How to Find Your SNP Data
- 1Log in to your 23andMe, AncestryDNA, or other genetic testing account
- 2Download your raw data file (usually .txt or .zip)
- 3Open in a text editor and search for the rsID (e.g., rs429358) โ or use Promethease, Genetic Genie, or SNPedia
- 4Find your genotype (e.g., CT, GG, AA) and look it up below
APOE โ Alzheimer's & Cardiovascular Risk
The single strongest genetic determinant of Alzheimer's risk
rs429358
APOE
Alzheimer's / CV
โพ
Together with rs7412, defines the APOE genotype (e2/e3/e4). The e4 allele (C at rs429358) is the strongest known genetic risk factor for late-onset Alzheimer's and also increases cardiovascular risk through effects on cholesterol metabolism.
| Genotype | Impact | Interpretation | Frequency |
|---|---|---|---|
| TT | Favorable | No e4 allele โ You do not carry APOE e4. This is the most common result, associated with baseline Alzheimer's risk. Your APOE type is e3/e3, e2/e3, or e2/e2 (check rs7412). | ~75% |
| CT | Unfavorable | One e4 allele โ You carry one copy of APOE e4 (likely e3/e4). Associated with ~2-3x increased late-onset Alzheimer's risk. Cardiovascular risk modestly elevated. Many e4 carriers never develop Alzheimer's. | ~22% |
| CC | Unfavorable | Two e4 alleles (e4/e4) โ Two copies of APOE e4. Associated with ~8-15x increased Alzheimer's risk. Present in ~2-3% of population but ~40-65% of Alzheimer's patients. Aggressive cardiovascular and cognitive prevention is especially important. | ~2-3% |
Actionable Steps
If e4 carrier: prioritize cardiovascular health (ApoB testing, statin consideration), excellent sleep (deprivation accelerates amyloid), regular exercise (strongest modifiable AD risk factor), early cognitive screening at 45-50, minimize alcohol. Discuss the FINGER trial lifestyle model with your physician.
Key References: Corder EH et al. Science. 1993;261:921-923 ยท Yamazaki Y et al. Nat Rev Neurol. 2019;15:501-518
rs7412
APOE
Alzheimer's / CV
โพ
Completes APOE genotype with rs429358. The T allele defines the protective e2 allele, associated with reduced Alzheimer's risk and increased longevity, though slightly elevated triglycerides.
| Genotype | Impact | Interpretation | Frequency |
|---|---|---|---|
| CC | Neutral | No e2 allele โ No APOE e2. Most common result. Check rs429358 to determine if e3/e3 or e3/e4. | ~85% |
| CT | Favorable | One e2 allele โ One copy of APOE e2. Reduced Alzheimer's risk, modestly protective for longevity. Monitor triglycerides. Likely e2/e3. | ~13% |
| TT | Favorable | Two e2 alleles (e2/e2) โ Rare genotype with lowest Alzheimer's risk. Can cause Type III hyperlipoproteinemia in some individuals. Monitor lipids. | ~1% |
Actionable Steps
If e2 carrier: generally favorable. Monitor lipids (especially triglycerides and remnant cholesterol). Standard longevity practices apply.
Key References: Corder EH et al. Nat Genet. 1994;7:180-184 ยท Suri S et al. Ann Neurol. 2013;73:236-245
FOXO3 โ Longevity & Stress Resistance
Most replicated longevity gene โ associated with exceptional lifespan in multiple populations
rs2802292
FOXO3
Longevity
โพ
The most studied longevity-associated SNP. The G allele upregulates FOXO3 expression through an intronic enhancer, promoting stress resistance, autophagy, DNA repair, and antioxidant defense. Replicated in Japanese, German, Italian, Chinese, Danish, and American populations.
| Genotype | Impact | Interpretation | Frequency |
|---|---|---|---|
| TT | Neutral | Common genotype โ Population baseline. Not associated with increased or decreased longevity. Longevity is 70-80% lifestyle. | ~42% |
| GT | Favorable | One longevity allele โ One copy of the FOXO3 longevity G allele. Modestly increased odds of reaching 90+. Enhanced FOXO3 expression and cellular stress response. | ~44% |
| GG | Favorable | Two longevity alleles โ Significantly enriched in centenarians. Highest odds of exceptional longevity. Enhanced FOXO3 expression activates oxidative defense, autophagy, and DNA repair. Effect may be stronger in men. | ~14% |
Actionable Steps
FOXO3 is activated by AMPK โ so fasting, exercise, cold exposure, metformin, and berberine all promote FOXO3 activity regardless of genotype. The lifestyle matters far more than the variant.
Key References: Willcox BJ et al. PNAS. 2008;105:13987 ยท Flachsbart F et al. PNAS. 2009;106:2700 ยท Grossi V et al. Nucleic Acids Res. 2018;46:5587
MTHFR โ Methylation & Folate Metabolism
Affects folate metabolism, homocysteine, and DNA methylation โ the most commonly searched variant
rs1801133
MTHFR
Methylation
โพ
MTHFR C677T reduces methylenetetrahydrofolate reductase activity, impairing conversion of folate to its active form (5-MTHF). Can elevate homocysteine โ a cardiovascular and cognitive risk factor. Clinical significance depends heavily on folate intake.
| Genotype | Impact | Interpretation | Frequency |
|---|---|---|---|
| CC | Neutral | Normal enzyme activity (~100%) โ Normal MTHFR function. Standard dietary folate is processed normally. | ~45% |
| CT | Mixed | Mildly reduced (~65%) โ One copy of 677T. Very common, usually compensated by adequate folate. Homocysteine may be mildly elevated if dietary folate is low. | ~42% |
| TT | Unfavorable | Significantly reduced (~30%) โ Two copies of 677T. Enzyme activity reduced to ~30%. Can elevate homocysteine and impair methylation. Supplement with methylfolate (not folic acid). | ~10-15% |
Actionable Steps
If CT or TT: use methylfolate (5-MTHF, 400-800mcg/day) not folic acid. Add methylcobalamin (B12), P5P (B6), and riboflavin (B2). Monitor homocysteine (optimal <8 ฮผmol/L). Eat folate-rich greens. If on metformin, B12 monitoring is doubly important.
Key References: Frosst P et al. Nat Genet. 1995;10:111 ยท Klerk M et al. JAMA. 2002;288:2023
rs1801131
MTHFR
Methylation
โพ
MTHFR A1298C is the second common variant. Reduces activity less than C677T but compounds the effect in compound heterozygotes (677CT + 1298AC). May also affect BH4 recycling for neurotransmitter synthesis.
| Genotype | Impact | Interpretation | Frequency |
|---|---|---|---|
| AA | Neutral | Normal at this position โ Common genotype. No MTHFR impact from this position. Check rs1801133 for primary variant. | ~53% |
| AC | Mixed | Mildly reduced โ One copy of 1298C. Minimal alone, but if also 677CT (compound heterozygous), methylation capacity may be meaningfully reduced. | ~38% |
| CC | Mixed | Reduced activity โ Two copies of 1298C. Modest reduction. May affect BH4 and neurotransmitter synthesis. Combined with any 677T, overall methylation is more impaired. | ~9% |
Actionable Steps
Same methylation support as C677T. If compound heterozygous (677CT + 1298AC), treat similarly to 677TT. Consider comprehensive B-vitamin complex with methylated forms.
Key References: van der Put NM et al. Am J Hum Genet. 1998;62:1044 ยท Weisberg I et al. Mol Genet Metab. 2001;74:415
SOD2 โ Mitochondrial Antioxidant Defense
Primary mitochondrial antioxidant enzyme โ determines oxidative stress handling capacity
rs4880
SOD2
Oxidative Stress
โพ
SOD2 encodes manganese superoxide dismutase, the primary mitochondrial antioxidant. The Val16Ala variant affects enzyme transport into mitochondria. High activity (Ala/Ala) converts superoxide efficiently but may increase hydrogen peroxide; low activity (Val/Val) leaves more superoxide unchecked.
| Genotype | Impact | Interpretation | Frequency |
|---|---|---|---|
| TT | Mixed | Ala/Ala โ High SOD2 โ High mitochondrial SOD2. Efficiently clears superoxide but may increase H2O2. Enhanced response to antioxidant supplementation. Some studies link to breast cancer risk modified by antioxidant intake. | ~25% |
| CT | Neutral | Val/Ala โ Intermediate โ Intermediate SOD2 activity. Most common, balanced antioxidant profile. | ~50% |
| CC | Mixed | Val/Val โ Lower SOD2 โ Lower mitochondrial SOD2. Reduced superoxide clearance. May accelerate aging under high oxidative stress. CoQ10 and dietary antioxidants especially beneficial. | ~25% |
Actionable Steps
CC: prioritize dietary antioxidants (berries, greens), CoQ10/ubiquinol, minimize oxidative exposures. TT: ensure adequate selenium (supports catalase to handle H2O2). Both: exercise upregulates endogenous antioxidant systems.
Key References: Ambrosone CB et al. Cancer Res. 1999;59:602 ยท Sutton A et al. Pharmacogenetics. 2003;13:309
IL-6 โ Inflammatory Baseline
Determines baseline inflammation โ chronic IL-6 elevation drives inflammaging
rs1800795
IL-6
Inflammation
โพ
IL-6 promoter variant (-174G>C) affects transcription levels. The G allele produces higher IL-6 โ beneficial for acute infection response but harmful when chronically elevated (inflammaging). CC genotype is enriched in some centenarian cohorts.
| Genotype | Impact | Interpretation | Frequency |
|---|---|---|---|
| GG | Unfavorable | Higher IL-6 production โ Higher baseline inflammation. More robust immune response but greater susceptibility to inflammaging. Anti-inflammatory strategies especially valuable. | ~35% |
| GC | Neutral | Intermediate IL-6 โ One of each allele. Standard inflammatory profile. | ~48% |
| CC | Favorable | Lower IL-6 production โ Lower baseline inflammation. Generally favorable for longevity. Found at higher frequency in some centenarian studies. | ~17% |
Actionable Steps
GG: Mediterranean diet, exercise, stress management, sleep optimization, omega-3 (2-3g/day), consider curcumin. Monitor hs-CRP annually. Minimize refined sugar and ultra-processed foods.
Key References: Fishman D et al. J Clin Invest. 1998;102:1369 ยท Franceschi C et al. Ann NY Acad Sci. 2000;908:244
CETP โ Lipid Metabolism & Longevity
Regulates cholesterol transfer โ variants produce exceptionally favorable lipid profiles
rs5882
CETP
Cardiovascular
โพ
CETP transfers cholesterol from HDL to LDL/VLDL. Reduced activity variants produce higher HDL, larger HDL particles, and reduced cardiovascular risk. The A allele at rs5882 (I405V) was found at significantly higher frequency in Ashkenazi Jewish centenarians.
| Genotype | Impact | Interpretation | Frequency |
|---|---|---|---|
| GG | Neutral | Normal CETP activity โ Standard HDL metabolism. Focus on ApoB reduction as primary cardiovascular target. | ~50% |
| GA | Favorable | Reduced CETP โ Higher HDL โ Moderately reduced CETP. Higher HDL, larger particles. Enriched in long-lived populations. | ~40% |
| AA | Favorable | Low CETP โ Longevity-associated โ Significantly reduced CETP. Highest HDL levels and particle size. Found at higher frequency in centenarians. Significant cardiovascular advantage. | ~10% |
Actionable Steps
GA/AA: your lipid profile is naturally favorable but don't neglect ApoB (atherogenic particle count). GG: standard cardiovascular optimization โ exercise, Mediterranean diet, consider statin if ApoB elevated.
Key References: Barzilai N et al. JAMA. 2003;290:2030 ยท Atzmon G et al. J Lipid Res. 2005;46:949
SIRT1 โ Sirtuin & Caloric Restriction
Central to the fasting/NAD+/sirtuin longevity pathway
rs2273773
SIRT1
Sirtuins
โพ
SIRT1 encodes the NAD+-dependent deacetylase central to caloric restriction longevity. This variant may affect SIRT1 expression. SIRT1 regulates DNA repair, inflammation, mitochondrial biogenesis, and is the target of resveratrol and NAD+ precursors.
| Genotype | Impact | Interpretation | Frequency |
|---|---|---|---|
| CC | Neutral | Common genotype โ Standard SIRT1 baseline. Activity is highly modifiable through fasting, exercise, and NAD+ precursors regardless of genotype. | ~70% |
| CT | Favorable | Potentially enhanced SIRT1 โ One copy of minor allele. Some studies associate with enhanced SIRT1 activity and improved metabolic parameters. May respond well to fasting protocols. | ~27% |
| TT | Favorable | Potentially enhanced SIRT1 โ Rare genotype associated with longevity in some populations. Evidence is preliminary. | ~3% |
Actionable Steps
Activate SIRT1 through: intermittent fasting, exercise, NMN or NR supplementation (provides NAD+ substrate), resveratrol (direct SIRT1 activator, take with fat), and cold exposure.
Key References: Howitz KT et al. Nature. 2003;425:191 ยท Hubbard BP et al. Science. 2013;339:1216
TERT โ Telomere Maintenance
Encodes the catalytic component of telomerase โ maintains chromosome end-caps
rs2736100
TERT
Telomeres
โพ
TERT encodes telomerase's catalytic subunit, which maintains telomere length. Shorter telomeres are a hallmark of aging, but very long telomeres may slightly increase cancer risk. This variant influences telomere length tendency.
| Genotype | Impact | Interpretation | Frequency |
|---|---|---|---|
| AA | Mixed | Shorter telomere tendency โ Tendency toward shorter telomeres. Standard age-related attrition. Clinical significance of this single variant is modest. | ~30% |
| AC | Neutral | Intermediate โ Most common genotype. Intermediate telomere length tendency. | ~48% |
| CC | Mixed | Longer telomere tendency โ Tendency toward longer telomeres. Generally favorable for aging but associated with slightly increased risk of certain cancers (glioma, lung). Net longevity effect is modestly positive. | ~22% |
Actionable Steps
Regardless of genotype: aerobic exercise (strongest modifiable factor for telomere maintenance), stress reduction, adequate sleep, Mediterranean diet, omega-3 fatty acids, and avoiding smoking. Telomere length is a biomarker, not a destiny.
Key References: Codd V et al. Nat Genet. 2013;45:422 ยท Bojesen SE et al. Nat Genet. 2013;45:371
PCSK9 โ Cholesterol Metabolism
Regulates LDL receptor recycling โ rare loss-of-function variants confer dramatic cardiovascular protection
rs11591147
PCSK9
Cardiovascular
โพ
PCSK9 promotes degradation of LDL receptors. Loss-of-function variants reduce PCSK9 activity, increasing LDL receptor availability and lowering lifelong LDL cholesterol. Carriers have dramatically reduced cardiovascular events โ a finding that led to the development of PCSK9 inhibitor drugs (evolocumab, alirocumab).
| Genotype | Impact | Interpretation | Frequency |
|---|---|---|---|
| GG | Neutral | Normal PCSK9 function โ Standard LDL receptor recycling. Normal cholesterol metabolism. Standard cardiovascular prevention applies. | ~97% |
| GT | Favorable | Reduced PCSK9 โ Lower lifelong LDL โ One copy of the loss-of-function T allele. Naturally lower LDL cholesterol throughout life. Associated with ~28% reduction in coronary heart disease risk in the ARIC study โ demonstrating the power of lifelong low LDL. | ~3% |
| TT | Favorable | Very low PCSK9 โ Very low LDL โ Extremely rare. Very low lifelong LDL cholesterol. Dramatically reduced cardiovascular risk. | <0.1% |
Actionable Steps
GT: your naturally lower LDL is a significant cardiovascular advantage. Continue healthy lifestyle to maintain it. GG: if LDL/ApoB is elevated, discuss statin therapy with your physician. The PCSK9 research demonstrates that lower LDL over a lifetime provides outsized cardiovascular protection.
Key References: Cohen JC et al. N Engl J Med. 2006;354:1264 ยท Abifadel M et al. Nat Genet. 2003;34:154
Enter an rsID above to look up a longevity-related gene variant
Genetic Information Disclaimer
This tool provides general educational information about genetic variants associated with longevity in published research. Genetic predisposition does not determine outcomes โ lifestyle, environment, and medical care have greater influence on healthspan. Genetics accounts for ~20-30% of lifespan variation. This is not a diagnostic test and should not be used for clinical decisions. Discuss results with a genetic counselor or physician.