Pillar 5

Genomics & Epigenomics

Inherited risk, gene expression, pharmacogenomics, nutrigenomics, polygenic risk, family history, epigenetic modulation, and gene-targeted therapies — interpreted with caution, counseling, and clinical actionability.

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This pillar distinguishes actionable genomics (CDC Tier 1 conditions like HBOC, Lynch, FH; pharmacogenomics; rare disease diagnosis; carrier/reproductive screening; selected polygenic-risk contexts) from speculative wellness genomics. Direct-to-consumer raw data is not a clinical diagnosis. A VUS is not a disease. CRISPR is not a wellness intervention.

Core concepts

DNA, genes, variants, alleles, SNPs, CNVs, indels
Germline vs somatic variants
Monogenic vs polygenic vs multifactorial
Penetrance & expressivity
Gene–environment interaction
Gene–microbiome interaction
Gene–drug interaction (PGx)
Gene–nutrient interaction
Gene–autonomic / inflammatory interaction
Pathogenic / Likely pathogenic / VUS / Likely benign / Benign
Why a VUS is not a diagnosis
Why DTC raw data needs clinical confirmation
Why family history still matters
Why genomics is not destiny

Conceptual flow

Inherited genome
  ↓
Variant risk architecture
  ↓
Epigenome + transcriptome
+ proteome + metabolome
  ↓
Microbiome / inflammation /
peptides / autonomic tone /
environment
  ↓
Clinical phenotype
  ↓
Labs, symptoms, imaging,
family history, outcomes
  ↓
Prevention · monitoring ·
treatment · referral ·
gene-targeted therapy