Podcast Summary: "Pharmacogenetics: How Genes Can Influence Prescribing"

Podcast: Healthier World with Quest Diagnostics
Host: Dr. Mason Lasko (A)
Guest: Kathleen O’Brien, Board Certified Genetic Counselor (B)
Episode: 31
Date: February 9, 2026
Length: ~20 minutes

Episode Overview

This episode shifts focus from Quest Diagnostics’ typical cardiometabolic topics to explore pharmacogenetics (PGX)—the study of how individual genetic variations impact drug metabolism, efficacy, and safety. Dr. Mason Lasko interviews Kathleen O’Brien about the clinical utility of PGX testing, integrating genetic information into routine care, and its growing impact across all areas of medicine.

Key Discussion Points & Insights

1. Pharmacogenetics—Foundations and Importance

What is PGX?

• Definition: The field studies how genetic variation impacts drug response, explaining why patients on the same dose of a medication may respond very differently.
• Historical Context: Traditionally, medication prescribing was a ‘trial and error’ process; PGX allows for rational, evidence-based personalization.

“For a long time it was largely trial and error prescribing … that can be really hard on a patient and a provider.” – Dr. Lasko [03:20]

• Clinical Utility: Approximately 18% of all commercially available medications have actionable pharmacogenetic associations.

“Statistics show that really about 18% of commercially available medications have an actionable pharmacogenetic association.” – O’Brien [04:49]

2. Impact Across Clinical Areas

Key therapeutic areas influenced by PGX:

• Psychiatry: Faster relief/remission due to optimal medication choices.
• Cardiology: PGX guides dosing of drugs like warfarin, reducing risks of clotting or bleeding.
• Oncology, Neurology, Pain Management, Metabolic Disorders.

Specific Examples:

• Warfarin (anticoagulant): Genetic insights allow safer, faster dosing.
• Statins (cholesterol-lowering): PGX testing can prevent muscle-related side effects.
• Stat: European study shows a 30% reduction in risk of adverse drug events with PGX testing [07:37].

“There are many studies that show the benefit of pharmacogenetic testing in optimizing medication selection and dosing … a 30% reduction in the risk of adverse drug events.” – O’Brien [07:47]

3. Evidence and Clinical Tools for Actionable Gene–Drug Associations

How do clinicians identify meaningful associations?

• Guidelines & Tools:
  • CPIC (Clinical Pharmacogenetics Implementation Consortium) guidelines are foundational.
  • FDA label information.
  • Decision support tools: ClinPGX PharmDog [08:47], Sequence to Script.
  • Quest offers integration with informed DNA for interpretative reports (test code 14271).

“CPIC has guidelines that really help bring pharmacogenetic data from bench to bedside … to help clinicians understand how to take that genetic result and make it clinically meaningful.” – O’Brien [08:27]

4. Prominent Genes in Pharmacogenetics

Major enzymes:

• CYP2D6: Metabolizes ~25% of all drugs; key for beta blockers, antidepressants, opioids, and tamoxifen [10:37].
• CYP2C19, CYP2C9: Metabolize a broad range of medication classes.

Other gene families:

• Drug transporters, drug targets, and HLA alleles (immune reactions/adverse effects).

“When we talk about genes that are common, important genes, CYP2D6 … about 25% of all medications are metabolized by CYP2D6.” – O’Brien [10:37]

Quest’s Polypharmacy Panel

• Covers 17 genes and 4 HLA alleles with strong clinical utility [11:47].
• Includes all AMP Tier 1 variants.

5. Interpretation of PGX Test Results

Metabolizer Statuses:

• Normal, Intermediate, Poor, Rapid, Ultra-rapid:
  • Describes the level of enzyme activity due to the patient’s genotype.
  • Implications: Enzyme activity changes drug concentration levels and risk of toxicity or ineffectiveness.

“Normal, intermediate, poor, rapid, and ultra rapid metabolizer … describe how much enzyme activity there is for a given genotype or diplotype.”—O’Brien [13:34]

Examples:

• Clopidogrel (prodrug): Poor CYP2C19 metabolizers fail to activate the drug.
• Citalopram (active drug): Poor metabolizers may have toxic blood levels.

“If someone has reduced levels of [CYP2C19], they’re going to have less of the active metabolite in their circulation, and so they’re more likely to experience drug failure.” – O’Brien [14:01]

6. Quest Diagnostics PGX Testing Offerings

Panels:

• Single-gene tests and Multi-gene Polypharmacy Panel
  • 17 genes + 4 HLA alleles
  • Includes all AMP Tier 1 variants
• Test codes 14271 and 14272: Both report diplotype & phenotype; 14271 includes a link to informed DNA for an expanded interpretive report.

“If the clinician orders test code 14271, they will also get a link that will take them to a different company, which is informed DNA, where they can get a report that has gene drug information on it.” – O’Brien [17:41]

7. Looking Ahead—The Future of PGX in Practice

• Prevalence: Nearly everyone will have a clinically actionable pharmacogenetic association.
• Longevity: One PGX panel can inform medication choices for life [18:29].
• Integration: Increasing uptake in EMRs; some institutions have prescribing alerts for gene-drug interactions.

“Over 90% of patients are going to have a clinically actionable pharmacogenetic association … a polypharmacy panel, you do it once, you pay for it once, and you have the results for the rest of your life.” – O’Brien [18:36]

Notable Quotes & Memorable Moments

• On Impact:
  “Pharmacogenetic testing has utility in nearly all areas of medicine.” – O’Brien [05:17]

• On Clinical Relevance:
  “There are many studies that show the benefit of pharmacogenetic testing in optimizing medication selection and dosing, and that therefore leads to improved outcomes.” – O’Brien [05:37]

• On Future Adoption:
  “PGX testing is going to become much more integrated into mainstream medical care in the future.” – O’Brien [19:38]

Important Segment Timestamps

| Segment | Time | |----------------------------------|-----------| | Introduction & Theme | 00:03–01:00| | Kathleen O’Brien’s Background | 01:04–02:16| | What is Pharmacogenetics? | 02:16–03:58| | Trial & Error vs. PGX | 03:58–05:17| | Clinical Area Impact & Studies | 05:17–07:58| | Evaluating Evidence/Guidelines | 07:58–09:53| | Key Genes & the Panel | 09:53–11:47| | Interpreting PGX Results | 12:54–16:47| | Quest’s Panel Details | 16:47–18:07| | Final Thoughts, Future Vision | 18:29–19:46|

Conclusion

This episode delivers a clear, practical overview of pharmacogenetics, translating emerging science into actionable clinical insights. PGX testing is positioned not only as cutting-edge, but also as a tool for immediate and long-term impact on patient safety and quality of care, with systems like Quest providing the resources, expertise, and education for broad adoption.
Essential takeaway: With a single PGX test, most patients can gain lifelong, actionable insights to guide safer, more effective prescribing.