Pharmacogenomic Testing 101: DNA Testing Essentials You Ought to Know

Anne-Marie Hays

Last Updated: August 17th, 2022

Imagine this:

You go to the doctor for help with depression.

She prescribes you an antidepressant.

Weeks pass and you can't tell if it is making a difference.

You get a four-week follow-up appointment and your medication dose gets adjusted or your prescriber gives you a different medicine, and you get to wait several more weeks to see if it's working. In the meantime, you have to put up with side effects like headaches, blurred vision, nausea, bad breath, bathroom troubles, and trouble sleeping — all for a medication that you don't know is even going to help you.

If this sounds familiar, you are not alone. Millions of Americans are living with depression. We don't yet fully understand what causes depression. Due to that, treating depression isn't easy and it's certainly not quick.

Over 12 percent of Americans take antidepressants — for 30 percent of them, meds don't work. When a person is prescribed a medication to treat depression, it is a process of trial and error. About half of patients with moderate to severe depression do not respond to their first medicine. You don't always get it right on the first try. 

For people looking for relief, this can be a huge problem. They are left feeling hopeless and alone. Life would be so much easier if your clinician could get it right on the first try. 

What if you could just take a simple test to figure out what medications would work best?

Fortunately, there an up-and-coming medical answer on the horizon — the field of pharmacogenomic testing. 

If you haven't used this type of test yet, it's likely that you will in the near future. In this article, we will be explaining pharmacogenomic (PGx) testing, its potential benefits and limitations, as well as different routes for accessing it.

pills of all shapes and sizes

What is pharmacogenomic testing?

Pharmacogenomic (PGx) testing combines two fields of study: pharmacology and genomics, to provide people with the medications and medication doses that they are best suited for, based on their genome found using DNA testing.

This emerging field of genetic testing offers many benefits to patients with more than just depression. PGx testing can provide helpful insights for all types of medications, whether treatment has already been started or not: 

  • If you are already taking medication, a PGx test can help you better understand why you are having side effects.
  • If you haven't started taking medication yet, a PGx test can help inform your doctor which medications would be most beneficial to you, with the lowest risk for negative side effects.

Before we dive further into the topic, let's clear up a few key terms that are often used in connection with this topic.

Pharmacogenomics, pharmacogenetics, and more key terms

Many different related terms are often used to refer to PGx. Some are synonymous, others are adjacent, and still others occupy a confusing in-between space where they sometimes mean the same thing, but not always. To better understand the topic, we are going to define a few useful key terms. These definitions come from the National Institute of General Medical Sciences Glossary

  • Genetic code — "The instructions in a gene that tell the cell how to make a specific protein."
  • Pharmacodynamics (PD) — "The study of how drugs act at target sites, called receptors, on organs and tissues in the body."
  • Pharmacogenetics (PG or PGt)— "The study of how people's genes affect their bodies’ responses to medicines, often one gene at a time."
  • Pharmacogenomics (PGx) — "The study of how people's genes affect their bodies’ responses to medicines, often encompassing the entire genome." 
  • Pharmacokinetics (PK) — "The study of the level of a drug and its breakdown products in the blood over time."
  • Precision medicine — "An emerging approach for disease prevention and treatment that takes into account individual differences in lifestyle, environment, and biology."
  • Side effect — "The effect of a drug, other than the desired effect, sometimes in an organ other than the target organ."

Note: The term pharmacogenetics is often used interchangeably with PGx; however, Pharmacogenomics Knowledgebase (PharmGKB) explains, "In general, pharmacogenetics usually refers to how variation in one single gene influences the response to a single drug. Pharmacogenomics is a broader term, which studies how all of the genes (the genome) can influence responses to drugs." In this article, we will be using them synonymously. 

Why is PGx testing important?

As we mentioned, PGx DNA testing has the potential to help more than just people with depression. It can help people who take all sorts of prescription drugs because drugs don't work the same for everyone who takes them. A UK drug executive made waves in the early 2000s by estimating that 90 percent of prescription medications work for less than half of people. This is where the study of pharmacogenomics has the potential to changes lives — by reducing trial and error treatment and helping to develop more specialized medicines. 

Benefit #1: Moving away from trial-and-error

The main goal of pharmacogenomic testing is to contribute to the field of tailored, personalized treatment. Known as precision medicine, this field aims to "target the right treatments to the right patients at the right time, "according to the FDA. Issam Zineh, Director of the Office of Clinical Pharmacology (OCP), explains, "Personalized medicine aims to streamline clinical decision making by using biological information available through a genetic test or biomarker, and then saying, 'based on this profile, I think you're more likely to respond to Drug A or Drug B, or less likely to have an adverse reaction with Drug C.' The idea is to get patients on the right medication and to get them on it sooner."

PGx information can help make sure that people are prescribed a medication that will help treat their symptoms as soon as possible. Genetic information can also help to avoid many adverse drug reactions (which bring more than 1 million people a year to the ER), and provide better dosing guidelines, to help patients avoid side effects. Starting a proper treatment plan earlier and steering clear of negative side effects and severe drug reactions will help to improve patient health. It will also help to save time and money, let alone stress and pain. 

Benefit #2: Developing better drugs

Studying the relationship between genetic variations and medication can help to revolutionize the pharmaceutical industry. Where before, the goal was to make drugs that worked for the largest about of people, with the fewest negative side effects, this data can help to identify subsets of people that will do better or worse on a prospective medication. This means that new drugs can be developed that work better for individual groups. So, in addition to bettering our understanding of existing medications, PGx study can aid the creation and marketing of more effective, tailored drugs. 

How do genes affect medication responses?

It's easier to understand how each person's DNA can make our medication experiences different if we need to have a basic knowledge of a drug's journey through our bodies, and the factors that affect this journey, both internal and external. 

In this section, we are going to explain how your genes can change drug responses from two perspectives: pharmacokinetics ( a drug's movement/pathway through the body) and pharmacodynamics (how drugs interact with their target sites in the body). 

A drug's journey through your body

Once a medicine enters your body, its life is broken up into four steps:

1. Absorption — This stage starts when a drug enters your body and lasts until it's in your bloodstream. Drugs enter the body in several different ways, but to explain this stage, we are going to explain using the most common example: orally. Once you swallow a pill, it gets absorbed in the tissues of your GI tract. From there, it travels through a special blood vessel to your liver. 

2. Distribution — From your liver, the drug disperses into tissues and intercellular fluids, where it can bind to receptors. Drug molecules can disconnect from receptors and enter the bloodstream. In this stage, you can feel the side effects of your meds when, during its flow through your bloodstream, organs other than the intended destination are affected by it. 

3. Metabolism — Once the medication has been distributed throughout the body and reached its target, its time to go. The drug molecules traveling through the bloodstream can undergo changes in a process called metabolism. This happens in your liver and other tissues. 

4. Excretion — Once your liver enzymes break down the medication, it is inactive. It gets excreted from your body in the normal course of waste elimination.

Your genes can interfere with the way that a drug is supposed to interact at each stage of the process. For example, if your genes block a drug from being absorbed, it can't move on to distribution, and you may need to try another medication or a different administration method. 

Most issues related to drug processing happen during step 3 — metabolism. If your genes make you code more enzymes than the average person, you will metabolize certain medications much more quickly. In this circumstance, you may do better on a different dosage or a different drug that is metabolized by different liver enzymes. 

Helpful resources: 

Pharmacogenomics of Drug Metabolizing Enzymes and Transporters: Relevance to Precision Medicine

Check out this helpful youtube video from Ted-Ed: How does your body process medicine?

How does PGx testing work?

A PGx test looks for genetic variations that would cause you to process a medication than the average person. DNA testing focuses either on a panel of medications related to diseases, targeted medication panel, or known variants and their influence. It's really just down to how the genetic testing company organizes the information.

PGx testing angles: targeting genes, drugs, and diseases

More than 400 FDA-approved medications include pharmacogenomic drug labelling information. In general, this information includes different actions to take based on biomarkers. It's a newer practice, but doctors have begun to use PGx testing in a few circumstances.

To get a better idea of the role that your genes play in your body's reaction to medications, let's examine some examples. Here are three different examples of drug-gene relationships, with three different angles:

  1. Gene function — starting from what we know about gene function, applying it to different medications that treat multiple diseases
  2. Medication function — starting from a disease-specific medication and finding out what genes and genetic variants that affect its ability to function optimally
  3. Disease-targeted needs — starting from a disease for which you need to be treated, and testing for genes known to affect disease-targeted meds, to find which meds will work best

Cytochrome P450 and known variants: Targeting insightful genes

Variations in the Cytochrome P450 (CYP450) family of genes are a great example of how genes affect medication response. The CYP450 family contains genes responsible for coding enzymes that affect drug metabolism — how quickly your body processes drugs. In fact, 70 to 80 percent of the enzymes that affect drug metabolism rates are cytochrome P450 enzymes.

Included in the cytochrome P450 enzyme family is CYP2D6, a gene related to the processing of many antipsychotic and antidepressant meds, among others. This gene is known to affect up to 25 percent of commonly prescribed medicines, including the following:

  • Antidepressants — Amitriptyline (Elavil), Clomipramine (Anafranil), Desipramine (Norpramin, Pertofrane), Doxepin (Sinequan), Fluoxetine (Prozac, Sarafem), Fluvoxamine (Luvox), Imipramine (Tofranil), Maprotiline (Ludiomil), Nortriptyline (Pamelor), Paroxetine (Paxil, Pexeva), Trimipramine (Surmontil), Venlafaxine (Effexor)
  • Antipsychotics — Aripiprazole (Abilify), Haloperidol (Haldol), Olanzapine (Zyprexa), Perphenazine (Trilafon), Risperidone (Risperdal), Thioridazine (Mellaril)
  • Pain meds — Codeine, hydrocodone, oxycodone, tramadol

Depending on your genetic variants, you can be classified as one of the following:

  • Poor metabolizer — You break down related medications slowly. Doctors can use this information to give you different doses.
  • Intermediate metabolizer — Your enzymes are working, but not as well as normal metabolizers.
  • Normal metabolizer — Your CYP2D6 enzymes are coded as normal. Standard prescribing and dosing recommendations should work best for you.
  • Ultra-rapid metabolizer — Based on your genetic variants, your CYP2D6 enzymes are very active, which causes you to break down related medications really quickly. You may need increased dosages or drugs unrelated to this gene for best results.
  • Indeterminate — The test wasn't able to predict your enzyme activity, so standard drug selection and dosing are recommended.

Read more: Mayo Clinic — Cytochrome P450 (CYP450) tests

Abacavir (Ziagen): Targeting genes based on a specific drug

Abacavir, brand name Ziagen, is an antiretroviral medication for HIV patients. In clinical trials, some patients developed a hypersensitivity reaction, with symptoms like headache, fever, rash, nausea, and more. When people stop taking the drug, symptoms go away. However, if they start taking it again, a "rapid, severe, and even life-threatening recurrence" can occur.

Now, before people are prescribed this medication, the FDA's drug label recommends they be screened for a genetic variation called HLA-B*5701. If tested positive, genetic screening helps you avoid the toxic and possibly life-threatening reaction.

Heart disease: Testing for multiple variants that affect the treatment of one disease

Cardiovascular disease (CVD) is the leading cause of death in the United States. The term actually refers to several heart conditions that affect your heart's ability to function properly. One example, coronary artery disease, happens when blockages decrease blood flow to your heart muscle, so it doesn't get the oxygen it needs.

When you have heart problems, in addition to lifestyle recommendations, your doctor will likely prescribe medications to help treat your symptoms. Examples include the following:

  • Angiotensin-converting enzyme (ACE) inhibitors, like benazepril (Lotensin), ramipril (Altace), and captopril, are prescribed to help help with high blood pressure by widening your blood vessels
  • Anticoagulants, like enoxaparin (Lovenox), heparin, and warfarin (Coumadin), are prescribed to help prevent heart attack, stroke, and other issues. They prevent blood clots from forming, so that a blockage doesn't shut off blood flow to your heart.
  • Beta-blockers, like metoprolol (Lopressor), labetalol (Trandate), and propranolol (Inderal), are often prescribed to help prevent heart attacks. They work by blocking chemicals that stimulate your heart, so it can beat more slowly.

These are just a few of the different categories of drugs that are used to manage heart disease and its symptoms. Because they target different things, it's common for doctors to prescribe multiple medications for people that have CVD. Pharmacogenomic testing has the potential to help improve the way that your cardiovascular disease is treated. People react in different ways to CVD treatments. Your genes can give us clues to the way that your drugs are absorbed, distributed in your body and how quickly they are metabolized.

Currently, CVD drugs with clinically actionable genomics-based FDA label recommendations are Warfarin and Clopidogrel. Warfarin dose adjustments are based on variants of CYP2C9 and VKORC1 and Clopidogrel recommendations are based on CYP2C19.

Read more: Opportunities and Challenges in Cardiovascular Pharmacogenomics

Where can you get PGx testing?: Access routes, examples, and recommendations

You can access PGx testing from your doctor or by ordering online. Tests that study relationships between genes and drugs have lots of names, including the following:

  • Pharmacogenomic (PGx) test
  • Pharmacogenetic (PG or PGt) test
  • Genetic pharmacology test
  • Medication response test
  • Drug response test
  • Personalized medication test

Either way, PGx test results are meant to be shared with your doctor, to help get the best medication or dosage for you.

Clinical PGx testing

If you are interested in learning about medications that work best for your or your dependents, and you have a current clinical reason, your first step should be your doctor. Your doctor can order clinical PGx testing at an accredited lab, if indeed it is recommended for your circumstance. In general, blood samples are used for these in-lab tests, although cheek swab samples are also used. When you take a clinically prescribed test, a big benefit is that insurance might cover the cost, depending on your coverage.

One example of clinical PGx testing is provided by Cincinnati Children's Hospital's Genetic Pharmacology Service. The hospital offers tests panels focused a couple different things:

  • The Psychiatry Pharmacogenetics Expanded Panel looks for genetic variations that are related to over 20 common psychiatric medications.
  • The Opioid CYP2D6 Pharmacogenetics Panel looks for genetic clues to how your body processes common opioids (codeine, tramadol, hydrocodone, and oxycodone).

In addition to these panels, there is another that looks for warfarin predisposition in CYP2C9 and VKORC1, as well as targeted genotyping for specific genes, including CYP2C19, CYP2C9, CYP2D6, CYP2D6 / CYP2C19, TPMT.

Physician-prescribed or referred PGx testing

On the other hand, many genetic testing companies work with physicians to provide low-cost (lower-than-clinical cost) DNA testing services for health purposes, including genetic health risks, carrier screening, and pharmacogenomics. In these cases, your doctor can prescribe a test, which you order online, based on your doctor's referral. Sometimes, a doctor will partner with a DNA testing company to offer in-office purchases for a DNA kit that a patient does on their own at home.

Availability depends on your doctor.

At-home and direct-to-consumer (DTC) PGx testing

If you want to take charge and proactively learn about your predisposition for certain medication responses, it's becoming more and more common to be able to order these tests online, provide a sample at home, mail it back to the lab, and receive your results online, which can be shared with your doctor. However, there are four different general groups of at-home tests and analysis that you should be aware of. Each has its own hoops to jump through, as well as test limitations, based on regulatory approval, lab location and accreditation, physician-involvement, and more.

Though the individual platforms and sellers of at-home DNA kits for PGx testing vary, at-home tests do not produce clinical results. They also often take longer than in-lab bloodwork or saliva sample tests, because of shipping and wait times typical for consumer DNA testing. Additionally, even when shared with your doctor, you may be required to take follow-up clinical testing to verify the test results. That's why it's best to ask your doctor first.

PGx testing via DTC online ordering

While the FDA has approved one company, 23andMe to provide DTC PGx testing, this service is not currently available, unless prescribed by a physician. Despite this, on Hong Kong-based genetics company offers an easy-to-order DTC test:

#1 CircleDNA

The Circle Premium DNA Test ($629) includes lots of health information and lifetime access to the platform. It also includes drug response information about 103 FDA-approved medications. The test includes two 30-minute phone consultations with Circle's trained staff to help you understand and benefit from the results, but doesn't require a physician to sign off on your order before it is approved.

PGx testing via online ordering (with independent or on-staff physician order approval)

#1 Color Genomics

Color offers medication response analysis with the Color Standard service (only available through employer programs or from healthcare providers, as well as in the Color Extended test ($249). Color tests can be ordered by your own physician or, when you place an online order, it is reviewed by an independent physician. Included in the cost of testing is a one-on-one genetic counseling session to help understand your options. The test includes 14 genes associated with common meds: CYP2C19, CYP2D6, CYP1A2, CYP2C9, CYP3A4, CYP3A5, CYP4F2, DPYD, F5, IFNL3, NUDTI15, SLCO1B1, TPMT, and VKORC1.


ONEOME offers a RightMed ($349), co-developed with Mayo Clinic. Itests for specific variants in 27 genes. This test isn't a DTC test because physician ordering is included. A 30-minute genetic consultation is included to help understand your results. Pay with a credit card, HSA card, or PayPal

This test offers gene-based results. It doesn't include information regarding specific drugs. This means that you do need to rely on follow-up to better understand your results and what they mean.

#3 Helix

Helix offers the Mayo Clinic GeneGuide test ($149), which among much other health information, including carrier status and disease risk, also includes four medication response reports, with information about Ibuprofen and Omeprazole. Includes physician ordering and genetic counseling. Not available for people in New York.

PGx testing via online ordering (requires physician approval to activate)

#1 GnomeDX

Rather than physician review at the time of order, with this DNA testing company, anyone can go to the website to order a DNA kit. From there, you need to go to the doctor who prescribes your test: CardiacDX, PsychDX, PainDX, or Complete DX.

  • CardiacDX ($250) covers inherited heart disease risk assessment as well as genes that relate to 40+ medications
  • PsychDX ($250) is recommended for people that have already been diagnosed with depression, anxiety, ADHD, bipolar disorder, epilepsy, and similar conditions. It covers 12 genes related to 92 mental health drugs
  • PainDX ($250) tests for genetic variations in seven genes that affect your reaction to more than 34 medications
  • CompleteDX ($250) doesn't include any disease risk assessment (CardiacDX), but it does cover genes related to 150 medications of various types — heart, pscyh, diabetes, pain, GI, and more

PGx information from analysis platforms

Some testing companies focus on providing an online platform focused on providing health information (including drug response details) first, and genetic testing second. Here are a couple of examples:

#1 Pharmazam

The Pharmazam PGx test ($499), which provides information on all prescription drugs (more than 130,000) and most over the counter meds. This isn't a DTC test. You can request the test online, but a Pharmazam doctor places your order. Additionally, your results are reviewed by medical staff before you get them.

For this test, you need to download the app and update your personal health information. In addition to genetic information, the app also reports interactions with other drugs, illnesses, allergies, foods, and lifestyle.

#2 SelfDecode

Whether you order a SelfDecode DNA test or you upload your raw DNA from another source, you can get access to more than 70 categories of health reporting, including pharmacogenomics. This DNA analysis platform requires an annual subscription ($59) or lifetime membership ($199).

6 Key PGx Takeaways

Now that we have covered the PGx basics and explained how to get a test, if you are interested, there are a few key points to share with you before you take a DNA test. Here are four key points that you should know before you take a PGx test. 

1. PGx is relatively new and interpretation of test results are evolving

Professor Peter Gregersen, MD, from the Institute of Molecular Medicine at the Feinstein Institutes for Medical Research shares this advice, "The data on pharmacogenetics is still in a relatively early stage of interpretation, although some can be useful." The issue for most consumers is understanding what actually constitutes useful information. 

Research is ongoing and, just as we don't yet understand all of the genetic components that relate to disease, we don't yet understand all the ways that your genes (and the proteins they encode) will affect or derail a medication's prescribed course through your body. 

If you are looking for a current reason why your medications aren't effective, your first stop should always be your physician or prescriber. They can let you know whether a PGx test would be helpful in your circumstances. 

2. PGx is just one part of the puzzle

It is important to know that your genetic variants are just one of many things that affect how your body responds to drugs. The Merck Manual on drug response shares the following factors: 

  • Genetic makeup
  • Age
  • Body size
  • Use of other drugs and dietary supplements (such as medicinal herbs)
  • Consumption of food (including beverages)
  • Presence of diseases (such as kidney or liver disease)
  • Storage of the drug (whether the drug was stored too long or in the wrong environment)
  • Development of tolerance and resistance

It's important to understand that PGx test results can provide helpful information, but there is much more at play than your genes. Those results aren't actionable until all of the other factors are taken into account. One company, PHARMAZAM, is trying to help people partially overcome this hurdle. Its platform lets you input your personal health and lifestyle information, including diseases and all of the drugs you are taking. From there, you can take a DNA test to add the genetic drug-response factors (that we know of) to the equation. 

3. PGx testing isn't yet routine

In 2015, President Obama gave precision medicine a shout out in the State of the Union address, announcing the new Precision Medicine Initiative. The group's mission statement is as follows:

"To enable a new era of medicine through research, technology, and policies that empower patients, researchers, and providers to work together toward development of individualized care."

Drug response DNA testing isn't currently a standardized clinically accepted practice, but it's expected to be a normal practice by 2023. While PGx tests are not yet a part of routine medical care, "Nevertheless, they are likely to be quite useful in certain cases," advises Gregersen, "so it is not a bad idea to have this information available to you."

The future goal is to have DNA info on file so that when you need a medicine, your doctor can guide your treatment, without needing to order additional testing and wait for results. However, we are nowhere near this point. Unfortunately, you may run into issues when requesting this type of test from your doctor. Survey results show that only 28 percent of genetic counselors feel comfortable ordering PGx tests. Worse than that, the survey also shows that only 13 percent of physicians report feeling comfortable doing it.

If doctors and genetic counselors aren't comfortable ordering a PGx test, how will they be with helping to interpret and provide actionable advice? "There is no harm in getting this info and having it available for your physician or pharmacist to interpret," says Gregersen. "But beware, not all physicians and pharmacists are knowledgeable about this, and there is still lack of agreement on interpretations and their utility, which is why these tests are not routinely part of medical care yet."

4. PGx test limitations, both general and test-specific

There are many limitations to the field and practice of PGx testing, including big and small issues. According to the Mayo Clinic, current PGx testing limitations include the following:

"One single pharmacogenomic test cannot be used to determine how you will respond to all medications. You may need more than one pharmacogenomic test if you are taking more than one medication.

Pharmacogenomic tests are not available for all medications. Because pharmacogenomic tests are available only for certain medications, your health care provider determines if you need to have a pharmacogenomic test prior to beginning a specific treatment.

There are currently no pharmacogenomic tests for aspirin and many over-the-counter pain relievers."

In addition to these industry-wide limitations, each PGx test itself has its own limitations. For example, the ONEOME test includes this disclaimer: "The test does not detect all known and unknown variations in the gene(s) tested, nor does absence of a detectable variant (designated as *1 for genes encoding drug metabolizing enzymes) rule out the presence of other, non-detected variants." — and that's not even the whole disclaimer. It goes on and on.

When you join an online health decoding platform or buy a DNA test, even those that include physician approval as part of the ordering process, are sure to state that test results are for educational purposes only, are subject to interpretation, and are not a substitute for medical advice. 

Additionally, each test is different. You need to make sure that genes relevant to your current situation are being studied. The extensiveness of a test depends on the number of known variants it is looking for, as well as the type of technology that is being utilized to look for them. For example, a simple microarray test will hunt for and record known variants, while a test that uses sequencing will record the whole gene in question, to show not only the most common variants, but even uncommon ones.  

Finally, with at-home DNA testing, Dr. Gregeresen advises, "Again, anything that you act on should be confirmed in a clinical approval lab."

5. PGx test results don't tell you which medication(s) are best for you

When you take a PGx test, you won't just get a result that says 'Drug A is always the drug one for you.' It's actually kind of the opposite. Results will explain how your genes affect your body's processing of drugs related to that gene. With interpretation, you can see drugs that may not be effective for you, drugs that you may need higher or lower doses of, or even those that you try to avoid for your own safety. 

It doesn't work the other way around. 

6. PGx test results don't make you a doctor

Pharmacology is complex. Taking a PGx test will provide you with detailed information, but it doesn't make you all-knowing. Don't change your medications or doses, or stop taking current medications without talking to a doctor. This is one of the biggest concerns when it comes to DTC-marketed PGx tests.

While drug-gene relationships can be helpful, you need to understand that your prescriber takes into account environmental interactions, your size and weight, and other possible drug interactions that affect a medication's efficacy and its side effects. Theirs is an educated, objective, integrative approach.

If you stop taking your medication or change your dosage on your own, without a green light from your prescriber, you put your own health at risk, in more ways than you may understand.

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