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DNA & Genomics

23andMe v3 • 963,067 SNPs • 59 clinically relevant variants analyzed

🧠Max, your genome tells a clear story. The biggest finding is TCF7L2 TT — you're homozygous for the strongest common diabetes risk variant. That doesn't mean you'll get diabetes, but it means monitoring HbA1c and insulin is non-negotiable. Your SLCO1B1 variant genetically validates why you're on Repatha instead of statins — your body literally can't transport them safely, and that likely explains the liver scare (ALT 141). The COMT Met/Met finding explains a lot about your stress response and pain sensitivity with the stenosis — it's not in your head, it's in your DNA. Your inflammatory genotype (IL-6 high + IL-10 low) is driving the calcium score and needs aggressive management. And the SHBG/SRD5A2 variants provide the genetic argument for TRT. Good news: APOE ε3/ε3 (no Alzheimer's risk), FOXO3 longevity allele, and no clotting disorders. Start the methylated B vitamins — your triple methylation impairment is the easiest win.

Key Findings

🔴

TCF7L2 TT — Diabetes Risk

High

Homozygous. ~1.7–1.8x increased T2D risk. Monitor HbA1c and fasting insulin every 6 months.

🔴

SLCO1B1 CT — Statin Myopathy

High

Genetically validates switch from statins to Repatha. May explain prior elevated ALT (141→21 after stopping).

🔴

MTHFR Compound Heterozygous

High

C677T + A1298C → ~50-60% reduced methylation. Use methylfolate, not folic acid. Use methylcobalamin, not cyanocobalamin.

🟠

COMT Met/Met — Slow COMT

Significant

3-4x slower catecholamine clearance. Higher stress/pain sensitivity (spinal stenosis relevance). Avoid over-methylation.

🔴

IL-6 GG + IL-10 CC — Pro-Inflammatory

High

High gas pedal + weak brakes = persistent inflammation. Drives calcium score progression and spinal stenosis.

🟡

SHBG + SRD5A2 — Low Free T Explained

Moderate

rs727428 CT (higher SHBG) + SRD5A2 CG (less DHT). Genetic basis for rising SHBG and low free testosterone. Supports TRT.

APOE ε3/ε3 — Normal

Low

No elevated Alzheimer's or cardiovascular APOE risk. Standard prevention protocols sufficient.

FOXO3 GT — Longevity Allele

Protective

One copy of the most replicated human longevity gene. Enhanced cellular stress resistance and autophagy.

Detailed Analysis by Category

How Your DNA Connects to Your Health

LDL managed via Repatha

SLCO1B1 CT + PCSK9 CC

Statins genetically risky for you. PCSK9 inhibition is the right call — your body doesn't naturally lower it.

Calcium score (44→49)

IL-6 GG + IL-10 CC + MTHFR

Inflammatory genotype drives calcification independent of LDL. Check homocysteine.

Liver normalized (ALT 141→21)

SLCO1B1 CT

Prior statin use likely caused hepatotoxicity via impaired transport. Removal resolved it.

Spinal stenosis L4-L5

IL-6 GG + IL-1B AG + COMT AA

Inflammatory genes accelerate disc degeneration. COMT Met/Met amplifies pain perception.

Free T low / SHBG rising

SHBG rs727428 CT + SRD5A2 CG

Genetic predisposition to higher SHBG + reduced DHT. Not just aging — it's your DNA.

Meningioma (stable 7+ yrs)

TP53 CC + IL-6 GG

IL-6 is a meningioma growth factor. Stability despite this is reassuring.

VAT improving (251→163)

FTO TT + PPARG CG

No genetic obesity burden. Metabolic improvement is achievable. Keep going to offset TCF7L2.

Genetically-Informed Action Plan

HIGH

Start methylated B vitamins: Methylfolate 400-800mcg + Methylcobalamin 1000-2000mcg sublingual + P5P 25-50mg

Because: MTHFR + MTRR + FUT2 + COMT

HIGH

Monitor HbA1c + fasting insulin every 6 months

Because: TCF7L2 TT

HIGH

Check homocysteine level

Because: MTHFR compound het

HIGH

Check Lp(a) if not already done (one-time test)

Because: Ashkenazi heritage, not fully captured by SNP array

MEDIUM

Anti-inflammatory protocol: EPA+DHA 2-4g/day + Curcumin 500-1000mg + Vitamin D to 50-70 ng/mL

Because: IL-6 GG + IL-10 CC + FADS1 CT

MEDIUM

TRT evaluation — share SHBG/SRD5A2 findings with endocrinologist

Because: SHBG CT + SRD5A2 CG

MEDIUM

Pharmacy alert: CYP2C9*2 carrier — lower NSAID doses, warfarin needs ~20% reduction

Because: CYP2C9*2 CT

MEDIUM

Magnesium glycinate 300-400mg at bedtime

Because: COMT cofactor + TCF7L2 + sleep

LOW

Dedicated Ashkenazi carrier panel (Invitae/JScreen) — 23andMe missed key founder mutations

Because: GBA, HEXA, BRCA2 6174delT not on chip

LOW

Post-meal walks 10-15 min, especially after carbs

Because: TCF7L2 TT

⚠️ Gaps in 23andMe v3 Coverage

8 of 67 queried SNPs were not on the array, including key Ashkenazi founder mutations:

• GBA (Gaucher carrier status)
• HEXA (Tay-Sachs carrier status)
• BRCA2 6174delT
• Prothrombin G20210A
• NOS3/eNOS vascular function
• ACE I/D
• VDR FokI
• ADRB1 short sleeper gene

Recommendation: Get a dedicated Ashkenazi carrier panel (Invitae or JScreen) for definitive coverage.