Pharmacogenomics is the study of how genes affect a person’s response to drugs. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that will be tailored to a person’s genetic makeup.

Many drugs that are currently available are “one size fits all,” but they don't work the same way for everyone. It can be difficult to predict who will benefit from a medication, who will not respond at all, and who will experience negative side effects (called adverse drug reactions). Adverse drug reactions are a significant cause of hospitalizations and deaths in the United States. With the knowledge gained from the Human Genome Project, researchers are learning how inherited differences in genes affect the body’s response to medications. These genetic differences will be used to predict whether a medication will be effective for a particular person and to help prevent adverse drug reactions. Conditions that affect a person’s response to certain drugs include clopidogrel resistance, warfarin sensitivity, warfarin resistance, malignant hyperthermia, Stevens-Johnson syndrome/toxic epidermal necrolysis, and thiopurine S-methyltransferase deficiency.

The field of pharmacogenomics is still in its infancy. Its use is currently quite limited, but new approaches are under study in clinical trials. In the future, pharmacogenomics will allow the development of tailored drugs to treat a wide range of health problems, including cardiovascular disease, Alzheimer disease, cancer, HIV/AIDS, and asthma.

​​​What is pharmacogenomics?

Pharmacogenomics (sometimes called pharmacogenetics) is a field of research that studies how a person’s genes affect how he or she responds to medications. Its long-term goal is to help doctors select the drugs and doses best suited for each person. It is part of the field of precision medicine, which aims to treat each patient individually.

What role do genes play in how medicines work?

Just as our genes determine our hair and eye color, they partly affect how our bodies respond to medicine.

Genes are instructions, written in DNA, for building protein molecules. Different people can have different versions of the same gene. Each version has a slightly different DNA sequence. Some of these variants are common, and some are rare. And some affect health, such as those gene variants linked to certain diseases.

Scientists know that certain proteins affect how drugs work. Pharmacogenomics looks at variations in genes for these proteins. Such proteins include liver enzymes that chemically change drugs. Sometimes chemical changes can make the drugs more—or less—active in the body. Even small differences in the genes for these liver enzymes can have a big impact on a drug’s safety or effectiveness.

One liver enzyme, known as CYP2D6, acts on a quarter of all prescription drugs. For example, it converts the painkiller codeine into its active form, morphine. There are more than 160 versions of the CYP2D6 gene. Many vary by only a single difference in their DNA sequence. Others have larger changes. Most of these variants don’t affect how people respond to the drug.

Typically, people have two copies of each gene. However, some people have hundreds or even thousands of copies of the CYP2D6 gene. Those with extra copies produce too much of the CYP2D6 enzyme and process the drug very fast. As a result, their bodies may convert codeine to morphine so quickly and completely that a standard dose can be an overdose. In contrast, some variants of CYP2D6 create an enzyme that doesn’t work. People with these variants process codeine slowly, if at all, leading to little, if any, pain relief. For them, doctors can prescribe a different drug.

How is pharmacogenomics affecting drug design, development, and prescribing guidelines?

The Food and Drug Administration (FDA) monitors drug safety in the United States. It now includes pharmacogenomic information on the labels of around 200 medications. This information can help doctors tailor drug prescriptions for individual patients by providing guidance on dose, possible side effects, or differences in effectiveness for people with certain gene variants.

Drug companies are also using pharmacogenomics to develop and market medicines for people with specific genetic profiles.By studying a drug only in people likely to benefit from it, drug companies might be able to speed up the drug’s development and maximize its therapeutic benefit.

In addition, if scientists can identify genes that cause serious side effects, doctors could prescribe those drugs only to people who do not have those genes. This would allow some individuals to receive potentially lifesaving medicines that otherwise might be banned because they pose a risk for other people.

How is pharmacogenomics affecting medical treatment?

Currently, doctors prescribe drugs based mostly on factors such as a patient’s age, weight, sex, and liver and kidney function. For a few drugs, researchers have identified gene variants that affect how people respond. In these cases, doctors can select the best medication and dose for each patient.

Additionally, learning how patients respond to medications helps to discern the different forms of their diseases.

What is pharmacogenomics?

Pharmacogenomics uses information about a person's genetic makeup, or genome, to choose the drugs and drug doses that are likely to work best for that particular person. This new field combines the science of how drugs work, called pharmacology, with the science of the human genome, called genomics.

What might pharmacogenomics mean for you?

Until recently, drugs have been developed with the idea that each drug works pretty much the same in everybody. But genomic research has changed that "one size fits all" approach and opened the door to more personalized approaches to using and developing drugs.

Depending on your genetic makeup, some drugs may work more or less effectively for you than they do in other people. Likewise, some drugs may produce more or fewer side effects in you than in someone else. In the near future, doctors will be able to routinely use information about your genetic makeup to choose those drugs and drug doses that offer the greatest chance of helping you.

Pharmacogenomics may also help to save you time and money. By using information about your genetic makeup, doctors soon may be able to avoid the trial-and-error approach of giving you various drugs that are not likely to work for you until they find the right one. Using pharmacogenomics, the "best-fit" drug to help you can be chosen from the beginning.

How is pharmacogenomic information being used today?

Doctors are starting to use pharmacogenomic information to prescribe drugs, but such tests are routine for only a few health problems. However, given the field's rapid growth, pharmacogenomics is soon expected to lead to better ways of using drugs to manage heart disease, cancer, asthma, depression and many other common diseases.

One current use of pharmacogenomics involves people infected with the human immunodeficiency virus (HIV). Before prescribing the antiviral drug abacavir (Ziagen), doctors now routinely test HIV-infected patients for a genetic variant that makes them more likely to have a bad reaction to the drug.

Another example is the breast cancer drug trastuzumab (Herceptin). This therapy works only for women whose tumors have a particular genetic profile that leads to overproduction of a protein called HER2.

The U.S. Food and Drug Administration (FDA) also recommends genetic testing before giving the chemotherapy drug mercaptopurine (Purinethol) to patients with acute lymphoblastic leukemia. Some people have a genetic variant that interferes with their ability to process the drug. This processing problem can cause severe side effects and increase risk of infection, unless the standard dose is adjusted according to the patient's genetic makeup.

The FDA also advises doctors to test colon cancer patients for certain genetic variants before administering irinotecan (Camptosar), which is part of a combination chemotherapy regimen. The reasoning is that patients with one particular variant may not be able to clear the drug from their bodies as quickly as others, resulting in severe diarrhea and increased infection risk. Such patients may need to receive lower doses of the drug.

What other uses of pharmacogenomics are being studied?

Much research is underway to understand how genomic information can be used to develop more personalized and cost-effective strategies for using drugs to improve human health.

In 2007, the FDA revised the label on the common blood-thinning drug warfarin (Coumadin) to explain that a person's genetic makeup might influence response to the drug. Some doctors have since begun using genetic information to adjust warfarin dosage. Still, more research is needed to conclusively determine whether warfarin dosing that includes genetic information is better than the current trial-and-error approach.

The FDA also is considering genetic testing for another blood-thinner, clopidogrel bisulfate (Plavix), used to prevent dangerous blood clots. Researchers have found that Plavix may not work well in people with a certain genetic variant.

Cancer is another very active area of pharmacogenomic research. Studies have found that the chemotherapy drugs, gefitinib (Iressa) and erlotinib (Tarceva), work much better in lung cancer patients whose tumors have a certain genetic change. On the other hand, research has shown that the chemotherapy drugs cetuximab (Erbitux) and panitumumab (Vecitibix) do not work very well in the 40 percent of colon cancer patients whose tumors have a particular genetic change.

Pharmacogenomics may also help to quickly identify the best drugs to treat people with certain mental health disorders. For example, while some patients with depression respond to the first drug they are given, many do not, and doctors have to try another drug. Because each drug takes weeks to take its full effect, patients' depression may grow worse during the time spent searching for a drug that helps.

Recently, researchers identified genetic variations that influence the response of depressed people to citalopram (Celexa), which belongs to a widely used class of antidepressant drugs called selective serotonin re-uptake inhibitors (SSRIs). Clinical trials are now underway to learn whether genetic tests that predict SSRI response can improve patients' outcomes.

Can pharmacogenomics be used to develop new drugs?

Yes. Besides improving the ways in which existing drugs are used, genome research will lead to the development of better drugs. The goal is to produce new drugs that are highly effective and do not cause serious side effects.

Until recently, drug developers usually used an approach that involved screening for chemicals with broad action against a disease. Researchers are now using genomic information to find or design drugs aimed at subgroups of patients with specific genetic profiles. In addition, researchers are using pharmacogenomic tools to search for drugs that target specific molecular and cellular pathways involved in disease.

Pharmacogenomics may also breathe new life into some drugs that were abandoned during the development process. For example, development of the beta-blocker drug bucindolol (Gencaro) was stopped after two other beta-blocker drugs won FDA approval to treat heart failure. But interest in Gencaro revived after tests showed that the drug worked well in patients with two genetic variants that regulate heart function. If Gencaro is approved by the FDA, it could become the first new heart drug to require a genetic test before prescription.

Did you know that the sequence of your genome can determine how you respond to certain medications? Understanding pharmacogenomics, or tailoring a person's medications based on their genome, would not be possible without sequencing the genomes of many people and comparing their responses to medicines.

One of the most important uses for DNA sequencing is not to just sequence one human genome - but rather to sequence many human genomes to understand how genomic differences relate to different traits. Some such traits reflect physical characteristics (like eye color), whereas others can be used to help in the clinical care of patients. Scientists in the field of pharmacogenomics study how specific variants in your genome sequence influence your response to medications.

Influencing How Medicines Work

In order for our bodies to use some medicines properly, the cells in our bodies must make a few chemical changes that convert them into an active form, just like we do when we eat food. Then, these active forms of the medicine must get to the right places in the body or inside cells to do the job that we want them to do. If we want to make sure this happens, it makes sense that we would target our bodies' pathways involved in changing the medicine's form or in getting medicines to the right places. For example, you probably know someone who takes an antidepressant. Many of these medicines get to the right places by interacting with a protein called ABCB1, which works like a traffic cop on the outside of your cells.

Given ABCB1's important role in controlling traffic, you might imagine that if someone has a genomic variant that changes the shape or function of their ABCB1 protein, they might have a different response than usual to any number of medicines. We now know that is the case for some antidepressants, as well as other medications like statins for cholesterol and certain chemotherapy medicines. As a result, there are at least 18 pharmacogenomic tests for variants in ABCB1 listed in the NIH's Genetic Test Registry, with suggestions that you be tested for these variants to help determine the correct dose for certain medications.

Stopping Dangerous Side Effects

Healthcare professionals and researchers are constantly seeking both to optimize medical treatments and to avoid adverse (or negative) reactions to treatments, which are estimated to affect between 7 percent and 14 percent of hospitalized patients. This makes adverse reactions a large cause of added days spent in a hospital, and the fourth leading cause of death in the United States.

One scary example of such an adverse reaction is Stevens-Johnson syndrome (SJS), a severe allergic reaction also called "scalded skin syndrome." It can be caused by infections, but also by very common medications like ibuprofen, anti-seizure medicines, or antibiotics. Patients may go from taking two pain pills to ending up in the hospital burn unit fighting for their lives if SJS progresses to a worse condition called toxic epidermal necrolysis (TEN). TEN is diagnosed when patients have shed at least one-third of the skin off of their bodies. Needless to say, anything we can do to prevent this allergic reaction is vitally important.

In Taiwan, married scientists Wen-Hung Chung (a physician) and Shuen-Iu Hung (an immunologist) noticed that SJS/TEN was much more common in patients taking carbamazepine, used to treat epilepsy and seizures, or allopurinol, used to treat gout. They showed that this was due to genomic variants in the HLA-B gene. Not surprisingly, this gene helps control the immune response. As a result of their work, the country of Thailand has implemented genomic testing before these medications are prescribed. The results of this "pharmacogenomic test" are used to decide whether it is safe to give a specific patient certain medicines, like carbamazepine or allopurinol. Thailand's government even covers the cost of this testing, and the frequency of SJS/TEN has been drastically reduced. We have since learned that different ancestries are associated with different HLA-B genomic variants, so countries may need to take different approaches to monitor which medications are most likely to be linked to SJS/TEN.

Relationships are Complicated

Understanding pharmacogenomics would not be possible without sequencing the genomes of many people and comparing them, and then comparing their response to medicines. But we have also learned that a person's genome sequence is not everything when it comes to medication responses. The human body is a very complicated machine, and the instructions written in our DNA are just part of the process.

There are some cases, as with the breast cancer treatment tamoxifen, where a small study showed that there might be a relationship between someone's response to the medicine and a variant in the CYP2D6 gene. However, this finding did not appear to be true in a larger study that involved many more people. That's why at this time, the U.S. Food and Drug Administration (FDA) labeling for tamoxifen does not recommend CYP2D6 pharmacogenomic testing, but the issue is still being reviewed as more research is conducted.

Another gene in the same CYP family, called CYP2C19, has variations which affect how your body can use clopidogrel (more commonly known as Plavix). This medication is a "blood thinner" which helps prevent blood clots, and thus reduces your risk of strokes or some heart attacks. If your CYP2C19 protein is not working properly due to a mutation in the gene, then you will not be able to process clopidogrel, and you need either a different dose or a different medication. As it turns out, these variants in CYP2C19 are also more common in those with Asian ancestry. Although testing for variants in this gene is also not routinely recommended, you may wish to speak with your healthcare provider about the test if you are given a prescription for clopidogrel, particularly if you have East Asian family members.

What is pharmacogenomics?

Pharmacogenomics is an important example of the field of precision medicine, which aims to tailor medical treatment to each person or to a group of people. Pharmacogenomics looks at how your DNA affects the way you respond to drugs. In some cases, your DNA can affect whether you have a bad reaction to a drug or whether a drug helps you or has no effect. Pharmacogenomics can improve your health by helping you know ahead of time whether a drug is likely to benefit you and be safe for you to take. Knowing this information can help your doctor find medicine that will work best for you.

How does pharmacogenomics work?

Drugs interact with your body in numerous ways, depending both on how you take the drug and where the drug acts in your body. After you take a drug, your body needs to break it down and get it to the intended area. Your DNA can affect multiple steps in this process to influence how you respond to the drug. Some examples of these interactions include

• Drug Receptors. Some drugs need to attach to proteins on the surface of cells called receptors in order to work properly. Your DNA determines what type of receptors you have and how many, which can affect your response to the drug. You might need a higher or lower amount of the drug than most people or a different drug.
  • Example: Breast Cancer and T-DM1. Some breast cancers make too much HER2, a receptor, and this extra HER2 helps the cancer develop and spread. The drug T-DM1 can be used to treat this type of breast cancer and works by attaching to HER2 on cancerous cells and killing them. If you have breast cancer, your doctor may test a sample of your tumor to determine if T-DM1 is the right treatment for you. If your tumor has a high amount of HER2 (HER2 positive), your doctor may prescribe T-DM1. If your tumor does not have enough HER2 (HER2 negative), T-DM1 will not work for you.

• Drug Uptake. Some drugs need to be actively taken into the tissues and cells in which they act. Your DNA can affect uptake of certain drugs. Decreased uptake can mean that the drug does not work as well and can cause it to build up in other parts of your body, which can cause problems. Your DNA can also affect how quickly some drugs are removed from the cells in which they act. If drugs are removed from the cell too quickly, they might not have time to act.
  • Example: Statins and Muscle Problems. Statins are a type of drug that act in the liver to help lower cholesterol. In order for statins to work correctly, they must first be taken into the liver. Statins are transported into the liver by a protein made by the SLCO1B1 gene. Some people have a specific change in this gene that causes less of a statin called simvastatin to be taken into the liver. When taken at high doses, simvastatin can build up in the blood, causing muscle problems, including weakness and pain. Before prescribing simvastatin, your doctor may recommend genetic testing for the SLCO1B1 gene to check if simvastatin is the best statin for you or to determine what dose would work best.

• Drug Breakdown. Your DNA can affect how quickly your body breaks down a drug. If you break the drug down more quickly than most people, your body gets rid of the drug faster and you might need more of the drug or a different drug. If your body breaks the drug down more slowly, you might need less of the drug.
  • Example: Depression and Amitriptyline. The breakdown of the antidepressant drug amitriptyline is influenced by two genes called CYP2D6 and CYP2C19. If your doctor prescribes amitriptyline, he or she might recommend genetic testing for the CYP2D6 and CYP2C19 genes to help decide what dose of the drug you need. If you breakdown amitriptyline too fast, you will need a higher dose for it to work, or you may need to use a different drug. If you breakdown amitriptyline very slowly, you will need to take a smaller dose or will need to take a different drug to avoid a bad reaction.

• Targeted Drug Development. Pharmacogenomic approaches to drug development target the underlying problem rather than just treating symptoms. Some diseases are caused by specific changes (mutations) in a gene. The same gene can have different types of mutations, which have different effects. Some mutations may result in a protein that does not work correctly, while others may mean that the protein is not made at all. Drugs can be created based on how the mutation affects the protein, and these drugs will only work for a specific type of mutation.
  • Example: Cystic Fibrosis and Ivacaftor. Cystic fibrosis is caused by mutations in the CFTR gene which affect the CFTR protein. The CFTR protein forms a channel, which acts as a passageway to move particles across the cells in your body. For most people the protein is made correctly, and the channel can open and close. Some mutations that cause cystic fibrosis result in a channel that is closed. The drug ivacaftor acts on this type of mutation by forcing the channel open. Ivacaftor would not be expected to work for people with cystic fibrosis whose mutations cause the channel not to be made at all.

Example: Cystic Fibrosis

What does this mean for your health?

While pharmacogenomic testing is currently used for only a few drugs, the field is growing very quickly. Improved understanding of how pharmacogenomics can protect your health and improve your treatment will be increasingly important. Talk to your healthcare provider about what pharmacogenomics might mean for your health.

You’re one of a kind. It’s not just your eyes, smile, and personality. Your health, risk for disease, and the ways you respond to medicines are also unique. Medicines that work well for some people may not help you at all. They might even cause problems. Wouldn’t it be nice if treatments and preventive care could be designed just for you?

The careful matching of your biology to your medical care is known as personalized medicine. It’s already being used by health care providers nationwide.

The story of personalized medicine begins with the unique set of genes you inherited from your parents. Genes are stretches of DNA that serve as a sort of instruction manual telling your body how to make the proteins and perform the other tasks that your body needs. These genetic instructions are written in varying patterns of only 4 different chemical “letters,” or bases.

The same genes often differ slightly between people. Bases may be switched, missing, or added here and there. Most of these variations have no effect on your health. But some can create unusual proteins that might boost your risk for certain diseases. Some variants can affect how well a medicine works in your body. Or they might cause a medicine to have different side effects in you than in someone else.

The study of how genes affect the way medicines work in your body is called pharmacogenomics.

“If doctors know your genes, they can predict drug response and incorporate this information into the medical decisions they make,” says Dr. Rochelle Long, a pharmacogenomics expert at NIH.

It’s becoming more common for doctors to test for gene variants before prescribing certain drugs. For example, children with leukemia might get the TPMT gene test to help doctors choose the right dosage of medicine to prevent toxic side effects. Some HIV-infected patients are severely allergic to treatment drugs, and genetic tests can help identify who can safely take the medicines.

“By screening to know who shouldn’t get certain drugs, we can prevent life-threatening side effects,” Long says.

Pharmacogenomics is also being used for cancer treatment. Some breast cancer drugs only work in women with particular genetic variations. If testing shows patients with advanced melanoma (skin cancer) have certain variants, 2 new approved drugs can treat them.

Even one of the oldest and most common drugs, aspirin, can have varying effects based on your genes. Millions of people take a daily aspirin to lower their risk for heart attack and stroke. Aspirin helps by preventing blood clots that could clog arteries. But aspirin doesn’t reduce heart disease risk in everyone.

NIH-funded researchers recently identified a set of genes with unique activity patterns that can help assess whether someone will benefit from taking aspirin for heart health. Scientists are now working to develop a standardized test for use in daily practice. If doctors can tell that aspirin won’t work in certain patients, they can try different treatments.

One NIH-funded research team studied a different clot-fighting drug known as clopidogrel (Plavix). It’s often prescribed for people at risk for heart attack or stroke. Led by Dr. Alan Shuldiner at the University of Maryland School of Medicine, the team examined people in an Amish community. Isolated communities like this have less genetic diversity than the general population, which can make it easier to study the effects of genes. But as in the general population, some Amish people have risk factors, such as eating a high-fat diet, that raise their risk for heart disease.

Many of the Amish people studied had a particular gene variant that made them less responsive to clopidogrel, the scientists found. Further research revealed that up to one-third of the general population may have similar variations in this gene, meaning they too probably need a different medicine to reduce heart disease risks.

The findings prompted the U.S. Food and Drug Administration (FDA) to change the label for this common drug to alert doctors that it may not be appropriate for patients who have certain gene variations. Two alternative drugs have since been developed. “If people have these gene variants, they know they have options,” says Shuldiner. “This is a great example of how study results made it onto a drug label and are beginning to be implemented into patient care.”

Getting a genetic test usually isn’t difficult. Doctors generally take a sample of body fluid or tissue, such as blood, saliva or skin, and send it to a lab. Most genetic tests used today analyze just one or a few genes, often to help diagnose disease. Newborns, for example, are routinely screened for several genetic disorders by taking a few drops of blood from their heels. When life-threatening conditions are caught early, infants can be treated right away to prevent problems.

The decision about whether to get a particular genetic test can be complicated. Genetic tests are now available for about 2,500 diseases, and that number keeps growing. Your doctor might advise you to get tested for specific genetic diseases if they tend to run in your family or if you have certain symptoms.

“While there are many genetic tests, they vary as to how well they predict risk,” says Dr. Lawrence Brody, a genetic testing expert at NIH.

For some diseases, such as sickle cell anemia or cystic fibrosis, inheriting 2 copies of abnormal genes means a person will get that disease. But for other diseases and conditions, the picture is more complex. For type 2 diabetes, testing positive for some specific gene variants may help predict risk, but no better than other factors—such as obesity, high blood pressure and having a close relative with the disease.

The latest approach to personalized medicine is to get your whole genome sequenced. That’s still expensive, but the cost has dropped dramatically over the past decade and will likely continue to fall. Since your genome essentially stays the same over time, this information might one day become part of your medical record, so doctors could consult it as needed.

You can start to get a sense of your genetic risks by putting together your family’s health history. A free online tool called My Family Health Portrait from the U.S. Surgeon General can help you and your doctor spot early warning signs of conditions that run in your family.

But personalized medicine isn’t just about genes. You can learn a lot about your health risks by taking a close look at your current health and habits. Smoking, a poor diet, and lack of exercise can raise your risks for life-threatening health problems, such as heart disease and cancer. Talk to your health care provider about the steps you can take to understand and reduce your unique health risks.

Test Your Genes?

Genetic tests aren’t necessarily for everyone. You and your doctor might consider analyzing your genes or genome:

• to diagnose a disease.
• if there’s a strong family history of a certain disease.
• if you’re pregnant or plan to have a child.
• to learn if you have, or are at risk for, an inherited disorder.
• to learn if you’re at risk for certain disorders that might be slowed or prevented if you make healthy changes.
• to guide your health care provider in choosing the best treatments for you.

There is a lot of overlap between the terms "precision medicine" and "personalized medicine." According to the National Research Council, "personalized medicine" is an older term with a meaning similar to "precision medicine." However, there was concern that the word "personalized" could be misinterpreted to imply that treatments and preventions are being developed uniquely for each individual; in precision medicine, the focus is on identifying which approaches will be effective for which patients based on genetic, environmental, and lifestyle factors. The Council therefore preferred the term "precision medicine" to "personalized medicine." However, some people still use the two terms interchangeably.

Pharmacogenomics is a part of precision medicine. Pharmacogenomics is the study of how genes affect a person’s response to particular drugs. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that are tailored to variations in a person’s genes.