The pharmacogenomic landscape of an Indigenous Australian population Article Swipe
Sumudu R. Samarasinghe
,
Wendy E. Hoy
,
Sudhir Jadhao
,
Brendan J. McMorran
,
Henk‐Jan Guchelaar
,
Shivashankar H. Nagaraj
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3389/fphar.2023.1180640
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3389/fphar.2023.1180640
Background: Population genomic studies of individuals of Indigenous ancestry have been extremely limited comprising <0.5% of participants in international genetic databases and genome-wide association studies, contributing to a “genomic gap” that limits their access to personalised medicine. While Indigenous Australians face a high burden of chronic disease and associated medication exposure, corresponding genomic and drug safety datasets are sorely lacking. Methods: To address this, we conducted a pharmacogenomic study of almost 500 individuals from a founder Indigenous Tiwi population. Whole genome sequencing was performed using short-read Illumina Novaseq6000 technology. We characterised the pharmacogenomics (PGx) landscape of this population by analysing sequencing results and associated pharmacological treatment data. Results: We observed that every individual in the cohort carry at least one actionable genotype and 77% of them carry at least three clinically actionable genotypes across 19 pharmacogenes. Overall, 41% of the Tiwi cohort were predicted to exhibit impaired CYP2D6 metabolism, with this frequency being much higher than that for other global populations. Over half of the population predicted an impaired CYP2C9, CYP2C19, and CYP2B6 metabolism with implications for the processing of commonly used analgesics, statins, anticoagulants, antiretrovirals, antidepressants, and antipsychotics. Moreover, we identified 31 potentially actionable novel variants within Very Important Pharmacogenes (VIPs), five of which were common among the Tiwi. We further detected important clinical implications for the drugs involved with cancer pharmacogenomics such as thiopurines and tamoxifen, immunosuppressants like tacrolimus and certain antivirals used in the hepatitis C treatment due to potential differences in their metabolic processing. Conclusion: The pharmacogenomic profiles generated in our study demonstrate the utility of pre-emptive PGx testing and have the potential to help guide the development and application of precision therapeutic strategies tailored to Tiwi Indigenous patients. Our research provides valuable insights on pre-emptive PGx testing and the feasibility of its use in ancestrally diverse populations, emphasizing the need for increased diversity and inclusivity in PGx investigations.
Related Topics
Concepts
Pharmacogenomics
Population
1000 Genomes Project
Medicine
Disease
Personalized medicine
Bioinformatics
Biology
Genetics
Genotype
Single-nucleotide polymorphism
Internal medicine
Gene
Environmental health
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fphar.2023.1180640
- OA Status
- gold
- Cited By
- 12
- References
- 71
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4377292411
All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4377292411Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3389/fphar.2023.1180640Digital Object Identifier
- Title
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The pharmacogenomic landscape of an Indigenous Australian populationWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-05-22Full publication date if available
- Authors
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Sumudu R. Samarasinghe, Wendy E. Hoy, Sudhir Jadhao, Brendan J. McMorran, Henk‐Jan Guchelaar, Shivashankar H. NagarajList of authors in order
- Landing page
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https://doi.org/10.3389/fphar.2023.1180640Publisher landing page
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
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https://doi.org/10.3389/fphar.2023.1180640Direct OA link when available
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Pharmacogenomics, Population, 1000 Genomes Project, Medicine, Disease, Personalized medicine, Bioinformatics, Biology, Genetics, Genotype, Single-nucleotide polymorphism, Internal medicine, Gene, Environmental healthTop concepts (fields/topics) attached by OpenAlex
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12Total citation count in OpenAlex
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2025: 3, 2024: 7, 2023: 2Per-year citation counts (last 5 years)
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71Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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