Journal of Personalized Medicine

Pharmacogenetic testing promises safer, personalized prescribing, yet its adoption in primary care in Singapore remains limited and underexplored. The aim of this study was to, 1) examine perceptions, attitudes, and beliefs about pharmacogenetic testing among primary care physicians (PCPs) and patients in Singapore, and 2) to compare acceptability between those who did and did not participate in a prior pharmacogenetic feasibility study. We conducted one-to-one semi-structured interviews with a...

IntroductionStatin-associated muscle symptoms (SAMS) contribute to the nonadherence to statin therapy. In a previous study, we successfully developed a pharmacological SAMS (PSAMS) phenotyping algorithm that distinguishes objective versus nocebo SAMS using structured and unstructured electronic health records (EHRs) data. Our aim in this paper was to develop a pharmacological SAMS risk stratification (PSAMS-RS) score using these same EHR data. MethodUsing our PSAMS phenotyping algorithm, SAMS c...

BackgroundGlucose metabolism disorders encompass abnormalities in glucose digestion, absorption, transport, utilization, and regulation, leading to broad physiological and pathological consequences. Although drug-induced disturbances are increasingly documented, they remain under-recognized in clinical practice and drug labeling. MethodsThis disproportionality analysis used publicly available data from the FDA Adverse Event Reporting System (FAERS), covering reports from Q4 2004 to Q1 2025. Aft...

Obesity and mental health disorders are among the greatest public health challenges of the twenty-first century. Interestingly, an altered microbiome profile has been associated with both conditions. The aim of this randomized, double-blind, placebo-controlled clinical trial was to evaluate the effects of dietary supplementation with a specific probiotic strain (Lactiplantibacillus plantarum KABP051) on body composition and gut microbiome balance, together with measures of mood state, in a popul...

PurposeThe purpose of our study was to investigate dronabinol prescribing in Medicare from 2014 to 2019 by provider specialty and state. MethodsData was collected and analyzed from the Centers for Medicare & Medicaid Services databases from 2014 to 2019. The mean number of prescriptions for each area of practice, each individual year, and for 2014 to 2019 overall for the 50 United States and District of Columbia was determined. The prescriptions were separated by state and the state totals were...

BackgroundFamilial dysbetalipoproteinemia (FDB) is a genetic lipoprotein disorder that can develop in patients homozygous for the APOE2 genotype ({varepsilon}2/{varepsilon}2). It is associated with decreased clearance of remnant lipoproteins and increased atherosclerotic cardiovascular disease (ASCVD) risk disproportionate to their level of LDL-C. A goal of this study was to develop a screening test for the {varepsilon}2/{varepsilon}2 genotype based on routinely available lipid tests and to dete...

BackgroundAlgorithms including both traditional risk factors and polygenic risk scores (PRS) can significantly improve prediction of atherosclerotic cardiovascular disease (ASCVD). However, the clinical benefit of adding PRS to clinical risk evaluation remains unclear. ObjectivesThe study evaluated the attitudes of 7,342 individuals (64% women, mean age 56 yrs) upon receiving personal genome-enhanced ASCVD risk information, and prospectively assessed the impact on the participants health behavi...

Clinical Pharmacogenomics Implementation Consortium (CPIC) guidelines exist for many medications commonly prescribed prior to hospital discharge, yet there is limited data regarding the contribution of gene-x-drug interactions to hospital readmissions. The present study evaluated the relationship between prescription of CPIC medications prescribed within 30 days of hospital admission and 90-day hospital readmission from 2010-2020 in a study population (N=10,104) who underwent sequencing with a 1...

Clinical PGx practice guidelines (PGx guidelines) may have limited generalizability for "marginalized" groups. We proposed the five-step Real-World Data for Genome-Guided Prescribing (ReGGRx) framework and, using All of Us research program (AoU) data, examined its ability to estimate disparities in concordance with and benefit from PGx guidelines for CYP2C19 testing when choosing antiplatelet and antidepressant drugs. The selected measures were intended to identify disparities in avoiding drug f...

BackgroundFamilial hypercholesterolemia (FH) is a prevalent genetic disorder with global implications for severe cardiovascular diseases. Amid ongoing advancements in genetic disease screening and treatment, the economic evaluation of FH is increasingly vital. Despite numerous studies, international disparities persist, necessitating a comprehensive analysis of the economic assessments of FH screening to provide valuable insights. This study aims to globally examine economic assessments of FH, s...

ObjectiveIn spite of evidence and recommendations reflecting the importance of pharmacogenomic testing, most prescriptions are still given without testing. We demonstrate the real world implications of the use of testing and evaluate adverse events and outcomes in individuals who did not receive pharmacogenomic testing for clopidogrel. MethodsWe analyzed ~100K individuals with paired EHR and exome sequencing data from population health studies administered at multiple medical centers using the ...

RationaleIntensive care units (ICU) patients are highly vulnerable to inaccurate drug dosing. Pharmacogenomics (PGx) characterizes the influence of inherited genetic variation on drug metabolism, playing an important role in the consequences of a given drug dose. ObjectivesTo assess the genetic-based risk of inaccurate drug dosing in the ICU. MethodsWe carried out whole genome sequencing (WGS) of 210 Qataris in ICU care at Hamad Medical Corporation (HMC), Doha, Qatar and assessed the WGS for p...

BackgroundUnderstanding the risk factors associated with coronary atherosclerosis (CA)--an evident cardiovascular disease--is vital. This study aimed to explore the causal relationship between neuroticism subclusters and CA, focusing on lipids as mediators, using genome-wide association studies and Mendelian randomization (MR). Methods and ResultsInstrumental variables were selected based on their genetic associations with neuroticism subclusters and CA. Causal effects were primarily assessed u...

ObjectiveAngiotensin-II Receptor Blockers (ARBs) are commonly prescribed; however, their adverse events may prompt new drug prescription(s), known as prescribing cascades. We aimed to identify potential ARB-induced prescribing cascades using high-throughput sequence symmetry analysis. MethodsUsing claims data from a national sample of Medicare beneficiaries (2011-2020), we identified new ARB users aged [≥]66 years with continuous enrollment [≥]360 days before and [≥]180 days after ARB ...

Background and ObjectivesClopidogrel is an antiplatelet used in both primary and secondary prevention of cardiovascular diseases. It is a prodrug, requiring CYP2C19 for its metabolism to the active metabolite. The ABCD-GENE score, combining clinical attributes (age, body mass index, chronic kidney disease, diabetes mellitus), with genetic information (presence of 1 or 2 loss of function (LOF) alleles in the CYP2C19 gene) has been shown to identify patients with higher risk of recurrent cardiovas...

BackgroundMore than 100 million cases of COVID-19 have been reported worldwide. A number of risk factors for infection or severe infection have been identified, however observational studies were subject to confounding bias. In addition, there is still limited knowledge about the complications or medical consequences of the disease. MethodsHere we performed bi-directional Mendelian randomization (MR) analysis to evaluate causal relationships between liability to COVID-19 (and severe/critical in...

AimTo describe self-reported use of medications with pharmacogenetic guidance in the Our Future Health (OFH) cohort. MethodsWe focused on four key pharmacogenes--CYP2C19, CYP2C9, CYP2D6, and SLCO1B1--and associated medications supported by high levels of evidence for clinical actionability according to the Clinical Pharmacogenetics Implementation Consortium (CPIC). We summarized self-reported pharmacogenetic medication use, assessed concurrent use, and stratified the findings by age, sex, and e...

PurposeIncidence rate estimates are sensitive to a range of factors, including age, sex, and geographical setting (data source). The magnitude of the impact of drug indication on incidence rates remains underexplored. MethodsWe conducted an observational cohort study using 13 healthcare databases to estimate the incidence rates of 73 health outcomes across 8 drug classes with multiple indications. We calculated incidence rates for each drug-outcome pair and performed random-effects meta-analyse...

AimsTo describe the 1-year direct and indirect transition probabilities to premature discontinuation of statin therapy after concurrently initiating statins and CYP3A4-inhibitor drugs. MethodsA retrospective new-user cohort study design was used to identify (N=160828) patients who concurrently initiated CYP3A4-inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4-metabolized statins (statin DDI exposed, n = 104774) vs. other statins (unexposed, n = 56054) from the MarketScan C...

BackgroundExisting polygenic scores (PGS) are derived primarily from studies performed in European populations. It is still unclear how these perform in improving risk predictions in East-Asians. MethodsWe generated 2,173 PGSs from 519 traits and assessed their associations with 58 baseline phenotypes in the Singapore Chinese Health Study (SCHS), a prospective cohort of 23,622 middle-aged and older Chinese residing in Singapore. We used linear regression to evaluate PGS performances for quantit...