Psychiatry pharmacogenomics: Africans are not at the table

Adiukwu, Frances; Essien, Emmanuel; Adesokun, Olufisayo; Ofori, Sandra

doi:10.1016/s2215-0366(22)00432-1

Cited by 4 publications

(7 citation statements)

References 3 publications

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“…The prevalence of actionable phenotypes observed in our predominantly European ancestry cohort is similar to previous studies of individuals of European ancestry [42], and marked differences in CYP2D6 CNV rates (~2-fold) have previously been observed between geographic cohorts [43,44]. The predominance of White patients in this cohort may be exacerbated by racial disparities in the U.S. in receiving PGx testing to guide their care [45,46]. Actionable phenotypes were observed across all race and ethnicity categories in this cohort, albeit at lower frequencies in minority groups.…”

Section: Discussionsupporting

confidence: 86%

Pharmacogenomic insights in psychiatric care: uncovering novel actionability, allele-specific CYP2D6 copy number variation, and phenoconversion in 15,000 patients

Patel,

Morris,

Torres

et al. 2024

Mol Psychiatry

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Pharmacogenomic testing has emerged as an aid in clinical decision making for psychiatric providers, but more data is needed regarding its utility in clinical practice and potential impact on patient care. In this cross-sectional study, we determined the real-world prevalence of pharmacogenomic actionability in patients receiving psychiatric care. Potential actionability was based on the prevalence of CYP2C19 and CYP2D6 phenotypes, including CYP2D6 allele-specific copy number variations (CNVs). Combined actionability additionally incorporated CYP2D6 phenoconversion and the novel CYP2C-TG haplotype in patients with available medication data. Across 15,000 patients receiving clinical pharmacogenomic testing, 65% had potentially actionable CYP2D6 and CYP2C19 phenotypes, and phenotype assignment was impacted by CYP2D6 allele-specific CNVs in 2% of all patients. Of 4114 patients with medication data, 42% had CYP2D6 phenoconversion from drug interactions and 20% carried a novel CYP2C haplotype potentially altering actionability. A total of 87% had some form of potential actionability from genetic findings and/or phenoconversion. Genetic variation detected via next-generation sequencing led to phenotype reassignment in 22% of individuals overall (2% in CYP2D6 and 20% in CYP2C19). Ultimately, pharmacogenomic testing using next-generation sequencing identified potential actionability in most patients receiving psychiatric care. Early pharmacogenomic testing may provide actionable insights to aid clinicians in drug prescribing to optimize psychiatric care.

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Section: Discussionsupporting

confidence: 86%

Pharmacogenomic insights in psychiatric care: uncovering novel actionability, allele-specific CYP2D6 copy number variation, and phenoconversion in 15,000 patients

Patel,

Morris,

Torres

et al. 2024

Mol Psychiatry

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show abstract

“…or CYP2C19 phenotype which corresponded to a GDI based on CPIC guidelines and the FDA The prevalence of actionable phenotypes observed in our predominantly European ancestry cohort is similar to previous studies of individuals of European ancestry [36] , and marked differences in CYP2D6 CNV rates (~2-fold) have previously been observed between geographic cohorts [37,38] . The predominance of White patients in this cohort may be exacerbated by racial disparities in the U.S. in receiving PGx testing to guide their care [39,40] .…”

Section: Discussionmentioning

confidence: 98%

Pharmacogenomic Insights in Psychiatric Care: Uncovering Novel Actionability, Allele-Specific CYP2D6 Copy Number Variation, and Phenoconversion in 15,000 Patients

Stanton,

Patel,

Morris

et al. 2023

Preprint

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Pharmacogenomic testing has emerged as an aid in clinical decision-making for psychiatric providers, but more data is needed regarding its utility in clinical practice and potential impact on patient care. In this cross-sectional study, we determined the real-world prevalence of pharmacogenomic actionability in patients receiving psychiatric care. Potential actionability was based on the prevalence of CYP2C19 and CYP2D6 phenotypes, including CYP2D6 allele-specific copy number variations (CNVs). Combined actionability additionally incorporated CYP2D6 phenoconversion and the novel CYP2C-TG haplotype in patients with available medication data. Across 15,000 patients, 65% had potentially actionable CYP2D6 and CYP2C19 phenotypes, and phenotype assignment was impacted by CYP2D6 allele-specific CNVs in 2% of patients. Of 4,114 patients with medication data, 42% had CYP2D6 phenoconversion from drug interactions and 20% carried a novel CYP2C haplotype potentially altering actionability. A total of 87% had some form of actionability from genetic findings and/or phenoconversion, and genetic variation detected via next-generation sequencing led to phenotype reassignment in 22% of individuals overall (2% in CYP2D6 and 20% in CYP2C19). Ultimately, pharmacogenomic testing using next-generation sequencing identified potential actionability in most patients receiving psychiatric care. Early pharmacogenomic testing may provide actionable insights to aid clinicians in drug prescribing to optimize psychiatric care.

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“…This review has revealed that the field of pharmacogenomics research and PGx in Africa is still in its early stages and is likely to encounter several challenges during its implementation [104]. Firstly, various factors such as insufficient financial support for research, inadequate infrastructure, and a shortage of trained staff, laboratories, and equipment to perform the tests could challenge researchers to conduct pharmacogenomic studies [105].…”

Section: Challenges and Opportunities For Pharmacogenomics In Africamentioning

confidence: 99%

Section: Challenges and Opportunities For Pharmacogenomics In Africamentioning

confidence: 99%

“…This review has revealed that the field of pharmacogenomics research and PGx in Africa is still in its early stages and is likely to encounter several challenges during its implementation (115) (118)(119)(120)(121). Thirdly, research ethics can be complex, and the research process may take longer than expected as it requires consideration of the diverse cultural and religious beliefs of the people and ensuring that the research is conducted with respect and ethical principles.…”

Section: Challenges and Opportunities For Pharmacogenomics In Africamentioning

confidence: 99%

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Pharmacogenomic Diversity in Psychiatry: Challenges and Opportunities in Africa

Ahmed,

Mulugeta,

Okewole

et al. 2024

Preprint

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Background: Pharmacogenomic studies on psychiatric drugs have slowly identified genetic variations that influence drug metabolism and treatment effectiveness in patients with mental illness. Because most of these studies predominantly centered on people of European descent, there remains a substantial knowledge gap on the clinical implications of current pharmacogenomic evidence in multi-ancestry populations such as Africans. Thus, whether pharmacogenomic (PGx) genetic testing implemented in European populations would be valid for a population of African origin is unknown. The objective of this review was to appraise previous psychiatric pharmacogenomic studies in Africa and highlight challenges and opportunities to initiate PGx testing in the region. Methods: A systematic literature search was conducted on PubMed, Scopus, and Web of Science to identify studies published in the English language from inception up to February 06, 2023. The primary outcomes were treatment response, remission, side effects, and drug metabolism in African psychiatric patients. Results: The review included 42 pharmacogenomic studies that explored the genetic profiles of psychiatric patients in Africa. Despite the limited number of studies, our review found strong evidence of pharmacogenomic diversity within the African populations, highlighting the importance of pharmacogenomic research in this population. A high degree of variability and differences in the frequencies of cytochrome P450 (CYPs) genotypes have been reported within the African population. It is estimated that 28% of North Africans and Ethiopians are ultrarapid metabolizers of several medications, mainly attributed to the increased activity of the CYP2D6 enzyme. This is significantly higher than the prevalence among Caucasians (10%), or Hispanics, Chinese, or Japanese populations (1%). Due to the defective CYP2C19*2 allele (at a frequency of 14%) and CYP2C19*3 allele (2% frequency), 5.2% of Ethiopians were identified as poor metabolizers of S-mephenytoin, a probe substrate used to assess the activity of the cytochrome P450 enzyme. In Tunisian patients with schizophrenia, genotyping the CYP1A2 gene and using therapeutic drug monitoring (TDM) improved the effectiveness and safety of clozapine. Among South African patients with schizophrenia, antipsychotic treatment response was associated with two gene variants (rs13025959 in the MYO7B gene with the C allele and rs10380 in the MTRR gene with the T allele). Conclusion: The review has identified evidence of pharmacogenomic diversity in African populations and recommended expanding pharmacogenomic studies while introducing PGx testing in this population. For the few characterized genes, Africans showed qualitative and quantitative differences in the profile of pharmacogenetic variants when compared to other ethnic groups. Limited research funding, inadequate infrastructure, and a shortage of skilled human resources might be a challenge, but by building upon local successes and through collaborations with international partners, it is possible to establish pharmacogenomic biobanks and leverage global genetic resources to initiate personalized treatment approaches in Africa. Keywords: Pharmacogenomics, Personalized medicine, Psychiatric disorders, Africa, Genetic variants, depression, schizophrenia

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Psychiatry pharmacogenomics: Africans are not at the table

Cited by 4 publications

References 3 publications

Pharmacogenomic insights in psychiatric care: uncovering novel actionability, allele-specific CYP2D6 copy number variation, and phenoconversion in 15,000 patients

Pharmacogenomic insights in psychiatric care: uncovering novel actionability, allele-specific CYP2D6 copy number variation, and phenoconversion in 15,000 patients

Pharmacogenomic Insights in Psychiatric Care: Uncovering Novel Actionability, Allele-Specific CYP2D6 Copy Number Variation, and Phenoconversion in 15,000 Patients

Pharmacogenomic Diversity in Psychiatry: Challenges and Opportunities in Africa

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