Whole Genome Sequencing for Pharmacogenetics: A Complete Guide

Whole genome sequencing gives you a VCF file: a near-complete readout of your DNA, sequenced base by base. What it does not give you is a guideline-based report on how those genes affect your medications. That is what Gene2Rx adds. Upload your VCF and Gene2Rx turns it into a pharmacogenetics report covering 110 medications, built on the same CPIC and FDA guidelines clinicians use. It runs in minutes, costs $5 for a starter report or $49 for the full report, plus a $15 surcharge for WGS and VCF uploads because they take more processing, so a full WGS report is $64. It needs no doctor's order and never expires, because your DNA does not change. WGS providers include Nebula, Dante Labs, Sequencing.com, Nucleus, Veritas, and clinical labs. You already paid to have your genome sequenced; this unlocks the part of it that affects prescriptions.

A genotyping chip tests a pre-specified set of positions, typically 500,000 to 1 million SNPs out of 3 billion bases. Whole genome sequencing reads every base, so your VCF can contain rare loss-of-function variants in genes like DPYD, TPMT, CYP2C19, and CYP2D6 that a chip was never designed to detect. That is where WGS data has a real edge for pharmacogenetics: fewer blind spots on the genes that drive the most consequential prescribing decisions. One limit to keep in mind, covered below, is that a VCF still does not capture every kind of variant.

Gene2Rx reads your VCF, calls your metabolizer phenotype for each pharmacogene (poor, intermediate, normal, rapid, or ultrarapid), and maps each phenotype to specific recommendations for 110 medications, with every recommendation traceable to its CPIC or FDA guideline. The report spans psychiatry (antidepressants, antipsychotics, ADHD medications), cardiology (clopidogrel, warfarin, statins, metoprolol), pain (codeine, tramadol), chemotherapy (capecitabine, fluorouracil), transplant, and gastrointestinal drugs. It is delivered in minutes, with no new sample and no prescriber required.

Most consumer WGS providers (Nebula, Dante Labs, Sequencing.com, Nucleus, Veritas) deliver a VCF file, sometimes alongside ancestry, trait, or general health reports. What they generally do not deliver is a comprehensive, CPIC-anchored pharmacogenetics report across your medication list. The raw sequence is there; the per-medication interpretation is the missing piece, and that is exactly what Gene2Rx generates from the file you already have.

WGS closes most of the gaps a genotyping chip leaves, but it is not magic. Gene2Rx works from the variant calls in your VCF, so it does not detect copy-number changes such as CYP2D6 gene duplications or deletions, which need raw alignment files rather than a finished VCF. Those particular CYP2D6 star alleles are not part of the report. For the large majority of pharmacogenetic decisions this does not matter, but if a CYP2D6 duplication or deletion is clinically pivotal for you, that specific question may still call for a clinical-grade test that targets copy number directly.

A clinical pharmacogenetic panel tests a fixed set of genes, so if new guidelines emerge for a gene off that panel you need a new test. WGS does not work that way. Because your VCF already contains every position in your genome, any pharmacogenetic analysis, current or future, can be re-run against the same file. As CPIC and FDA guidance is updated, you can regenerate a fresh report from the same VCF with no new lab work. Your pharmacogenetic profile does not change, so a single VCF is a reference you will use for decades.

These are the main genes Gene2Rx reads out of your WGS VCF and what each one affects. The biology is the same no matter which data source you start from; what WGS provides is the most complete raw readout at these positions.

Your WGS VCF contains the genotypes for all of these genes; the only thing standing between that and actionable guidance is interpretation. Gene2Rx translates your genotypes into metabolizer phenotypes for each gene, then maps those phenotypes to specific medication recommendations anchored to CPIC^[8] and FDA^[9] guidelines, so the output reads the same way a clinical pharmacogenetic report would. Because WGS observes more of the underlying variation directly rather than inferring it, confidence in each phenotype assignment is typically higher than for genotyping-based reports.

If you already have WGS data, there is little reason to wait: the data exists and the starter report is $5 plus the $15 WGS surcharge. It is most valuable if you are starting or already taking a medication with pharmacogenetic guidelines, if you have had side effects or poor response in the past, or if you simply want the information on file for future prescribing. Because your genotype never changes, one report serves you for life, and you can re-run the same VCF as guidelines evolve.

• 23andMe Pharmacogenetics: How to Get a Drug Response Report From Your Existing Data
• AncestryDNA for Drug Testing: Get Pharmacogenetics From Your Ancestry Data
• MyHeritage Pharmacogenetics: Use Your MyHeritage DNA for a Drug Response Report
• Nebula Genomics Pharmacogenetics: How to Get a Drug Response Report From Your WGS Data
• Nebula Genomics Drug Response: What You'll Actually See in a Report From Your WGS Data
• Dante Labs Pharmacogenetics: Turn Your Dante WGS Data Into a PGx Report

Buying WGS only for pharmacogenetics is usually not the cheapest path; a genotyping chip's raw data (23andMe, AncestryDNA) is typically enough for the common variants. But if you already have WGS data for ancestry, health, or research, pharmacogenetic analysis is a high-value add-on. Upload it to Gene2Rx for $5 (starter) or $49 (full), plus the $15 WGS surcharge.

Most consumer WGS providers (Nebula, Dante Labs, Sequencing.com, Nucleus, Veritas) provide a VCF on request, often through your member portal. 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, and Gene2Rx accepts those files too. WGS has an edge for rare variants that chips do not probe. It also future-proofs you: new PGx variants added to guidelines later are already present in your VCF, so you can re-run the same file. Note that Gene2Rx does not call CYP2D6 copy-number changes (gene duplications or deletions) from any file, because that needs raw alignment data we do not process.

Gene2Rx supports VCFs aligned to GRCh37 and GRCh38, and the pipeline auto-detects the build from the header or infers it from variant positions. You do not need to lift over the file before uploading.