∫Integrated Systems Health
Evidence grader

171 graded claims, plain language.

Filter by domain or grade. Each claim separates what is true, what is not proven, what is actionable, and which references support the grade. Genomics, epigenomics, pharmacogenomics, polygenic risk, nutrigenomics, and gene therapy are covered in depth.

Grading rubric

Each claim is graded A–F using a reference-backed rubric adapted from GRADE, USPSTF, ACMG/AMP, CPIC, and CDC genomic-application tiers. The grade reflects the strength of evidence AND the clarity of clinical action — not novelty, intuition, or marketing.

171 of 171
  • F
    Microbiome
    mb-1

    "Stool diversity scores can diagnose disease."

    True when:
    Diversity is a research-useful summary statistic.
    Not proven:
    It does not diagnose discrete disease in individuals.
    Actionability:
    Use as context, not as a diagnosis.
    Why this grade:
    F: claim exceeds validated use of an ecological summary statistic.
    Marketing red flags:
    diversity score = health score
    ReferencesMicroba
  • A
    Microbiome
    mb-2

    "FMT has strong evidence for recurrent C. difficile."

    True when:
    Recurrent CDI after standard therapy.
    Not proven:
    Routine use for IBS/autoimmunity at population level.
    Actionability:
    Refer to qualified service; follow current guidance.
    Why this grade:
    A: guideline-supported indication with consistent RCT data.
    Referral:
    Gastroenterology / ID
    References360bio
  • F
    Microbiome
    mb-3

    "Probiotics work the same regardless of strain or dose."

    True when:
    —
    Not proven:
    Effects are strain- and indication-specific.
    Actionability:
    Match strain to indication; do not generalize.
    Why this grade:
    F: contradicted by strain-specific trial data.
    Marketing red flags:
    any probiotic for any condition
  • B
    Microbiome
    mb-4

    "Fiber-derived SCFAs influence host immune and metabolic biology."

    True when:
    Mechanistic and translational evidence.
    Not proven:
    That a single SCFA test predicts clinical outcomes.
    Actionability:
    Increase fermentable fiber as tolerated.
    Why this grade:
    B: convergent mechanistic + cohort evidence; outcome data still emerging.
  • A
    Peptides
    pp-1

    "GLP-1 receptor agonists improve weight and glycemic outcomes in eligible adults."

    True when:
    Approved indications, monitored use.
    Not proven:
    Risk-free for all populations or for cosmetic-only goals.
    Actionability:
    Use within indication, monitor labs and tolerability.
    Why this grade:
    A: multiple RCTs and regulatory approval on hard endpoints.
    Pair with labs:
    HbA1c, Lipids, Renal, Body composition
    ReferencesPeptiter
  • F
    Peptides
    pp-2

    "BPC-157 cures injuries in humans."

    True when:
    Preclinical signals exist.
    Not proven:
    Robust human RCT efficacy or long-term safety.
    Actionability:
    Disclose evidence gap; avoid grey-market sources.
    Why this grade:
    F: claim exceeds preclinical evidence; no human RCT.
    Marketing red flags:
    miracle healing peptide
  • F
    Peptides
    pp-3

    "All injectable peptides require the same monitoring regardless of class."

    True when:
    —
    Not proven:
    Monitoring depends on mechanism, dose, comorbidities.
    Actionability:
    Tailor monitoring to drug class and patient.
  • D
    Vagus
    vg-1

    "HRV is a single, definitive measure of autonomic health."

    True when:
    HRV correlates with autonomic state on average.
    Not proven:
    Single-day HRV diagnoses individual disease.
    Actionability:
    Use trends, not single values.
    Why this grade:
    D: signal is real at population level; individual diagnostic claims unsupported.
    ReferencesVagus Academy
  • C
    Vagus
    vg-2

    "Auricular tVNS shows promise in select inflammatory and DGBI conditions."

    True when:
    Small trials, biomarker shifts, some symptom benefit.
    Not proven:
    Routine first-line use across conditions.
    Actionability:
    Trial in selected patients with measurable endpoints.
    Why this grade:
    C: limited human evidence; promising but ancestry/condition-restricted.
  • A
    Labs
    lb-1

    "ApoB is a stronger marker of atherogenic particle burden than LDL-C alone."

    True when:
    Evidence consistent across cohorts.
    Not proven:
    —
    Actionability:
    Order ApoB when discordance suspected.
    Why this grade:
    A: consistent cohort evidence; endorsed by lipid guidelines.
    ReferencesAHA
  • F
    Labs
    lb-2

    "IgG food panels diagnose food sensitivity."

    True when:
    —
    Not proven:
    IgG reflects exposure, not pathology.
    Actionability:
    Avoid as a diagnostic; use elimination/reintroduction.
    Why this grade:
    F: contradicted by allergy society position statements.
    Marketing red flags:
    IgG panel = sensitivity test
  • F
    Genomics
    gn-1

    "Genes are destiny."

    True when:
    —
    Not proven:
    Most disease is multifactorial; environment and behavior matter.
    Actionability:
    Frame as risk architecture, not fate.
    Why this grade:
    F: contradicted by twin, GWAS, and exposome data.
    Patient script:
    "Your genes describe possibilities, not certainties."
    ReferencesNHGRI CDC
  • A
    Genomics
    gn-2

    "Genomics can identify some actionable inherited risks before symptoms appear."

    True when:
    Tier 1 conditions (HBOC, Lynch, FH) and similar.
    Not proven:
    All findings change outcomes equally.
    Actionability:
    Screen, prevent, refer per guideline.
    Why this grade:
    A: CDC Tier 1 + ACMG SF v3.3 explicitly designate actionability.
    ReferencesCDC ACMG
  • F
    Genomics
    gn-3

    "Family history is obsolete once genome sequencing is available."

    True when:
    —
    Not proven:
    Pedigree captures penetrance, environment, and unsequenced risk.
    Actionability:
    Take a three-generation pedigree at intake.
    Why this grade:
    F: contradicted by CDC family-history evidence reviews.
    ReferencesCDC
  • F
    Genomics
    gn-4

    "A VUS should be treated as pathogenic if symptoms seem to match."

    True when:
    —
    Not proven:
    VUS classification means evidence is insufficient.
    Actionability:
    Do not act on a VUS; reanalyze over time; refer to genetics.
    Why this grade:
    F: violates ACMG/AMP variant interpretation standard.
    ReferencesACMG/AMP NCBI
  • F
    Genomics
    gn-5

    "Raw direct-to-consumer SNP data is sufficient for clinical diagnosis."

    True when:
    —
    Not proven:
    Confirmation in an accredited lab is required.
    Actionability:
    Confirm clinically before action.
    Why this grade:
    F: FTC and ACMG explicitly warn against unconfirmed DTC use.
    Marketing red flags:
    DTC raw data report = diagnosis
    ReferencesFTC NCBI
  • A
    Genomics
    gn-6

    "Pathogenic BRCA1/BRCA2 variants change cancer screening and prevention."

    True when:
    Guideline-driven surveillance and risk-reduction options.
    Not proven:
    —
    Actionability:
    Refer to genetics + oncology.
    Why this grade:
    A: NCCN + USPSTF guideline-supported.
    Referral:
    Clinical genetics / oncology
    ReferencesNCCN USPSTF ACMG
  • A
    Genomics
    gn-7

    "Identifying Lynch syndrome can change colonoscopy and family screening."

    True when:
    Guideline-based intervals and cascade testing.
    Not proven:
    —
    Actionability:
    Refer; cascade test relatives.
    Why this grade:
    A: NCCN + CDC Tier 1.
    Referral:
    Genetics / GI
    ReferencesNCCN CDC
  • A
    Genomics
    gn-8

    "Familial hypercholesterolemia is often missed without family history and lipid testing."

    True when:
    Underdiagnosis is well documented.
    Not proven:
    —
    Actionability:
    Screen LDL-C in young adults with FH suspicion; consider genetic testing.
    Why this grade:
    A: ESC/EAS consensus and CDC Tier 1.
    Pair with labs:
    LDL-C, ApoB, Lp(a)
    ReferencesESC/EAS USPSTF CDC
  • F
    Nutrigenomics
    gn-9

    "MTHFR status alone determines whether someone needs methylated vitamins."

    True when:
    —
    Not proven:
    Population effect is small; clinical action requires labs and context.
    Actionability:
    Use homocysteine and clinical picture; do not prescribe by SNP alone.
    Why this grade:
    F: ACMG explicitly recommends against MTHFR testing in adults.
    Marketing red flags:
    MTHFR = methyl-folate for life
    ReferencesACMG
  • A
    Nutrigenomics
    gn-10

    "Homocysteine is influenced by genes, nutrients, renal function, thyroid, medications, and lifestyle."

    True when:
    Multifactorial determinants are well established.
    Not proven:
    —
    Actionability:
    Interpret in full clinical context.
    Why this grade:
    A: well-established multifactorial biology.
    Pair with labs:
    B12, Folate, Creatinine, TSH
  • F
    Genomics
    gn-11

    "APOE status can be safely interpreted without counseling."

    True when:
    —
    Not proven:
    Implications for dementia/CVD risk warrant counseling.
    Actionability:
    Offer pre/post-test counseling.
    Why this grade:
    F: NSGC counseling and GINA/insurance considerations.
    ReferencesNSGC EEOC / NHGRI
  • A
    Pharmacogenomics
    gn-12

    "HLA variants can be relevant to medication safety."

    True when:
    HLA-B*57:01 (abacavir), HLA-B*15:02 (carbamazepine), HLA-A*31:01.
    Not proven:
    —
    Actionability:
    Test before initiating relevant drugs per guideline.
    Why this grade:
    A: CPIC Level A, FDA labeling.
    ReferencesCPIC CPIC FDA
  • A
    Pharmacogenomics
    gn-13

    "CPIC-style pharmacogenomics helps translate results into prescribing decisions."

    True when:
    Established gene–drug pairs with curated guidance.
    Not proven:
    —
    Actionability:
    Use CPIC tables; document phenotype.
    Why this grade:
    A: CPIC is the canonical translation framework.
    ReferencesCPIC CPIC Stanford
  • F
    Pharmacogenomics
    gn-14

    "Pharmacogenomics replaces clinical monitoring."

    True when:
    —
    Not proven:
    PGx is one input; renal/hepatic/interaction monitoring still required.
    Actionability:
    Continue standard monitoring.
    Why this grade:
    F: explicitly contradicted by ACMG PGx standards.
    ReferencesACMG
  • F
    Polygenic risk
    gn-15

    "Polygenic risk scores are diagnostic tests."

    True when:
    —
    Not proven:
    PRS estimate probabilistic risk, not disease.
    Actionability:
    Communicate as risk stratification only.
    Why this grade:
    F: NHGRI/PGS Catalog explicitly frame PRS as risk, not diagnosis.
    ReferencesNHGRI EBI / NHGRI
  • C
    Polygenic risk
    gn-16

    "PRS can sometimes aid risk stratification, depending on ancestry, calibration, and clinical context."

    True when:
    Selected conditions in calibrated populations.
    Not proven:
    Universal performance across ancestries.
    Actionability:
    Use cautiously; check derivation cohort.
    Why this grade:
    C: PRS performance well documented but ancestry-restricted.
    ReferencesEBI / NHGRI Nature Genetics Nature Genetics
  • A
    Polygenic risk
    gn-17

    "Most PRS were derived in European-ancestry cohorts and may underperform in others."

    True when:
    Documented across multiple GWAS.
    Not proven:
    —
    Actionability:
    Disclose ancestry calibration; avoid action when poorly calibrated.
    Why this grade:
    A: Martin 2019 and All of Us program both confirm.
    ReferencesNature Genetics NIH
  • F
    Polygenic risk
    gn-18

    "A PRS percentile means an individual will develop the disease."

    True when:
    —
    Not proven:
    Percentile is a relative-risk estimate, not certainty.
    Actionability:
    Frame in absolute risk and time horizon.
    Why this grade:
    F: misinterpretation of relative vs absolute risk.
    ReferencesNHGRI
  • B
    Polygenic risk
    gn-19

    "PRS can sometimes reclassify CAD risk among intermediate Framingham/PCE patients."

    True when:
    Validated CAD PRS in calibrated populations.
    Not proven:
    Universal mortality reduction from PRS-guided care.
    Actionability:
    Use as one input alongside ApoB, Lp(a), and family history.
    Why this grade:
    B: cohort evidence with limited RCT outcomes data.
    Pair with labs:
    ApoB, Lp(a), LDL-C
    ReferencesNature Genetics EBI / NHGRI
  • B
    Polygenic risk
    gn-20

    "PRS combines additively with monogenic findings (e.g., FH + CAD PRS)."

    True when:
    Demonstrated in FH and HBOC cohorts.
    Not proven:
    —
    Actionability:
    Consider PRS modifiers when monogenic risk is known.
    Why this grade:
    B: replicated cohort evidence.
    ReferencesEBI / NHGRI ESC/EAS
  • F
    Polygenic risk
    gn-21

    "Two PRS for the same disease will give the same answer."

    True when:
    —
    Not proven:
    Different SNP sets, weights, and cohorts produce different scores.
    Actionability:
    Cite the specific PRS and its derivation cohort.
    Why this grade:
    F: contradicted by PGS Catalog comparisons.
    ReferencesEBI / NHGRI
  • F
    Polygenic risk
    gn-22

    "PRS should be used to deny insurance or employment."

    True when:
    —
    Not proven:
    Prohibited by GINA in many U.S. contexts; ethically problematic globally.
    Actionability:
    Counsel patients on legal protections and limits.
    Why this grade:
    F: GINA-protected discrimination.
    ReferencesEEOC / NHGRI
  • F
    Polygenic risk
    gn-23

    "PRS removes the need for lifestyle counseling."

    True when:
    —
    Not proven:
    High-PRS individuals often benefit MORE from lifestyle.
    Actionability:
    Pair PRS with behavior change support.
    Why this grade:
    F: contradicted by PRS-by-lifestyle interaction studies.
    ReferencesNature Genetics
  • D
    Polygenic risk
    gn-24

    "PRS for psychiatric conditions are ready for clinical decision-making."

    True when:
    Research signals exist.
    Not proven:
    Validated clinical pathways.
    Actionability:
    Do not use for prescribing or diagnosis.
    Why this grade:
    D: research-grade only.
    ReferencesEBI / NHGRI
  • A
    Polygenic risk
    gn-25

    "Clinicians should record which PRS version was used in the chart."

    True when:
    Reproducibility and audit standard.
    Not proven:
    —
    Actionability:
    Document PGS Catalog ID and date.
    Why this grade:
    A: reproducibility/quality standard.
    ReferencesEBI / NHGRI
  • A
    Genomics
    gn-26

    "ACMG/AMP defines five tiers: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign."

    True when:
    Standard nomenclature since 2015.
    Not proven:
    —
    Actionability:
    Use these tiers in every report.
    Why this grade:
    A: foundational standard.
    ReferencesACMG/AMP
  • A
    Genomics
    gn-27

    "A variant's classification can change over time as evidence accumulates."

    True when:
    ClinVar/ClinGen reanalysis routinely reclassifies variants.
    Not proven:
    —
    Actionability:
    Re-query VUS at least every 1–2 years.
    Why this grade:
    A: documented reclassification rates in ClinVar.
    ReferencesNCBI ClinGen
  • A
    Genomics
    gn-28

    "gnomAD allele frequencies are useful for assessing variant pathogenicity."

    True when:
    Population frequency is one ACMG/AMP criterion (BA1/BS1).
    Not proven:
    —
    Actionability:
    Cross-check candidate variants against gnomAD.
    Why this grade:
    A: ACMG/AMP-defined criterion.
    ReferencesBroad Institute ACMG/AMP
  • F
    Genomics
    gn-29

    "All labs report variants using the same naming conventions."

    True when:
    —
    Not proven:
    HGVS conventions exist but historical naming varies.
    Actionability:
    Confirm transcript and nomenclature when comparing reports.
    Why this grade:
    F: variability documented in ClinVar submissions.
    ReferencesNCBI NCBI
  • F
    Genomics
    gn-30

    "A negative panel result rules out genetic risk."

    True when:
    —
    Not proven:
    Coverage, panel scope, and unsequenced regions limit sensitivity.
    Actionability:
    Document panel content; consider broader testing if pretest probability remains high.
    Why this grade:
    F: limited by panel scope.
    ReferencesNCBI Bookshelf
  • A
    Genomics
    gn-31

    "Whole exome and whole genome sequencing find clinically actionable variants in a minority of patients."

    True when:
    Diagnostic yield ~25–40% in selected cohorts; secondary findings ~1–3%.
    Not proven:
    Universal benefit in unselected adults.
    Actionability:
    Reserve for indicated patients; counsel on yield.
    Why this grade:
    A: yield well characterized.
    ReferencesACMG NCBI Bookshelf
  • F
    Genomics
    gn-32

    "Carrier screening is the same as disease-risk prediction."

    True when:
    —
    Not proven:
    Carrier status informs reproductive risk, not personal disease for autosomal-recessive conditions.
    Actionability:
    Frame appropriately in counseling.
    Why this grade:
    F: ACMG carrier-screening definition.
    ReferencesACMG
  • F
    Genomics
    gn-33

    "Tumor sequencing and germline sequencing answer the same question."

    True when:
    —
    Not proven:
    Somatic vs inherited differ in implications.
    Actionability:
    Distinguish in reports and conversations.
    Why this grade:
    F: distinct biology.
  • F
    Genomics
    gn-34

    "Somatic cancer variants are always inherited."

    True when:
    —
    Not proven:
    Most are acquired.
    Actionability:
    Confirm with germline testing if indicated.
    Why this grade:
    F: contradicted by tumor biology.
  • A
    Genomics
    gn-35

    "Cascade testing can protect relatives when a pathogenic inherited variant is found."

    True when:
    Standard of care for many actionable conditions.
    Not proven:
    —
    Actionability:
    Discuss family communication and offer testing.
    Why this grade:
    A: standard of care.
    ReferencesCDC NCCN
  • A
    Genomics
    gn-36

    "HFE variants need interpretation with ferritin, transferrin saturation, symptoms, and family context."

    True when:
    Clinical iron-overload workup.
    Not proven:
    —
    Actionability:
    Test labs before action.
    Why this grade:
    A: AASLD guideline.
    Pair with labs:
    Ferritin, Transferrin sat, ALT
    ReferencesAASLD
  • F
    Genomics
    gn-37

    "Variant penetrance is the same regardless of family history."

    True when:
    —
    Not proven:
    Penetrance varies with modifiers, sex, and environment.
    Actionability:
    Integrate pedigree into risk estimates.
    Why this grade:
    F: contradicted by penetrance literature.
  • A
    Genomics
    gn-38

    "Mosaicism can complicate interpretation of germline tests."

    True when:
    Variant allele fractions <50% may indicate mosaicism.
    Not proven:
    —
    Actionability:
    Confirm with orthogonal sample/tissue when relevant.
    Why this grade:
    A: established laboratory standard.
  • F
    Genomics
    gn-39

    "Genetic test results expire after one year."

    True when:
    —
    Not proven:
    Variants do not change; classifications may.
    Actionability:
    Reanalyze periodically rather than retest.
    Why this grade:
    F: misunderstanding of reanalysis vs retesting.
    ReferencesNCBI
  • A
    Genomics
    gn-40

    "A genomic report is clinically useful only when it changes prevention, monitoring, prescribing, referral, or counseling."

    True when:
    Actionability is the core test.
    Not proven:
    —
    Actionability:
    Apply this filter to every finding.
    Why this grade:
    A: CDC actionability framework.
    ReferencesCDC ACMG
  • A
    Genomics
    gn-41

    "BRCA testing is appropriate for women with a strong family history of breast or ovarian cancer."

    True when:
    USPSTF B recommendation; NCCN criteria.
    Not proven:
    —
    Actionability:
    Apply NCCN criteria; refer for counseling.
    Why this grade:
    A: USPSTF + NCCN.
    Referral:
    Clinical genetics
    ReferencesUSPSTF NCCN
  • A
    Genomics
    gn-42

    "Men with BRCA pathogenic variants have elevated prostate, breast, and pancreatic cancer risk."

    True when:
    Documented across cohorts.
    Not proven:
    —
    Actionability:
    Offer male-specific surveillance per NCCN.
    Why this grade:
    A: NCCN includes male-specific recommendations.
    ReferencesNCCN
  • A
    Genomics
    gn-43

    "PALB2, CHEK2, ATM, and other moderate-penetrance genes change management."

    True when:
    Risk estimates and surveillance defined.
    Not proven:
    —
    Actionability:
    Use NCCN tables; tailor to specific gene.
    Why this grade:
    A: gene-specific NCCN guidance.
    ReferencesNCCN ClinGen
  • A
    Genomics
    gn-44

    "MMR-deficient tumors may respond to immune checkpoint inhibitors."

    True when:
    FDA approvals for MSI-H/dMMR tumors.
    Not proven:
    —
    Actionability:
    Test MMR/MSI status in eligible tumors.
    Why this grade:
    A: FDA tumor-agnostic approval.
    ReferencesNCCN FDA
  • F
    Genomics
    gn-45

    "Lynch syndrome is rare and not worth screening for."

    True when:
    —
    Not proven:
    Affects ~1 in 279 people; universal tumor screening recommended.
    Actionability:
    Screen all CRC and endometrial tumors per NCCN.
    Why this grade:
    F: contradicted by epidemiology and NCCN.
    ReferencesNCCN CDC
  • B
    Genomics
    gn-46

    "All breast cancer patients should receive germline testing."

    True when:
    ASCO and NCCN have moved toward broader testing.
    Not proven:
    Universal benefit on outcomes.
    Actionability:
    Discuss germline testing with all newly diagnosed breast cancer patients.
    Why this grade:
    B: evolving guideline support; universal benefit not yet established.
    ReferencesNCCN
  • A
    Genomics
    gn-47

    "Li-Fraumeni syndrome (TP53) requires lifelong intensive surveillance."

    True when:
    Toronto protocol/NCCN-defined surveillance.
    Not proven:
    —
    Actionability:
    Refer to specialty center; annual whole-body MRI.
    Why this grade:
    A: established surveillance protocol.
    ReferencesClinGen NCBI Bookshelf
  • A
    Genomics
    gn-48

    "FAP and MUTYH-associated polyposis warrant early colonoscopy and surgical planning."

    True when:
    NCCN and CDC Tier 1 frameworks.
    Not proven:
    —
    Actionability:
    Refer to high-risk GI program.
    Why this grade:
    A: NCCN guideline.
    ReferencesNCCN CDC
  • B
    Polygenic risk
    gn-49

    "Polygenic risk scores for breast cancer can refine risk in BRCA-negative high-risk families."

    True when:
    Validated PRS in calibrated populations.
    Not proven:
    Universal benefit; ancestry generalization.
    Actionability:
    Offer when validated PRS is available alongside family history.
    Why this grade:
    B: cohort validation; ancestry-limited.
    ReferencesEBI / NHGRI NCCN
  • A
    Genomics
    gn-50

    "VHL, MEN1, MEN2, and PTEN syndromes change endocrine surveillance."

    True when:
    Hereditary endocrine syndrome guidelines.
    Not proven:
    —
    Actionability:
    Refer to endocrine genetics; tailored surveillance.
    Why this grade:
    A: GeneReviews protocols.
    ReferencesNCBI Bookshelf ClinGen
  • F
    Genomics
    gn-51

    "Liquid biopsy ctDNA replaces germline testing."

    True when:
    —
    Not proven:
    ctDNA reflects tumor; germline testing requires constitutional DNA.
    Actionability:
    Use both when indicated; do not substitute.
    Why this grade:
    F: distinct sample types and questions.
  • A
    Genomics
    gn-52

    "BRCA results should be communicated to first-degree relatives when the patient consents."

    True when:
    Standard cascade-testing practice.
    Not proven:
    —
    Actionability:
    Provide family letter; coordinate with genetic counselor.
    Why this grade:
    A: NSGC + NCCN.
    ReferencesNSGC NCCN
  • A
    Genomics
    gn-53

    "Tumor-only sequencing can flag possible germline variants that need confirmation."

    True when:
    Documented in pan-cancer studies.
    Not proven:
    —
    Actionability:
    Confirm suspected germline findings with constitutional testing.
    Why this grade:
    A: standard practice.
    ReferencesClinGen NCCN
  • F
    Genomics
    gn-54

    "BRCA prevalence is uniform across populations."

    True when:
    —
    Not proven:
    Founder variants are more common in Ashkenazi Jewish, Icelandic, and other populations.
    Actionability:
    Adapt screening criteria to founder populations.
    Why this grade:
    F: contradicted by population genetics.
    ReferencesNCCN Broad Institute
  • A
    Genomics
    gn-55

    "Hereditary cancer testing benefits unaffected relatives only after the proband is tested."

    True when:
    Cascade testing principle.
    Not proven:
    —
    Actionability:
    Test the affected proband first whenever possible.
    Why this grade:
    A: clinical-genetics standard.
    ReferencesNCCN NSGC
  • A
    Genomics
    gn-56

    "PARP inhibitors are useful in BRCA-mutated cancers."

    True when:
    FDA approvals in ovarian, breast, prostate, pancreatic cancers.
    Not proven:
    —
    Actionability:
    Test for BRCA/HRD status in eligible patients.
    Why this grade:
    A: regulatory + RCT evidence.
    ReferencesFDA NCCN
  • F
    Genomics
    gn-57

    "All hereditary cancer panels test the same genes."

    True when:
    —
    Not proven:
    Panels vary widely in gene content.
    Actionability:
    Review panel content before ordering.
    Why this grade:
    F: documented variation in GTR.
    ReferencesNCBI
  • A
    Genomics
    gn-58

    "Risk-reducing salpingo-oophorectomy reduces ovarian cancer risk in BRCA carriers."

    True when:
    Consistent cohort evidence.
    Not proven:
    —
    Actionability:
    Discuss timing per NCCN.
    Why this grade:
    A: NCCN-supported risk-reduction.
    ReferencesNCCN
  • A
    Genomics
    gn-59

    "Universal tumor screening for Lynch syndrome is cost-effective."

    True when:
    Replicated in cost-effectiveness analyses.
    Not proven:
    —
    Actionability:
    Implement reflex MMR/MSI testing in CRC and endometrial cancers.
    Why this grade:
    A: CDC Tier 1 + cost-effectiveness data.
    ReferencesNCCN CDC
  • F
    Genomics
    gn-60

    "A negative BRCA result eliminates breast cancer risk."

    True when:
    —
    Not proven:
    Sporadic and polygenic risks remain.
    Actionability:
    Continue age-appropriate screening.
    Why this grade:
    F: contradicted by population breast-cancer baseline risk.
    ReferencesNCCN
  • A
    Labs
    gn-61

    "Lp(a) is largely genetically determined."

    True when:
    ~70–90% heritable.
    Not proven:
    —
    Actionability:
    Measure once in adults; communicate as inherited risk.
    Why this grade:
    A: AHA scientific statement.
    Pair with labs:
    Lp(a), ApoB
    ReferencesAHA
  • A
    Genomics
    gn-62

    "FH carriers benefit from earlier and more aggressive lipid lowering."

    True when:
    ESC/EAS and USPSTF support.
    Not proven:
    —
    Actionability:
    Initiate statin therapy early; consider PCSK9 inhibitors when needed.
    Why this grade:
    A: ESC/EAS consensus.
    ReferencesESC/EAS USPSTF
  • A
    Genomics
    gn-63

    "Cascade screening of relatives is cost-effective in FH."

    True when:
    Multiple cost-effectiveness analyses.
    Not proven:
    —
    Actionability:
    Offer cascade testing to first-degree relatives.
    Why this grade:
    A: CDC Tier 1.
    ReferencesESC/EAS CDC
  • C
    Polygenic risk
    gn-64

    "9p21 SNP alone reliably predicts CAD risk."

    True when:
    Single SNP modestly associated with CAD.
    Not proven:
    Single-SNP clinical decision-making.
    Actionability:
    Do not act on isolated 9p21; use validated PRS in context.
    Why this grade:
    C: limited single-SNP evidence.
    ReferencesEBI / NHGRI
  • A
    Genomics
    gn-65

    "TTR variants can cause hereditary amyloidosis with cardiac and neurologic phenotypes."

    True when:
    Established disease gene with FDA-approved therapies.
    Not proven:
    —
    Actionability:
    Refer for cardiology/neurology evaluation; consider testing in unexplained HFpEF.
    Why this grade:
    A: established disease gene.
    ReferencesNCBI Bookshelf FDA
  • A
    Genomics
    gn-66

    "Hypertrophic cardiomyopathy genetic testing changes family screening."

    True when:
    AHA/ACC and ESC guidelines.
    Not proven:
    Universal change in proband management from genotype alone.
    Actionability:
    Refer; cascade screen.
    Why this grade:
    A: cardiology guideline-supported.
    ReferencesNCBI Bookshelf ClinGen
  • A
    Genomics
    gn-67

    "Long QT and Brugada syndrome genetic testing informs prophylaxis."

    True when:
    Genotype-phenotype correlations exist (LQT1/2/3).
    Not proven:
    —
    Actionability:
    Refer to inherited arrhythmia clinic.
    Why this grade:
    A: established arrhythmia genetics.
    ReferencesNCBI Bookshelf
  • A
    Genomics
    gn-68

    "PCSK9 loss-of-function carriers have lower CAD risk."

    True when:
    Replicated in multiple cohorts.
    Not proven:
    —
    Actionability:
    Use as biological proof-of-concept for PCSK9 inhibition.
    Why this grade:
    A: replicated cohort evidence.
  • F
    Genomics
    gn-69

    "Type 2 diabetes is monogenic in most cases."

    True when:
    —
    Not proven:
    Most T2D is polygenic; MODY accounts for a small fraction.
    Actionability:
    Consider MODY testing in atypical presentations.
    Why this grade:
    F: contradicted by epidemiology.
    ReferencesNCBI Bookshelf
  • A
    Genomics
    gn-70

    "MODY testing can change diabetes management."

    True when:
    GCK-MODY and HNF1A-MODY have specific implications.
    Not proven:
    —
    Actionability:
    Test in young, lean, antibody-negative diabetes.
    Why this grade:
    A: genotype-driven management.
    ReferencesNCBI Bookshelf
  • A
    Labs
    gn-71

    "Coronary artery calcium adds independent prognostic information beyond PRS."

    True when:
    Replicated MESA and other cohorts.
    Not proven:
    —
    Actionability:
    Use complementary tools, not as substitutes.
    Why this grade:
    A: replicated cohort evidence.
    ReferencesAHA
  • F
    Nutrigenomics
    gn-72

    "ApoE ε4 carriers should avoid all dietary fat."

    True when:
    —
    Not proven:
    Evidence does not support blanket fat restriction by APOE genotype.
    Actionability:
    Use lipid trends and overall pattern, not genotype-only prescriptions.
    Why this grade:
    F: oversimplified extrapolation.
  • A
    Genomics
    gn-73

    "ApoE ε4 modestly increases late-onset Alzheimer's disease risk."

    True when:
    Replicated globally.
    Not proven:
    Deterministic prediction.
    Actionability:
    Counsel; emphasize modifiable risk factors.
    Why this grade:
    A: replicated risk allele.
    ReferencesClinGen NCBI Bookshelf NSGC
  • F
    Genomics
    gn-74

    "ApoE ε4 status should be disclosed without counseling."

    True when:
    —
    Not proven:
    Pre/post-test counseling improves understanding and reduces harm.
    Actionability:
    Offer counseling before disclosure.
    Why this grade:
    F: violates counseling standards.
    ReferencesNSGC EEOC / NHGRI
  • B
    Nutrigenomics
    gn-75

    "CETP, FADS, and APOC3 variants can modify lipid response to diet."

    True when:
    Documented gene–diet interactions.
    Not proven:
    Reliable individual-level dietary prescriptions.
    Actionability:
    Use as context, with lipid follow-up.
    Why this grade:
    B: replicated gene–diet interactions; clinical utility limited.
  • A
    Pharmacogenomics
    gn-76

    "CYP2C19 status changes clopidogrel choice after PCI."

    True when:
    Poor metabolizers have reduced clopidogrel activation.
    Not proven:
    —
    Actionability:
    Use prasugrel/ticagrelor in poor metabolizers per CPIC.
    Why this grade:
    A: CPIC Level A; FDA boxed warning.
    ReferencesCPIC FDA
  • A
    Pharmacogenomics
    gn-77

    "CYP2C19 variants affect SSRI dosing."

    True when:
    Citalopram/escitalopram exposure varies by phenotype.
    Not proven:
    —
    Actionability:
    Adjust dose or choose alternative per CPIC.
    Why this grade:
    A: CPIC guideline.
    ReferencesCPIC
  • A
    Pharmacogenomics
    gn-78

    "CYP2D6 ultra-rapid metabolizers face risk with codeine."

    True when:
    Documented infant deaths; FDA warning.
    Not proven:
    —
    Actionability:
    Avoid codeine in known UMs and breastfeeding.
    Why this grade:
    A: regulatory action.
    ReferencesCPIC FDA
  • C
    Pharmacogenomics
    gn-79

    "CYP2D6 status affects tamoxifen efficacy in all patients."

    True when:
    Endoxifen exposure varies.
    Not proven:
    Consistent outcomes signal across all studies.
    Actionability:
    Use clinical context; consider phenotype-guided dosing in selected cases.
    Why this grade:
    C: mixed clinical-outcome data.
    ReferencesStanford
  • A
    Pharmacogenomics
    gn-80

    "TPMT/NUDT15 testing prevents thiopurine toxicity."

    True when:
    CPIC Level A; documented life-threatening myelosuppression averted.
    Not proven:
    —
    Actionability:
    Test before initiating azathioprine/6-MP.
    Why this grade:
    A: CPIC Level A.
    ReferencesCPIC
  • A
    Pharmacogenomics
    gn-81

    "DPYD testing prevents fluoropyrimidine toxicity."

    True when:
    EMA and DPWG support pretreatment testing.
    Not proven:
    —
    Actionability:
    Test before 5-FU/capecitabine.
    Why this grade:
    A: regulatory and CPIC support.
    ReferencesCPIC KNMP
  • A
    Pharmacogenomics
    gn-82

    "CYP2C9/VKORC1 genotyping personalizes warfarin dosing."

    True when:
    Improves time-in-therapeutic-range vs clinical dosing.
    Not proven:
    Mortality benefit consistently shown.
    Actionability:
    Use when genotype is rapidly available.
    Why this grade:
    A: CPIC Level A; outcome data mixed.
    ReferencesCPIC
  • A
    Pharmacogenomics
    gn-83

    "SLCO1B1 status affects simvastatin myopathy risk."

    True when:
    Replicated risk allele *5.
    Not proven:
    —
    Actionability:
    Limit simvastatin dose or choose alternative.
    Why this grade:
    A: CPIC Level A.
    ReferencesCPIC
  • A
    Pharmacogenomics
    gn-84

    "UGT1A1 *28 genotype increases irinotecan toxicity."

    True when:
    FDA labeling.
    Not proven:
    —
    Actionability:
    Reduce dose in homozygotes.
    Why this grade:
    A: FDA + CPIC.
    ReferencesCPIC FDA
  • A
    Pharmacogenomics
    gn-85

    "G6PD deficiency increases hemolysis risk with oxidant drugs."

    True when:
    Well established for primaquine, rasburicase, dapsone.
    Not proven:
    —
    Actionability:
    Test before high-risk drugs.
    Why this grade:
    A: CPIC + FDA.
    ReferencesCPIC FDA
  • B
    Pharmacogenomics
    gn-86

    "Pharmacogenomic panels are useful for psychiatric prescribing."

    True when:
    Specific gene–drug pairs (CYP2C19/CYP2D6 + SSRIs/TCAs) supported.
    Not proven:
    Aggregate combinatorial PGx panels improving outcomes broadly.
    Actionability:
    Use CPIC pairs; do not over-interpret combinatorial scores.
    Why this grade:
    B: gene-pair evidence strong; combinatorial score evidence weaker.
    ReferencesCPIC CPIC Stanford
  • A
    Pharmacogenomics
    gn-87

    "PGx test results are valid for life and travel with the patient."

    True when:
    Germline genotype is stable.
    Not proven:
    Phenoconversion (drug interactions) does not occur.
    Actionability:
    Document phenotype in chart; reassess when interacting drugs change.
    Why this grade:
    A: germline stability + recognized phenoconversion.
    ReferencesCPIC
  • A
    Pharmacogenomics
    gn-88

    "Phenoconversion can shift a CYP2D6 normal metabolizer to a poor metabolizer phenotype."

    True when:
    Strong inhibitors (e.g., paroxetine, bupropion) recognized.
    Not proven:
    —
    Actionability:
    Reassess interactions whenever PGx-guided dosing is applied.
    Why this grade:
    A: documented in CPIC guidelines.
    ReferencesCPIC
  • C
    Pharmacogenomics
    gn-89

    "Methadone dosing is straightforward to predict by genotype."

    True when:
    —
    Not proven:
    Multiple genes contribute; clinical titration remains essential.
    Actionability:
    Do not dose methadone by genotype alone.
    Why this grade:
    C: limited and complex.
    ReferencesStanford
  • B
    Pharmacogenomics
    gn-90

    "PGx can reduce ADRs in polypharmacy patients."

    True when:
    Multiple cohort and pragmatic trials suggest benefit.
    Not proven:
    Universal mortality benefit.
    Actionability:
    Consider PGx panel in patients on ≥5 medications with PGx-relevant drugs.
    Why this grade:
    B: pragmatic-trial evidence with limitations.
    ReferencesCPIC KNMP
  • A
    Pharmacogenomics
    gn-91

    "CYP3A4/5 variants meaningfully change tacrolimus dosing."

    True when:
    CYP3A5 expressers need higher doses.
    Not proven:
    —
    Actionability:
    Use CPIC-guided initial dosing.
    Why this grade:
    A: CPIC Level A.
    ReferencesCPIC
  • F
    Pharmacogenomics
    gn-92

    "Codeine is a safe analgesic for all postpartum patients."

    True when:
    —
    Not proven:
    Ultra-rapid metabolizers can produce dangerous morphine concentrations in breastmilk.
    Actionability:
    Avoid codeine while breastfeeding when phenotype unknown.
    Why this grade:
    F: FDA contraindication.
    ReferencesCPIC FDA
  • A
    Pharmacogenomics
    gn-93

    "Allopurinol hypersensitivity is associated with HLA-B*58:01 in some populations."

    True when:
    Strong association in Han Chinese, Thai, Korean populations.
    Not proven:
    —
    Actionability:
    Test in high-prevalence populations before allopurinol.
    Why this grade:
    A: CPIC + ACR.
    ReferencesCPIC FDA
  • A
    Pharmacogenomics
    gn-94

    "Star-allele nomenclature is required to communicate PGx phenotypes accurately."

    True when:
    PharmVar standard.
    Not proven:
    —
    Actionability:
    Report star alleles, not raw SNPs.
    Why this grade:
    A: PharmVar standard.
    ReferencesStanford
  • F
    Pharmacogenomics
    gn-95

    "PGx applies only to oncology drugs."

    True when:
    —
    Not proven:
    Cardiology, psychiatry, transplant, infectious disease, and pain medicine all have CPIC guidelines.
    Actionability:
    Look across CPIC for relevant pairs.
    Why this grade:
    F: contradicted by FDA Table of PGx Biomarkers.
    ReferencesCPIC FDA
  • F
    Pharmacogenomics
    gn-96

    "SSRI failure is always due to the wrong gene."

    True when:
    —
    Not proven:
    Many causes; PGx is one input.
    Actionability:
    Use stepwise psychiatry with PGx as adjunct.
    Why this grade:
    F: oversimplified causality.
  • A
    Pharmacogenomics
    gn-97

    "PGx results should be visible in the EHR at the point of prescribing."

    True when:
    Implementation literature supports embedded CDS.
    Not proven:
    —
    Actionability:
    Build PGx CDS rules; document phenotype.
    Why this grade:
    A: implementation best practice.
    ReferencesCPIC
  • F
    Pharmacogenomics
    gn-98

    "PGx removes the need for therapeutic drug monitoring (TDM) when both are available."

    True when:
    —
    Not proven:
    TDM addresses adherence, interactions, and physiology PGx cannot.
    Actionability:
    Use both for narrow-therapeutic-index drugs.
    Why this grade:
    F: contradicted by clinical pharmacology principles.
  • C
    Pharmacogenomics
    gn-99

    "Combinatorial PGx scoring gives more predictive power than gene-by-gene rules."

    True when:
    Some signals reported.
    Not proven:
    Reproducible outcomes superiority over CPIC pairs.
    Actionability:
    Prefer CPIC pairs as the evidence base.
    Why this grade:
    C: limited evidence; methodological debate.
    ReferencesCPIC Stanford
  • F
    Pharmacogenomics
    gn-100

    "PGx is irrelevant if the patient takes only over-the-counter medicines."

    True when:
    —
    Not proven:
    OTC PPIs and NSAIDs interact with CYP2C19/CYP2C9.
    Actionability:
    Include OTC drugs in interaction review.
    Why this grade:
    F: contradicted by interaction data.
    ReferencesCPIC
  • A
    Epigenomics
    gn-101

    "Epigenetic changes can alter gene expression without changing DNA sequence."

    True when:
    Methylation, histone marks, ncRNA.
    Not proven:
    —
    Actionability:
    Frame epigenome as the modifiable expression layer.
    Why this grade:
    A: NHGRI fact sheet + CDC review.
    ReferencesNHGRI CDC
  • B
    Epigenomics
    gn-102

    "Lifestyle can influence the epigenome, but not all epigenetic markers are clinically actionable."

    True when:
    Methylation responds to behavior and environment.
    Not proven:
    Most panels lack validated clinical decisions.
    Actionability:
    Educate; avoid panel-driven prescriptions.
    Why this grade:
    B: convergent translational evidence; limited clinical utility.
    ReferencesCDC NHGRI
  • F
    Epigenomics
    gn-103

    "DNA methylation clocks prove that a protocol reverses aging."

    True when:
    —
    Not proven:
    Clock changes are not validated outcomes.
    Actionability:
    Do not market as 'age reversal'.
    Why this grade:
    F: surrogate is not outcome.
    Marketing red flags:
    age reversal proven by clock
    ReferencesGenome Biology Aging
  • B
    Epigenomics
    gn-104

    "Microbial metabolites may influence host epigenetic pathways."

    True when:
    SCFAs (HDAC), folate, B12, bile acids.
    Not proven:
    Specific protocol → specific epigenetic outcome in patients.
    Actionability:
    Support fiber and microbial diversity broadly.
    Why this grade:
    B: mechanistic + translational.
    ReferencesCDC
  • B
    Epigenomics
    gn-105

    "Stress physiology and sleep can influence gene-expression biology."

    True when:
    HPA axis and circadian effects on transcription.
    Not proven:
    —
    Actionability:
    Treat sleep and stress as biological inputs.
    Why this grade:
    B: convergent translational evidence.
    ReferencesNHGRI
  • A
    Epigenomics
    gn-106

    "Exercise alters molecular pathways related to gene expression and metabolic adaptation."

    True when:
    Robust transcriptomic and methylation evidence.
    Not proven:
    —
    Actionability:
    Prescribe activity as a foundational intervention.
    Why this grade:
    A: replicated multi-omics evidence.
    ReferencesNHGRI
  • B
    Epigenomics
    gn-107

    "Methylation-age clocks (Horvath, GrimAge) are research tools with growing prognostic signal."

    True when:
    Predict mortality and morbidity in cohorts.
    Not proven:
    Validated clinical decisions from individual scores.
    Actionability:
    Use only in research or with explicit caveats.
    Why this grade:
    B: cohort prognostic signal; clinical action limited.
    ReferencesGenome Biology Aging
  • A
    Epigenomics
    gn-108

    "Imprinting disorders (Prader–Willi, Angelman, Beckwith–Wiedemann) have clinical implications."

    True when:
    Established clinical syndromes.
    Not proven:
    —
    Actionability:
    Test for imprinting defects when phenotype suggests.
    Why this grade:
    A: GeneReviews.
    ReferencesNCBI Bookshelf
  • F
    Epigenomics
    gn-109

    "Histone modifications can be measured in routine clinical care."

    True when:
    —
    Not proven:
    No validated routine clinical assays.
    Actionability:
    Do not order; research only.
    Why this grade:
    F: no validated assays.
  • A
    Nutrigenomics
    gn-110

    "Folate and B12 status influence one-carbon metabolism relevant to methylation."

    True when:
    Established biochemistry.
    Not proven:
    Specific methyl-folate prescriptions improve outcomes for all.
    Actionability:
    Maintain adequate B-vitamin status; avoid mega-dosing without indication.
    Why this grade:
    A: biochemistry; B: clinical specifics.
    Pair with labs:
    B12, Folate, Homocysteine
  • B
    Epigenomics
    gn-111

    "Early-life adversity can leave detectable epigenetic signatures."

    True when:
    Replicated in cohort studies.
    Not proven:
    Individual diagnostic claims.
    Actionability:
    Use trauma-informed care; do not 'test' for adversity.
    Why this grade:
    B: cohort evidence.
  • A
    Epigenomics
    gn-112

    "Smoking leaves a durable methylation signature (e.g., AHRR)."

    True when:
    Replicated globally.
    Not proven:
    —
    Actionability:
    Counsel on cessation; durable risk reduction over time.
    Why this grade:
    A: replicated across cohorts.
    ReferencesNHGRI
  • B
    Epigenomics
    gn-113

    "Maternal nutrition can influence offspring epigenetic patterns."

    True when:
    Dutch Hunger Winter and replication studies.
    Not proven:
    —
    Actionability:
    Support periconceptional nutrition.
    Why this grade:
    B: cohort evidence with mechanistic plausibility.
  • F
    Epigenomics
    gn-114

    "All commercially marketed 'biological age' tests are clinically validated."

    True when:
    —
    Not proven:
    Validation varies; many are not clinically actionable.
    Actionability:
    Treat as research; disclose limits.
    Why this grade:
    F: validation gap.
    Marketing red flags:
    biological age = decision-grade test
    ReferencesGenome Biology Aging
  • C
    Epigenomics
    gn-115

    "Methylation at specific CpGs reliably predicts cancer recurrence in routine practice."

    True when:
    Specific assays exist (e.g., glioma methylation classifier).
    Not proven:
    Universal applicability.
    Actionability:
    Use only validated, regulator-cleared assays.
    Why this grade:
    C: validated only in defined contexts.
  • A
    Epigenomics
    gn-116

    "Circadian disruption has measurable molecular and metabolic effects."

    True when:
    Multi-omics and physiology evidence.
    Not proven:
    —
    Actionability:
    Counsel on sleep and shift work.
    Why this grade:
    A: replicated multi-omics evidence.
    ReferencesNHGRI
  • B
    Epigenomics
    gn-117

    "Pollution exposure has epigenetic correlates relevant to health."

    True when:
    Replicated in cohorts; effects differ by exposure.
    Not proven:
    Individual-level diagnostics.
    Actionability:
    Address modifiable exposures (PM2.5, smoking, BPA, etc.).
    Why this grade:
    B: cohort evidence.
  • A
    Epigenomics
    gn-118

    "Epigenetic drugs already exist for selected oncology indications."

    True when:
    DNMT and HDAC inhibitors are FDA-approved.
    Not proven:
    —
    Actionability:
    Refer; specialist use only.
    Why this grade:
    A: FDA approvals.
    ReferencesFDA
  • B
    Epigenomics
    gn-119

    "Microbiome composition can shape host immune gene expression."

    True when:
    Strong mechanistic and translational data.
    Not proven:
    Individual prescriptions from microbiome → epigenome.
    Actionability:
    Use diet-first strategies.
    Why this grade:
    B: mechanistic strength.
    References360bio
  • F
    Epigenomics
    gn-120

    "Epigenome-wide association studies (EWAS) prove causation."

    True when:
    —
    Not proven:
    EWAS show association; causality requires additional methods.
    Actionability:
    Avoid causal claims from EWAS alone.
    Why this grade:
    F: confuses association with causation.
  • B
    Nutrigenomics
    gn-121

    "Genes influence diet response; labs and outcomes still matter."

    True when:
    LCT, ALDH2, FADS, etc. show real effects.
    Not proven:
    —
    Actionability:
    Combine with phenotype and labs.
    Why this grade:
    B: replicated gene–diet interactions.
  • F
    Nutrigenomics
    gn-122

    "Nutrigenomics can personalize every diet with high precision."

    True when:
    —
    Not proven:
    Effect sizes are usually small; outcomes still drive plans.
    Actionability:
    Use as context, not prescription.
    Why this grade:
    F: oversells small effect sizes.
    Marketing red flags:
    DNA-based perfect diet
  • B
    Nutrigenomics
    gn-123

    "LCT variants may help explain lactose tolerance, but symptoms and dietary response still matter."

    True when:
    Genotype–phenotype correlation in many populations.
    Not proven:
    —
    Actionability:
    Confirm with diet trial.
    Why this grade:
    B: validated genotype-phenotype.
  • B
    Nutrigenomics
    gn-124

    "ALDH2 variants change alcohol-risk counseling."

    True when:
    Increased flushing and cancer-risk implications.
    Not proven:
    —
    Actionability:
    Counsel reduction/avoidance.
    Why this grade:
    B: replicated cancer associations.
  • F
    Nutrigenomics
    gn-125

    "FUT2 status alone determines gut health."

    True when:
    —
    Not proven:
    Modest microbiome and B12 associations; not deterministic.
    Actionability:
    Do not over-claim.
    Why this grade:
    F: oversimplified.
  • F
    Nutrigenomics
    gn-126

    "Detox-gene panels can diagnose toxin overload."

    True when:
    —
    Not proven:
    No validated diagnostic claim.
    Actionability:
    Avoid; use exposure history and clinical labs.
    Why this grade:
    F: no validated assay.
    Marketing red flags:
    detox SNP panel
  • B
    Nutrigenomics
    gn-127

    "Caffeine response is partly mediated by CYP1A2 genotype."

    True when:
    Replicated CYP1A2 effects on caffeine metabolism.
    Not proven:
    Reliable individual prescriptions for cardiovascular outcomes.
    Actionability:
    Use cautiously; outcome-driven.
    Why this grade:
    B: pharmacokinetic evidence stronger than outcome data.
  • C
    Polygenic risk
    gn-128

    "TCF7L2 variants are useful for routine diabetes screening decisions."

    True when:
    Effect size modest.
    Not proven:
    Reliable individual decisions.
    Actionability:
    Use clinical risk tools first.
    Why this grade:
    C: small effect, no individual decision rule.
  • F
    Nutrigenomics
    gn-129

    "Vitamin D receptor (VDR) genotype dictates optimal vitamin D dose."

    True when:
    —
    Not proven:
    Dose by 25-OH vitamin D, not by VDR SNP.
    Actionability:
    Test serum 25-OH vitamin D; ignore SNP-based dosing.
    Why this grade:
    F: contradicted by endocrine guidelines.
    Pair with labs:
    25-OH Vit D
  • B
    Nutrigenomics
    gn-130

    "Omega-3 response is partially modified by FADS genotype."

    True when:
    Replicated FADS-fatty acid interactions.
    Not proven:
    —
    Actionability:
    Consider as one input; pair with omega index.
    Why this grade:
    B: replicated interaction.
    Pair with labs:
    Omega-3 index
  • F
    Nutrigenomics
    gn-131

    "MTHFR-only testing without homocysteine measurement is sufficient for clinical decisions."

    True when:
    —
    Not proven:
    MTHFR status without homocysteine and B-vitamin status is not actionable.
    Actionability:
    Order homocysteine, B12, folate first.
    Why this grade:
    F: ACMG explicitly recommends against MTHFR-only decisions.
    Pair with labs:
    Homocysteine, B12, Folate
    ReferencesACMG
  • F
    Nutrigenomics
    gn-132

    "GST/COMT/CYP variants justify selling personalized 'detox' supplements."

    True when:
    —
    Not proven:
    Insufficient outcome evidence; commercial conflict of interest.
    Actionability:
    Decline; address modifiable exposures.
    Why this grade:
    F: marketing claim.
    Marketing red flags:
    personalized detox supplements
  • B
    Nutrigenomics
    gn-133

    "Body-composition response to exercise has a genetic component."

    True when:
    Heritability of training response replicated.
    Not proven:
    Individual prescriptions from genotype alone.
    Actionability:
    Adapt training based on response, not genotype.
    Why this grade:
    B: heritable but not individually predictive.
  • A
    Nutrigenomics
    gn-134

    "Caffeine, salt, and alcohol responses are best individualized by clinical response — with genotype as context."

    True when:
    Convergent clinical and genetic data.
    Not proven:
    —
    Actionability:
    Default to outcome; use genotype as context.
    Why this grade:
    A: convergent practice.
  • F
    Nutrigenomics
    gn-135

    "Ketogenic diets are universally appropriate based on APOE/PPAR genotype."

    True when:
    —
    Not proven:
    No genotype reliably indicates universal keto benefit.
    Actionability:
    Use clinical context, lipids, and goals.
    Why this grade:
    F: oversimplified.
  • F
    CRISPR
    gn-136

    "CRISPR can be used as a wellness optimization tool."

    True when:
    —
    Not proven:
    —
    Actionability:
    Never. Specialist therapies only.
    Why this grade:
    F: not approved; ethically and legally prohibited outside trials/indications.
    Marketing red flags:
    DIY CRISPR · wellness gene editing
    ReferencesFDA FDA
  • A
    CRISPR
    gn-137

    "Approved CRISPR/gene-editing therapies are specialist treatments for specific serious diseases."

    True when:
    Approved CRISPR/Cas9 therapy for sickle cell and transfusion-dependent beta-thalassemia.
    Not proven:
    —
    Actionability:
    Refer eligible patients to certified treatment centers.
    Why this grade:
    A: FDA approval + ASH guidance.
    Referral:
    Hematology / specialist gene therapy center
    ReferencesFDA American Society of Hematology
  • F
    Gene therapy
    gn-138

    "Gene therapy removes the need for long-term safety monitoring."

    True when:
    —
    Not proven:
    Long-term surveillance is part of every approved program.
    Actionability:
    Maintain follow-up per protocol.
    Why this grade:
    F: contradicted by FDA post-market requirements.
    ReferencesFDA
  • A
    Gene therapy
    gn-139

    "Gene-targeted therapy should be considered only within approved indications or regulated trials."

    True when:
    Regulatory and ethical standard.
    Not proven:
    —
    Actionability:
    Refer; do not improvise.
    Why this grade:
    A: regulatory standard.
    ReferencesFDA
  • A
    Gene therapy
    gn-140

    "Voretigene neparvovec (Luxturna) treats biallelic RPE65-mediated inherited retinal dystrophy."

    True when:
    FDA-approved indication.
    Not proven:
    —
    Actionability:
    Refer to ocular gene therapy center.
    Why this grade:
    A: FDA approval.
    ReferencesFDA
  • A
    Gene therapy
    gn-141

    "Onasemnogene abeparvovec (Zolgensma) treats SMA in eligible infants."

    True when:
    FDA approval; clinical efficacy.
    Not proven:
    —
    Actionability:
    Refer to SMA specialty center.
    Why this grade:
    A: FDA approval.
    ReferencesFDA
  • A
    Gene therapy
    gn-142

    "Etranacogene dezaparvovec (Hemgenix) is approved for hemophilia B."

    True when:
    FDA approval.
    Not proven:
    —
    Actionability:
    Refer to hematology center.
    Why this grade:
    A: FDA approval.
    ReferencesFDA
  • A
    CRISPR
    gn-143

    "Casgevy (exa-cel) requires myeloablative conditioning and specialist care."

    True when:
    FDA-labeled treatment process.
    Not proven:
    —
    Actionability:
    Counsel on full treatment burden and risks.
    Why this grade:
    A: regulatory + clinical standard.
    ReferencesFDA American Society of Hematology
  • A
    CRISPR
    gn-144

    "Germline editing in humans is currently outside accepted clinical practice."

    True when:
    International scientific and regulatory consensus.
    Not proven:
    —
    Actionability:
    Do not offer; do not endorse.
    Why this grade:
    A: international consensus.
    ReferencesFDA
  • F
    CRISPR
    gn-145

    "Gene-edited cell therapies are interchangeable with standard cell therapies."

    True when:
    —
    Not proven:
    Distinct manufacturing, monitoring, and regulatory pathways.
    Actionability:
    Use product-specific pathways.
    Why this grade:
    F: distinct pathways.
  • A
    CRISPR
    gn-146

    "Off-target editing is a known risk of CRISPR therapeutics that requires ongoing surveillance."

    True when:
    Recognized in FDA review.
    Not proven:
    —
    Actionability:
    Counsel; follow registry/PV programs.
    Why this grade:
    A: FDA-recognized.
    ReferencesFDA
  • F
    Gene therapy
    gn-147

    "AAV-based gene therapies are universally safe regardless of pre-existing immunity."

    True when:
    —
    Not proven:
    Pre-existing AAV immunity can preclude or complicate dosing.
    Actionability:
    Screen for AAV antibodies as required by product labeling.
    Why this grade:
    F: contradicted by labeling.
    ReferencesFDA FDA
  • A
    Gene therapy
    gn-148

    "Gene therapy outcomes can include hard endpoints like transfusion independence."

    True when:
    Documented in TDT/SCD pivotal trials.
    Not proven:
    —
    Actionability:
    Use hard endpoints in counseling.
    Why this grade:
    A: pivotal-trial endpoints.
    ReferencesFDA American Society of Hematology
  • A
    Gene therapy
    gn-149

    "Patients should be counseled on long-term registry participation when receiving gene therapy."

    True when:
    Standard regulatory expectation.
    Not proven:
    —
    Actionability:
    Document registry enrollment.
    Why this grade:
    A: regulatory expectation.
    ReferencesFDA
  • A
    Genomics
    gn-150

    "Ethical, legal, and social implications (ELSI) should be discussed before any genomic test."

    True when:
    NSGC and ACMG counseling standards.
    Not proven:
    —
    Actionability:
    Pre-test counseling and consent for all clinical genomic testing.
    Why this grade:
    A: counseling standard.
    ReferencesNSGC EEOC / NHGRI FTC ACMG
  • F
    Genomics
    gn-151

    "Functional medicine should ignore ACMG/ClinGen/CPIC guidance."

    True when:
    —
    Not proven:
    —
    Actionability:
    Integrate authoritative guidance into holistic care.
    Why this grade:
    F: violates standard of care.
    ReferencesACMG ClinGen CPIC
  • A
    Genomics
    gn-152

    "Holistic genomics combines genetic risk with environment, labs, family history, and patient values."

    True when:
    Best-practice integration.
    Not proven:
    —
    Actionability:
    Make this the default care model.
    Why this grade:
    A: integrative best practice.
    ReferencesCDC NSGC
  • F
    Genomics
    gn-153

    "GINA fully protects U.S. patients from all genetic discrimination."

    True when:
    —
    Not proven:
    GINA does not cover life, disability, or long-term-care insurance.
    Actionability:
    Counsel patients accurately on legal protections.
    Why this grade:
    F: contradicted by GINA scope.
    ReferencesEEOC / NHGRI
  • A
    Genomics
    gn-154

    "Clinicians should document the source, version, and date of any genomic interpretation used in care."

    True when:
    Reproducibility standard.
    Not proven:
    —
    Actionability:
    Cite ClinVar/ClinGen/CPIC versions in chart.
    Why this grade:
    A: reproducibility standard.
    ReferencesNCBI ClinGen CPIC
  • F
    Genomics
    gn-155

    "Direct-to-consumer ancestry testing is the same as clinical genetic testing."

    True when:
    —
    Not proven:
    Different analytical validity, coverage, and regulatory oversight.
    Actionability:
    Confirm DTC findings clinically before action.
    Why this grade:
    F: regulatory and analytical distinction.
    ReferencesFTC NCBI
  • B
    Genomics
    gn-156

    "Counseling reduces patient anxiety after positive genomic findings."

    True when:
    Cohort and trial evidence.
    Not proven:
    —
    Actionability:
    Offer pre/post-test counseling.
    Why this grade:
    B: replicated counseling-outcome data.
    ReferencesNSGC
  • F
    Genomics
    gn-157

    "All genomic findings warrant equal communication intensity."

    True when:
    —
    Not proven:
    Tiered disclosure aligns intensity with actionability.
    Actionability:
    Prioritize Tier-1 actionable findings; contextualize others.
    Why this grade:
    F: tiered communication is the standard.
    ReferencesCDC ACMG
  • A
    Genomics
    gn-158

    "Genomic information for minors should follow age-appropriate disclosure and assent."

    True when:
    ACMG/AAP statements on pediatric testing.
    Not proven:
    —
    Actionability:
    Defer adult-onset testing where appropriate; ensure assent.
    Why this grade:
    A: pediatric ethics standard.
    ReferencesACMG NSGC
  • A
    Genomics
    gn-159

    "Re-analysis of historical exome data finds new diagnoses over time."

    True when:
    Replicated reanalysis yields ~5–15% new diagnoses.
    Not proven:
    —
    Actionability:
    Re-engage labs every 1–2 years for unsolved cases.
    Why this grade:
    A: replicated reanalysis literature.
    ReferencesNCBI ClinGen
  • A
    Genomics
    gn-160

    "A genomic finding is the floor, not the ceiling, of personalized care."

    True when:
    Integrative model: genome + epigenome + microbiome + peptides + autonomic + labs.
    Not proven:
    —
    Actionability:
    Use the five-pillar framework as the default care model.
    Why this grade:
    A: integrative course thesis.
    ReferencesCDC NHGRI CPIC