Dataset Information

Applying an equity lens to pharmacogenetic research and translation to under-represented populations.

ABSTRACT: Since the publication of the Human Genome Project, genetic information has been used as an accepted, evidence-based biomarker to optimize patient care through the delivery of precision health. Pharmacogenetics (PGx) uses information about genes that encode proteins involved in pharmacokinetics, pharmacodynamics, and hypersensitivity reactions to guide clinical decision making to optimize medication therapy selection. Clinical PGx implementation is growing from the dramatic increase in PGx studies over the last decade. However, an overwhelming lack of genetic diversity in current PGx studies is evident. This lack of diverse representation in PGx studies will impede equitable clinical implementation through potentially inappropriate application of gene-based dosing algorithms, whereas representing a missed opportunity for identification of population specific single nucleotide variants and alleles. In this review, we discuss the challenges of studying PGx in under-represented populations, highlight two successful PGx studies conducted in non-European populations, and propose a path forward through community-based participatory research for equitable PGx research and clinical translation.

SUBMITTER: Luczak T

PROVIDER: S-EPMC8604241 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Applying an equity lens to pharmacogenetic research and translation to under-represented populations.

Luczak Tiana T Stenehjem David D Brown Jacob J

Clinical and translational science 20210730 6

Since the publication of the Human Genome Project, genetic information has been used as an accepted, evidence-based biomarker to optimize patient care through the delivery of precision health. Pharmacogenetics (PGx) uses information about genes that encode proteins involved in pharmacokinetics, pharmacodynamics, and hypersensitivity reactions to guide clinical decision making to optimize medication therapy selection. Clinical PGx implementation is growing from the dramatic increase in PGx studie ...[more]

PMID: 34268895

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Project description:Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses 'solved' or 'possibly solved' ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% 'solved' and ∼13% 'possibly solved' outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally.

Dataset Information

Applying an equity lens to pharmacogenetic research and translation to under-represented populations.

Publications

Applying an equity lens to pharmacogenetic research and translation to under-represented populations.

Similar Datasets

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