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An increasing number of economic evaluations are published annually investigating the economic effectiveness of pharmacogenomic (PGx) testing. This work was designed to provide a comprehensive summary of the available utility methods used in cost–effectiveness/cost–utility analysis studies of PGx interventions. A comprehensive review was conducted to identify economic analysis studies using a utility valuation method for PGx testing. A total of 82 studies met the inclusion criteria. A majority of studies were from the USA and used the EuroQol-5D questionnaire, as the utility valuation method. Cardiovascular disorders was the most studied therapeutic area while discrete-choice studies mainly focused on patients' willingness to undergo PGx testing. Future research in applying other methodologies in PGx economic evaluation studies would improve the current research environment and provide better results.

Patients with severe mental disorders such as bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD) show a substantial reduction in life expectancy, increased incidence of comorbid medical conditions commonly observed with advanced age and alterations of aging hallmarks. While severe mental disorders are heritable, the extent to which genetic predisposition might contribute to accelerated cellular aging is not known. We used bivariate causal mixture models to quantify the trait-specific and shared architecture of mental disorders and 2 aging hallmarks (leukocyte telomere length [LTL] and mitochondrial DNA copy number), and the conjunctional false discovery rate method to detect shared genetic loci. We integrated gene expression data from brain regions from GTEx and used different tools to functionally annotate identified loci and investigate their druggability. Aging hallmarks showed low polygenicity compared with severe mental disorders. We observed a significant negative global genetic correlation between MDD and LTL (rg= −0.14, p= 6.5E−10), and no significant results for other severe mental disorders or for mtDNA-cn. However, conditional QQ plots and bivariate causal mixture models pointed to significant pleiotropy among all severe mental disorders and aging hallmarks. We identified genetic variants significantly shared between LTL and BD (n= 17), SCZ (n= 55) or MDD (n= 19), or mtDNA-cn and BD (n= 4), SCZ (n= 12) or MDD (n= 1), with mixed direction of effects. The exonic rs7909129 variant in the SORCS3gene, encoding a member of the retromer complex involved in protein trafficking and intracellular/intercellular signaling, was associated with shorter LTL and increased predisposition to all severe mental disorders. Genetic variants underlying risk of SCZ or MDD and shorter LTL modulate expression of several druggable genes in different brain regions. Genistein, a phytoestrogen with anti-inflammatory and antioxidant effects, was an upstream regulator of 2 genes modulated by variants associated with risk of MDD and shorter LTL. While our results suggest that shared heritability might play a limited role in contributing to accelerated cellular aging in severe mental disorders, we identified shared genetic determinants and prioritized different druggable targets and compounds.

Personalized medicine is a novel frontier in health care that is based on each person’s unique genetic makeup. It represents an exciting opportunity to improve the future of individualized health care for all individuals. Pharmacogenomics, as the main part of personalized medicine, aims to optimize and create a more targeted treatment approach based on genetic variations in drug response. It is predicted that future treatments will be algorithm-based instead of evidence-based that will consider a patient’s genetic, transcriptomic, proteomic, epigenetic, and lifestyle factors resulting in individualized medication. A generative pretrained transformer (GPT) is an artificial intelligence (AI) tool that generates language resembling human-like writing enabling users to engage in a manner that is practically identical to speaking with a human being. GPT’s predictive algorithms can respond to questions that have never been addressed. Chat Generative Pretrained Transformer (ChatGPT) is an AI chatbot’s advanced with conversational capabilities. In the present study, questions were asked from ChatGPT about the future of personalized medicine and pharmacogenomics. ChatGPT predicted both to be a promising approach with a bright future that holds great promises in improving patient outcomes and transforming the field of medicine. But it still has several limitations that need to be solved.

The analysis of past epidemics and pandemics, either spontaneous or of human origin, may revise the physical history of microbiota and create a temporal context in our understanding regarding pathogen attributes like virulence, evolution, transmission and disease dynamics. The data of high-tech scientific methods seem reliable, but their interpretation may still be biased when tackling events of the distant past. Such endeavors should be adjusted to other cognitive resources including historical accounts reporting the events of interest and references in alien medical cultures and terminologies; the latter may contextualize them differently from current practices. Thus ‘historical microbiology’ emerges. Validating such resources requires utmost care, as these may be susceptible to different biases regarding the interpretation of facts and phenomena; biases partly due to methodological limitations.

The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene–drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed.

The heterogeneity of psychiatric disorders and the lack of reliable biomarkers for prediction and treatments follow-up pose difficulties towards recognition and understanding of the molecular basis of psychiatric diseases. However, several studies based on NGS approaches have shown that miRNAs could regulate gene expression during onset and disease progression and could serve as potential diagnostic and pharmacogenomics biomarkers during treatment. We provide herein a detailed overview of circulating miRNAs and their expression profiles as biomarkers in schizophrenia, bipolar disorder and major depressive disorder and their role in response to specific treatments. Bioinformatics analysis of miR-34a, miR-106, miR-134 and miR-132, which are common among SZ, BD and MDD patients, showed brain enrichment and involvement in the modulation of critical signaling pathways, which are often deregulated in psychiatric disorders. We propose that specific miRNAs support accurate diagnosis and effective precision treatment of psychiatric disorders.

Association between genomic variants and athletic performance has seen a high degree of controversy, as there is often conflicting data as far as the association of genomic variants with endurance, speed and strength is concerned. Here, findings from a thorough meta-analysis from 4228 articles exploring the association of genomic variants with athletic performance in power and endurance sports are summarized, aiming to confirm or overrule the association of genetic variants with athletic performance of all types. From the 4228 articles, only 107 were eligible for further analysis, including 37 different genes. From these, there were 21 articles for the ACEgene, 29 articles for the ACTN3gene and 8 articles for both the ACEand ACTN3genes, including 54,382 subjects in total, from which 11,501 were endurance and power athletes and 42,881 control subjects. These data show that there is no statistically significant association between genomic variants and athletic performance either for endurance or power sports, underlying the fact that it is highly risky and even unethical to make such genetic testing services for athletic performance available to the general public. Overall, a strict regulatory monitoring should be exercised by health and other legislative authorities to protect the public from such services from an emerging discipline that still lacks the necessary scientific evidence and subsequent regulatory approval.

Background: Pharmacogenomics (PGx) constitutes an important part of personalized medicine and has several clinical applications. PGx role in clinical practice is known, however, it has not been widely adopted yet. In this study, we aim to investigate the perspectives of Greek physicians regarding the implementation of PGx testing in clinical practice and the key issues associated with it. Methods: Fourteen interviews were conducted with physicians of various specialties for which PGx applications are available. A semi-structured interview guide was utilized based on the Consolidated Framework for Implementation Research (CFIR) context and the Diffusion of Innovation model. Transcripts were coded independently and compared by two members of the research team. Descriptive statistics were generated using Microsoft Excel. Results: Six main themes emerged: awareness and use of PGx testing; source of information; key stakeholders of the PGx supply chain, their interactions and change agents; clinical benefit and significance of PGx testing; barriers and lack of reimbursement; and recommendations to boost the PGx adoption rate. Most respondents were aware of PGx applications, but only three had already recommended PGx testing. Peer-reviewed journals along with clinical guidelines were regarded as the most used source of information while stakeholders of the PGx supply chain were discussed. PGx was considered that promote patient-centered care, enhance medication clinical effectiveness, decrease the risk of side effects, and reduce healthcare costs. Lack of reimbursement, scarcity of resources, and high PGx cost were the foremost barriers affecting PGx adoption. Conclusions: It was concluded that if case PGx testing is reimbursed and physicians’ training is reinforced, PGx implementation will be boosted and improved shortly.

Background: Clopidogrel is a widely prescribed prodrug that requires activation via specific pharmacogenes to exert its anti-platelet function. Genetic variations in the genes encoding its transporter, metabolizing enzymes, and target receptor lead to variability in its activation and platelet inhibition and, consequently, its efficacy. This variability increases the risk of secondary cardiovascular events, and therefore, some variations have been utilized as genetic biomarkers when prescribing clopidogrel. Methods: Our study examined clopidogrel-related genes (CYP2C19, ABCB1, PON1,and P2Y12R)in a cohort of 298 healthy Emiratis individuals. The study used whole exome sequencing (WES) data to comprehensively analyze pertinent variations of these genes, including their minor allele frequencies, haplotype distribution, and their resulting phenotypes. Results: Our data shows that approximately 37% (n= 119) of the cohort are likely to benefit from the use of alternative anti-platelet drugs due to their classification as intermediate or poor CYP2C19metabolizers. Additionally, more than 50% of the studied cohort exhibited variants in ABCB1, PON1, and P2YR12genes, potentially influencing clopidogrel’s transport, enzymatic clearance, and receptor performance. Conclusions: Recognizing these alleles and genotype frequencies may explain the clinical differences in medication response across different ethnicities and predict adverse events. Our findings underscore the need to consider genetic variations in prescribing clopidogrel, with potential implications for implementing personalized anti-platelet therapy among Emiratis based on their genetic profiles.

The objective of this study was to estimate the cost-effectiveness of CYP3A5genotype-guided tacrolimus dosing in kidney, liver, heart, and lung transplant recipients relative to standard of care (SOC) tacrolimus dosing, from a US healthcare payer perspective. We developed decision-tree models to compare economic and clinical outcomes between CYP3A5genotype-guided and SOC tacrolimus therapy in the first six months post-transplant. We derived inputs for CYP3A5 phenotype frequencies and physician use of genotype test results to inform clinical care from literature; tacrolimus exposure [high vs low tacrolimus time in therapeutic range using the Rosendaal algorithm (TAC TTR-Rosendaal)] and outcomes (incidences of acute tacrolimus nephrotoxicity, acute cellular rejection, and death) from real-world data; and costs from the Medicare Fee Schedule and literature. We calculated cost per avoided event and performed sensitivity analyses to evaluate the robustness of the results to changes in inputs. Incremental costs per avoided event for CYP3A5genotype-guided vs SOC tacrolimus dosing were $176,667 for kidney recipients, $364,000 for liver recipients, $12,982 for heart recipients, and $93,333 for lung recipients. The likelihood of CYP3A5genotype-guided tacrolimus dosing leading to cost-savings was 19.8% in kidney, 32.3% in liver, 51.8% in heart, and 54.1% in lung transplant recipients. Physician use of genotype results to guide clinical care and the proportion of patients with a high TAC TTR-Rosendaal were key parameters driving the cost-effectiveness of CYP3A5genotype-guided tacrolimus therapy. Relative to SOC, CYP3A5genotype-guided tacrolimus dosing resulted in a slightly greater benefit at a higher cost. Further economic evaluations examining intermediary outcomes (e.g., dose modifications) are needed, particularly in populations with higher frequencies of CYP3A5 expressers.

Fragoulakis et al. claimed in previous work that pharmacogenomics-guided clopidogrel strategy represents a cost-effective treatment for patients undergoing PCI. We present here a formalization of that claim, stating that all things of class “pharmacogenomics guided clopidogrel therapy” that are in the context of a thing of class “patient undergoing PCI” generally have a relation of type “enables” to a thing of class “cost-effective treatment” in the same context.

Aim:Regardless of the plethora of next-generation sequencing studies in the field of pharmacogenomics (PGx), the potential effect of covariate variables on PGx response within deeply phenotyped cohorts remains unexplored. Materials & methods:We explored with advanced statistical methods the potential influence of BMI, as a covariate variable, on PGx response in a Greek cohort with psychiatric disorders. Results:Nine PGx variants within UGT1A6, SLC22A4, GSTP1, CYP4B1, CES1, SLC29A3and DPYDwere associated with altered BMI in different psychiatric disorder groups. Carriers of rs2070959 (UGT1A6), rs199861210 (SLC29A3) and rs2297595 (DPYD) were also characterized by significant changes in the mean BMI, depending on the presence of psychiatric disorders. Conclusion:Specific PGx variants are significantly associated with BMI in a Greek cohort with psychiatric disorders.

Carbamazepine (CBZ)-induced Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are strongly associated with the HLA-B*15:02allele. Screening HLA-B*15:02before CBZ administration might prevent CBZ-induced SJS/TEN by enabling clinicians to prescribe alternative therapy for positive patients. Similar to other Southeastern Asian countries, HLA-B*15:02is highly prevalent in Indonesia. Therefore, we assessed the economic value of HLA-B*15:02screening before CBZ prescription to patients with epilepsy in Indonesia. A generic cost-effectiveness model and decision support tool, developed to enable users to perform an initial cost-effectiveness analysis from a healthcare provider/payer perspective, were used to assess the value of HLA-B*15:02genotyping. The incremental cost-effectiveness ratio of adopting universal HLA-B*15:02screening was 656,444,671 Indonesian Rupiah (IDR)/quality-adjusted life year (QALY) gained for patients compared with 2,634,975,574 IDR/QALY gained for providing valproic acid (alternative drug) without screening. Thus, neither HLA-B*15:02screening nor substitution with VPA meets the Indonesian threshold for cost effectiveness. However, the improved outcomes with this test in other Asian countries may inform the desirability of implementation in Indonesia even with suboptimal cost-effectiveness.

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Pharmacogenomics is considered to be the low-hanging fruit in the tree of genomic medicine with numerous examples of its successful implementation in the clinic. In this perspective, we provide details about the potential clinical application of pharmacogenomics in African populations by using relevant drug cases and high-throughput genomics approaches; involving numerous countries and stakeholders; and most importantly exploiting the existing knowledge of respective large-scale initiatives. We emphasize on the necessity of constructing appropriate frameworks for government policies in African countries. We also provide input about different initiatives in the field of genomics medicine implementation in Africa, not only for their potential for synergy and collaboration among them, but also as models for replication in other regions worldwide, aiming for healthcare improvement.

Nowadays, many relevant drug–gene associations have been discovered, but pharmacogenomics (PGx)-guided treatment needs to be cost-effective as well as clinically beneficial to be incorporated into standard health care. To address current challenges, this systematic review provides an update regarding previously published studies, which assessed the cost-effectiveness of PGx testing for the prescription of antidepressants and antipsychotics. From a total of 1159 studies initially identified by literature database querying, and after manual assessment and curation of all of them, a mere 18 studies met our inclusion criteria. Of the 18 studies evaluations, 16 studies (88.89%) drew conclusions in favor of PGx testing, of which 9 (50%) genome-guided interventions were cost-effective and 7 (38.9%) were less costly compared to standard treatment based on cost analysis. More precisely, supportive evidence exists for CYP2D6and CYP2C19drug–gene associations and for combinatorial PGx panels, but evidence is limited for many other drug–gene combinations. Amongst the limitations of the field are the unclear explanation of perspective and cost inputs, as well as the underreporting of study design elements, which can influence though the economic evaluation. Overall, the findings of this article demonstrate that although there is growing evidence on the cost-effectiveness of genome-guided interventions in psychiatric diseases, there is still a need for performing additional research on economic evaluations of PGx implementation with an emphasis on psychiatric disorders.

Pharmacogenomics (PGx) implementation in clinical practice is steadily increasing. PGx uses genetic information to personalize medication use, which increases medication efficacy and decreases side effects. The availability of clinical PGx guidelines is essential for its implementation in clinical settings. Currently, there are few organizations/associations responsible for releasing those guidelines, including the Clinical Pharmacogenetics Implementation Consortium, Dutch Pharmacogenetics Working Group, the Canadian Pharmacogenomics Network for Drug Safety and the French National Network of Pharmacogenetics. According to the US FDA, oncology medications are highly correlated to PGx biomarkers. Therefore, summarizing the PGx guidelines for oncology drugs will positively impact the clinical decisions for cancer patients. This review aims to scrutinize side-by-side available clinical PGx guidelines in oncology.

The pharmacists’ role is potentially vital in the growing field of personalized medicine, and well-defined guidelines and knowledge that support this role need to be established. To address the knowledge gap, over the past two decades, pharmacy schools have started providing pharmacogenomics-related courses, a field that overlaps with pharmacy and personalized medicine. Given the fact that pharmacists lead 50% of the Clinical Pharmacogenetics Implementation Consortium implementers’ sites, their role can be particularly crucial to move forward the integration of precision medicine in clinical practice. Herein, we aim to identify the educational challenges for pharmacogenomics integration into clinical practice and their impact on pharmacists’ knowledge and confidence, in addition to underscoring pharmacists’ role in pharmacogenomics as a whole.

Clinical implementation of pharmacogenomics and personalized medicine interventions relies on addressing important financial aspects of the delivery of genetic testing to the patients, be it from public or private providers. Details on how to determine the cost items of the genetic testing are often limited. The goal of this study is to present a costing methodology in order to estimate and measure the costs as far as the technical process of pharmacogenomics testing is concerned. Moreover, an overall cost mindset strategy based on the selective genotyping workflow to guide specialized laboratories of interest effectively is provided. We particularly accounted for the resources consumed within the laboratory premises such as cost of reagents for DNA isolation, cost of consumables, cost of personnel, while costs associated with patient recruitment, blood sample collection and maintenance, administration costs in the hospital, and costs of blood sample shipment were not taken into consideration. Our article presents the first-time detailed information on a costing framework for pharmacogenomic testing that could be employed to laboratories involved in routine clinical implementation of pharmacogenomics.

The incorporation of personalized medicine interventions into routine healthcare constitutes an opportunity to improve patients' quality of life, as it empowers implementation of innovative, individualized clinical interventions that maximize efficacy and/or minimize the risk of adverse drug reactions. In order to ensure equal access to genomic testing for all patients, the costs associated with these interventions must be reimbursed by payers and insurance bodies. As such, it is of utmost importance to thoroughly evaluate these interventions both in terms of their clinical effectiveness and their economic cost. This article discusses the impact of personalized medicine interventions in terms of both health outcomes and value, which directly impacts on their pricing and reimbursement by the various national healthcare systems.

Myelodysplastic syndromes (MDS) consist of a group of hematological malignancies characterized by ineffective hematopoiesis, cytogenetic abnormalities, and often a high risk of transformation to acute myeloid leukemia (AML). So far, there have been only a very limited number of studies assessing the epigenetics component contributing to the pathophysiology of these disorders, but not a single study assessing this at a genome-wide level. Here, we implemented a generic high throughput epigenomics approach, using methylated DNA sequencing (MeD-seq) of LpnPI digested fragments to identify potential epigenomic targets associated with MDS subtypes. Our results highlighted that PCDHGand ZNFgene families harbor potential epigenomic targets, which have been shown to be differentially methylated in a variety of comparisons between different MDS subtypes. Specifically, CpG islands, transcription start sites and post-transcriptional start sites within ZNF124, ZNF497and PCDHGfamily are differentially methylated with fold change above 3,5. Overall, these findings highlight important aspects of the epigenomic component of MDS syndromes pathogenesis and the pharmacoepigenomic basis to the hypomethylating agents drug treatment response, while this generic high throughput whole epigenome sequencing approach could be readily implemented to other genetic diseases with a strong epigenetic component.

Background: Cardiovascular diseases and especially Acute Coronary Syndrome (ACS) constitute a major health issue impacting millions of patients worldwide. Being a leading cause of death and hospital admissions in many European countries including Spain, it accounts for enormous amounts of healthcare expenditures for its management. Clopidogrel is one of the oldest antiplatelet medications used as standard of care in ACS. Methods: In this study, we performed an economic evaluation study to estimate whether a genome-guided clopidogrel treatment is cost-effective compared to conventional one in a large cohort of 243 individuals of Spanish origin suffering from ACS and treated with clopidogrel. Data were derived from the U-PGx PREPARE clinical trial. Effectiveness was measured as survival of individuals while study data on safety and efficacy, as well as on resource utilization associated with each adverse drug reaction were used to measure costs to treat these adverse drug reactions. A generalized linear regression model was used to estimate cost differences for both study groups. Results: Based on our findings, PGx-guided treatment group is cost-effective. PGx-guided treatment demonstrated to have 50% less hospital admissions, reduced emergency visits and almost 13% less ADRs compared to the non-PGx approach with mean QALY 1.07 (95% CI, 1.04–1.10) versus 1.06 (95% CI, 1.03–1.09) for the control group, while life years for both groups were 1.24 (95% CI, 1.20–1.26) and 1.23 (95% CI, 1.19–1.26), respectively. The mean total cost of PGx-guided treatment was 50% less expensive than conventional therapy with clopidogrel [€883 (95% UI, €316–€1582), compared to €1,755 (95% UI, €765–€2949)]. Conclusion: These findings suggest that PGx-guided clopidogrel treatment represents a cost-effective option for patients suffering from ACS in the Spanish healthcare setting.

Background: Pharmacists’ contribution to pharmacogenomics (PGx) implementation in clinical practice is vital, but a great proportion of them are not aware of PGx and its applications. This highlights the university education’s crucial role to prepare pharmacists to face future challenges in such a constantly evolving and demanding environment. Objectives: Our study aims to examine pharmacy students’ training satisfaction, knowledge, self-confidence and attitudes towards PGx on their intentions for postgraduate training in PGx and personalised medicine (PM). Methods: An initial model on students’ intention to pursue postgraduate training in PGx and PM and its predicting factors, based on the Theory of Planned Behaviour (TPB), was proposed. Based on it, a questionnaire was developed and distributed to 346 pharmacy students of all study years, capturing the selected factors influencing students’ intentions to postgraduate training in PGx and PM, as well as their demographics. Structural equation modelling (SEM) analysis was employed to determine the effects of both the examined factors and demographics on students’ intentions. Results: Students did not consider themselves adequately prepared for using PGx in clinical practice. Their attitudes towards PGx implementation were the most important factor influencing their intentions to pursue postgraduate training in PGx and PM. Other factors such as self-confidence and training satisfaction also affected students’ intentions, but to a lower extent. Students of the last two study years (40% of the whole sample) and male (36%) students stated to be less willing to pursue PGx-related studies in the future. Only 10% of the participants claimed to have undergone a recent PGx or genetic test, but this did not affect their intentions. Conclusion: There is an important gap in pharmacy school curriculum regarding PGx and PM training which coupled with the slow rate of PGx and PM implementation into clinical practice seems to restrain students’ aspiration to further expand their knowledge and horizons in terms of PGx and PM.

Background: This pilot study aims to identify and functionally assess pharmacovariants in whole exome sequencing data. While detection of known variants has benefited from pharmacogenomic-dedicated bioinformatics tools before, in this paper we have tested novel deep computational analysis in addition to artificial intelligence as possible approaches for functional analysis of unknown markers within less studied drug-related genes. Methods: Pharmacovariants from 1800 drug-related genes from 100 WES data files underwent (a) deep computational analysis by eight bioinformatic algorithms (overall containing 23 tools) and (b) random forest (RF) classifier as the machine learning (ML) approach separately. ML model efficiency was calculated by internal and external cross-validation during recursive feature elimination. Protein modelling was also performed for predicted highly damaging variants with lower frequencies. Genotype–phenotype correlations were implemented for top selected variants in terms of highest possibility of being damaging. Results: Five deleterious pharmacovariants in the RYR1, POLG, ANXA11, CCNH, and CDH23genes identified in step (a) and subsequent analysis displayed high impact on drug-related phenotypes. Also, the utilization of recursive feature elimination achieved a subset of 175 malfunction pharmacovariants in 135 drug-related genes that were used by the RF model with fivefold internal cross-validation, resulting in an area under the curve of 0.9736842 with an average accuracy of 0.9818 (95% CI: 0.89, 0.99) on predicting whether a carrying individuals will develop adverse drug reactions or not. However, the external cross-validation of the same model indicated a possible false positive result when dealing with a low number of observations, as only 60 important variants in 49 genes were displayed, giving an AUC of 0.5384848 with an average accuracy of 0.9512 (95% CI: 0.83, 0.99). Conclusion: While there are some technologies for functionally assess not-interpreted pharmacovariants, there is still an essential need for the development of tools, methods, and algorithms which are able to provide a functional prediction for every single pharmacovariant in both large-scale datasets and small cohorts. Our approaches may bring new insights for choosing the right computational assessment algorithms out of high throughput DNA sequencing data from small cohorts to be used for personalized drug therapy implementation.

The unique physiological and genetic characteristics of individuals influence their reactions to different dietary constituents and nutrients. This notion is the foundation of personalized nutrition. The field of nutrigenetics has witnessed significant progress in understanding the impact of genetic variants on macronutrient and micronutrient levels and the individual's responsiveness to dietary intake. These variants hold significant value in facilitating the development of personalized nutritional interventions, thereby enabling the effective translation from conventional dietary guidelines to genome-guided nutrition. Nevertheless, certain obstacles could impede the extensive implementation of individualized nutrition, which is still in its infancy, such as the polygenic nature of nutrition-related pathologies. Consequently, many disorders are susceptible to the collective influence of multiple genes and environmental interplay, wherein each gene exerts a moderate to modest effect. Furthermore, it is widely accepted that diseases emerge because of the intricate interplay between genetic predisposition and external environmental influences. In the context of this specific paradigm, the utilization of advanced "omic" technologies, including epigenomics, transcriptomics, proteomics, metabolomics, and microbiome analysis, in conjunction with comprehensive phenotyping, has the potential to unveil hitherto undisclosed hereditary elements and interactions between genes and the environment. This review aims to provide up-to-date information regarding the fundamentals of personalized nutrition, specifically emphasizing the complex triangulation interplay among microbiota, dietary metabolites, and genes. Furthermore, it highlights the intestinal microbiota's unique makeup, its influence on nutrigenomics, and the tailoring of dietary suggestions. Finally, this article provides an overview of genotyping versus microbiomics, focusing on investigating the potential applications of this knowledge in the context of tailored dietary plans that aim to improve human well-being and overall health.

Introduction: The adoption and implementation of genomic medicine and pharmacogenomics (PGx) in healthcare systems have been very slow and limited worldwide. Major barriers to knowledge translation into clinical practice lie in the level of literacy of the public of genetics and genomics. The aim of this study was to assess the knowledge, attitudes, and perceptions of the United Arab Emirates (UAE) multi-ethnic communities toward genomic medicine and genetic testing. Method: A cross-sectional study using validated questionnaires was distributed to the participants. Descriptive statistics were performed, and multivariable logistic regression models were used to identify factors associated with knowledge of genomics. Results: 757 individuals completed the survey. Only 7% of the participants had a good knowledge level in genetics and genomics (95% CI 5.3–9.0%). However, 76.9% of the participants were willing to take a genetic test if their relatives had a genetic disease. In addition, the majority indicated that they would disclose their genetic test results to their spouses (61.5%) and siblings (53.4%). Conclusions: This study sets the stage for the stakeholders to plan health promotion and educational campaigns to improve the genomic literacy of the community of the UAE as part of their efforts for implementing precision and personalized medicine in the country.

The Pharmacogenomics Access & Reimbursement Symposium, a landmark event presented by the Golden Helix Foundation and the Pharmacogenomics Access & Reimbursement Coalition (PARC), was a one-day interactive meeting comprised of plenary keynotes from thought leaders across health care that focused on value-based strategies to improve patient access to personalized medicine. Stakeholders including patients, healthcare providers, industry, government agencies, payer organizations, health systems and health policy organizations convened to define opportunities to improve patient access to personalized medicine through best practices, successful reimbursement models, high-quality economic evaluations, and strategic alignment. Session topics included health technology assessment, health economics, health policy, and value-based payment models and innovation.

Implementation of personalized medicine in the clinic is a lengthy and multifaceted approach that is also dependent on the raising of the general public's awareness of genomics. The Festival of Genetics and Personalized Medicine aims to familiarize the general public with the principles and applications of genetics and personalized medicine using numerous approaches – namely, a theatrical performance; a roundtable discussion of emerging topics in the field, such as pharmacogenomics, clinical genetics, bioinformatics, bioethics and health economics; the ‘Genome: Unlocking Life's Code’ exhibition, with its do-it-yourself format; and a live demonstration of 2MoBiL, a portable molecular biology laboratory. This festival attracted more than 900 participants and helped disseminate to a broader audience the principles of genetics and personalized medicine.

The Pharmacogenomics Access & Reimbursement Symposium, a landmark event presented by the Golden Helix Foundation and the Pharmacogenomics Access & Reimbursement Coalition, was a 1-day interactive meeting comprised of plenary keynotes from thought leaders across healthcare that focused on value-based strategies to improve patient access to personalized medicine. Stakeholders including patients, healthcare providers, industry, government agencies, payer organizations, health systems and health policy organizations convened to define opportunities to improve patient access to personalized medicine through best practices, successful reimbursement models, high quality economic evaluations and strategic alignment. Session topics included health technology assessment, health economics, health policy and value-based payment models and innovation.

Clopidogrel is an antiplatelet drug given to patients before and after having a percutaneous coronary intervention (PCI). Genomic variants in the CYP2C19gene are associated with variable enzyme activities affecting drug metabolism and hence, patients with reduced or increased enzymatic function have increased risk of bleeding. We conducted a cost-effectiveness analysis to compare a pharmacogenomics versus a non-pharmacogenomics-guided clopidogrel treatment for coronary artery syndrome patients undergoing PCI in the Spanish healthcare setting. A total of 549 patients diagnosed with coronary artery disease followed by PCI were recruited. Dual antiplatelet therapy was administrated to all patients from 1 to 12 months after PCI. Patients were classified into two groups: the Retrospective group was treated with clopidogrel based on the clinical routine practice and the Prospective group were initially genotyped for the presence of CYP2C19variant alleles before treatment with those carrying more than one CYP2C19variant alleles given prasugrel treatment. We collected data on established clinical and health outcome measures, including, per treatment arm: the percentage of patients that suffered from (a) myocardial infraction, (b) major bleeding and minor bleeding, (c) stroke, (d) the number of hospitalization days, and (e) the number of days patients spent in Intensive Care Unit. Our primary outcome measure for the cost-effectiveness analysis was Quality Adjusted Life Years (QALYs). To estimate the treatment cost for each patient, individual data on its resource used were combined with unit price data, obtained from Spanish national sources. The analysis predicts a survival of 0.9446 QALYs in the pharmacogenomics arm and 0.9379 QALYs in the non-pharmacogenomics arm within a 1-year horizon. The cumulative costs per patient were €2971 and €3205 for the Prospective and Retrospective groups, respectively. The main cost driver of total cost in both arms was hospitalization costs. The incremental cost-effectiveness ratio (ICER) was negative indicating that the PGx was a dominant option. Our data show that pharmacogenomics-guided clopidogrel treatment strategy may represent a cost-effective choice compared with non-pharmacogenomics-guided strategy for patients undergoing PCI.

Aim:β-Type hemoglobinopathies are characterized by vast phenotypic diversity as far as disease severity is concerned, while differences have also been observed in hydroxyurea (HU) treatment efficacy. These differences are partly attributed to the residual expression of fetal hemoglobin (HbF) in adulthood. The Krüppel-like family of transcription factors (KLFs) are a set of zinc finger DNA-binding proteins which play a major role in HbF regulation. Here, we explored the possible association of variants in KLFgene family members with response to HU treatment efficacy and disease severity in β-hemoglobinopathies patients. Materials & methods:Six tag single nucleotide polymorphisms, located in four KLFgenes, namely KLF3, KLF4, KLF9and KLF10, were analyzed in 110 β-thalassemia major patients (TDT), 18 nontransfusion dependent β-thalassemia patients (NTDT), 82 sickle cell disease/β-thalassemia compound heterozygous patients and 85 healthy individuals as controls. Results:Our findings show that a KLF4genomic variant (rs2236599) is associated with HU treatment efficacy in sickle cell disease/β-thalassemia compound heterozygous patients and two KLF10genomic variants (rs980112, rs3191333) are associated with persistent HbF levels in NTDT patients. Conclusion:Our findings provide evidence that genomic variants located in KLF10gene may be considered as potential prognostic biomarkers of β-thalassemia clinical severity and an additional variant in KLF4gene as a pharmacogenomic biomarker, predicting response to HU treatment.

Aim:Microbiota–host–xenobiotics interactions in humans become of prime interest when clinical pharmacogenomics is to be implemented. Despite the advent of technology, information still needs to be translated into knowledge for optimum patient stratification and disease management. Material & methods:Herein, we mined metagenomic, pharmacometagenomic and pharmacomicrobiomic datasets to map microbiota–host–drugs networks. Results:Datasets were multifaceted and voluminous. Interoperability, data sparsity and scarcity remain a challenge. Mapping microbiota–host–drugs networks allowed the prediction of drug response/toxicity and modulation of the microbiota–host–drugs interplay. Conclusion:Our approach triangulated microbiota, host and drug networks revealing the need for contextual data and open science via microattribution to accelerate knowledge growth. Our findings may serve as a data storehouse for a user-friendly query system, coupled with databanks and databases.

We aimed to clarify the emerging epigenetic landscape in a group of genes classified as “modifier genes” of the β-type globin genes (HBBcluster), known to operate in transto accomplish the two natural developmental switches in globin expression, from embryonic to fetal during the first trimester of conception and from fetal to adult around the time of birth. The epigenetic alterations were determined in adult sickle cell anemia (SCA) homozygotes and SCA/β-thalassemia compound heterozygotes of Greek origin, who are under hydroxyurea (HU) treatment. Patients were distinguished in HU responders and HU non-responders (those not benefited from the HU) and both, and in vivo and in vitro approaches were implemented. We examined the CpG islands’ DNA methylation profile of BCL11A, KLF1, MYB, MAP3K5, SIN3A, ZBTB7A, and GATA2, along with γ-globin and LRF/ZBTB7Aexpression levels. In vitro treatment of hematopoietic stem cells (HSCs) with HU induced a significant DNA hypomethylation pattern in ZBTB7A(p*, 0.04) and GATA2(p*, 0.03) CpGs exclusively in the HU non-responders. Also, this group of patients exhibited significantly elevated baseline methylation patterns in ZBTB7A, before the HU treatment, compared to HU responders (p*, 0.019) and to control group of healthy individuals (p*, 0.021), which resembles a potential epigenetic barrier for the γ-globin expression. γ-Globin expression in vitro matched with detected HbF levels during patients’ monitoring tests (in vivo) under HU treatment, implying a good reproducibility of the in vitro HU epigenetic effect. LRF/ZBTB7Aexpression was elevated only in the HU non-responders under the influence of HU. This is one of the very first pharmacoepigenomic studies indicating that the hypomethylation of ZBTB7Aduring HU treatment enhances the LRF expression, which by its turn suppresses the HbF resumption in the HU non-responders. Its role as an epigenetic regulator of hemoglobin switching is also supported by the wide distribution of ZBTB7A-binding sites within the 5′ CpG sequences of all studied human HBBcluster “modifier genes.” Also, the baseline methylation level of selective CpGs in ZBTB7Aand GATA2could be an indicator of the negative HU response among the β-type hemoglobinopathy patients.

Mood stabilizers are the cornerstone in treatment of mood disorders, but their use is characterized by high interindividual variability. This feature has stimulated intensive research to identify predictive biomarkers of response and disentangle the molecular bases of their clinical efficacy. Nevertheless, findings from studies conducted so far have only explained a small proportion of the observed variability, suggesting that factors other than DNA variants could be involved. A growing body of research has been focusing on the role of epigenetics and metabolomics in response to mood stabilizers, especially lithium salts. Studies from these approaches have provided new insights into the molecular networks and processes involved in the mechanism of action of mood stabilizers, promoting a systems-level multiomics synergy. In this article, we reviewed the literature investigating the involvement of epigenetic mechanisms, noncoding RNAs and metabolomic modifications in bipolar disorder and the mechanism of action and clinical efficacy of mood stabilizers.

Amyotrophic lateral sclerosis (ALS) is a devastating disease whose complex pathology has been associated with a strong genetic component in the context of both familial and sporadic disease. Herein, we adopted a next-generation sequencing approach to Greek patients suffering from sporadic ALS (together with their healthy counterparts) in order to explore further the genetic basis of sporadic ALS (sALS). Whole-genome sequencing analysis of Greek sALS patients revealed a positive association between FTOand TBC1D1gene variants and sALS. Further, linkage disequilibrium analyses were suggestive of a specific disease-associated haplotype for FTOgene variants. Genotyping for these variants was performed in Greek, Sardinian, and Turkish sALS patients. A lack of association between FTOand TBC1D1variants and sALS in patients of Sardinian and Turkish descent may suggest a founder effect in the Greek population. FTOwas found to be highly expressed in motor neurons, while in silico analyses predicted an impact on FTOand TBC1D1mRNA splicing for the genomic variants in question. To our knowledge, this is the first study to present a possible association between FTOgene variants and the genetic etiology of sALS. In addition, the next-generation sequencing-based genomics approach coupled with the two-step validation strategy described herein has the potential to be applied to other types of human complex genetic disorders in order to identify variants of clinical significance.

Human erythropoiesis is characterized by distinct gene expression profiles at various developmental stages. Previous studies suggest that fetal-to-adult hemoglobin switch is regulated by a complex mechanism, in which many key players still remain unknown. Here, we report our findings from whole transcriptome analysis of erythroid cells, isolated from erythroid tissues at various developmental stages in an effort to identify distinct molecular signatures of each erythroid tissue. From our in-depth data analysis, pathway analysis, and text mining, we opted to focus on the VEGFAgene, given its gene expression characteristics. Selected VEGFAgenomic variants, identified through linkage disequilibrium analysis, were explored further for their association with elevated fetal hemoglobin levels in β-type hemoglobinopathy patients. Our downstream analysis of non-transfusion-dependent β-thalassemia patients, β-thalassemia major patients, compound heterozygous sickle cell disease/β-thalassemia patients receiving hydroxyurea as fetal hemoglobin augmentation treatment, and non-thalassemic individuals indicated that VEGFAgenomic variants were associated with disease severity in β-thalassemia patients and hydroxyurea treatment efficacy in SCD/β-thalassemia compound heterozygous patients. Our findings suggest that VEGFAmay act as a modifier gene of human globin gene expression and, at the same time, serve as a genomic biomarker in β-type hemoglobinopathy disease severity and hydroxyurea treatment efficacy.

The Israeli National and Ethnic Mutation database (http://server.goldenhelix.org/israeli) was launched in September 2006 on the ETHNOSsoftware to include clinically relevant genomic variants reported among Jewish and Arab Israeli patients. In 2016, the database was reviewed and corrected according to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar) and ExAC (http://exac.broadinstitute.org) database entries. The present article summarizes some key aspects from the development and continuous update of the database over a 10-year period, which could serve as a paradigm of successful database curation for other similar resources. In September 2016, there were 2444 entries in the database, 890 among Jews, 1376 among Israeli Arabs, and 178 entries among Palestinian Arabs, corresponding to an ~4× data content increase compared to when originally launched. While the Israeli Arab population is much smaller than the Jewish population, the number of pathogenic variants causing recessive disorders reported in the database is higher among Arabs (934) than among Jews (648). Nevertheless, the number of pathogenic variants classified as founder mutations in the database is smaller among Arabs (175) than among Jews (192). In 2016, the entire database content was compared to that of other databases such as ClinVar and ExAC. We show that a significant difference in the percentage of pathogenic variants from the Israeli genetic database that were present in ExAC was observed between the Jewish population (31.8%) and the Israeli Arab population (20.6%). The Israeli genetic database was launched in 2006 on the ETHNOSsoftware and is available online ever since. It allows querying the database according to the disorder and the ethnicity; however, many other features are not available, in particular the possibility to search according to the name of the gene. In addition, due to the technical limitations of the previous ETHNOS software, new features and data are not included in the present online version of the database and upgrade is currently ongoing.

Despite the significant advances achieved in pediatric acute lymphocytic leukemia (ALL) treatment, adverse side effects of drugs remain a challenging issue. Numerous ALL pharmacogenomic studies have been conducted to elucidate the predisposing genetic factors for their development. Plausible pharmacogenomic data are available for the osteonecrosis associated with glucocorticoids, the neurotoxicity associated with vincristine and the cardiotoxicity related to anthracyclines. However, these data have not been fully translated into the clinic due to several limitations, most importantly the lack of reliable evidence. The most robust pharmacogenomics data are those for thiopurines and methotrexate use, with evidence-based preemptive testing recommendations for the former. Pharmacogenomics has a significant potential utility in pediatric ALL treatment regimens. In this review, gaps and limitations in this field are emphasized, which may provide a useful guide for future research design.

Celiac disease is a complex chronic immune-mediated disorder of the small intestine. Today, the pathobiology of the disease is unclear, perplexing differential diagnosis, patient stratification, and decision-making in the clinic. Herein, we adopted a next-generation sequencing approach in a celiac disease trio of Greek descent to identify all genomic variants with the potential of celiac disease predisposition. Analysis revealed six genomic variants of prime interest: SLC9A4c.1919G>A, KIAA1109c.2933T>C and c.4268_4269delCCinsTA, HoxB6c.668C>A, HoxD12c.418G>A, and NCK2c.745_746delAAinsG, from which NCK2c.745_746delAAinsG is novel. Data validation in pediatric celiac disease patients of Greek (n= 109) and Serbian (n= 73) descent and their healthy counterparts (n= 111 and n= 32, respectively) indicated that HoxD12c.418G>A is more prevalent in celiac disease patients in the Serbian population (P< 0.01), while NCK2c.745_746delAAinsG is less prevalent in celiac disease patients rather than healthy individuals of Greek descent (P= 0.03). SLC9A4c.1919G>A and KIAA1109c.2933T>C and c.4268_4269delCCinsTA were more abundant in patients; nevertheless, they failed to show statistical significance. The next-generation sequencing-based family genomics approach described herein may serve as a paradigm towards the identification of novel functional variants with the aim of understanding complex disease pathobiology.

The Pharmacogenomics and Personalized Medicine group belongs to the Laboratory of Molecular Biology and Immunology, Department of Pharmacy and is active since 2009 mainly in the field of pharmacogenomics and personalized medicine. Herein, we describe the research interests, collaborations and accomplishments of the Pharmacogenomics and Personalized Medicine group together with the teaching activities of the group that greatly enhance the pharmacogenomics knowledge of graduate/postgraduate students and healthcare professionals.

Aims:Hemoglobinopathies, particularly β-thalassemia and sickle cell disease, are characterized by great phenotypic variability in terms of disease severity, while notable differences have been observed in hydroxyurea treatment efficacy. In both cases, the observed phenotypic diversity is mostly dependent on the elevated fetal hemoglobin levels, resulting from the persistent fetal globin gene expression in the adult erythroid stage orchestrated by intricate mechanisms that still remain only partly understood. We have previously shown that several protein factors act as modifiers of fetal hemoglobin production, exerting their effect via different pathways. Materials & methods:Here, we explored whether SIN3A could act as a modifier of fetal globin gene expression, as it interacts with KLF10, a known modifier of fetal hemoglobin production. Results:We show that SIN3Agenomic variants are associated both with β-thalassemia disease severity (rs11072544) as well as hydroxyurea treatment response (rs7166737) in β-hemoglobinopathies patients. Conclusion:Our findings further underline that fetal hemoglobin production is the result of a complex interplay in which several human globin gene cluster variants interact with protein factors encoded by modifier genes to produce the observed clinical outcome.

Introduction:Clopidogrel, which is activated by the CYP2C19 enzyme, is among the drugs for which all major regulatory agencies recommend genetic testing to be performed to identify a patient's CYP2C19genotype in order to determine the optimal antiplatelet therapeutic scheme. The CYP2C192and CYP2C193variants are loss-of-function alleles, leading to abolished CYP2C19 function and thus have the risk of thrombotic events for carriers of these alleles on standard dosages, while the CYP2C1917allele results in CYP2C19 hyperactivity. Aims:Here, we report our findings from a retrospective study to assess whether genotyping for the CYP2C192allele was cost effective for myocardial infarction patients receiving clopidogrel treatment in the Serbian population compared with the nongenotype-guided treatment. Results:We found that 59.3 of the CYP2C191/1patients had a minor or major bleeding event versus 42.85 of the CYP2C191/2and 2/2, while a reinfarction event occurred only in 2.3 of the CYP21C91/1patients, compared with 11.2 of the CYP2C191/2and CYP2C192/2patients. There were subtle differences between the two patient groups, as far as the duration of hospitalization and rehabilitation is concerned, in favor of the CYP2C191/1group. The mean cost for the CYP2C191/1patients was estimated at €2547 versus €2799 in the CYP2C191/2and CYP2C192/2patients. Furthermore, based on the overall CYP2C191/2genotype frequencies in the Serbian population, a break-even point analysis indicated that performing the genetic test prior to drug prescription represents a cost-saving option, saving €13 per person on average. Conclusion:Overall, our data demonstrate that pharmacogenomics-guided clopidogrel treatment may represent a cost-saving approach for the management of myocardial infarction patients undergoing primary percutaneous coronary intervention in Serbia.

On 8–9 November 2022, the European Society of Pharmacogenomics and Personalised Therapy organized its sixth biennial congress, in Belgrade, Serbia (congress website: www.sspt.rs). The congress aimed to address the current status and future perspectives of pharmacogenomics, share latest knowledge in the field of precision medicine and showcase the implementation of clinical applications in pharmacogenomics/pharmacogenetics. The 2 day congress consisted of 17 lectures given by key-opinion leaders and included a poster session plus discussions. The meeting was a great success by generating an informal environment and enabling the exchange of information between 162 participants from 16 different countries.

Background: There is an increasing interest worldwide in investigating healthcare stakeholders’ perceptions and intentions to adopt pharmacogenomics (PGx) into clinical practice. However, the existing inquiries based on well-established theories and models that interpret their intentions to implement PGx are scarce. This study is the first that examines the impact of selected factors on health science students’ intention to adopt genetic testing applications using the technology acceptance model while it compares two different cultural groups: Greeks (Europe; Christian) and Malays (Asia; Muslim). Results: Malay students were more persuaded about benefits of genomics for drug management compared to their Greek counterparts. However, participants from both countries appear to be particularly convinced about the benefits of genomics on disease management. Moreover, students from both countries considered the potential misuse of genetic information by corporate or government bodies as their most important concern; Greek students appeared to be considerably less worried than Malay about other probable hazards such as the deficient protection of privacy and confidentiality, which could be attributed to their religious background. Participants from both samples expressed very positive attitudes towards genetic research and testing and their favourable intentions to adopt genetic testing for personal use. Exploratory factors analysis and path analysis yielded quite similar results for both samples. Path analysis revealed that the factors of attitudes, concerns, drug management benefits and disease management benefits significantly influenced students’ intentions to adopt genetic testing for personal use, with attitudes being the most inspirational factor with rather high impact, while training did not seem to affect participant’s intentions. The squared multiple correlation of both models was quite satisfactory reaching to 0.55 for the Malaysian sample. Conclusion: Similarities in the results of the two groups along with the relevant validity and reliability tests indicate that the proposed model is a good fit for future studies to interpret stakeholders’ intentions to adopt genetic testing. Therefore, it can provide a promising and reliable basis for future model development to explain the relationships between intentions to adopt genetic testing and its predictors.

Background: Pharmacogenomic (PGx) testing has proved its utility and cost-effectiveness for some commonly prescribed cardiovascular disease (CVD) medications. In addition, PGx-guided dosing guidelines are now available for multiple CVD drugs, including clopidogrel, warfarin, and statins. The United Arab Emirates (UAE) population is diverse and multiethnic, with over 150 nationalities residing in the country. PGx-testing is not part of the standard of care in most global healthcare settings, including the UAE healthcare system. The first pharmacogenomic implementation clinical study in CVD has been approved recently, but multiple considerations needed evaluation before commencing. The current report appraises the PGx-clinical implementation procedure and the potential benefits of pursuing PGx-implementation initiatives in the UAE with global implications. Methods: Patients prescribed one or more of the following drugs: clopidogrel, atorvastatin, rosuvastatin, and warfarin, were recruited. Genotyping selected genetic variants at genes interacting with the study drugs was performed by real-time PCR. Results: For the current pilot study, 160 patients were recruited. The genotypes and inferred haplotypes, diplotypes, and predicted phenotypes revealed that 11.9% of the participants were poor CYP2C19 metabolizers, 35% intermediate metabolizers, 28.1% normal metabolizers, and 25% rapid or ultrarapid metabolizers. Notably, 46.9% of our cohort should receive a recommendation to avoid using clopidogrel or consider an alternative medication. Regarding warfarin, only 20% of the participants exhibited reference alleles at VKORC1-1639G > A, CYP2C9*2, and CYP2C9*3, leaving 80% with alternative genotypes at any of the two genes that can be integrated into the warfarin dosing algorithms and can be used whenever the patient receives a warfarin prescription. For statins, 31.5% of patients carried at least one allele at the genotyped SLCO1B1variant (rs4149056), increasing their risk of developing myopathy. 96% of our cohort received at least one PGx-generated clinical recommendation for the studied drugs. Conclusion: The current pilot analysis verified the feasibility of PGx-testing and the unforeseen high frequencies of patients currently treated with suboptimal drug regimens, which may potentially benefit from PGx testing.

Background: It has been suggested that bipolar disorder (BD) is associated with clinical and biological features of accelerated aging. In our previous studies, we showed that long-term lithium treatment was correlated with longer leukocyte telomere length (LTL) in BD patients. A recent study explored the role of TL in BD using patients-derived lymphoblastoid cell lines (LCLs), showing that baseline TL was shorter in BD compared to controls and that lithium in vitro increased TL but only in BD. Here, we used the same cell system (LCLs) to explore if a 7-day treatment protocol with lithium chloride (LiCl) 1 mM was able to highlight differences in TL between BD patients clinically responders (Li-R; n= 15) or non-responders (Li-NR; n= 15) to lithium, and if BD differed from non-psychiatric controls (HC; n= 15). Results: There was no difference in TL between BD patients and HC. Moreover, LiCl did not influence TL in the overall sample, and there was no difference between diagnostic or clinical response groups. Likewise, LiCl did not affect TL in neural precursor cells from healthy donors. Conclusions: Our findings suggest that a 7-day lithium treatment protocol and the use of LCLs might not represent a suitable approach to deepen our understanding on the role of altered telomere dynamics in BD as previously suggested by studies in vivo.