Pharmacogenomics & Personalized Medicine

Definitions, scope & terminology

• Pharmacogenetics — the study of the genetic basis for variation in drug response, historically implying large effects of a small number of DNA variants — a single genetic marker predicting drug response.
• Pharmacogenomics — studies larger numbers of variants across an individual or population to explain genetic influences on drug response; recognises that >1 variant contributes. The terms are often used interchangeably (FDA: pharmacogenomics = variation in DNA & RNA related to drug response; pharmacogenetics = DNA sequence related to drug response).
• Precision / personalized medicine — uses an individual's molecular, genomic, clinical, behavioural & environmental data to guide drug & dose selection — the right drug at the right dose at the right time; pharmacogenomics is the operational basis of personalized medicine.
• Core tasks of the field — discover which variants have functional consequences, validate them, and apply them to patient care and to drug discovery.
• Key terms — polymorphism = sequence variant in ≥1% of population (vs mutation <1%); SNP/SNV = single base substitution (commonest); CNV = large deletion/duplication; haplotype = alleles inherited together on one chromosome; diplotype = the maternal+paternal allele pair (e.g. *1/*17); linkage disequilibrium = non-random, population-specific co-inheritance of alleles.