The feedback layer.

Atherogenic particle count.

Sample:

Serum

Order when:

Risk assessment, LDL/triglyceride discordance.

Avoid when:

Acute illness with distorted lipids.

Tells you:

Particle burden.

Doesn't tell you:

Plaque burden directly.

Heritable cardiovascular risk modifier.

Sample:

Serum

Order when:

Once in adulthood; family CVD history.

Avoid when:

Routine repeat testing.

Tells you:

Inherited risk magnitude.

Doesn't tell you:

Whether disease is currently progressing.

Glycemic control and insulin resistance signal.

Sample:

Serum

Order when:

Metabolic risk, weight changes, peptide therapy monitoring.

Avoid when:

Hemoglobinopathy without adjusted method.

Tells you:

Average glycemia + insulin context.

Doesn't tell you:

Acute glucose excursions (use CGM).

Low-grade systemic inflammation.

Sample:

Serum

Order when:

CV risk, chronic disease monitoring.

Avoid when:

Acute infection.

Tells you:

Inflammatory state at baseline.

Doesn't tell you:

Source of inflammation.

Iron stores; HFE workup.

Sample:

Serum

Order when:

Fatigue, family history of hemochromatosis, HFE variant.

Avoid when:

Acute inflammation alone (ferritin is acute-phase).

Tells you:

Iron overload or deficiency context.

Doesn't tell you:

Tissue iron without imaging.

Functional B-vitamin/methylation marker.

Sample:

Serum

Order when:

When result will change a decision (e.g., MTHFR context).

Avoid when:

Routine 'methylation' panels without indication.

Tells you:

Functional B12/folate/renal/thyroid context.

Doesn't tell you:

MTHFR genotype directly.

Multifactorial; do not over-attribute to MTHFR.

Compositional / functional snapshot.

Sample:

Stool

Order when:

Research-curious patients; symptom correlation in select cases.

Avoid when:

As a stand-alone diagnostic.

Tells you:

Relative abundance, diversity proxies.

Doesn't tell you:

Disease diagnosis; causality.

Test selected genes for a clinical question.

Sample:

Blood/saliva

Order when:

Defined phenotype or family history.

Avoid when:

Wellness curiosity without indication.

Tells you:

Pathogenic/likely-pathogenic variants in panel genes.

Doesn't tell you:

Variants outside panel; CNVs unless designed for them.

Counseling: Recommended

Diagnostic in unexplained disease.

Sample:

Blood/saliva

Order when:

Rare disease workup, multisystem features.

Avoid when:

Population screening.

Tells you:

Coding variants across the exome.

Doesn't tell you:

Most non-coding, structural, repeat-expansion variants.

Counseling: Required

Broadest genomic interrogation.

Sample:

Blood/saliva

Order when:

Specialist context; some rare-disease pathways.

Avoid when:

Routine wellness.

Tells you:

Coding + much non-coding/structural variation.

Doesn't tell you:

All clinical meaning of every variant.

Counseling: Required

Detect CNVs and large structural changes.

Sample:

Blood

Order when:

Developmental delay, congenital anomalies.

Avoid when:

SNV-only questions.

Tells you:

Copy-number changes.

Doesn't tell you:

Single-nucleotide variants.

Counseling: Recommended

Mitochondrial disease workup.

Sample:

Blood/tissue

Order when:

Suspected mitochondrial syndrome.

Avoid when:

Wellness screening.

Tells you:

mtDNA variants, heteroplasmy.

Doesn't tell you:

Nuclear-encoded mitochondrial disease alone.

Counseling: Required

Reproductive planning.

Sample:

Blood/saliva

Order when:

Pre-conception or early pregnancy.

Avoid when:

As a personal disease-risk test.

Tells you:

Carrier status for screened conditions.

Doesn't tell you:

Personal risk for most screened conditions.

Counseling: Recommended

Therapy selection in oncology.

Sample:

Tumor tissue

Order when:

Per oncology pathway.

Avoid when:

Without oncology coordination.

Tells you:

Somatic variants guiding therapy.

Doesn't tell you:

Inherited risk (germline test required).

Counseling: Recommended

Test relatives for a known family variant.

Sample:

Blood/saliva

Order when:

After a pathogenic finding in proband.

Avoid when:

Without a confirmed proband variant.

Tells you:

Carrier status for that variant.

Doesn't tell you:

Other inherited risks.

Counseling: Recommended

Metabolism of many psychotropics, opioids.

Sample:

Blood/saliva

Order when:

Before/at suboptimal response or toxicity.

Avoid when:

Without a relevant prescribing decision.

Tells you:

Predicted phenotype.

Doesn't tell you:

All drug response variability.

Clopidogrel, PPIs, SSRIs.

Sample:

Blood/saliva

Order when:

Cardiology referral or SSRI/PPI decisions.

Avoid when:

Routine wellness.

Tells you:

Metabolizer phenotype.

Doesn't tell you:

All clinical outcomes.

Warfarin dosing context.

Sample:

Blood/saliva

Order when:

Initiation of warfarin in selected cases.

Avoid when:

Routine.

Tells you:

Dosing context.

Doesn't tell you:

INR; still monitor.

Statin-associated muscle symptom risk.

Sample:

Blood/saliva

Order when:

Considering high-dose simvastatin or recurrent SAMS.

Avoid when:

Routine.

Tells you:

Risk phenotype.

Doesn't tell you:

Whether SAMS will occur.

Thiopurine toxicity risk.

Sample:

Blood/saliva

Order when:

Before thiopurines.

Avoid when:

Without thiopurine plan.

Tells you:

Toxicity risk phenotype.

Doesn't tell you:

All adverse events.

Fluoropyrimidine toxicity risk.

Sample:

Blood/saliva

Order when:

Before 5-FU/capecitabine.

Avoid when:

Without plan for these agents.

Tells you:

Severe toxicity risk.

Doesn't tell you:

All toxicity.

Irinotecan and atazanavir context.

Sample:

Blood/saliva

Order when:

Per oncology/ID protocol.

Avoid when:

Routine.

Tells you:

Phenotype context.

Doesn't tell you:

All response.

Abacavir hypersensitivity.

Sample:

Blood/saliva

Order when:

Before abacavir.

Avoid when:

Without that decision.

Tells you:

Risk allele presence.

Doesn't tell you:

Reaction certainty.

Carbamazepine SJS risk in selected ancestries.

Sample:

Blood/saliva

Order when:

Before carbamazepine in higher-risk ancestry.

Avoid when:

Without that decision.

Tells you:

Risk allele.

Doesn't tell you:

All SJS risk.

Carbamazepine cutaneous reactions.

Sample:

Blood/saliva

Order when:

Per guideline.

Avoid when:

Routine.

Tells you:

Risk allele.

Doesn't tell you:

All response.

Hemolysis risk with select drugs/foods.

Sample:

Blood

Order when:

Per guideline; family or ancestry context.

Avoid when:

Routine.

Tells you:

Activity level.

Doesn't tell you:

All hemolytic events.

Hereditary hemochromatosis context.

Sample:

Blood/saliva

Order when:

Iron studies abnormal; family history.

Avoid when:

Without iron-study context.

Tells you:

Common HFE variants.

Doesn't tell you:

All iron-overload causes.

Lactase persistence context.

Sample:

Blood/saliva

Order when:

When result changes plan.

Avoid when:

Routine.

Tells you:

Genotype context.

Doesn't tell you:

Symptoms or response.

Alcohol metabolism / risk counseling.

Sample:

Blood/saliva

Order when:

Relevant ancestry, alcohol-related decisions.

Avoid when:

Routine.

Tells you:

Metabolizer status.

Doesn't tell you:

All risk.

Cardiometabolic / neurodegenerative risk context.

Sample:

Blood/saliva

Order when:

With counseling; specific clinical questions.

Avoid when:

Without counseling.

Tells you:

Allele combination.

Doesn't tell you:

Whether disease will occur.

Counseling: Required

Common polymorphism; over-claimed.

Sample:

Blood/saliva

Order when:

Rarely; pair with homocysteine and clinical context.

Avoid when:

Routine 'methylation' panels.

Tells you:

Genotype.

Doesn't tell you:

Whether you 'need methylated vitamins'.

Do not over-prescribe based on SNP alone.

Fatty acid metabolism variants.

Sample:

Blood/saliva

Order when:

Research/select context.

Avoid when:

Routine.

Tells you:

Genotype.

Doesn't tell you:

Personal omega ratios.

Microbiome/B12 association context.

Sample:

Blood/saliva

Order when:

Research/curiosity with caveats.

Avoid when:

Routine clinical decision-making.

Tells you:

Secretor status.

Doesn't tell you:

Disease risk on its own.

Diabetes/obesity polygenic context.

Sample:

Blood/saliva

Order when:

Polygenic risk research/selected cases.

Avoid when:

As single-SNP diagnosis.

Tells you:

Single-variant context.

Doesn't tell you:

Personal disease risk alone.

Heritable CV risk pairing.

Sample:

Blood

Order when:

Family CVD; precision lipid workup.

Avoid when:

Without lab context.

Tells you:

Inherited CV risk magnitude.

Doesn't tell you:

Acute events.

Research / education tool.

Sample:

Blood/saliva

Order when:

Education; rarely changes care.

Avoid when:

As stand-alone diagnostic or 'age reversal' proof.

Tells you:

Methylation summary statistics.

Doesn't tell you:

Clinical disease state.

Research-grade biological-age estimate.

Sample:

Blood/saliva

Order when:

Education only.

Avoid when:

As proof of clinical rejuvenation.

Tells you:

A model-derived age estimate.

Doesn't tell you:

Disease, mortality, or that any protocol works.