# Ben: full genetics reference

Source: Geneus DNA raw export, 631,500 SNPs, analysed 17 February 2026.

## Contents

1. Identity and phenotype summary
2. APOE and Alzheimer's core
3. Extended Alzheimer's loci (polygenic)
4. Dopamine system
5. Serotonin system
6. GABA and glutamate
7. Adrenergic and stress
8. Neuroplasticity
9. Pharmacogenomics, CYP enzymes
10. Drug transport and other pharmacogenomics
11. Cardiovascular and lipid genetics
12. Weight, appetite, GLP-1 response
13. Methylation and vitamin D receptor
14. Inflammation
15. Sleep and circadian

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## 1. Identity and phenotype summary

- Male, born 26 October 1982
- Based Bangkok, splits time with Dubai
- Body composition at last panel: approx 70 kg, approx 15% body fat, cutting toward 10%, target 84 kg lean long term
- Chronic baseline issues on record: 3 to 5am waking pattern, anxiety that is GABA sensitive and glutamate driven, tinnitus, rosacea / seb derm
- Documented phenotype summary: high dopamine and noradrenaline tone, low serotonin capacity, strong neuroplasticity, blunted oxytocin signalling, strong cortisol clearance, pro inflammatory cytokine baseline, elevated CAD and Alzheimer's genetic risk

## 2. APOE and Alzheimer's core

| SNP | Genotype | Interpretation | Significance |
|---|---|---|---|
| rs7412 | CC | No e2 protective allele | No protection |
| rs4420638 (proxy) | AG | Heterozygous e4 proxy | Likely e3/e4 |
| rs2075650 (proxy) | AG | Heterozygous e4 proxy | Confirms e4 carrier |
| rs769449 (proxy) | AG | Additional e4 proxy | Consistent with e3/e4 |

Three independent proxies heterozygous plus CC at rs7412 strongly supports e3/e4. One e4 copy roughly triples lifetime Alzheimer's risk (approx 10 to 12% baseline to approx 25 to 30%). Probabilistic, not deterministic. BDNF Val/Val and FKBP5 CC are meaningful counterweights.

**Direct rs429358 genotyping is still outstanding.** Current status is proxy inferred with high confidence.

## 3. Extended Alzheimer's loci (polygenic)

| Gene | SNP | Genotype | Assessment |
|---|---|---|---|
| CLU | rs11136000 | TT | Protective |
| CLU | rs9331896 | CC | Risk allele present |
| BIN1 | rs6733839 | TC | One risk allele |
| BIN1 | rs744373 | AA | No risk allele |
| CR1 | rs6656401 | GG | No risk allele |
| CR1 | rs3818361 | GG | No risk allele |
| PICALM | rs3851179 | CC | Risk allele |
| ABCA7 | rs3764650 | TT | No risk allele |
| MS4A6A | rs11218343 | TT | Protective |
| EPHA1 | rs11767557 | TT | Protective |
| CD2AP | rs10948363 | AA | No risk allele |
| PTK2B | rs28834970 | TC | One risk allele |
| HLA-DRB5 | rs9271192 | AC | One risk allele |
| CASS4 | rs7561528 | GG | No risk allele |
| ZCWPW1 | rs1476679 | TT | No risk allele |
| CD33 | rs3865444 | not genotyped | Unknown |
| INPP5D | rs10808026 | not genotyped | Unknown |

Outside APOE the polygenic picture is favourable. Primary driver of elevated risk is e4, with CLU rs9331896 CC secondary.

## 4. Dopamine system

| Gene / SNP | Genotype | Function | Impact |
|---|---|---|---|
| COMT rs4680 | AG (Val/Met) | Dopamine clearance | Intermediate clearance |
| COMT rs6269 | AG | Haplotype modifier | Intermediate |
| COMT rs4633 | TC | Haplotype modifier | Intermediate |
| MAOA rs6323 | TT | Monoamine oxidase A | Reduced activity, elevated DA and NE |
| DRD2/ANKK1 rs1800497 | GG (Taq1A) | D2 receptor density | Normal density |
| DRD2 rs6277 | AA | D2 mRNA stability | Reduced D2 expression |
| DRD2 rs1079597 | CC | D2 receptor TaqB | Typical |
| DRD4 rs1800955 | CC | D4 promoter | Reduced transcription |
| DRD4 rs752306 | CC | D4 variant | Typical |
| SLC6A3 (DAT) rs27072 | CC | Dopamine transporter | Normal reuptake |
| SLC6A3 (DAT) rs6347 | TC | Dopamine transporter | Slightly altered reuptake |

Net: elevated dopaminergic tone with reduced postsynaptic feedback. Drives reward sensitivity and amplifies impulsive reward loops. Relevant to trading behaviour, stimulant response, and GLP-1 style reward dampening.

## 5. Serotonin system

| Gene / SNP | Genotype | Function | Impact |
|---|---|---|---|
| TPH2 rs4570625 | TT | Serotonin synthesis rate | Reduced synthesis capacity |
| HTR2A rs6311 | TC | 5-HT2A promoter | Intermediate expression |
| HTR2A rs6313 | AG | 5-HT2A receptor | Intermediate activity |
| HTR1A rs6295 | CC | 5-HT1A autoreceptor | Higher autoreceptor density, less serotonin release |
| SLC6A4 rs25532 | no call | Serotonin transporter | Undetermined |

Double hit: low synthesis (TPH2 TT) plus increased autoreceptor braking (HTR1A CC). Consistently low serotonin capacity. Explains mood fragility under sleep debt and why sleep repair moves mood more than direct serotonergic agents.

## 6. GABA and glutamate

| Gene / SNP | Genotype | Function | Impact |
|---|---|---|---|
| GABRA2 rs279858 | TT | GABA-A subunit | Altered GABA sensitivity, anxiety linked |
| CACNA2D1 rs17584499 | CC | Pregabalin binding target | Normal binding site |
| GRIN2A rs1805502 | AG | NMDA NR2A subunit | Intermediate function |
| GRIN2A rs890 | AC | NMDA variant | Heterozygous |
| GRIK4 rs1954787 | TC | Glutamate ionotropic receptor | Linked to antidepressant response |
| GRIN3A | C/T | NMDA subunit | Moderate NMDA sensitivity (noted in clinical context) |

CACNA2D1 CC explains clean clinical response to pregabalin 75 mg. Anxiety profile is GABA responsive and glutamate driven, not primarily serotonergic.

Note for neurosteroid questions: pregnenolone sulfate is a negative allosteric modulator at GABA-A and a positive modulator at NMDA, which is the inverse of the pregabalin and theanine direction. Given GABRA2 TT and the glutamate driven anxiety profile, compounds acting on these two arms will produce noticeably different subjective effects in him, and stacking opposing ones the same day is partly self cancelling.

## 7. Adrenergic and stress

| Gene / SNP | Genotype | Function | Impact |
|---|---|---|---|
| ADRA2A rs1800545 | GG | Alpha 2A receptor, clonidine target | Normal receptor, clonidine should work as expected |
| ADRB2 rs1042713 | GG (Arg/Arg) | Beta 2 receptor | Enhanced agonist response |
| ADRB2 rs1042714 | GG (Gln/Gln) | Beta 2 receptor | Typical |
| FKBP5 rs1360780 | CC | Cortisol receptor sensitivity | Resilient, efficient HPA recovery |
| OXTR rs53576 | AA | Oxytocin receptor | Blunted social bonding signal |

MAOA TT plus ADRB2 Arg/Arg plus CLOCK AA is the genetic substrate of the 3 to 5am noradrenergic waking pattern.

## 8. Neuroplasticity

| Gene / SNP | Genotype | Function | Impact |
|---|---|---|---|
| BDNF rs6265 | CC (Val/Val) | Activity dependent BDNF secretion | Optimal neuroplasticity, protective |
| BDNF rs7124442 | TC | Expression modifier | Intermediate |

BDNF Val/Val is the single strongest protective factor in the profile. Exercise response and experience dependent plasticity are both favoured. Directly buffers e4 risk.

## 9. Pharmacogenomics, CYP enzymes

| Enzyme | SNP | Genotype | Phenotype | Relevance |
|---|---|---|---|---|
| CYP2C19 | rs12248560 | CC | Normal metaboliser | SSRIs, PPIs, clopidogrel |
| CYP2C19 | rs4986893 | GG | Normal, no *3 | SSRIs, benzodiazepines |
| CYP2C9 | rs1799853 (*2) | CC | Normal metaboliser | NSAIDs, warfarin |
| CYP2C9 | rs1057910 (*3) | CC | Normal metaboliser | NSAIDs, warfarin |
| CYP1A2 | rs762551 | AC | **Intermediate metaboliser** | Caffeine, melatonin |
| CYP3A5 | rs776746 | TC (*1/*3) | Intermediate metaboliser | Tacrolimus, statins |
| CYP3A4 | rs2740574 | TT | Normal metaboliser | Over 50% of all drugs |

CYP1A2 AC means slow caffeine clearance. Combined with CLOCK AA, afternoon caffeine materially degrades sleep architecture. Hard cutoff by noon is the genotype indicated rule.

## 10. Drug transport and other pharmacogenomics

| Gene / SNP | Genotype | Function | Impact |
|---|---|---|---|
| SLCO1B1 rs4149056 | TT | Statin hepatic uptake | Normal transport, low myopathy risk, statins fully available |
| SLCO1B1 rs2306283 | AG | Transport modifier | Intermediate |
| ABCB1 rs1128503 | AG | Blood brain barrier P-gp | Intermediate BBB permeability |
| VKORC1 rs9923231 | CC | Warfarin sensitivity | Normal dosing |
| OPRM1 rs1799971 | AA | Mu opioid receptor | Normal opioid response |
| UGT1A1 rs887829 | CC | Bilirubin conjugation | Normal, no Gilbert's |
| DPYD rs3918290 | CC | 5-FU metabolism | Normal, safe |

## 11. Cardiovascular and lipid genetics

| Gene / SNP | Genotype | Function | Risk |
|---|---|---|---|
| 9p21 rs10757274 | AA | CAD risk locus | **Elevated** |
| 9p21 rs4977574 | AA | CAD risk locus | **Elevated** |
| 9p21 rs1333049 | GG | CAD risk locus | **Elevated** |
| APOB rs693 | AG | ApoB levels | Intermediate |
| APOB rs515135 | TT | ApoB variant | Typical |
| PCSK9 rs11206510 | TC | LDL receptor recycling | One protective allele |
| PCSK9 rs11591147 | GG | PCSK9 loss of function | Normal, no LOF |
| LPA rs10455872 | AA | Lp(a) levels | Normal Lp(a), protective |
| LPA rs3798220 | TT | Lp(a) levels | Normal Lp(a), protective |
| LDLR rs6511720 | TG | LDL receptor | One protective allele |
| SH2B3 rs3184504 | TC | CV inflammation | Intermediate |
| SORT1 rs646776 | TC | LDL-C levels | Intermediate |
| AGT rs699 | AG | Angiotensinogen | Intermediate BP risk |
| GNB3 rs5443 | CC | G protein signalling | Normal |
| NOS3 rs1799983 | queried, see raw file | Endothelial NO synthase | Record from raw export if needed |

**Headline finding: triple homozygous risk at the 9p21 locus.** This is the strongest known common genetic risk factor for coronary artery disease. Stacked with e4 impaired cholesterol clearance and a pro inflammatory cytokine profile, cardiovascular management outranks nearly everything else in priority. Standard LDL-C alone will understate risk. ApoB and LDL-P are the correct instruments and neither has ever been measured.

Offsetting: Lp(a) genetics are clean at both SNPs, which removes a major independent risk factor.

## 12. Weight, appetite, GLP-1 response

| Gene / SNP | Genotype | Function | Impact |
|---|---|---|---|
| FTO rs9939609 | TT | Fat mass and obesity | No risk allele, protective |
| FTO rs1558902 | TT | Fat mass and obesity | No risk allele, protective |
| MC4R rs17782313 | TC | Appetite regulation | One risk allele, increased appetite |
| MC4R rs571312 | AC | Appetite regulation | One risk allele |
| GLP1R rs2268657 | TC | GLP-1 receptor | Heterozygous, may modulate GLP-1 drug dose response |

Relevant to retatrutide: GLP1R TC may alter receptor sensitivity. Monitor dose response empirically rather than assuming standard titration.

## 13. Methylation and vitamin D receptor

| Gene / SNP | Genotype | Function | Impact |
|---|---|---|---|
| MTHFR rs1801133 (C677T) | **GG** | Folate metabolism | **Normal function, wild type** |
| MTHFR rs1801131 (A1298C) | TG (het) | Folate metabolism | Mildly reduced |
| VDR rs731236 (TaqI) | AG | Vitamin D receptor | Intermediate activity |
| VDR rs7975232 (ApaI) | AC | Vitamin D receptor | Intermediate |
| VDR rs1544410 (BsmI) | TC | Vitamin D receptor | Intermediate |

Methylated B support is defensible but **not genotype mandated**. Homocysteine testing settles it and has still never been run. Any advice that leans on "he has MTHFR" is working from a corrected error.

## 14. Inflammation

| Gene / SNP | Genotype | Function | Impact |
|---|---|---|---|
| IL-6 rs1800795 | GG | IL-6 production | **Higher IL-6** |
| IL-10 rs1800896 | CC | Anti inflammatory IL-10 | **Lower IL-10** |
| IL-10 rs3024505 | AG | IL-10 modifier | Intermediate |
| TNF-alpha rs1800629 | GG | TNF production | Normal |
| TNF-alpha rs361525 | GG | TNF promoter | Normal |
| IL-1beta rs1143634 | AG | IL-1beta production | Intermediate |
| IL-2RA rs2104286 | TT | IL-2 receptor alpha | Typical |
| IL-6R rs2228145 | AA | IL-6 receptor signalling | Normal |

High IL-6 production plus low IL-10 braking equals a pro inflammatory baseline. e4 carriers with high inflammation show faster cognitive decline, so hsCRP is a tracking marker, not an optional one. Omega 3, exercise and sleep have outsized returns on this specific combination.

## 15. Sleep and circadian

| Gene / SNP | Genotype | Function | Impact |
|---|---|---|---|
| CLOCK rs1801260 | AA | Master circadian clock | Evening chronotype, sleep maintenance insomnia link |
| PER2 rs2287019 | TC | Period protein | Intermediate |
| ADORA2A rs73598374 | CC | Adenosine receptor, caffeine target | Normal caffeine sensitivity at receptor |

Note the split: receptor sensitivity to caffeine is normal (ADORA2A CC), but clearance is slow (CYP1A2 AC). The problem is duration in system, not subjective jitteriness. This is why a single morning espresso suits him and repeated small daily doses do not.