This website is intended to help healthcare professionals understand select pharmacogenetic test results using available FDA label information and independent clinical guidelines* published in peer-reviewed journals.
This information is for reference only and has not been reviewed by the FDA. This information does not constitute medical advice and does not take the place of routine clinical monitoring. Clinicians should use professional judgment in the interpretation of any clinical recommendations.
*The guidelines referenced herein reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time these guidelines were written and are intended only to assist clinicians in decision making and to identify questions for further research. New evidence may have emerged since the time a guideline was submitted for publication. Guidelines are limited in scope and are not applicable to interventions or diseases that are not specifically identified. Guidelines do not account for individual variations among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the healthcare provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient.
Please refer to cpicpgx.org or pharmgkb.org to access the most current guideline content.
Cardiology
Gastroenterology
Infectious Disease
Neurology
Cardiology
Gastroenterology
Infectious Disease
Neurology
Cardiology
Gastroenterology
Infectious Disease
Neurology
Cardiology
Gastroenterology
Infectious Disease
Neurology
Cardiology
Gastroenterology
Infectious Disease
Neurology
Oncology
Oncology
Oncology
Cardiology
Cardiology
Cardiology
23andMe Pharmacogenetics reports* provide information about DNA variants that may influence the body’s ability to process certain medications. Having a variant means that some medications may be processed faster or slower than normal, which, depending on the medication, may reduce effectiveness or increase the chance of experiencing side effects. However, most medications won’t be affected by having these DNA variants.
23andMe Pharmacogenetics reports are intended to provide genetic information that may aid discussions between consumers and healthcare professionals about therapeutic options.
Currently, 23andMe provides three Pharmacogenetics reports to customers, along with two CYP2C19-related Medication Insight reports:
23andMe Pharmacogenetics reports have been authorized by the FDA and meet similar FDA standards of clinical and analytical validity as the 23andMe Carrier Status* and Genetic Health Risk* reports. All saliva samples are processed in CLIA-certified and CAP-accredited labs and are genotyped using a custom version of the Illumina Global Screening Array (GSA).
Accuracy was determined by comparing results from the 23andMe genotyping array with results from Sanger sequencing. Greater than 99% of test results were correct. While unlikely, the 23andMe Pharmacogenetics test may provide false positive or false negative results.
The 23andMe CYP2C19 Drug Metabolism report tests for three variants in the CYP2C19 gene:
The 23andMe DPYD Drug Metabolism report tests for two variants in the DPYD gene:
The 23andMe SLCO1B1 Drug Transport report tests for one variant in the SLCO1B1 gene:
Keep in the mind that there are other DNA variants in these genes and other genes that could also alter the processing of certain medications. 23andMe only tests for common pharmacogenetic variants. Variants not included in the test may be rare, may not be available on the 23andMe genotyping platform, or may not pass 23andMe testing standards.
The 23andMe Pharmacogenetics reports:
The Genetic Testing Registry (GTR®) provides a central location for genetic test providers to describe their test offerings, including pharmacogenetic tests.
Website: ncbi.nlm.nih.gov/gtr/
GTR® is hosted by the National Center for Biotechnology Information (NCBI), which is funded by the National Institutes of Health (NIH).
The 23andMe Pharmacogenetics reports are intended to provide genetic information that may aid discussions between consumers and healthcare professionals about therapeutic options. This portal provides overviews of peer-reviewed pharmacogenetic guidelines and relevant FDA-approved drug labels that may enhance these discussions. The guideline recommendations included from the Clinical Pharmacogenetics Implementation Consortium(CPIC®) are rated by CPIC as “strong” unless otherwise noted.
It’s important to note that pharmacogenetic guidelines are optional and are intended for reference only, as many other factors besides genetics are considered in clinical decision-making. Pharmacogenetic information may be most helpful before treatment has begun, but it may also provide insights into some cases of non-response or unexpected side effects once therapy is underway. Patients who are already on a stable dose of medication that is working well may be less likely to benefit from dosing changes based on genetic information. Clinicians should use professional judgment in the interpretation of pharmacogenetic information and clinical guidelines.
The field of pharmacogenetics explores how DNA variants influence the body’s ability to process medications. “Pharmacogenetics” and “pharmacogenomics” are sometimes used interchangeably, but pharmacogenetics more often refers to genetic testing for variants in specific genes, while pharmacogenomics is used in the broader context of whole-genome sequencing or genetics-guided drug development.
Most pharmacogenetic variants are inherited, germline DNA differences that can impact pharmacokinetics (what the body does to the drug) or pharmacodynamics (what the drug does to the body). Pharmacokinetic effects include altering absorption, distribution, metabolism, and elimination, while pharmacodynamic effects may include altering the body’s sensitivity to a drug or altering the drug target itself. Many pharmacogenetic variants are found in genes that code for metabolizing enzymes, while other pharmacogenetic variants can affect proteins that transport medications, play a role in the immune system, or impact the clearance of a specific virus.
Depending on the medication, pharmacogenetic variants may reduce effectiveness, increase the chance of experiencing side effects, or have no effect. Researchers have determined that variants in approximately 20 genes may affect about 80 medications. More specifically, the Clinical Pharmacogenetics Implementation Consortium (CPIC®) has classified approximately 50 gene-drug pairs as having a high level of evidence and being actionable through dosing or medication changes.
It’s worth noting that not all pharmacogenetic variants are inherited; some are acquired DNA changes that are found only in cancer cells. Some oncologists may screen patients for these kinds of variants in order to help target cancer treatments more effectively.
Many pharmacogenetic variants are found in genes that code for metabolizing enzymes, which play a key role in breaking down and eliminating medications from the body. Most of these variants result in enzymes with decreased function, but a few result in enzymes with increased function. Depending on the gene and a person’s specific combination of variants (genotype), they may be classified as a poor, intermediate, normal, rapid, or ultrarapid metabolizer for that specific enzyme.
Poor and intermediate metabolizers process some drugs slower than normal, which may lead to higher drug levels and an increased chance of side effects. But in the case of prodrugs (e.g. clopidogrel), poor and intermediate metabolizers activate prodrugs slower than normal and may experience reduced medication effectiveness.
Rapid and ultrarapid metabolizers, on the other hand, process some drugs faster than normal, which may lead to lower drug levels and an increased chance of non-response with standard dosing. In the case of prodrugs, rapid and ultrarapid metabolizers may activate prodrugs faster than normal and may experience increased medication effectiveness.
CPIC® stands for the Clinical Pharmacogenetics Implementation Consortium. CPIC® is an international consortium of clinicians and researchers that helps facilitate the use of pharmacogenetic information for patient care. CPIC evaluates the available clinical evidence supporting gene-drug pairs and publishes genotype-based dosing guidelines to help healthcare professionals interpret genetic information for use in their prescribing practices.
Website: cpicpgx.org
The PharmGKB is a pharmacogenomics knowledge resource that encompasses clinical information including clinical guidelines and drug labels, potentially clinically actionable gene-drug associations, and genotype-phenotype relationships. PharmGKB collects, curates, and disseminates knowledge about the impact of human genetic variation on drug responses.
Website: pharmgkb.org
You can learn more about pharmacogenetics and clinical implementation from the following resources:
National Center for Biotechnology Information (NCBI) — Medical Genetics Summaries: Pharmacogenetics
Genetics Home Reference — What is pharmacogenomics?
American Family Physician — Pharmacogenetics: Using Genetic Information to Guide Drug Therapy
U.S. Food and Drug Administration (FDA) — Table of Pharmacogenetic Associations
Relling MV et al. (2015). “Pharmacogenomics in the clinic.” Nature 526(7573):343-350.
Relling MV et al. (2011). “CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenetics Research Network.” Clin Pharmacol Ther. 89(3):464-7. Website: cpicpgx.org
Whirl-Carrillo M et al. (2012). “Pharmacogenomics knowledge for personalized medicine.” Clin Pharmacol Ther. 92(4): 414-417. Website: pharmgkb.org
This website may occasionally be updated based on new information.
This Change Log describes updates and revisions.
Date
1 Feb 2020
Change
Pharmacogenetics for Healthcare Professionals website created.
Date
5 Jan 2021
Change
Content update. Information from the Clinical Pharmacogenetics Implementation Consortium (CPIC®) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing was added, and information from the Dutch Pharmacogenetics Working Group was removed.
Date
19 May 2021
Change
Content update. The section titled “Common Questions about 23andMe Pharmacogenetic Reports” was updated to reflect updates in the 23andMe consumer product: 1) the release of Medication Insight reports for citalopram and clopidogrel, and 2) the removal of the confirmatory testing requirement for certain genotypes in the CYP2C19 Drug Metabolism report.
This pharmacogenetics web portal is intended as an educational resource for healthcare professionals practicing in the United States. Please note it is for informational purposes only and includes information that has not been reviewed by the U.S. Food and Drug Administration.
If you are NOT a licensed healthcare professional, please discuss any questions you have regarding your 23andMe Pharmacogenetics reports with a doctor, pharmacist, or nurse.
* Healthcare professionals include doctors, nurses, physician assistants, pharmacists, and genetic counselors.
