Whole genome sequencing (WGS) reads nearly every base in your DNA, making it the most thorough genetic test available to consumers. For pharmacogenetics, that completeness matters: many clinically important variants — especially in genes like CYP2D6, DPYD, and HLA — are difficult or impossible to call accurately from genotyping chips. If you have WGS data from Nebula, Dante Labs, Sequencing.com, Nucleus Genomics, Veritas, DNA Complete, or a clinical provider, the variants that determine your drug response are already in your VCF. You just need a service that knows how to extract them.
A pharmacogenetic report is informational and does not replace clinical judgment. Never change, stop, or start medications based on genetic results alone. Always consult your prescribing provider.
A genotyping chip tests a pre-specified set of positions — typically 500,000 to 1 million SNPs out of 3 billion bases. Any pharmacogenetic variant not on the chip is invisible. Whole genome sequencing reads every position, so rare star alleles in CYP2D6, CYP2C19, and DPYD that would be missed on a chip are directly observable in a WGS dataset.
CYP2D6 is notorious for copy number variation, hybrid alleles, and high-homology pseudogenes. HLA-B has thousands of allele variants. These genes are difficult for genotyping platforms to call accurately. WGS resolves them more reliably, which is particularly relevant for opioid metabolism (CYP2D6) and allergy/hypersensitivity risk (HLA-B*57:01, HLA-B*15:02).
A clinical pharmacogenetic panel tests a fixed set of genes. If new guidelines emerge for a gene not on that panel, you need a new test. With WGS, any pharmacogenetic analysis — current or future — can be re-run against the same VCF. The data ages well.
Running your existing WGS data through a pharmacogenetic analysis does not require new lab work. Once the sequencing is paid for, each downstream interpretation (pharmacogenetics, ancestry, trait predictions, health risk) is cheap. WGS owners often underestimate how much value they can unlock from a file they already have.
A WGS-based pharmacogenetic report covers the full set of clinically actionable pharmacogenes.
Involved in the metabolism of approximately 25% of prescribed drugs including many antidepressants, opioids, atomoxetine, tamoxifen, and beta-blockers. WGS helps resolve copy number and hybrid alleles that genotyping arrays struggle with.
Affects SSRIs, clopidogrel (Plavix), and proton pump inhibitors. WGS captures rare loss-of-function and gain-of-function alleles beyond the common *2 and *17.
Together drive warfarin dosing and also influence NSAID and phenytoin metabolism.
Critical for fluoropyrimidine chemotherapy safety (fluorouracil, capecitabine). Several clinically important DPYD variants are rare enough that they are under-represented on genotyping arrays — WGS captures them more reliably.
Determine safe dosing for thiopurine drugs (azathioprine, mercaptopurine, thioguanine). Poor metabolizers risk severe bone marrow suppression.
Affects irinotecan toxicity and atazanavir-related hyperbilirubinemia. The relevant TA repeat polymorphism is directly readable from WGS.
HLA-B*57:01 for abacavir, HLA-B*15:02 for carbamazepine, HLA-B*58:01 for allopurinol — all known risk alleles for severe drug reactions. WGS is particularly well-suited to HLA typing.
Statin-associated muscle pain risk, especially with simvastatin.
Every gene above yields a metabolizer phenotype (poor, intermediate, normal, rapid, or ultrarapid) when analyzed. A WGS-based pharmacogenetic report then maps each phenotype to specific drug-level recommendations from CPIC and FDA guidelines. Because more of the underlying variation is directly observed rather than inferred, the confidence in each assignment is typically higher than for genotyping-based reports.
Anyone with WGS data should run it through a pharmacogenetic analysis at least once. The incremental cost is low, your DNA does not change, and having the information on file before a prescribing decision is valuable. It is especially useful before starting antidepressants, anticoagulants, chemotherapy, or any medication with a known PGx guideline.
Learn how genetics may affect your response to these related medications:
Buying WGS only for pharmacogenetics is usually not the cheapest path — a dedicated PGx test or a genotyping chip's raw data is typically enough. But if you are already doing WGS for ancestry, health, or research, pharmacogenetic analysis is a high-value add-on at low incremental cost.
Most consumer WGS providers (Nebula, Dante Labs, Sequencing.com, Nucleus Genomics, DNA Complete, Veritas) provide a VCF file on request. Clinical sequencing providers may require explicit opt-in to receive the raw data. Check your account or customer support to confirm.
For common pharmacogenetic variants, high-quality genotyping data (23andMe, AncestryDNA, MyHeritage) is very accurate. WGS has an edge for rare variants, for complex genes like CYP2D6 and HLA, and for future-proofing — new PGx variants added to guidelines later are already present in your WGS file.
Gene2Rx supports VCFs aligned to GRCh37 (hg19) and GRCh38 (hg38). The file should be bgzipped and indexed where possible. Check upload documentation for the current list of accepted formats.
Find out how your DNA may influence your response to Sertraline and other medications with a Gene2Rx pharmacogenetics report.
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