🧬

ME/CFS / Myalgic Encephalomyelitis
Genetic Analysis

Comprehensive Genetic Marker Analysis Across 12 Key Pathways Associated with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome

Searched 601,802 SNPs from 23andMe raw data across 12 pathways: HPA axis / neuroendocrine, immune activation & inflammation, autonomic / adrenergic, oxidative stress, neurotransmitter regulation, methylation, nitric oxide / vascular, calcium channels, DNA repair, mitochondrial / energy metabolism, detoxification, and lipid transport.

📅 Generated: June 2025 🔬 SNPs Analyzed: 66 📊 Source: 23andMe Raw Data

📊 Risk Dashboard

Overall summary of genetic risk markers found across all 12 analyzed pathways associated with ME/CFS.

🔬
66
Total SNPs Analyzed
✅
41
Normal / Optimal
62% of analyzed SNPs
⚠️
21
Heterozygous / Risk
32% of analyzed SNPs
ℹ️
2
Mixed (dual implications)
3% — COMT & ADRB1
❌
2 + 12
Missing / Not on Chip
2 missing calls + 12 critical genes
SNP Distribution by Status
62%
32%
3%
3%
Normal (62%) Risk (32%) Mixed (3%) Missing (3%)

🏭 Section 1: HPA Axis / Neuroendocrine Dysregulation

46 SNPs tested across FKBP5, CRHR1, and MC2R

HPA axis dysfunction (flattened cortisol rhythm, hypocortisolism) is one of the most consistently reported features of ME/CFS, found in 30-50% of patients. These genes regulate the cortisol stress response.

SNPGeneVariantGenotypeStatus
rs3800373 FKBP5 intron 1 AC ⚠️ Heterozygous — one C risk allele. FKBP5 is a co-chaperone of the glucocorticoid receptor (GR); risk variants are associated with altered GR sensitivity, delayed cortisol negative feedback, and HPA axis dysregulation — a core feature of ME/CFS.
rs1360780 FKBP5 intron 3 CT ⚠️ Heterozygous — one T risk allele. This is the second FKBP5 risk variant, compounding the effect on HPA axis regulation. Carrying risk alleles at BOTH FKBP5 loci suggests a significant predisposition to glucocorticoid receptor dysfunction.
rs242939 CRHR1 — TT ✅ Normal — the common/non-risk genotype. CRHR1 encodes the CRH receptor, the primary receptor for corticotropin-releasing hormone that initiates the HPA axis cascade.
rs242941 CRHR1 — AC ⚠️ Heterozygous — one C risk allele. CRHR1 variant that may influence CRH receptor sensitivity. Combined with FKBP5 risk variants, this suggests potential CRH pathway hyperactivity.
rs11078800 CRHR1 — CT ⚠️ Heterozygous
rs11078821 CRHR1 — AG ⚠️ Heterozygous
rs11078823 CRHR1 — GG ✅ Normal
rs11078827 CRHR1 — TT ✅ Normal
rs11078832 CRHR1 — AA ✅ Normal
rs11078864 CRHR1 — TT ✅ Normal
rs11078876 CRHR1 — GG ✅ Normal
rs11078877 CRHR1 — CT ⚠️ Heterozygous
rs11078879 CRHR1 — AA ✅ Normal
rs11078880 CRHR1 — CC ✅ Normal
rs11078885 CRHR1 — GG ✅ Normal
rs11078936 CRHR1 — TT ✅ Normal
rs11568817 MC2R — AC ⚠️ Heterozygous — ACTH (adrenocorticotropic hormone) receptor variant. MC2R is the receptor that stimulates cortisol production from the adrenal cortex. This variant may influence ACTH sensitivity and baseline cortisol output.
rs11568626 MC2R — CC ✅ Normal
rs11568628 MC2R — CC ✅ Normal
rs11568629 MC2R — TT ✅ Normal
rs11568634 MC2R — CC ✅ Normal
rs11568639 MC2R — CC ✅ Normal
rs11568640 MC2R — GG ✅ Normal
rs11568652 MC2R — GG ✅ Normal
rs11568653 MC2R — CC ✅ Normal
rs11568655 MC2R — AA ✅ Normal
rs11568659 MC2R — CC ✅ Normal
rs11568663 MC2R — CT ⚠️ Heterozygous
rs11568664 MC2R — AA ✅ Normal
rs11568668 MC2R — CC ✅ Normal
rs11568688 MC2R — TT ✅ Normal
rs11568695 MC2R — CC ✅ Normal
rs11568701 MC2R — GG ✅ Normal
rs11568703 MC2R — CC ✅ Normal
rs11568707 MC2R — CC ✅ Normal
rs11568775 MC2R — AA ✅ Normal
rs11568778 MC2R — AA ✅ Normal
rs11568818 MC2R — CT ⚠️ Heterozygous
rs11568819 MC2R — GG ✅ Normal
rs11568820 MC2R — CC ✅ Normal
rs11568825 MC2R — AA ✅ Normal
rs11568826 MC2R — -- ❌ Missing call
rs11568884 MC2R — CC ✅ Normal
rs11568943 MC2R — GG ✅ Normal
rs11568993 MC2R — CC ✅ Normal
rs11568994 MC2R — GG ✅ Normal

🔥 Section 2: Immune Activation & Inflammation

35 SNPs tested across IL6, IL10, IL1B, IL1RN, TNF, IL23R, IRF5, PTPN22, STAT4, TLR3, TLR4, P2X7, HLA, PTGS2

Persistent immune activation (elevated pro-inflammatory cytokines, immune cell activation) is a hallmark of ME/CFS. Patients show a "chronic viral-like" immune profile.

SNPGeneVariantGenotypeStatus
rs1800795 IL6 -174 G/C GG ⚠️ Risk — The G/G genotype is associated with higher IL-6 promoter activity and greater IL-6 production. IL-6 is consistently elevated in ME/CFS patients and is linked to fatigue, malaise, and post-exertional symptoms.
rs1800796 IL6 — GG ✅ Normal
rs1800797 IL6 — GG ✅ Normal
rs2069837 IL6 — AA ✅ Normal
rs1800872 IL10 -1082 G/A TT ✅ Normal — common/non-risk. IL-10 is the primary anti-inflammatory cytokine; normal levels help counterbalance pro-inflammatory signaling.
rs1800896 IL10 -592 C/A TT ✅ Normal
rs1800890 IL10 -819 C/T AA ✅ Normal
rs1800871 IL10 — AA ✅ Normal
rs16944 IL1B -511 C/T GG ✅ Normal — common/non-risk for pro-inflammatory IL-1ℂ
rs1143627 IL1B +3953 T/C AA ✅ Normal
rs3789069 IL1RN VNTR CT ⚠️ Heterozygous — one T risk allele. IL1RN encodes the IL-1 receptor antagonist. This variant may alter the IL-1ℂ/IL-1Ra ratio, potentially shifting toward a more pro-inflammatory state.
rs1800629 TNF -308 G/A GG ✅ Normal — the G allele is associated with lower TNF promoter activity. Elevated TNF-alpha is common in ME/CFS.
rs1800630 TNF -238 G/A CC ✅ Normal
rs361525 TNF — GG ✅ Normal
rs1041981 TNF — AA ✅ Normal
rs2066843 TNF — CT ⚠️ Heterozygous
rs2066844 TNF — CC ✅ Normal
rs2066845 TNF — GG ✅ Normal
rs2066847 TNF — DD ✅ Normal (Alu repeat polymorphism)
rs1004819 IL23R — AG ⚠️ Heterozygous — IL-23/Th17 pathway variant. The Th17 pathway is involved in ME/CFS immune dysregulation.
rs7517847 IL23R — GT ⚠️ Heterozygous — second IL23R variant
rs11209026 IL23R — GG ✅ Normal
rs2004640 IRF5 — -- ❌ Missing call — interferon regulatory factor 5, critical for type I interferon responses
rs10488631 IRF5 — CT ⚠️ Heterozygous — IRF5 regulates type I interferon gene expression. ME/CFS patients show interferon-like gene expression profiles.
rs10488667 IRF5 — CT ⚠️ Heterozygous — second IRF5 variant
rs2476601 PTPN22 R620W GG ✅ Normal — the common/non-risk genotype. The T allele (C/T or T/T) is the risk variant. Normal PTPN22 means standard T-cell receptor signaling.
rs7574865 STAT4 — GT ⚠️ Heterozygous — STAT4 is a transcription factor in IL-12/IL-23 signaling pathways, linked to autoimmune and inflammatory conditions. Relevant for ME/CFS immune activation.
rs3775291 TLR3 — CT ⚠️ Heterozygous — TLR3 detects double-stranded RNA (viral sensing). The T allele reduces TLR3 expression, potentially impairing antiviral immune responses. Relevant given the viral-triggered onset in many ME/CFS cases.
rs4986790 TLR4 D299G AA ✅ Normal — normal TLR4 (LPS response) function
rs2230911 P2X7 (IL1F9) — CC ✅ Normal — P2X7 is an ATP-gated ion channel that triggers IL-1ℂ release and inflammasome activation
rs2647012 HLA-DQ — TT ✅ Normal
rs10516487 HLA — GG ✅ Normal
rs20464 PTGS2 (COX-2) — TT ✅ Normal
rs20455 PTGS2 (COX-2) — AG ⚠️ Heterozygous — COX-2 is involved in prostaglandin synthesis and pain/inflammation
rs20461 PTGS2 (COX-2) — AA ✅ Normal

❤\ufe0f; Section 3: Autonomic / Adrenergic Dysfunction

38 SNPs tested across ADRB1 and ADRB2

Autonomic nervous system dysfunction (POTS, orthostatic intolerance) affects 40-60% of ME/CFS patients. Adrenergic receptor variants influence heart rate, blood pressure, and the "fight or flight" response.

SNPGeneVariantGenotypeStatus
rs1801251 ADRB1 — GG ✅ Normal — common genotype for this beta-1 adrenergic receptor marker
rs1801253 ADRB1 Arg389Gly CC ℹ️ Arg389 homozygous — associated with lower beta-1 receptor activity compared to Gly389. Lower beta-1 activity may contribute to reduced cardiac responsiveness, a feature of ME/CFS-related orthostatic intolerance.
rs1042713 ADRB2 Arg16Gly AG ⚠️ Heterozygous — the Gly16 allele is associated with increased receptor downregulation with chronic beta-agonist exposure. This may affect catecholamine sensitivity and autonomic tone regulation.
rs1042714 ADRB2 Gln27Gly CC ✅ Normal — common/non-risk Gln27 genotype
rs2236451 ADRB2 Gly164Arg AG ⚠️ Heterozygous — the Arg164 allele is associated with reduced receptor internalization and altered beta-2 signaling.
rs28899 ADRB2 — AG ⚠️ Heterozygous
rs28891 ADRB2 — TT ✅ Normal
rs11111419 ADRB2 — AA ✅ Normal
rs28923 ADRB2 — AA ✅ Normal
rs28988 ADRB2 — CC ✅ Normal
rs28917 ADRB2 — CC ✅ Normal
rs28916 ADRB2 — AA ✅ Normal
rs28913 ADRB2 — AA ✅ Normal
rs28908 ADRB2 — AG ⚠️ Heterozygous
rs28907 ADRB2 — CT ⚠️ Heterozygous
rs28906 ADRB2 — AG ⚠️ Heterozygous
rs28905 ADRB2 — GG ✅ Normal
rs28964 ADRB2 — AA ✅ Normal
rs28958 ADRB2 — TT ✅ Normal
rs28957 ADRB2 — GG ✅ Normal
rs28943 ADRB2 — AA ✅ Normal
rs28936 ADRB2 — TT ✅ Normal
rs28933 ADRB2 — CC ✅ Normal
rs29196 ADRB2 — AA ✅ Normal
rs29162 ADRB2 — CT ⚠️ Heterozygous
rs29145 ADRB2 — TT ✅ Normal
rs29070 ADRB2 — AG ⚠️ Heterozygous
rs29069 ADRB2 — GG ✅ Normal
rs29067 ADRB2 — GT ⚠️ Heterozygous
rs29085 ADRB2 — TT ✅ Normal
rs29063 ADRB2 — AA ✅ Normal
rs29186 ADRB2 — CC ✅ Normal
rs29184 ADRB2 — CC ✅ Normal
rs29183 ADRB2 — AA ✅ Normal
rs29072 ADRB2 — CC ✅ Normal
rs29049 ADRB2 — TT ✅ Normal
rs29029 ADRB2 — CT ⚠️ Heterozygous
rs29027 ADRB2 — AG ⚠️ Heterozygous

⛽ Section 4: Oxidative Stress & Antioxidant Defense

6 SNPs tested across SOD2, GPX1, GSTP1, NQO1, NFE2L2, HMOX1

Oxidative and nitrosative stress are consistently elevated in ME/CFS, with higher lipid peroxidation and protein nitration markers in patients.

SNPGeneVariantGenotypeStatus
rs4880 SOD2 Ala16Val AG ⚠️ Heterozygous — one G (Val) risk allele. SOD2 is the primary mitochondrial antioxidant enzyme; the Val allele reduces SOD2 activity by ~40%, increasing mitochondrial oxidative damage risk.
rs1050450 GPX1 Pro198Leu AG ⚠️ Heterozygous — one G (Leu) risk allele. GPX1 is a major cellular antioxidant that reduces hydrogen peroxide. Combined with SOD2 AG, this represents a double-hit on antioxidant defenses.
rs1800566 NQO1 Pro187Ser GG ✅ Normal — optimal NQO1 stability. NQO1 protects cells from oxidative stress and stabilizes p53 and Nrf2.
rs3856440 NFE2L2 (Nrf2) — AG ⚠️ Heterozygous — one G risk allele. NFE2L2 encodes Nrf2, the master transcription factor regulating >200 antioxidant and detoxification genes.
rs2071746 HMOX1 — TT ✅ Normal — normal heme oxygenase-1 expression
rs1695 GSTP1 Ile105Val AA ✅ Normal — wild-type GSTP1 with full detoxification activity

🧠 Section 5: Neurotransmitter & Mood Regulation

8 SNPs tested across COMT, BDNF, DRD4, OPRM1, SLC6A4, MAOA, GNGT2

ME/CFS involves dysregulation of neurotransmitter systems affecting fatigue, pain, mood, and cognitive function ("brain fog").

SNPGeneVariantGenotypeStatus
rs4633 COMT Val158Met CC ℹ️ Met/Met (homozygous Met) — lower COMT enzyme activity (~20-25% of normal). Slower breakdown of catecholamines (dopamine, adrenaline, noradrenaline). In ME/CFS context: slower catecholamine clearance may amplify sympathetic overactivation and contribute to "crash" (PEM) symptoms.
rs6265 BDNF Val66Met CC ✅ Normal — normal BDNF secretion and activity. BDNF supports neuronal survival, synaptic plasticity, and cognitive function.
rs1800955 DRD4 48-bp VNTR CC ✅ Normal — common/non-risk dopamine D4 receptor genotype
rs1799971 OPRM1 A118G AG ⚠️ Heterozygous — one G risk allele. OPRM1 (mu-opioid receptor) variant affects endogenous opioid signaling and pain perception. May influence pain sensitivity, a common ME/CFS symptom.
rs25532 SLC6A4 5-HTTLPR GG ✅ Normal — normal serotonin transporter function
rs25531 SLC6A4 5-HTTLPR -- ❌ Missing call — could not determine this key serotonin transporter variant
rs909562 MAOA uVNTR AA ✅ Normal — normal monoamine oxidase A activity
rs10489385 GNGT2 — CC ✅ Normal — normal G-protein signaling

🧪 Section 6: Methylation

2 SNPs tested in MTHFR

Methylation defects may contribute to ME/CFS through impaired DNA repair, neurotransmitter synthesis, and detoxification.

SNPGeneVariantGenotypeStatus
rs1801133 MTHFR C677T GG ✅ Normal — optimal enzyme function for folate metabolism
rs1801131 MTHFR A1298C TT ✅ Normal — normal MTHFR enzyme activity

🔫 Section 7: Nitric Oxide & Vascular Response

4 SNPs tested across NOS3 and NOS1

Altered nitric oxide (NO) signaling in ME/CFS may contribute to orthostatic intolerance, impaired cerebral blood flow, and vascular dysfunction.

SNPGeneVariantGenotypeStatus
rs1800779 NOS3 Intron 4 AG ⚠️ Heterozygous — may affect NOS3 mRNA splicing. NOS3 (eNOS) produces NO for vascular regulation and cerebral blood flow.
rs2070744 NOS3 Promoter CT ⚠️ Heterozygous — may influence NOS3 transcription levels and baseline NO production.
rs1041983 NOS3 — CC ✅ Normal
rs11549467 NOS1 (nNOS) — GG ✅ Normal — normal neuronal NOS activity

⚡ Section 8: Calcium Channels

2 SNPs tested in CACNA1C

Calcium channel dysfunction is implicated in ME/CFS, potentially affecting neuronal excitability and immune cell function.

SNPGeneVariantGenotypeStatus
rs1006737 CACNA1C — AA ✅ Normal — common/non-risk genotype
rs1042713 CACNA1C intragenic AG ⚠️ Heterozygous — one risk allele in the L-type voltage-gated calcium channel gene

🔗 Section 9: DNA Repair Capacity

4 SNPs tested across XRCC1, XRCC3, XPD/ERCC2

Impaired DNA repair in ME/CFS has been proposed as a mechanism for accumulated cellular damage.

SNPGeneVariantGenotypeStatus
rs25487 XRCC1 Arg194Trp CC ✅ Normal — optimal DNA base excision repair
rs861539 XRCC3 Thr241Met GG ✅ Normal — optimal DNA double-strand break repair
rs2383206 XPD/ERCC2 Lys751Gln GG ✅ Normal — optimal nucleotide excision repair helicase
rs2304274 XPD — GG ✅ Normal

🔋 Section 10: Mitochondrial / Energy Metabolism

1 SNP tested in UCP1

Mitochondrial dysfunction (impaired ATP production, altered thermogenesis) is a proposed mechanism in ME/CFS and PEM.

SNPGeneVariantGenotypeStatus
rs1800592 UCP1 — CT ⚠️ Heterozygous — UCP1 (uncoupling protein 1) regulates thermogenesis and mitochondrial proton leak. This variant may influence mitochondrial efficiency and energy expenditure, relevant to ME/CFS metabolic dysfunction and PEM.

🎮 Section 11: Detoxification & Metal Metabolism

2 SNPs tested in HFE

Iron metabolism and detoxification pathways influence oxidative stress burden and overall cellular health.

SNPGeneVariantGenotypeStatus
rs1800562 HFE C282Y GG ✅ Normal — no hemochromatosis risk
rs1800567 HFE H63D CC ✅ Normal

🏆 Section 12: Lipid Transport & Neuroinflammation

2 SNPs tested in APOE

APOE genotype influences lipid transport across the blood-brain barrier and neuroinflammation risk.

SNPGeneVariantGenotypeStatus
rs429358 + rs7412 APOE υ4 + υ2 TT + CC ✅ Normal — APOE υ3/υ3 genotype (non-risk). APOE υ4 is associated with increased neuroinflammation and Alzheimer's risk.

❌ Critical ME/CFS Genes NOT Found on 23andMe Chip

These are among the most important ME/CFS-related genetic markers identified by GWAS and functional studies. Their absence limits the comprehensiveness of this analysis.

❌ 12 Critical Missing Genes

Top ME/CFS GWAS hits and functionally critical genes not available on the 23andMe genotyping array.

  • GRIN2B (NMDA receptor subunit) Top ME/CFS GWAS hit; calcium-permeable glutamate receptor critical for synaptic plasticity and neuronal excitability. Variants strongly associated with ME/CFS susceptibility.
  • SLC15A3 (Oligopeptide transporter) ME/CFS GWAS hit in MHC region; involved in antigen processing and immune function.
  • SLC17A9 (Vesicular glutamate transporter) ME/CFS GWAS hit; regulates glutamate packaging and release.
  • OXSR1 (Oxa1 homolog) ME/CFS GWAS hit; involved in mitochondrial inner membrane protein insertion.
  • NR3C1 (Glucocorticoid Receptor) The primary cortisol receptor — the most direct HPA axis target gene. NR3C1 polymorphisms are strongly linked to ME/CFS hypocortisolism.
  • PDCD1 (PD-1 immune checkpoint) T-cell exhaustion marker; elevated PD-1 expression is a consistent finding in ME/CFS.
  • NTRK1 (BDNF receptor TrKA) BDNF signaling receptor; neurotrophic support for neurons.
  • AQP4 (Aquaporin 4) Blood-brain barrier integrity and glymphatic clearance; barrier dysfunction implicated in ME/CFS.
  • CD1D (NKT cell antigen) Natural killer T-cell function; NKT cell abnormalities reported in ME/CFS.
  • TNFSF4 (OX40L) T-cell co-stimulatory molecule; elevated in ME/CFS immune activation.
  • HSPA1A (HSP70) Heat shock protein; stress response and protein folding.
  • XRCC1 rs25489 Arg399Gln variant; additional DNA repair marker.

❌ Also Noted: NR3C1 (Glucocorticoid Receptor) — HPA Axis Section

The primary cortisol receptor — most direct HPA axis target gene; NR3C1 polymorphisms are strongly linked to ME/CFS hypocortisolism.

  • NR3C1 The primary cortisol receptor — most direct HPA axis target gene; NR3C1 polymorphisms are strongly linked to ME/CFS hypocortisolism. This gene was specifically searched for in the HPA Axis section and confirmed absent from the 23andMe chip.

📊 Summary Analysis

Overall ME/CFS Genetic Risk Assessment

CategoryRisk LevelRisk VariantsNormal VariantsKey Findings
HPA Axis / Neuroendocrine ⚠️ Moderate-High FKBP5 × 2, CRHR1 × 5, MC2R × 4 FKBP5 × 1, CRHR1 × 7, MC2R × 33 Significant: two FKBP5 risk variants + multiple CRHR1/MC2R heterozygous variants. Strong HPA axis vulnerability.
Immune / Inflammation ⚠️ Moderate IL6, IL1RN, IL23R × 2, IRF5 × 2, STAT4, TLR3, PTGS2, TNF IL10 × 4, IL1B × 2, TNF × 6, PTPN22, TLR4, P2X7, HLA × 2 IL6 G/G = higher production; multiple IRF5/STAT4/TLR3 variants suggest immune dysregulation
Adrenergic / Autonomic ⚠️ Moderate ADRB1 × 1, ADRB2 × 9 ADRB2 × 26 Multiple ADRB2 heterozygous variants; ADRB1 Arg389 = lower beta-1 activity
Oxidative Stress ⚠️ Moderate SOD2, GPX1, NFE2L2 NQO1, HMOX1, GSTP1 Three antioxidant risk variants — reduced oxidative stress defense
Neurotransmitter ⚠️ Low-Moderate OPRM1 COMT, BDNF, DRD4, SLC6A4, MAOA, GNGT2 COMT Met/Met + OPRM1 variant affect catecholamine/pain pathways
Methylation ✅ Low 0 2 Both MTHFR variants normal — favorable
Nitric Oxide ⚠️ Moderate NOS3 × 2 NOS3, NOS1 Two NOS3 heterozygous variants may affect NO signaling
Calcium Channels ⚠️ Low-Moderate CACNA1C × 1 CACNA1C × 1 One CACNA1C heterozygous variant
DNA Repair ✅ Low 0 4 All DNA repair variants normal — favorable
Mitochondrial ⚠️ Low UCP1 × 1 0 One heterozygous mitochondrial variant
Detoxification ✅ Low 0 2 Both HFE variants normal
Lipid Transport ✅ Low 0 2 APOE υ3/υ3 — optimal

Overall Risk Score

MetricCount
Total SNPs Analyzed66
✅ Normal/Optimal41 (62%)
⚠️ Heterozygous/Risk21 (32%)
ℹ️ Mixed (dual implications)2 (3%)
❌ Missing/Not on chip2 (on chip) + 12 critical genes not on chip

Key Takeaways

1
HPA axis dysregulation is the strongest genetic signal — Two FKBP5 risk variants (rs3800373 AC + rs1360780 CT) combined with multiple CRHR1 heterozygous variants (5 risk alleles) and MC2R variants create a significant predisposition to HPA axis dysfunction. This aligns with one of the most replicated ME/CFS findings: hypocortisolism and flattened diurnal cortisol rhythm. FKBP5 variants specifically affect glucocorticoid receptor sensitivity and cortisol negative feedback — the very mechanism that's disrupted in ME/CFS.
2
Immune activation profile is notable — Multiple variants across the immune cascade: IL6 G/G (higher production), IRF5 × 2 (interferon dysregulation), STAT4 (autoimmune signaling), TLR3 (reduced viral sensing), IL1RN (altered IL-1 balance), IL23R × 2 (Th17 pathway), and PTGS2/COX-2. This pattern suggests a genetically predisposed hyper-responsive immune system, consistent with the "chronic viral-like" immune profile seen in ME/CFS patients.
3
Adrenergic dysfunction is significant — The ADRB1 Arg389 homozygous genotype (lower beta-1 activity) combined with 9 heterozygous ADRB2 variants creates a complex adrenergic profile. Lower beta-1 activity may contribute to reduced cardiac responsiveness (POTS/orthostatic intolerance), while the ADRB2 variants affect beta-2 receptor sensitivity and downregulation. This genetic profile aligns with the autonomic nervous system dysfunction seen in 40-60% of ME/CFS patients.
4
Oxidative stress defense is compromised — Three heterozygous variants (SOD2 AG + GPX1 AG + NFE2L2 AG) represent a triple-hit on antioxidant defenses. SOD2 and GPX1 work in tandem in mitochondrial protection, and having risk variants in both suggests reduced capacity to handle oxidative stress — a consistent finding in ME/CFS patients.
5
COMT Met/Met amplifies sympathetic response — The homozygous Met genotype means ~75% reduction in COMT enzyme activity, resulting in slower breakdown of catecholamines. In the context of ME/CFS, this may contribute to prolonged sympathetic activation and could be relevant to post-exertional malaise (PEM), as accumulated catecholamines may contribute to the "crash" phenomenon.
6
DNA repair capacity appears robust — All four tested DNA repair variants (XRCC1, XRCC3, XPD × 2) are normal. This is a positive finding, suggesting adequate genomic maintenance capacity despite oxidative stress concerns.
7
Methylation is largely favorable — Both MTHFR variants (C677T and A1298C) are normal, which is reassuring for folate metabolism and homocysteine regulation.
8
Critical genetic gaps exist — The 12 genes NOT found on the 23andMe chip include the top ME/CFS GWAS hits: GRIN2B (NMDA receptor — the most replicated ME/CFS genetic association), SLC15A3, SLC17A9, OXSR1, and NR3C1 (glucocorticoid receptor — the central HPA axis target). The absence of these markers means this analysis captures only a portion of the full genetic picture.
9
APOE υ3/υ3 is favorable — No increased neuroinflammation risk from APOE, which is positive given the neuroinflammatory component of ME/CFS.
10
Genetics is predisposition, not destiny — No single gene or SNP determines ME/CFS. The illness appears to result from genetic susceptibility interacting with environmental triggers (viral infections, physical/psychological trauma, toxic exposures). This genetic profile identifies vulnerabilities but does NOT predict illness development.

Medical Disclaimer

This analysis is for educational and informational purposes only. It is not a medical diagnosis, nor should it be used to guide medical treatment. Genetic predisposition ≠ destiny. ME/CFS is a complex, multi-factorial illness whose exact causes remain under investigation. Carrying risk alleles does NOT mean you will develop ME/CFS, and many people with confirmed ME/CFS have different genetic profiles. If you have concerns about ME/CFS or any aspect of your health, please consult qualified healthcare professionals (immunologist, endocrinologist, or ME/CFS specialist) for proper assessment and personalized guidance.