Role of Genetic Testing in Management of Dyslipidemia

This session provided insights from the scientific statement put forward by the National Lipid Association on genetic testing in dyslipidemia, published in 2020; the statement paper discusses mainly the applications of genetic testing in patients with dyslipidemias and laboratory methods; technical, biological, clinical, and ethical implications.

• Genetic testing can help diagnosing dyslipidemias with underlying DNA mutations (variants).
• However, clinical indications for genetic testing for most dyslipidemias are not clearly established and currently no guidelines exist.

What are monogenic and polygenic dyslipidemias?

Monogenic dyslipidemias:

• Rare, large-effect DNA variants (mutations) that cause monogenic/Mendelian dyslipidemias, with FH being the most common Polygenic dyslipidemias:

Polygenic dyslipidemias:

• Result from concurrent contributions of multiple common variants whose aggregate effect on lipoprotein levels can resemble large-effect rare variant
• Inheritance does not follow Mendelian rules
• Impact of such common variant is quantified using a polygenic score
• Clinical utility of polygenic score is not clear

What are the potential indications for genetic testing in dyslipidemia?

• Strong clinical suspicion of a genetic dyslipidemia
• Strong family history of dyslipidemia or its complications
• Presence of related syndromic features
• Evidence that testing might change the management
• Existence of available and effective early interventions
• Eligibility for new or investigational drugs
• Patient preference
• Family planning
• Other indications, including different therapies depending on results, access to specialized therapies, and insurance coverage

What are the potential outcomes of genetic testing in dyslipidemia?

• Aid in clinical diagnosis and targeted treatment of specific disorders
• Guide optimal management and prevention strategies
• Increase patient compliance and motivation
• Provide early identification of affected family members through cascade screening
• Contribute to scientific advancement
• Indication for access to novel therapies
• Eligibility for insurance coverage for certain therapies

What should be considered while planning genetic testing?

• Intensity of FH treatment should be guided by LDL-C elevation rather than the underlying genotype
• Not all genetic tests are created equal
• Review analytic and clinical validity of a test prior to medical management decisions
• Attributing pathogenicity to a DNA variant can differ between laboratories
• Confirmation using clinical genetic test is recommended to avoid false-positive/false-negative results by direct-to-consumer genetic testing
• Polygenic scores for dyslipidemia are not standardized and not recommended or appropriate for clinical use in dyslipidemia

What are the components of genetic counselling?

Genetic counselling is offered to patients and their families before and after genetic testing.

Before ordering a genetic test:

• Obtain an informed consent form
• Counsel the patient regarding the risk and benefits of genetic testing After ordering a genetic test:

After ordering a genetic test:

• Test results should be disclosed by a clinician with expertise in genetics or by a certified genetic counselor
• Genetic counselling should be provided to patients and their families even if the results are negative
• Definitive incidental findings in certain genes that are unrelated to lipids should also be communicated to the patients
• Results should be tailored to the patient-specific circumstances, level of understanding, and literacy

DNA, deoxyribonucleic acid; FH, familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol.

*Infographic