Genetics β€” Patrick

23andMe v5 (2022) + Promethease (2026-05-21, 25,225 SNPs) Β· consolidated triage Β· scoped to action-affecting variants only

🎯 Top 5 actionable findings (everything else is supporting detail)

  1. LOXL1 rs2165241 T;T + rs3825942 G;G β€” >10Γ— pseudoexfoliation glaucoma (PEX) risk. Augenarzt before 40, slit-lamp + IOP + OCT, q2-3y until 50. Tell them: "LOXL1-Homozygot, Pseudoexfoliationsrisiko."
  2. 2 thyroid cancer variants (rs944289 T;T + rs965513 A;G) + maternal grandfather thyroid cancer + DIO1 A;A T4β†’T3 conversion impaired. Thyroid ultrasound + Calcitonin + TRAb + anti-TPO/TG + fT3/rT3. Calcitonin = medullary screen, direct ICD-anchor.
  3. HLA-B27 + AS/RA/SLE autoimmune cluster (HLA-B27 tag + 4.6Γ— AS + 5.2Γ— RA + ITGAM 1.78Γ— SLE + IL23R Graves) + grandmother arthritis. HLA-B27 standalone + anti-CCP + RF + ANA + dsDNA + C3/C4. KΓ€fer (Balingen) is the right doctor.
  4. NOS3 rs891512 A;G β€” impaired endothelial NO synthesis. Directly validates the endothelial-Bart hypothesis (council R3+R4) β€” and EMPIRICALLY CONFIRMED by PEA differential test 2026-05-22: pure mast-cell stabilization gives only partial signature, antimicrobial kill is load-bearing. Justifies L-citrulline 6g + beetroot + NAC stack genetically + clinically.
  5. KITLG rs4474514 A;A β€” >3Γ— testicular cancer risk. Peak window 20-40y. Monthly self-exam, free, 1 min.

🟒 Protective findings (Promethease's "good news")

APOE Ξ΅2/Ξ΅3Lower Alzheimer risk + favorable lipid profile. No E4 β€” MB / psilocybin / future ketamine genetically safe.
BDNF Val/Val (rs6265)Normal BDNF function. Neuroplasticity baseline good β€” psilocybin / MB protocols genetically favored.
KIBRA rs17070145 T;TGreatly enhanced episodic memory. Felt-effect journaling has unusually high signal β€” trust your calibration more than population reference.
No G6PD deficiency variantMB methemoglobinemia risk minimal (14Γ— safety margin at 0.5mg/kg oral).
No SLCO1B1 statin-intoleranceStatins safe if ever needed (e.g. pitavastatin for Bart angiogenesis).
No VKORC1 / CYP2C9 high-sensitivityAnticoagulation tolerable, standard INR monitoring.
No HFE C282Y / H63DNo hemochromatosis β€” iron supplementation safe.
HLA-DRB1*1501 GGNot high-risk MS variant β€” MS less likely on differential.
No BRCA / Lynch / MUTYH / APC / MSH / MLH hitsNo additional cancer-pred panel justified.
Favorable lipid genetics (APOE Ξ΅2/Ξ΅3 + HDL+ cluster + low-LDL)Don't preemptively restrict dietary fat. Still get ApoB + Lp(a) once for ground-truth baseline.

A. Cancer screening

Gene / rsIDGenotypeRiskAction
rs944289 (NKX2-1)T;T1.69Γ— thyroid CaThyroid US + full panel + calcitonin. Repeat US q2y.
rs965513 (FOXE1)A;G1.77Γ— thyroid Ca (independent)Stacks with rs944289 β€” same panel
LOXL1 rs2165241 + rs3825942T;T + G;G>10Γ— PEX glaucomaAugenarzt before 40, slit-lamp + IOP + OCT, q2-3y to 50
KITLG rs4474514A;A>3Γ— testicular CaMonthly self-exam (peak window 20-40y)
ATM rs1801516A;A2.76Γ— pancreatic CaWatch only at 35; escalate if FH surfaces
rs4430796 (HNF1B) + rs11672691 (PCAT19)A;A + G;G1.38Γ— + 1.39Γ— prostate CaPSA at 45 (not 50). Free-PSA + total.
rs1015362G;G2-4Γ— sun sensitivity β†’ melanomaAnnual Hautarzt skin check. Aggressive SPF on scalp.

B. Autoimmune / Spondyloarthropathy cluster (Council R4 reframe: "autoimmune amplifier")

Council round 4 framing: Patrick has aggressive autoimmune hardware. Bart drives the trigger; the genotype determines the autoimmune amplitude. Anti-inflammatory scaffolding is co-equal with kill protocol.
Gene / rsIDGenotypeRiskAction
rs4349859 (MICA, HLA-B27 tag)A;GHLA-B27 likely carrierOrder HLA-B27 standalone. If +: SI MRI + rheum referral.
rs7743761A;C4.6Γ— AS riskSame workup as HLA-B27
rs6457617T;T5.2Γ— rheumatoid arthritisanti-CCP + RF + ANA panel. Rheum referral.
rs9268839 (HLA-DR)A;G2Γ— RA riskSame panel
rs3738919 (ITGAV)A;C1.94Γ— RASame panel
IL23R rs10889677 + rs2201841A;C + C;T1.5Γ— AS/Crohn's, 2Γ— Graves'Add TRAb to thyroid panel
ITGAM rs1143679A;G1.78Γ— SLEANA + anti-dsDNA + C3/C4

C. Methylation + xenobiotic metabolism

GeneGenotypeAction
MTHFR C677T (rs1801133)AG het~30% reduced 5,10-MTHFR. Methylated B-complex (5-MTHF + methyl-B12), not megadose.
MTHFR A1298C (rs1801131)TT normalNo additional concern
COMT V158M (rs4680)AG hetModerate COMT β€” sticky thoughts inflammation-driven, not genetic. Avoid high-dose methyl donors during flares.
CYP1A2 *1F (rs762551)AA fastCaffeine metabolism fine. Autonomic load is the limit, not metabolism.
NAT2 (rs1799929)CT intermediateRifampin tolerable with LFT monitoring q2 weeks during kill course.
GSTP1 I105V (rs1695)AG reduced GSTNAC 1200-1800mg/day permanent β€” essential during mold/biotoxin/kill phases.

D. Vit D axis (justifies dose bump)

GeneGenotypeAction
VDR BsmICC variantBump Vit D3 to 7000-10000 IU short-term until 25(OH)D 60-80 ng/mL, then back to 5000 IU maintenance. Always with K2-MK7 100mcg + Mg + fat. Retest q8 weeks.
VDR TaqIAA variant
VDR ApaICC variant
CYP2R1GG slower 25-hydroxylation

E. Endothelial / vascular (validates council R3+R4 hypothesis)

NOS3 rs891512A;GImpaired eNOS. Validates endothelial-Bart hypothesis at genotype level. L-citrulline 6g + beetroot 500ml + NAC genetically targeted.
9p21 CV cluster (rs1333049 +4)positive1.5Γ— CAD. Aspirin microdose validated. Add Lp(a) once-in-life lab.
HDL+ cluster + rs174537favorableLipid genetics good β€” don't preemptively restrict dietary fat.

F. Connective tissue

COL5A1 rs12722TT variant homoEDS-spectrum genotype BUT phenotype-negative for hypermobility ("no hypermobility anywhere"). Vasculitis-flavored connective tissue phenotype better fit. Informs ganglion-cyst + cervical workup.
CILP rs2073711CCLumbar disc disease ↑. Inform June cervical MRI.
rs7639618 (COL6A4P1)C;T1.45Γ— osteoarthritis. Ganglion cyst + ankle clicking context.
rs9525638T;TWeaker bone density. DEXA at 40.

G. Innate immunity (supports chronic intracellular pathogen model)

CCR5 Ξ”32 het (i3003626)D;IPartial Ξ”32 β€” modified intracellular pathogen response. Permissive niche for chronic Bart.
IL12B C;C (rs3212227)β€”Atypical mycobacteria susceptibility. Mycobacterial coinfection differential if Bart kill stalls.
CCL2 rs1024611C;TChronic TB / intracellular biology. Supports Doxy+Rifa combo over Rifa-mono.
TLR4 D299G (rs4986790)AA normalNormal TLR4 β€” no LPS hyporesponsiveness.

H. Other

DIO1 rs2235544A;AReduced T4β†’T3 conversion β†’ metabolic-fatigue backbone. If thyroid Rx ever needed: prefer T3-containing (Armour/T3 add-on) over T4-only.
OXTR rs53576A;GAtypical oxytocin signaling. Mild OCD-spectrum overlap. Reframe only, no protocol change. Brother schizophrenia context β€” sitter + integration for psychedelic sessions (already default).
SLC2A9 rs7442295?~4Γ— hyperuricemia. Watch on purine load β€” check uric acid if joint flares appear.
rs2395185?2.72Γ— T1D (LADA possibility). Fasting C-peptide once if labs drift.
DRD2 -141C (rs1799732)IIBaseline D2 density.
rs4654748 (NBPF3)C;T1.45 ng/mL lower B6. Already in B-complex; aim PLP upper-mid range if measured.

What's NOT measured (still need wet labs)

Drug-response cheat sheet (for Tier 3 planning)

DrugGenotype impactVerdict
Methylene blueNo G6PD deficiency β€” methemoglobinemia margin 14Γ— at 0.5mg/kgβœ… Genetically safe. Serotonergic interaction risk = pharmacology, not genetics.
RifampinNAT2 intermediate + no CYP issuesβœ… Tolerable with q2-week LFTs
Statins / pitavastatinNo SLCO1B1 intoleranceβœ… Safe
WarfarinNo VKORC1 / CYP2C9 high-sensitivityβœ… Standard dosing + monitoring
Doxycycline, atovaquone, LDN, cimetidineNo relevant variantsβœ… Standard dosing
Thyroid hormone replacement (if Hashimoto progresses)DIO1 A;A reduced T4β†’T3Prefer T3-containing (Armour / NDT / T3 add-on)
Pseudoephedrine / sympathomimeticsNOS3 + CV cluster⚠️ Avoid high-dose; use less aggressive decongestants
Aspirin / nattokinaseNOS3 endothelial variantβœ… Antiplatelet approach genetically justified. Continue.

File handling

All findings reviewed by 3 model council (rounds 1-5). Substrate model with R4 framing lives at action plan. Print this page for Promethease-relevant doctor visits (PEX/Augenarzt, Endo, Rheumatologe).