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Genes Oct 2020Digital health (DH) is the use of digital technologies and data analytics to understand health-related behaviors and enhance personalized clinical care. DH is... (Review)
Review
Digital health (DH) is the use of digital technologies and data analytics to understand health-related behaviors and enhance personalized clinical care. DH is increasingly being used in clinical trials, and an important field that could potentially benefit from incorporating DH into trial design is pharmacogenetics. Prospective pharmacogenetic trials typically compare a standard care arm to a pharmacogenetic-guided therapeutic arm. These trials often require large sample sizes, are challenging to recruit into, lack patient diversity, and can have complicated workflows to deliver therapeutic interventions to both investigators and patients. Importantly, the use of DH technologies could mitigate these challenges and improve pharmacogenetic trial design and operation. Some DH use cases include (1) automatic electronic health record-based patient screening and recruitment; (2) interactive websites for participant engagement; (3) home- and tele-health visits for patient convenience (e.g., samples for lab tests, physical exams, medication administration); (4) healthcare apps to collect patient-reported outcomes, adverse events and concomitant medications, and to deliver therapeutic information to patients; and (5) wearable devices to collect vital signs, electrocardiograms, sleep quality, and other discrete clinical variables. Given that pharmacogenetic trials are inherently challenging to conduct, future pharmacogenetic utility studies should consider implementing DH technologies and trial methodologies into their design and operation.
Topics: Computational Biology; Humans; Medical Informatics; Pattern Recognition, Automated; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; Telemedicine; Wearable Electronic Devices
PubMed: 33114567
DOI: 10.3390/genes11111261 -
Genes Sep 2021This narrative review aims to provide an overview of the main Machine Learning (ML) techniques and their applications in pharmacogenetics (such as antidepressant,... (Review)
Review
This narrative review aims to provide an overview of the main Machine Learning (ML) techniques and their applications in pharmacogenetics (such as antidepressant, anti-cancer and warfarin drugs) over the past 10 years. ML deals with the study, the design and the development of algorithms that give computers capability to learn without being explicitly programmed. ML is a sub-field of artificial intelligence, and to date, it has demonstrated satisfactory performance on a wide range of tasks in biomedicine. According to the final goal, ML can be defined as Supervised (SML) or as Unsupervised (UML). SML techniques are applied when prediction is the focus of the research. On the other hand, UML techniques are used when the outcome is not known, and the goal of the research is unveiling the underlying structure of the data. The increasing use of sophisticated ML algorithms will likely be instrumental in improving knowledge in pharmacogenetics.
Topics: Computational Biology; Machine Learning; Pharmacogenetics
PubMed: 34680905
DOI: 10.3390/genes12101511 -
Trends in Genetics : TIG Apr 2023Genome-wide association studies (GWAS) have now correlated hundreds of genetic variants with complex genetic diseases and drug efficacy. Functional characterization of... (Review)
Review
Genome-wide association studies (GWAS) have now correlated hundreds of genetic variants with complex genetic diseases and drug efficacy. Functional characterization of these factors remains challenging, particularly because of the lack of human model systems. Molecular and nanotechnological advances, in particular the ability to generate patient-specific PSC lines, differentiate them into diverse cell types, and seed and combine them on microfluidic chips, have led to the establishment of organ-on-a-chip (OoC) platforms that recapitulate organ biology. OoC technology thus provides unique personalized platforms for studying the effects of host genetics and environmental factors on organ physiology. In this review we describe the technology and provide examples of how OoCs may be used for disease modeling and pharmacogenetic research.
Topics: Humans; Induced Pluripotent Stem Cells; Microphysiological Systems; Pharmacogenetics; Genome-Wide Association Study; Human Genetics
PubMed: 36746737
DOI: 10.1016/j.tig.2023.01.002 -
Journal of Child and Adolescent... Feb 2024The efficacy and tolerability of psychotropic medications can vary significantly among children and adolescents, and some of this variability relates to pharmacogenetic... (Review)
Review
The efficacy and tolerability of psychotropic medications can vary significantly among children and adolescents, and some of this variability relates to pharmacogenetic factors. Pharmacogenetics (PGx) in child and adolescent psychiatry can potentially improve treatment outcomes and minimize adverse drug reactions. This article reviews key pharmacokinetic and pharmacodynamic genes and principles of pharmacogenetic testing and discusses the evidence base for clinical decision-making concerning PGx testing. This article reviews current guidelines from the United States Food and Drug Administration (FDA), the Clinical Pharmacogenetics Implementation Consortium (CPIC), and the Dutch Pharmacogenetics Working Group (DPWG) and explores potential future directions. This review discusses key clinical considerations for clinicians prescribing psychotropic medications in children and adolescents, focusing on antidepressants, antipsychotics, stimulants, norepinephrine reuptake inhibitors, and alpha-2 agonists. Finally, this review synthesizes the practical use of pharmacogenetic testing and clinical decision support systems.
Topics: United States; Child; Humans; Adolescent; Pharmacogenetics; Adolescent Psychiatry; Psychotropic Drugs; Antidepressive Agents; Pharmacogenomic Testing
PubMed: 38377525
DOI: 10.1089/cap.2023.0074 -
Clinical Pharmacology and Therapeutics Jul 2023Over 20% of US Food and Drug Administration (FDA)-approved drugs in the United States are metabolized by the hepatic enzyme cytochrome P450 2D6 (CYP2D6). The gene... (Review)
Review
Over 20% of US Food and Drug Administration (FDA)-approved drugs in the United States are metabolized by the hepatic enzyme cytochrome P450 2D6 (CYP2D6). The gene encoding CYP2D6 is highly polymorphic and genetic variation has been shown to impact drug response for many commonly dispensed drugs including opioids and antidepressants. Thus, it is important to understand an individual's CYP2D6 metabolizer status to optimize treatment outcomes for patients taking medications that are metabolized by this enzyme. Consequently, clinical CYP2D6 pharmacogenetic testing is being implemented by a growing number of health centers. Furthermore, clinical guidelines currently recommend adapting therapeutic regimens based on CYP2D6 genotype-informed phenotype. However, CYP2D6 genetic variation varies considerably across global populations and many allelic variants, or star alleles, are predominantly found in certain ancestral populations. Although CYP2D6 genetic variation has been extensively studied, there is still a paucity of information for many non-European populations. As has been shown for other pharmacogenes in randomized controlled trials, results from European populations cannot simply be extrapolated to other groups and, in some cases, even has the potential to cause harm. Therefore, enhanced inclusion in pharmacogenetic studies is urgently needed to increase ancestral representation, determine the extent of global CYP2D6 genetic variation (e.g., ancestry-specific variants), and determine the clinical impact of this variation on clinical treatment outcome. This review highlights knowledge gaps, challenges, and future directions in CYP2D6 pharmacogenomics through a unique pharmacoequity lens to address health inequities that hamper our ability to optimize drug therapy for improved pharmacological outcomes in diverse populations globally.
Topics: Cytochrome P-450 CYP2D6; Pharmacogenetics; Genotype; Antidepressive Agents; Pharmaceutical Preparations
PubMed: 36924260
DOI: 10.1002/cpt.2890 -
Pharmacopsychiatry Jul 2020Pharmacogenetics is the division of science addressing how genetic factors contribute to the metabolism, response, and side effects of a given medication. What was once... (Review)
Review
Pharmacogenetics is the division of science addressing how genetic factors contribute to the metabolism, response, and side effects of a given medication. What was once regarded as a subdivision of genetics and pharmacology is now recognized as its own field and has its own unique story of origin. While the term "pharmacogenetics" was coined by Friedrich Vogel in 1959, the relevance of inherited genetic traits in affecting the clinical outcome to xenobiotics has been observed long before. In fact, there is much hope that pharmacogenetics can help unravel the "mysteries" as to why different people may display variable responses to the same medication as well as identify new drug targets. This article will highlight the conceptual framework for pharmacogenetics advanced by pioneer scientists Arno Motulsky and Friedrich Vogel (both human geneticists), as well as Werner Kalow (clinical pharmacologist), leading up to the creation of modern pharmacogenetics. Finally, the practical implications and first steps toward implementation for current psychiatric treatment are reviewed followed by an outlook on future studies.
Topics: Germany; History, 20th Century; History, 21st Century; Humans; Mental Disorders; Pharmacogenetics; Precision Medicine; Psychiatry
PubMed: 31546266
DOI: 10.1055/a-0979-2322 -
Medicina Clinica Feb 2024
Topics: Humans; Pharmacogenetics; Precision Medicine
PubMed: 38142210
DOI: 10.1016/j.medcli.2023.11.008 -
Personalized Medicine Nov 2020The field of pharmacogenetic testing was hailed as one of the early successful clinical applications arising from the personalized (or precision) medicine revolution.... (Review)
Review
The field of pharmacogenetic testing was hailed as one of the early successful clinical applications arising from the personalized (or precision) medicine revolution. Substantial progress has been made to identify genes and genetic variants involved in drug response and establish clinical implementation programs. Yet, drug response is a complex trait and recent work has highlighted the key role played by the gut microbiome. As the study of the gut microbiome and pharmacogenetics converge, it may be possible to generate more precise predictions of drug response and improve health outcomes to treatments. Substantial effort will be needed to understand the dynamic impact of the microbiome and the interplay with host genetics and how to implement expanded pharmacogenetic testing.
Topics: Biomarkers, Pharmacological; Humans; Microbiota; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 33026284
DOI: 10.2217/pme-2020-0077 -
Methods in Molecular Biology (Clifton,... 2022Antipsychotics are the mainstay treatment for schizophrenia. There is large variability between individuals in their response to antipsychotics, both in efficacy and...
Antipsychotics are the mainstay treatment for schizophrenia. There is large variability between individuals in their response to antipsychotics, both in efficacy and adverse effects of treatment. While the source of interindividual variability in antipsychotic response is not completely understood, genetics is a major contributing factor. The identification of pharmacogenetic markers that predict antipsychotic efficacy and adverse reactions is a growing area of research and holds the potential to replace the current trial-and-error approach to treatment selection in schizophrenia with a personalized medicine approach.In this chapter, we provide an overview of the current state of pharmacogenetics in schizophrenia treatment. The most promising pharmacogenetic findings are presented for both antipsychotic response and commonly studied adverse reactions. The application of pharmacogenetics to schizophrenia treatment is discussed, with an emphasis on the clinical utility of pharmacogenetic testing and directions for future research.
Topics: Antipsychotic Agents; Humans; Pharmacogenetics; Precision Medicine; Schizophrenia
PubMed: 36068471
DOI: 10.1007/978-1-0716-2573-6_14 -
Clinical and Experimental Pharmacology... Aug 2019Genetic polymorphisms impact biological responses to drugs. Current pharmacogenomics guidelines formulated by different countries, such as the Clinical Pharmacogenetics... (Review)
Review
Genetic polymorphisms impact biological responses to drugs. Current pharmacogenomics guidelines formulated by different countries, such as the Clinical Pharmacogenetics Implementation Consortium, the Dutch Pharmacogenetics Working Group, the Canadian Pharmacogenomics Network for Drug Safety, and the French National Network (Réseau) of Pharmacogenetics, play important roles in clinical practices. However, the standards for these guidelines vary significantly, resulting in differences in recommendations. The present article discusses these differences by head-to-head comparison of the existing pharmacogenomics guidelines and proposes new strategies for their future development.
Topics: Guidelines as Topic; Humans; Pharmacogenetics
PubMed: 31009088
DOI: 10.1111/1440-1681.13097