Can common genetic tests like ancestry.com detect CYP2D6 (cytochrome P450 2D6) genetic variants?

Common Genetic Tests Like Ancestry.com Cannot Detect CYP2D6 Genetic Variants

Common direct-to-consumer genetic tests like Ancestry.com do not detect CYP2D6 genetic variants, as these tests require specialized clinical pharmacogenomic testing methodologies that are not included in ancestry or consumer-oriented genetic testing platforms. 1

Why CYP2D6 Testing Requires Specialized Methods

• CYP2D6 testing is complex due to the gene's high polymorphism, with over 70 allelic variants and numerous subvariants that affect enzyme function, requiring specialized detection methods 2
• The CYP2D6 gene has significant sequence similarity with pseudogenes (particularly CYP2D7 and CYP2D8), making accurate genotyping challenging without specialized techniques 3, 4
• CYP2D6 is subject to complex structural variations including gene deletions, duplications, multiplications, and gene rearrangements that require specific testing methodologies to detect 1
• Copy number variations (CNVs) are present in approximately 13.1% of individuals and account for 7% of total CYP2D6 variants, requiring specialized detection methods beyond standard genotyping 5

Clinical Pharmacogenomic Testing for CYP2D6

• Clinical laboratories use several approaches for CYP2D6 testing:

  • FDA-approved tests like the Roche AmpliChip® CYP450 Test 1
  • Laboratory-developed tests (LDTs) that target specific variants 1
  • Next-generation sequencing approaches specifically designed to handle the complexities of CYP2D6 4

• Targeted pharmacogenomic testing typically focuses on selected star allele haplotypes cataloged by PharmVar (Pharmacogene Variation Consortium) 1

• Proper CYP2D6 testing requires methods that can detect:

  • Single nucleotide variants (SNVs) that define specific alleles 1
  • Copy number variations including gene deletions and duplications 1, 6
  • Gene rearrangements and fusion genes involving CYP2D6 and CYP2D7 4

Limitations of Consumer Genetic Tests

• Consumer genetic tests like Ancestry.com primarily focus on ancestry-informative markers and some health-related variants, but do not include comprehensive pharmacogenomic testing 1
• These tests typically use genotyping arrays that are not designed to capture the complex structural variations in CYP2D6 1
• Even when consumer tests detect some genetic variants, they do not provide the comprehensive coverage needed for accurate CYP2D6 phenotype prediction 1

Clinical Significance of CYP2D6 Testing

• CYP2D6 metabolizes approximately 25% of clinically prescribed drugs, including antidepressants, antipsychotics, beta-blockers, and opioids 2
• CYP2D6 activity varies widely in the population, with individuals categorized as poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), or ultra-rapid metabolizers (UMs) 1, 7
• Accurate CYP2D6 testing can help prevent adverse drug reactions and treatment failures by guiding medication selection and dosing 7

Specialized Testing Requirements

• The American College of Medical Genetics and Genomics (ACMG) recommends that laboratories performing CYP2D6 testing establish specific performance characteristics during validation 1
• Testing should include evaluation of at least 20 previously characterized samples representing various alleles/haplotypes that can be detected by the platform 1
• Proper CYP2D6 testing requires phasing information (determining if variants are on the same chromosome) or population-based assumptions when phasing is ambiguous 1

For individuals seeking CYP2D6 testing, specialized clinical pharmacogenomic testing through healthcare providers or clinical laboratories is necessary, as common direct-to-consumer genetic tests do not provide adequate coverage of this complex gene 1.