#392 - Genetic testing: when it's valuable, how to choose the right test, and what to do with the results

1. Test with Clear Intention

Before undergoing any genetic testing, define what you are looking for, what actions you will take if you find it, and what you will do if you don’t. This ensures the test serves a meaningful purpose.

2. Ask Foundational Questions First

Prior to genetic testing, ask yourself: What exactly am I trying to learn? Is genetics the best tool, or is direct phenotypic measurement better? What will I do differently with the results, and am I mentally prepared for the answer?

3. Prioritize Phenotype for Common Diseases

For common conditions like cardiovascular and metabolic diseases, directly measuring the phenotype (e.g., cholesterol, blood pressure, insulin resistance) is usually more informative and actionable than genetic predisposition. Use genetic testing only if the clinical picture raises a specific, unanswered question.

4. Assess Psychological Impact

Consider the potential psychological weight of genetic information. If a result is likely to cause fear or confusion without leading to constructive changes in screening, treatment, or planning, its costs may outweigh its benefits for your well-being.

5. Evaluate Genetic Effect Size and Actionability

When considering a genetic test, evaluate both the magnitude of the genetic variant’s effect on disease risk and how much knowing this information will actually change your clinical management or behavior. Prioritize tests with high effect size and clear actionability.

6. Choose Clinical-Grade Cancer Panels

For meaningful cancer genetic risk assessment (e.g., BRCA, Lynch syndrome), opt for clinical-grade gene panel testing that sequences specific genes in depth, rather than consumer genotyping products which only scan for a limited number of common variants and can provide false reassurance.

7. Be Skeptical of Functional Medicine Panels

Approach functional medicine genetic panels (e.g., MTHFR, COMT, detox, nutrigenomics) with skepticism. The leap from common variants to specific supplement protocols or personality profiles is often not supported by sufficient clinical evidence and may lead to unnecessary spending.

8. Utilize Pharmacogenetics for Medication Guidance

Consider pharmacogenetic testing to guide medication selection and dosing, especially when treatment involves trial and error, severe side effects, or variable metabolism. This can optimize specific treatment decisions and improve drug safety and efficacy.

9. Match Test Type to Specific Question

Select the genetic test type (e.g., single gene, gene panel, whole exome/genome sequencing) that precisely matches the clinical question you are trying to answer. Avoid the ‘more is better’ fallacy, as broader tests can generate overwhelming data and incidental findings without increasing clarity.

10. Understand Test Coverage and Limitations

Before ordering, explicitly understand what specific mutations a test detects and what it misses. Discuss with a clinician or genetic counselor what a negative result truly means to avoid misinterpretation or false reassurance.

11. Interpret Negative Results Carefully

A negative genetic test result indicates no pathogenic variant was found on the specific test ordered, but it does not override a strong phenotype or family history, nor does it guarantee the absence of all genetic risk.

12. Ensure Actionable Follow-Up

Every genetic test result should lead to a clear ‘what now?’ plan. If the finding does not confirm a diagnosis, increase screening, change treatments, inform family members, or aid in planning, then question the overall purpose and value of the test.

13. Consider Genetic Testing for Inherited Cardiac Conditions

For inherited cardiac conditions like arrhythmias, cardiomyopathies, or structural heart disease, genetic testing can uncover specific risks not obvious from routine screening, especially with a family history of sudden cardiac death, prompting more regular and targeted testing.

14. Use ApoE Status for Alzheimer’s Planning

Knowing ApoE status can inform more aggressive management of modifiable Alzheimer’s disease risk factors (e.g., lipids, metabolic health) and facilitate long-term financial, career, or care planning, even if direct therapeutic interventions are still emerging.

15. Confirm Familial Hypercholesterolemia Genetically

If a patient has markedly elevated LDL and a family history suggestive of a monogenic lipid disorder, genetic confirmation of familial hypercholesterolemia can solidify the diagnosis and prompt cascading screenings for affected relatives.

16. Investigate Misleading HDL Levels

Be aware that rare mutations, such as in SCARB1, can cause HDL cholesterol to appear falsely elevated, masking a substantially higher cardiovascular risk. In such cases, genetic testing can reveal information not obvious from a standard lipid panel, prompting additional testing.

17. Leverage Genetic Data for Behavioral Motivation

Genetic data can serve as a psychological lever, motivating patients to adopt lifestyle changes or adhere to treatments they were previously resistant to, by reframing their risk in a way that feels less like a personal failure.

18. Select CLIA-Certified Labs with Expertise

For any genetic test informing medical decisions, use a CLIA-certified laboratory with demonstrated expertise in the relevant area and carefully review their data privacy policies due to the sensitive and permanent nature of genetic information.