CYP2D6 Allele Frequencies and Pharmacological Relevance Across Ancestral Groups

89 CYP2D6 alleles were identified with ClinVar 'drug response' significance, with 64% of a subset more frequent in the East Asian ancestry subgroup. The analysis of 6,262 'undefined' significance alleles found 60 with elevated frequencies in specific ancestral subgroups, and 27% of those map to star allele haplotypes with definitive evidence. This dataset, authored by Rachele M. Hendricks-Sturrup and updated in April 2026, originates from the NIH All of Us Research Program.

Use Cases

• Identify ancestry-specific pharmacogenomic risk factors based on differential CYP2D6 allele frequencies.
• Prioritize variants for clinical reclassification based on 'undefined' alleles with high subgroup frequency.
• Validate star allele haplotypes by cross-referencing PharmVar evidence levels with population data.
• Assess the inclusivity of pharmacogenomic databases by comparing variant distributions across ancestral subgroups.

Strengths

• Focuses on a pharmacogenomically critical gene (CYP2D6) with high polymorphism.
• Analyzes a substantial number of alleles (6,262) classified as 'undefined' significance.
• Provides specific frequency thresholds (≥0.10) for identifying subgroup relevance.
• Cross-references expert resources like the PharmVar Consortium for variant evidence.

Limitations

• Column-level documentation is absent; field semantics must be inferred after download.
• Row count is unknown, which may limit suitability assessment.
• The 391.2 KB file size suggests a limited scope, likely summary statistics rather than raw genetic data.

Provenance

Source

National Institute of Health All of Us Research Program Data Browser

Collection Method

Allele frequency analysis and ClinVar/PharmVar cross-referencing as described in the paper.

Time Range

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Freshness

Last updated 2026-04-13 05:44:05

Geography

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