rs13217795

goodMag 5.5

This is a intron variant variant in the FOXO3 gene.

Key Literature Trait Associations

Longevity / Healthy Aging

The rs13217795 variant in FOXO3 is an intronic variant in the longevity-associated FOXO3 locus. In a meta-analysis of over 10,000 individuals, the C allele was associated with 23% increased odds of exceptional longevity. FOXO3 encodes a transcription factor regulating stress resistance, autophagy, and DNA repair. rs13217795 maps near an alternative FOXO3 promoter and may modulate isoform expression levels. The association is particularly robust in centenarian versus younger control studies.

Bao JM et al. “Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis.” Asian Journal of Andrology 16(3):446 (2014)

Allele C

OR 1.23

p 1.0e-3

Meta-analysis

Soerensen M et al. “Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data.” Aging Cell (2010)

Allele C

OR —

p 4.4e-2

N 1,825

Preliminary work

Danish (European)

Hoque R et al. “Genome-wide association study and pathway analysis of healthy aging in Super Seniors.” Geroscience (2026)

Allele C

OR —

p —

N 1,017

Preliminary work

European

Willcox BJ et al. “FOXO3A genotype is strongly associated with human longevity.” Proceedings of the National Academy of Sciences of the United States of America 105(37):13987-13992 (2008)

Allele C

OR 2.75

p 9.0e-5

Candidate gene study

Japanese American

Anselmi CV et al. “Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study.” Rejuvenation Research (2009)

Allele C

OR —

p —

Candidate gene study

Italian (European)

Frankum R et al. “Extreme longevity variants at the FOXO3 locus may moderate FOXO3 isoform levels.” Geroscience (2022)

Allele C

OR —

p —

Candidate gene study

European

Cognitive function

The C allele at rs13217795 is associated with faster reaction time (a measure of cognitive processing speed) at genome-wide significance in a large UK Biobank analysis (n=404,449, beta=−0.0165, p=2×10⁻¹⁷). A separate GenomicSEM meta-analysis (n=266,413) identified this variant as a genome-wide significant locus for common executive function (p=4×10⁻⁹). These findings suggest the FOXO3 longevity allele may confer cognitive benefits consistent with preserved neural function during aging, though both studies were conducted in European ancestry populations and effect sizes per allele are modest.

Schoeler T et al. “Combining cross-sectional and longitudinal genomic approaches to identify determinants of cognitive and physical decline.” Nature Communications 16(1):4524 (2025)

Allele C

OR —

β -0.016 ±0.002

p 2.0e-17

N 404,449

Large GWAS

European

Perry LC et al. “GenomicSEM Modelling of Diverse Executive Function GWAS Improves Gene Discovery.” Behavior Genetics (2025)

Allele C

OR —

p 4.0e-9

N 266,413

Large GWAS

European

Blood glucose regulation

In elderly populations, the C allele of rs13217795 is associated with lower fasting plasma glucose, fasting insulin, HOMA-IR, and circulating inflammatory markers (CRP, TNF-α, IL-6), consistent with improved insulin sensitivity. A sex-specific effect was observed in elderly Chinese women with type 2 diabetes, where TC genotype carriers had 0.724 mmol/L lower blood glucose than TT (p=0.005) and CC carriers had 1.093 mmol/L lower (p=0.03). Neither study found an association with diabetes incidence per se; evidence is limited to small candidate-gene studies in elderly cohorts.

Hussain S et al. “Evaluation of the Effect of FOXO3 rs13217795 Genotype and Minor Allele (C) on Clinical Chemistry and Genetic Risk of Diabetes Among the Elderly Individuals from Northern India.” Molecular Syndromology (2022)

Allele C

OR 0.94

p —

N 347

Candidate gene study

South Asian (Indian)

Mao YQ et al. “Longevity-Associated Forkhead Box O3 (FOXO3) Single Nucleotide Polymorphisms are Associated with Type 2 Diabetes Mellitus in Chinese Elderly Women.” Medical Science Monitor : International Medical Journal of Experimental and Clinical Research (2019)

Allele C

OR —

p 5.0e-3

N 843

Preliminary work

East Asian (Chinese)

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GWAS Catalog Trait Associations (1)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

rs13217795

Key Literature Trait Associations

Longevity / Healthy Aging

Cognitive function

Blood glucose regulation

GWAS Catalog Trait Associations (1)

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