome Browser: View 13q14.11 on the UCSC genome browser
OMIM: 136533
Ensembl: ENSG00000150907
UniProt/Swiss-Prot: FOXO1_HUMAN
Entrez Gene: 2308
UniGene: 370666
1000 Genomes: 1000 Genomes

Homologs in model organisms

Caenorhabditis elegans: daf-16
Danio rerio: foxo1a
Danio rerio: foxo1b
Drosophila melanogaster: foxo
Mus musculus: Foxo1
Rattus norvegicus: Foxo1
Saccharomyces cerevisiae: HCM1

In other databases

GenAge model organism genes

A homolog of this gene for Caenorhabditis elegans is present as daf-16
A homolog of this gene for Drosophila melanogaster is present as foxo
A homolog of this gene for Saccharomyces cerevisiae is present as HCM1

GenAge human genes

This gene is present as FOXO1

GenDR gene manipulations

A homolog of this gene for Drosophila melanogaster is present as foxo
A homolog of this gene for Caenorhabditis elegans is present as daf-16

CellAge

This gene is present as FOXO1

Studies (9)

Significant/Non-significant: 3/6

Study 1

Longevity Association

Non-significant

Population

Study Design

The (T/C, 97347 bp) polymorphism was examined in healthy people 17-85 yr of age (n= 278; mean age, 54.8; 76 males and 202 females) and in healthy people 86-109 yr of age (n= 218; mean age, 98.0; 56 males and 162 females)

Conclusions

No significant differences relative to longevity were found

Indentifier

Reference

Study 2

Longevity Association

Non-significant

Population

Study Design

3 intronic polymorphisms were examined in 122 Japanese semisupercentenarians (older than 105, 107 female, 15 male, mean age 106.8 years) and 122 healthy younger controls (105 female, 17 male, mean age 33.33)

Conclusions

No significant differences relative to longevity were found

Indentifier

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: Two SNPs of FOXO1A were found to be associated with longevity in women (P = 0.01-0.005)
Indentifier

Study 4

Longevity Association: Non-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 variants in ADIPOQ, FOXO1A, SIRT1 and COQ7 were not associated with longevity
Indentifier

Study 5

Longevity Association

Population

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

Reference

Study 6

Longevity Association: Non-significant
Population: American (Caucasian)
Study Design: Genome-wide association study for longevity-related traits in up to 1345 Framingham Study participants from 330 families; 713 participants achieved age 65 years or greater. A total of 79 potential candidate genes and regions associated with longevity were also studied.
Conclusions: Although no genome-wide associations were significant, several SNPs in some previously associated genes with longevity had suggestive associations with age at death or morbidity-free survival at age 65 years. Noteworthy results included two SNPs within FOXO1A (rs10507486 and rs4943794) associated with age at death.
Indentifier

Study 7

Longevity Association: Non-significant
Population: Germany, Italian, Chinese (Han)
Study Design: 36 haplotype-tagging SNPs (htSNPs) in the gene regions of FOXO1, FOXO4, and FOXO6 were examined in Germany cohort which consist of 1447 centenarians/nonagenarians (95-110 y, mean age: 98.8 y, approx. 75% female) and 1029 younger controls (60-75 y, mean age: 66.8 y, approx. 75% female) for longevity association analysis. Then these htSNPs were examined in Italian women samples which consist of 166 long-lived individuals (90–109 years, mean age: 98.39 years) and 216 younger controls (18–48 years; mean age: 31.06 years).
Conclusions: None of the FOXO1, FOXO4, and FOXO6 genes plays a significant role in the ability to reach old age in Germany. FOXO1 was not associated with longevity in Italian either.
Indentifier

Study 8

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: In FOXO1A, rs2755209 and rs2755213 were found to be negatively associated with longevity in women (OR = 0.70 and 0.71, p = .007 and .015; dominant model). In the dominant model for men, FOXO1A-rs2755213 was marginally and negatively associated with longevity (OR = 0.65, p = .025) and the association of FOXO1A- rs2755209 is not significant (OR = 0.73, p = .093).
Indentifier

Study 9

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