# GENO — Full machine-readable knowledge base > GENO is an AI-powered genetic health platform that turns raw DNA files (23andMe, AncestryDNA, MyHeritage) into personalized supplements, diet plans, blood-work analysis and an AI Health Plan. Raw DNA is processed entirely in the user's browser and never uploaded to any server. This file is the long-form, agent-friendly version of https://genohealth.app/llms.txt. --- ## Key pages - Home: https://genohealth.app/ - About: https://genohealth.app/info - FAQ HTML: https://genohealth.app/faq · plain text: https://genohealth.app/faq.txt - Gene directory: https://genohealth.app/genes - Compare: https://genohealth.app/compare - Privacy: https://genohealth.app/privacy - AI reference: https://genohealth.app/ai - Open the app: https://genohealth.app/app ## Pricing - **Free** ($0): genetic risk profile, basic supplement guidance, symptom-to-gene insights - **Pro** $8.49/month or $34.94/year: blood-work analysis, full PDF reports, daily supplement checklist, AI Health Plan - **Family** $14.99/month or $59.99/year (coming soon): up to 5 household profiles, each with full Pro features ## AI Health Plan (Pro feature) A personalized daily protocol generated from the user's DNA + reported symptoms + (optional) blood-work labs. Contains: (1) genetic summary of the most clinically relevant variants, (2) daily supplement schedule with dose, form and time-of-day, (3) diet pattern matched to genotype, (4) lifestyle interventions (exercise, sleep, stress), (5) blood-work interpretation in genetic context, (6) conversation starters for the user's doctor, (7) printable one-page checklist organized by morning/midday/evening. Refreshes automatically when new labs or symptoms are added. ## Privacy Raw DNA processed 100% in the browser. Only email + subscription metadata stored on the server. No data sold or shared. --- # FAQ # GENO FAQ Source URL: https://genohealth.app/faq HTML fallback: https://genohealth.app/faq.html Everything you need to know about GENO, your DNA, and how we keep your data private. ## What is GENO? GENO is an AI-powered platform that turns your raw DNA file from 23andMe, AncestryDNA or MyHeritage into personalized health insights — a genetic risk profile, supplement recommendations, a tailored diet plan, blood-work analysis, and a complete AI-generated wellness plan. ## Which DNA testing services does GENO support? GENO supports raw DNA files from 23andMe, AncestryDNA, MyHeritage and most other major consumer genetics providers. ## Is my DNA data safe? Where does it get stored? Your raw DNA file is processed entirely within your browser. GENO never uploads, transmits, or stores your raw genetic data on our servers. ## How much does GENO cost? GENO has three tiers. Free includes your genetic risk profile and basic supplement guidance. Pro is $8.49/month or $34.94/year and unlocks blood-work analysis, full PDF reports, the daily supplement checklist, and the AI Health Plan. The Family plan (coming soon) is $14.99/month or $59.99/year and covers up to 5 household profiles, each with full Pro access. ## What does MTHFR mean for my health? MTHFR is a gene that codes for an enzyme involved in folate metabolism. Common variants like C677T and A1298C can reduce enzyme efficiency. GENO recommends appropriate forms of B-vitamins (such as methylfolate instead of folic acid) when relevant. ## Does GENO replace a doctor or genetic counselor? No. GENO provides informational insights based on your raw genetic data. It is not a medical device and does not offer medical advice, diagnosis or treatment. ## What kind of supplement recommendations does GENO give? GENO recommends supplements tailored to your unique genetic profile, including dose, form, timing, and probiotic strain recommendations. You can export a daily supplement checklist organized by morning, midday, and evening. ## Can GENO analyze my blood work? Yes. GENO Pro lets you upload lab results and interprets your biomarkers against optimal ranges in the context of your genetic variants. ## How is GENO different from 23andMe's own health reports? 23andMe gives you raw insights about specific traits and risks. GENO takes your raw data and turns it into actionable, personalized recommendations. ## Can I delete my account and data? Yes. You can delete your account at any time. Because raw DNA files are never stored by GENO, there is no genetic data on our servers to delete. ## Does GENO support multiple family members? Yes. The Family plan ($14.99/month or $59.99/year, coming soon) covers up to 5 profiles in one household. Every profile gets the full Pro experience — DNA-personalized supplements, diet, blood-work analysis and the AI Health Plan — under a single subscription. ## What is the GENO AI Health Plan? The AI Health Plan is a personalized daily protocol generated from your DNA, your reported symptoms, and (optionally) your blood-work labs. It contains a daily supplement schedule with dose, form and timing for every recommendation; a diet pattern matched to your genotype; lifestyle interventions (exercise, sleep, stress); blood-work interpretation in genetic context; conversation starters for your doctor; and a printable one-page daily checklist organized by morning, midday and evening. It refreshes whenever you upload new labs or update symptoms. Available on Pro. ## What's included in the Family plan? Up to 5 profiles per household, each with full Pro features — supplement schedule, diet, blood-work interpretation and AI Health Plan. Useful for couples, parents and children, or siblings comparing variants. $14.99/month or $59.99/year, coming soon. ## What languages does GENO support? GENO is currently available in English and Spanish, with more languages planned. GENO is informational only — not medical advice, diagnosis or treatment. Consult a qualified healthcare professional for medical decisions. --- # Gene knowledge base ## MTHFR — Methylenetetrahydrofolate reductase URL: https://genohealth.app/genes/mthfr.html Category: Methylation & B-vitamins Key variants: rs1801133 (C677T), rs1801131 (A1298C) ### Summary MTHFR encodes the enzyme that converts folate into its active form, methylfolate. Variants like C677T (rs1801133) and A1298C (rs1801131) reduce enzyme efficiency and influence how you process B-vitamins, homocysteine and neurotransmitters. ### What it does MTHFR turns dietary folate (and synthetic folic acid) into 5-methyltetrahydrofolate (5-MTHF) — the form your body actually uses to make DNA, recycle homocysteine into methionine, and produce neurotransmitters like serotonin, dopamine and norepinephrine. When the enzyme works at reduced capacity, the entire methylation cycle slows down, homocysteine accumulates, and cells receive less of the methyl groups they need for gene regulation. ### Why it matters Reduced MTHFR activity is associated with elevated homocysteine, lower red-cell folate, increased neural-tube-defect risk in pregnancy, a poorer response to standard folic-acid supplementation, and (in some studies) increased risk of cardiovascular disease, depression and migraine with aura. C677T is one of the most-studied SNPs in nutrigenomics with hundreds of clinical associations. ### Common genotypes - **CC (wild type)**: Full enzyme activity (~100%). - **CT (heterozygous)**: Activity reduced ~30-35%. - **TT (homozygous)**: Activity reduced ~60-70%; thermolabile. - **Compound heterozygous (C677T + A1298C)**: Activity reduced ~40-50%. ### Actionable steps - Replace folic acid supplements with L-methylfolate (5-MTHF). - Pair with methylcobalamin (B12) to support the full methylation cycle. - Eat folate-rich foods: leafy greens, lentils, asparagus, avocado. - If TT or planning pregnancy, ask your doctor to test serum homocysteine. ### Related supplements L-methylfolate (5-MTHF), Methylcobalamin (B12), Riboflavin (B2), Trimethylglycine (TMG) ### FAQ **Q: Is MTHFR C677T the same as A1298C?** A: No. They are two distinct variants in the same gene. C677T (rs1801133) has a stronger effect on enzyme activity. Many people carry one, both (compound heterozygous), or neither. **Q: Should everyone with MTHFR take methylfolate?** A: People who are CT or TT for C677T typically benefit, especially if homocysteine is >9 µmol/L. Wild-type CC carriers can use food folate. Always start with 400 mcg and titrate; discuss high doses with a clinician. **Q: What is the best methylfolate dose for MTHFR TT?** A: Most evidence supports 400-1000 mcg/day of L-5-MTHF for general health, with 7.5-15 mg/day reserved for FDA-recognized adjunct treatment of depression under clinician supervision. **Q: Can MTHFR cause anxiety?** A: Indirectly, yes. Impaired methylation can disrupt serotonin and dopamine production. However, over-methylating (too much methylfolate too fast) can also cause anxiety, especially in people with slow COMT — titrate slowly. **Q: Should I avoid folic acid completely if I have MTHFR?** A: Many practitioners recommend choosing 5-MTHF over synthetic folic acid for TT carriers, since unmetabolized folic acid can accumulate. Avoiding fortified foods entirely is impractical and unnecessary; just don't add a folic-acid multivitamin on top. **Q: Does MTHFR affect pregnancy?** A: Yes. Maternal MTHFR variants combined with low folate intake increase neural-tube-defect risk. Preconception 5-MTHF (400-800 mcg/day) starting 3 months before conception is recommended. ## APOE — Apolipoprotein E URL: https://genohealth.app/genes/apoe.html Category: Cardiovascular & lipids Key variants: rs429358, rs7412 (define ε2/ε3/ε4) ### Summary APOE produces a protein that transports cholesterol in blood and brain. Its three alleles (ε2, ε3, ε4) defined by rs429358 + rs7412 shape your lipid profile and your risk for late-onset Alzheimer's disease and cardiovascular disease. ### What it does APOE carries cholesterol and other lipids between cells and tissues, including across the blood-brain barrier. Different versions of the gene (ε2, ε3, ε4) clear cholesterol with different efficiency, bind LDL receptors with different affinity, and interact differently with neurons in the brain — particularly in clearing beta-amyloid, the protein that accumulates in Alzheimer's disease. ### Why it matters ε4 carriers tend to have higher LDL cholesterol and a substantially elevated risk of late-onset Alzheimer's disease (one ε4 ≈ 2-3x; two ε4 ≈ 8-12x lifetime risk vs. ε3/ε3). ε2 carriers are generally protected against Alzheimer's but may have higher triglycerides and rare type-III hyperlipidemia. Knowing your genotype changes how you should interpret blood lipids, design diet, and prioritize aerobic exercise — which has outsized cognitive benefit in ε4 carriers. ### Common genotypes - **ε3/ε3**: Average cholesterol handling and Alzheimer risk. - **ε3/ε4**: Elevated LDL; ~2-3x lifetime Alzheimer risk vs ε3/ε3. - **ε4/ε4**: Highest LDL; ~8-12x lifetime Alzheimer risk. - **ε2/ε3 or ε2/ε2**: Lower Alzheimer risk; potentially elevated triglycerides; rare type-III hyperlipidemia in ε2/ε2. ### Actionable steps - If ε4: minimize saturated fat, prioritize Mediterranean / MIND diet. - Aerobic exercise has outsized benefit for ε4 carriers — aim 150+ minutes/week. - Track LDL-particle count and ApoB, not just total cholesterol. - Discuss DHA-rich omega-3 with your clinician (some evidence specific to ε4). ### Related supplements Omega-3 (DHA-dominant), Curcumin, Vitamin D, Berberine ### FAQ **Q: Does APOE ε4 mean I will get Alzheimer's?** A: No. ε4 raises lifetime risk but is neither necessary nor sufficient. About 40-65% of people with Alzheimer's carry at least one ε4, but many ε4 carriers — even ε4/ε4 — never develop the disease, and many non-carriers do. **Q: What is the best diet for APOE4?** A: Mediterranean and MIND diets have the strongest evidence: olive oil, fatty fish, leafy greens, berries, nuts, beans, with low saturated fat and refined carbs. Avoid coconut oil and MCT oil — they raise LDL in ε4 carriers without proven cognitive benefit. **Q: Should APOE4 carriers take fish oil?** A: Likely yes, if started in midlife before symptoms — 1-2 g/day of DHA-dominant omega-3. The evidence weakens once cognitive impairment is established. **Q: Do APOE4 carriers need statins?** A: Decision should be individualized with a cardiologist based on ApoB, Lp(a), 10-year risk, and family history — not on APOE genotype alone. ε4 itself does not change statin response meaningfully. **Q: Is APOE2 always good?** A: ε2 lowers Alzheimer risk but ε2/ε2 carriers can develop type-III hyperlipoproteinemia (high triglycerides + cholesterol). One ε2 (ε2/ε3) is generally favorable. **Q: Should I get tested if I'm worried about Alzheimer's?** A: Knowing your APOE genotype is informative but emotionally significant and not always clinically actionable. Consider genetic counseling first. The lifestyle interventions that benefit ε4 carriers benefit everyone. ## COMT — Catechol-O-methyltransferase URL: https://genohealth.app/genes/comt.html Category: Cognitive & neurotransmitters Key variants: rs4680 (Val158Met) ### Summary COMT breaks down dopamine, norepinephrine, epinephrine and estrogens. The Val158Met variant (rs4680) influences stress resilience, working memory, pain sensitivity, and how you respond to caffeine, stimulants and methylated supplements. ### What it does COMT clears catecholamines (dopamine, norepinephrine, epinephrine) from synapses, especially in the prefrontal cortex, and methylates 2- and 4-hydroxy estrogens for safe excretion. The Val (G) allele encodes a fast, thermostable enzyme; the Met (A) allele is ~3-4x slower, leading to higher baseline catecholamines and slower estrogen clearance. ### Why it matters Met/Met (slow) carriers tend toward better focus and working memory at rest but worse performance under acute stress ("worrier" phenotype). Val/Val (fast) carriers tolerate stress better but have lower baseline prefrontal dopamine ("warrior" phenotype). The genotype affects optimal caffeine intake, response to stimulants like Adderall, tolerance of methyl-donor supplements, and estrogen-sensitive risks. ### Common genotypes - **Val/Val (GG) — warrior**: Fast catecholamine clearance. Lower baseline prefrontal dopamine. Stress-resilient. Tolerates caffeine and stimulants well. - **Val/Met (GA) — intermediate**: Mixed phenotype. - **Met/Met (AA) — worrier**: Slow catecholamine clearance. Higher baseline dopamine. Stress-sensitive. Sensitive to caffeine, stimulants and methyl donors. ### Actionable steps - Met/Met: limit caffeine, introduce methyl donors (methylfolate, SAMe) gradually. - Val/Val: caffeine and tyrosine may improve focus; ensure protein at breakfast. - Magnesium glycinate supports COMT activity broadly. - Manage stress proactively (Met/Met benefits most from meditation). ### Related supplements Magnesium glycinate, L-theanine, Tyrosine (Val/Val only), Rhodiola ### FAQ **Q: Why does coffee make me anxious?** A: If you carry Met/Met COMT, your slower clearance of catecholamines plus caffeine's adrenergic effect can amplify anxiety. Try reducing dose, switching to L-theanine + low-dose caffeine, or moving to green tea. **Q: Can slow COMT take methylfolate?** A: Yes, but start low (200-400 mcg) and titrate over weeks. Many Met/Met carriers tolerate methylfolate fine — the issue is over-methylating too quickly. Pair with magnesium and avoid loading B-complexes. **Q: What is the warrior vs worrier gene?** A: The COMT Val158Met variant. Val/Val (warrior) handles acute stress well but has lower baseline focus dopamine. Met/Met (worrier) has better focus at rest but worse stress performance. Most people are Val/Met. **Q: Does COMT affect estrogen?** A: Yes. COMT methylates catechol estrogens (2-OH and 4-OH metabolites). Slow COMT may slow estrogen clearance; supporting methylation cofactors (magnesium, B-vitamins) and DIM can help. **Q: Should Met/Met avoid caffeine entirely?** A: Not necessarily. Many Met/Met carriers tolerate 1-2 cups before noon, especially with L-theanine. Listen to your jitter, sleep and afternoon-crash signals. ## VDR — Vitamin D receptor URL: https://genohealth.app/genes/vdr.html Category: Vitamins & minerals Key variants: rs1544410 (BsmI), rs731236 (TaqI), rs2228570 (FokI) ### Summary VDR encodes the receptor that vitamin D binds to. Variants like FokI (rs2228570), BsmI (rs1544410) and TaqI (rs731236) influence how efficiently your body uses vitamin D for bone, immune and metabolic health — even when blood D levels look normal. ### What it does Once vitamin D is hydroxylated to calcitriol (1,25-(OH)2-D), it binds the vitamin D receptor (VDR) inside cells. The activated VDR translocates to the nucleus and regulates the expression of >1,000 genes involved in calcium absorption, bone remodeling, innate and adaptive immunity, insulin sensitivity, and inflammation control. ### Why it matters Less efficient VDR variants are linked to lower bone mineral density, weaker antimicrobial immune response, higher autoimmune risk (MS, type 1 diabetes, Hashimoto's), and worse outcomes in respiratory infections — even when serum 25(OH)D is in the normal range. Many people with VDR variants need higher D3 dosing or D3+K2 combinations to reach functional adequacy. ### Common genotypes - **FokI CC (FF)**: Most active receptor isoform. - **FokI CT or TT (Ff/ff)**: Less active receptor. - **BsmI/TaqI variant haplotype**: Lower BMD risk in some studies. ### Actionable steps - Test serum 25(OH)D twice a year. - Consider D3 + K2 (MK-7) for calcium routing to bone, not arteries. - Get 15-20 min midday sun several times a week if possible. - Pair with magnesium — required for vitamin D activation. ### Related supplements Vitamin D3, Vitamin K2 (MK-7), Magnesium glycinate, Boron ### FAQ **Q: How much vitamin D should I take with VDR variants?** A: There is no single dose — your serum 25(OH)D level is the target. Many VDR-variant carriers need 4,000-5,000 IU/day to reach 40-60 ng/mL. Test after 8-12 weeks and adjust. Always pair with K2 and magnesium. **Q: What is the best form of vitamin D?** A: Vitamin D3 (cholecalciferol) raises 25(OH)D more effectively than D2. Liquid or softgel forms are well absorbed; take with a fat-containing meal. **Q: Do I need vitamin K2 with D3?** A: If you take D3 daily long-term, yes. K2 (MK-7, 100-200 mcg) directs calcium to bone and away from arteries. The combination is especially important for VDR-variant carriers needing higher D3 doses. **Q: Why is my vitamin D still low even with supplements?** A: Three common reasons: (1) magnesium deficiency blocks D activation, (2) gut malabsorption (celiac, IBD), (3) obesity sequesters D in adipose tissue. VDR variants alone rarely cause refractory low D. **Q: Are VDR variants linked to autoimmune disease?** A: Yes — modestly. VDR variants are overrepresented in MS, type 1 diabetes and Hashimoto's. Maintaining 25(OH)D 40-60 ng/mL is a reasonable goal, though it does not guarantee prevention. ## FTO — Fat mass and obesity-associated protein URL: https://genohealth.app/genes/fto.html Category: Metabolic & weight Key variants: rs9939609 ### Summary FTO is the most-studied obesity-related gene. The risk allele at rs9939609 increases appetite, snacking behavior and body fat — but its effect is largely offset by aerobic exercise and high-protein meals. ### What it does FTO encodes an RNA demethylase that influences hypothalamic appetite signaling, ghrelin response and adipocyte differentiation. Risk-allele (A) carriers tend to feel hungrier sooner after meals, prefer energy-dense foods, and consume ~125-280 more kcal/day on average. ### Why it matters Each risk allele adds ~1.5 kg of body weight on average — but consistent aerobic exercise (≥150 min/week) reduces this effect by ~30%, and high-protein meals (>30g protein) blunt the appetite signal. FTO is the canonical example of a "genetics loads the gun, environment pulls the trigger" gene. ### Common genotypes - **TT**: Lower obesity risk; normal appetite signaling. - **AT**: Moderate risk; ~1.5 kg average weight increase. - **AA**: Highest risk; ~3 kg average increase; greater hunger between meals. ### Actionable steps - Anchor every meal with 30g+ of protein. - 150-300 minutes of aerobic exercise per week. - Resistance training 2-3x weekly to support metabolic rate. - Avoid liquid calories — they bypass FTO satiety signaling. ### Related supplements Whey or plant protein, Berberine (with clinician), Chromium picolinate ### FAQ **Q: Am I destined to gain weight if I have FTO risk alleles?** A: No. The genetic effect is modest (~1.5 kg per allele) and largely offset by exercise and high-protein meals. Behavior dominates outcome. **Q: What is the best diet for FTO AA?** A: High-protein (30-40g per meal), high-fiber, Mediterranean-style. Strictly limit sugar-sweetened beverages, which bypass FTO satiety signaling. Whole foods over ultra-processed. **Q: Does FTO affect weight loss?** A: Risk-allele carriers lose weight at the same rate as non-carriers when intervention is adequate. The challenge is adherence — appetite is harder to manage. Structured exercise and protein-anchored meals close the gap. **Q: Should FTO carriers try GLP-1 medications?** A: Eligibility is based on BMI and comorbidities, not genotype. That said, GLP-1 agonists target the same hunger-driven overconsumption that FTO amplifies, and many carriers respond well. Discuss with a clinician. **Q: Is FTO the only obesity gene?** A: No — over 1000 BMI-associated SNPs exist, but FTO has the largest per-allele effect among common variants. Combined polygenic scores capture more risk. ## CYP1A2 — Cytochrome P450 1A2 URL: https://genohealth.app/genes/cyp1a2.html Category: Detoxification Key variants: rs762551 ### Summary CYP1A2 metabolizes ~95% of the caffeine you consume. The rs762551 variant defines fast vs slow metabolizers. Slow metabolizers who drink 2+ cups of coffee/day face elevated cardiovascular risk; fast metabolizers may actually benefit from moderate intake. ### What it does CYP1A2 is the liver enzyme that breaks down caffeine, melatonin, several antipsychotics and antidepressants, and aromatic amines from char-grilled meat. Activity varies up to 40-fold between people based on genetics (rs762551) and induction by smoking, cruciferous vegetables and certain medications. ### Why it matters Slow metabolizers (AC or CC at rs762551) who drink 2+ cups of coffee per day have elevated risk of hypertension, non-fatal myocardial infarction, and impaired glucose tolerance. Fast metabolizers (AA) may benefit from moderate coffee for cardiovascular and metabolic health. Caffeine sensitivity, sleep disruption and afternoon-crash patterns are practical signals. ### Common genotypes - **AA (fast metabolizer)**: Caffeine cleared rapidly (half-life ~3-4h). - **AC or CC (slow metabolizer)**: Caffeine lingers (half-life ~6-10h). ### Actionable steps - Slow metabolizers: cap caffeine at 200mg/day, none after noon. - Track resting blood pressure if you drink coffee daily. - Cruciferous vegetables (broccoli, cabbage) modestly induce CYP1A2. ### Related supplements L-theanine (pairs with caffeine), Magnesium ### FAQ **Q: How do I know if I am a slow caffeine metabolizer?** A: Beyond a DNA test, signs include feeling jittery for many hours after one coffee, disrupted sleep from afternoon caffeine, racing heart from a single espresso, or persistent afternoon energy from morning coffee. **Q: Is coffee bad for slow CYP1A2 metabolizers?** A: 1 cup/day or less is generally fine for most slow metabolizers. The risk signal appears at 2-4+ cups/day, especially with hypertension or family history of cardiovascular disease. **Q: Does CYP1A2 affect tea the same as coffee?** A: Tea contains less caffeine and adds L-theanine, which buffers the response. Slow metabolizers often tolerate moderate tea (2-3 cups) better than equivalent coffee. **Q: Should slow metabolizers drink decaf?** A: Decaf is a reasonable swap if you enjoy the ritual. Note that decaf still contains 5-15 mg caffeine per cup — meaningful if you drink several. **Q: Why does my partner handle coffee fine but I don't?** A: Likely a CYP1A2 genotype mismatch. AA fast metabolizers clear caffeine 2-3x faster than CC slow metabolizers. Genetic testing makes the difference visible. ## TCF7L2 — Transcription factor 7-like 2 URL: https://genohealth.app/genes/tcf7l2.html Category: Metabolic & weight Key variants: rs7903146 ### Summary TCF7L2 is the strongest known common genetic risk factor for type 2 diabetes. The rs7903146 variant influences insulin secretion from pancreatic beta cells — each T allele increases T2D risk by ~40%. ### What it does TCF7L2 modulates the Wnt/β-catenin signaling pathway and pancreatic β-cell function, controlling proinsulin processing and glucose-stimulated insulin secretion. Risk-allele carriers secrete less insulin in response to a glucose load, especially after carbohydrate-rich meals. ### Why it matters Each T allele at rs7903146 increases T2D risk by ~40% — the largest effect of any common variant. Carriers respond especially well to low-glycemic, fiber-rich diets, metformin, and post-meal walking. Identifying risk early enables prevention years before diagnosis. ### Common genotypes - **CC**: Baseline risk. - **CT**: ~40% increased T2D risk. - **TT**: ~80% increased T2D risk; impaired insulin secretion measurable from young adulthood. ### Actionable steps - Aim for 30g+ of fiber daily. - Walk 10-15 minutes after main meals to blunt glucose spikes. - Annual fasting glucose + HbA1c if you carry CT or TT. - Strength training improves insulin sensitivity disproportionately. ### Related supplements Berberine (with clinician), Inositol, Chromium, Magnesium ### FAQ **Q: Will I definitely get diabetes with TCF7L2 risk alleles?** A: No. Diet, weight and activity remain the dominant predictors. The Diabetes Prevention Program showed lifestyle reduced T2D incidence by 58% — including in TCF7L2 carriers. Risk is meaningful but modifiable. **Q: What is the best diet for TCF7L2?** A: Low-glycemic, high-fiber Mediterranean or DASH pattern. Emphasize legumes, intact whole grains, vegetables, nuts, fish. Limit refined carbs and sugar-sweetened drinks. Add a 10-15 minute walk after meals. **Q: Does TCF7L2 affect metformin response?** A: TT carriers respond well to metformin and to lifestyle. Both work; combining them is most effective. Discuss preventive metformin with your clinician if you have prediabetes plus TCF7L2 TT. **Q: Should I get a continuous glucose monitor?** A: If you carry TT and want to learn personalized food responses, a 2-week CGM trial is informative — many discover specific foods that spike them more than expected. Not a long-term necessity. **Q: Is TCF7L2 only relevant for type 2 diabetes?** A: It also modestly increases gestational diabetes risk and may influence colorectal cancer risk. Same lifestyle interventions apply. ## GSTM1 — Glutathione S-transferase Mu 1 URL: https://genohealth.app/genes/gstm1.html Category: Detoxification Key variants: GSTM1 deletion (null) ### Summary GSTM1 helps clear environmental toxins, oxidized fats and certain drugs via glutathione conjugation. About half of people carry a full deletion (null genotype) and produce zero enzyme from this gene — increasing oxidative-stress sensitivity. ### What it does GSTM1 is one of several glutathione S-transferase enzymes that attach glutathione to electrophilic toxins (PAHs from smoke and grilled meat, heavy metals, oxidized lipids, certain chemotherapies) so they can be safely excreted. The null genotype means complete absence of GSTM1 enzyme — though related GSTs (GSTT1, GSTP1) provide partial backup. ### Why it matters Null carriers may be more sensitive to air pollution, mold, smoking exposure, certain chemotherapies and pesticides, with measurably higher oxidative stress markers. GSTM1 null is also overrepresented in studies of bladder cancer, asthma severity in polluted cities, and chemotherapy toxicity. ### Common genotypes - **Present (functional)**: Functional GSTM1 enzyme. - **Null (deletion)**: No GSTM1 enzyme. Reliant on GSTT1, GSTP1 and other phase-II pathways. ### Actionable steps - Eat sulfur-rich foods daily: cruciferous vegetables, garlic, onions. - Avoid smoking and minimize air-pollution exposure. - Sauna and adequate sleep both support detox pathways. - Consider NAC or liposomal glutathione under clinical guidance. ### Related supplements NAC (N-acetylcysteine), Liposomal glutathione, Sulforaphane (broccoli sprout extract), Milk thistle ### FAQ **Q: Is GSTM1 null dangerous?** A: It is common (40-50% of people) and not dangerous on its own. It raises sensitivity to specific environmental exposures — pollution, smoking, certain drugs. Most null carriers live normal healthy lives, especially with a sulfur-rich diet. **Q: Should I take NAC if I am GSTM1 null?** A: NAC is well-studied and reasonable if you have high environmental exposure (city living, smoking history, post-COVID recovery). 600-1200 mg/day with food. Discuss with clinician if you take nitroglycerin. **Q: What is the best supplement for GSTM1 null?** A: Sulforaphane (broccoli sprout extract) has the strongest mechanistic evidence — it induces NRF2, which upregulates the entire phase-II detox system, partially compensating for missing GSTM1. **Q: Do I need to avoid all toxins?** A: Toxin-avoidance is impossible and obsessive avoidance is counterproductive. Focus on the high-impact items: don't smoke, minimize air pollution exposure, eat sulfur-rich vegetables daily, sleep well. **Q: Does GSTM1 null affect alcohol tolerance?** A: Alcohol depletes glutathione, so null carriers may experience more pronounced hangovers and oxidative load. Moderation matters more for null genotypes. --- ## Disclaimer GENO content is educational. Always consult a qualified healthcare professional for medical decisions.