Can I use my ancestry genetic test results to get a Pillcheck report?

Consumer ancestry tests are a great introduction to genetics for many people. They can estimate where your ancestors came from, how much Neanderthal DNA you carry or whether you are likely to have blue eyes. They are affordable, entertaining and have changed the way many of us think about our DNA. Many people who have taken one wonder whether the same data could also tell them how they respond to medications. The short answer is: not reliably. This article explains why.

What do ancestry genetic tests look at?

Every genetic test looks for DNA variants, small differences that explain why some people have curly hair, dislike cilantro or break down certain medications faster. Which variants a test reads depends on its purpose. Ancestry tests aim to give a broad picture of your background, so they read hundreds of thousands of common variants spread across the whole genome. Variants that are rare, or that matter mainly for how you respond to medications, may not be included at all.

Many ancestry companies let customers download their raw genetic data, and third-party websites offer to interpret it for health conditions or medication response. These interpretations use data that was not designed or checked for medical use.

How is genotyping different from sequencing?

Two main technologies are used for genetic testing:

• Genotyping checks pre-selected variants at specific locations in your DNA. It is fast and affordable, and most ancestry tests use it. A genotyping test can only find the variants it was designed to look for.
• Sequencing reads each letter of a gene or of the whole genome. It is better at finding rare variants and is often used in medical testing, for example for hereditary cancer genes such as BRCA1 and BRCA2. The cost of sequencing a whole genome has fallen dramatically over the past two decades.

Both technologies can be used for medical testing, but what matters is which variants are covered and whether the test has been validated in a clinical laboratory.

Why isn't raw ancestry data reliable for medication decisions?

• False results. A clinical laboratory reviewed 49 samples from people whose raw consumer data showed a health-related variant and who were referred for confirmation testing. In 40% of the variants checked, the clinical test did not confirm the result. Some variants labelled "increased risk" by third-party interpretation services were actually common and harmless.
• Missing variants. Drug-response genes often have many important variants, listed by the Association for Molecular Pathology as a minimum set (Tier 1) and an extended set (Tier 2) for clinical testing, and some of them are common only in certain populations. A chip designed for ancestry may miss them, leading to a "normal" result for someone who is actually a poor or ultrarapid metabolizer. Read more about how ethnicity affects drug response.
• Gene deletions and extra copies. Some of the most important changes in drug-response genes are not single-letter variants. CYP2D6, which helps break down about 20% of commonly used medications, can be deleted entirely or present in extra copies. Experts from the Association for Molecular Pathology, the College of American Pathologists and the Dutch Pharmacogenetics Working Group recommend that clinical CYP2D6 tests detect these changes, but tests designed for ancestry are not built to do so.
• No interpretation for your medications. Raw data is a list of letters, not a medication plan. Turning it into recommendations requires up-to-date guidelines and a review of everything you take.

What does a clinical pharmacogenetic test include?

A clinical pharmacogenetic test focuses on genes that affect how medications are absorbed, activated, broken down and act in the body, with many more variants checked in each gene. To promote consistent testing, expert groups publish recommended minimum sets of variants that clinical laboratories should include for key genes such as CYP2D6, CYP2C19 and CYP2C9. Results are reported using standard terms such as poor, intermediate, normal, rapid and ultrarapid metabolizer, and are linked to dosing guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and drug labels.

Even among clinical tests, the genes and variants covered and the evidence used to make recommendations differ, which is one reason why different genetic tests can give different advice.

What about the privacy of my genetic data?

Genetic data is personal and permanent, so privacy matters with any genetic test. Some consumer genetics companies use customers' data for research, including research with pharmaceutical companies, when customers consent. Before taking any genetic test, read how your sample and data will be stored, used and shared, and whether you can ask for them to be deleted.

With Pillcheck, your DNA sample is destroyed within 30 days after the test is completed, and your data is never sold to third parties.

How can a Pillcheck test help?

Pillcheck uses its own dedicated laboratory test, focused on the genes that affect drug response, rather than raw data from ancestry tests. It includes rare and ancestry-specific variants that are sometimes missed by other tests, and a greater number of tested variants means more medications can be included in your report.

With Pillcheck, a pharmacist reviews your results together with all of your current medications, accounts for drug-drug-gene interactions and prepares recommendations that you can share with your doctor. Doctors are often more comfortable acting on results from a clinical laboratory that come with a pharmacist's interpretation. Read more about getting a pharmacogenetic test in Canada.

Pillcheck testing is performed in CAP- and COLA-accredited clinical genetic laboratories located in Canada. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. The Pillcheck test panel ensures high accuracy for people of non-European and admixed ancestries. Your results last a lifetime, and report updates are free of charge.

Summary

• Ancestry tests read many common variants across the genome, but are not designed or validated for medication decisions.
• Raw consumer data can contain false results and can miss rare variants, gene deletions and extra copies that change how you respond to medications.
• Clinical pharmacogenetic tests check more variants in each drug-response gene and link results to dosing guidelines.
• Pillcheck uses its own dedicated test, reviewed by a pharmacist together with all of your medications.

Frequently asked questions

Can I upload my ancestry raw data to get a Pillcheck report?

No. Ancestry data does not include all of the variants Pillcheck reports, so Pillcheck uses its own dedicated laboratory test.

My ancestry test says I'm a poor metabolizer. Should I change my medication?

Not on your own. Results from raw consumer data should be confirmed with a clinical test, and any change in medication should be made with your doctor or pharmacist.

Is whole-genome sequencing better than a pharmacogenetic panel?

Sequencing reads more of your DNA, but some important drug-response changes, such as CYP2D6 extra copies, can be difficult to detect with standard sequencing, and the results still need expert interpretation. A focused, validated pharmacogenetic test is designed for medication decisions.

References

Tandy-Connor S, Guiltinan J, Krempely K, et al. False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care. Genet Med. 2018;20(12):1515-1521.

Pratt VM, Cavallari LH, Del Tredici AL, et al. Recommendations for clinical CYP2D6 genotyping allele selection: a joint consensus recommendation of the Association for Molecular Pathology, College of American Pathologists, Dutch Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association, and the European Society for Pharmacogenomics and Personalized Therapy. J Mol Diagn. 2021;23(9):1047-1064.

Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013;138(1):103-141.

Caudle KE, Dunnenberger HM, Freimuth RR, et al. Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC). Genet Med. 2017;19(2):215-223.