Efficacy of Warfarin Therapy Guided by Pharmacogenetics: A Real-world Investigation Among Han Taiwanese

Liu, Ting-Yuan; Hsu, Hsing-Yu; You, Ying-Shu; Hsieh, Ying‐Hen; Lin, Tzu-Ching; Peng, Changhong; Huang, Hsin‐Yi; Chang, Shih‐Sheng; Tsai, Fuu‐Jen

doi:10.1016/j.clinthera.2023.04.006

Cited by 7 publications

(4 citation statements)

References 44 publications

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“…Moreover, the Mann-Whitney U test was performed to evaluate the PRS in different target groups. The p value was adjusted using the false-discovery-rate Benjamini-Hochberg Procedure to prevent type I error, and an adjusted p value of <0.05 was considered statistically significant [53].…”

Section: Discussionmentioning

confidence: 99%

Identification of 13 Novel Loci in a Genome-Wide Association Study on Taiwanese with Hepatocellular Carcinoma

Liu,

Liao,

Chang

et al. 2023

IJMS

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Liver cancer is caused by complex interactions among genetic factors, viral infection, alcohol abuse, and metabolic diseases. We conducted a genome-wide association study and polygenic risk score (PRS) model in Taiwan, employing a nonspecific etiology approach, to identify genetic risk factors for hepatocellular carcinoma (HCC). Our analysis of 2836 HCC cases and 134,549 controls revealed 13 novel associated loci such as the FAM66C gene, noncoding genes, liver-fibrosis-related genes, metabolism-related genes, and HCC-related pathway genes. We incorporated the results from the UK Biobank and Japanese database into our study for meta-analysis to validate our findings. We also identified specific subtypes of the major histocompatibility complex that influence both viral infection and HCC progression. Using this data, we developed a PRS to predict HCC risk in the general population, patients with HCC, and HCC-affected families. The PRS demonstrated higher risk scores in families with multiple HCCs and other cancer cases. This study presents a novel approach to HCC risk analysis, identifies seven new genes associated with HCC development, and introduces a reproducible PRS model for risk assessment.

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Section: Discussionmentioning

confidence: 99%

Identification of 13 Novel Loci in a Genome-Wide Association Study on Taiwanese with Hepatocellular Carcinoma

Liu,

Liao,

Chang

et al. 2023

IJMS

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“…We gathered hearing loss data from the CMUH between January 2003 and December 2020, which offers a diverse range of health data, from clinical records to genetic details. Further information on CMUH database is available in prior research [ 16 ].…”

Section: Methodsmentioning

confidence: 99%

Increased risk of hearing loss associated with MT-RNR1 gene mutations: a real-world investigation among Han Taiwanese Population

Chen,

Hsieh,

Hsu

et al. 2024

BMC Med Genomics

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Background Previous studies have implicated inherited mutations in mitochondrial DNA (mtDNA) in sensorineural hearing loss (SNHL). However, the definitive association between mitochondrial 12S rRNA (MT-RNR1) variants and hearing loss in the population has not been well established, particularly in Asia. The objective of this retrospective cohort study was to assess the association between MT-RNR1 variants and the risk of SNHL in patients in Taiwan. Methods The cohort included 306,068 participants from Taiwan between January 2003 and December 2020. Participants were classified based on genetic variants, particularly mitochondrial mutations (rs267606618, rs267606619, rs267606617). MT-RNR1 variant cases were matched 1:10 with non-mutant patients by age, gender, and visit year, excluding those with pre-existing hearing loss. The primary endpoint was SNHL, identified using specific ICD-TM codes with a 90% positive predictive value. Medication exposure history was determined via self-report or electronic medical records in the hospital. Cox proportional hazard regression models were used to assess the association between MT-RNR1 variants and hearing loss, adjusting for various covariates. Kaplan-Meier survival curves and log-rank tests compared hearing loss incidence between groups. Results The mean age of the mtDNA variants group is 32.4 years, with a standard deviation of 19.2 years. The incidence density of hearing loss for the mutation group was 36.42 per 10,000 person-years (95% Confidence Interval [CI], 27.21–47.73), which was higher than the 23.77per 10,000 person-years (95% CI, 21.32–26.42) in the wild-type group (p = 0.0036). Additionally, diabetes mellitus was associated with an increased risk of developing SNHL in individuals with MT-RNR1 variants (adjusted hazard ratio = 1.76 [95% CI, 1.00-3.09], p < 0.05). Conclusion This study highlights the increased risk of hearing loss in patients carrying MT-RNR1 variants, particularly those with diabetes mellitus. Future research that integrates genetic and clinical data is crucial for developing more precise interventions to monitor and treat hearing loss in this vulnerable population.

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“…In addition to genetic factors, non‐genetic factors such as age, smoking status, concurrent medication use, and comorbid conditions account for roughly 50% of dose variability, with dose variations reaching up to 40% in Qatari patients 27 . Those with the VKORC1–1639G>A variant are typically more sensitive to warfarin, while carriers of the LOF CYP2C92 and VKORC1 alleles require lower doses due to impaired metabolism 28,29 …”

Section: Stepwise Approach For Pgx Clinical Implementationmentioning

confidence: 99%

QPGx‐CARES: Qatar pharmacogenetics clinical applications and research enhancement strategies

Abdel‐latif,

Badji,

Mohammed

et al. 2024

Clinical Translational Sci

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Pharmacogenetic (PGx)‐informed medication prescription is a cutting‐edge genomic application in contemporary medicine, offering the potential to overcome the conventional “trial‐and‐error” approach in drug prescription. The ability to use an individual's genetic profile to predict drug responses allows for personalized drug and dosage selection, thereby enhancing the safety and efficacy of treatments. However, despite significant scientific and clinical advancements in PGx, its integration into routine healthcare practices remains limited. To address this gap, the Qatar Genome Program (QGP) has embarked on an ambitious initiative known as QPGx‐CARES (Qatar Pharmacogenetics Clinical Applications and Research Enhancement Strategies), which aims to set a roadmap for optimizing PGx research and clinical implementation on a national scale. The goal of QPGx‐CARES initiative is to integrate PGx testing into clinical settings with the aim of improving patient health outcomes. In 2022, QGP initiated several implementation projects in various clinical settings. These projects aimed to evaluate the clinical utility of PGx testing, gather valuable insights into the effective dissemination of PGx data to healthcare professionals and patients, and identify the gaps and the challenges for wider adoption. QPGx‐CARES strategy aimed to integrate evidence‐based PGx findings into clinical practice, focusing on implementing PGx testing for cardiovascular medications, supported by robust scientific evidence. The current initiative sets a precedent for the nationwide implementation of precision medicine across diverse clinical domains.

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Efficacy of Warfarin Therapy Guided by Pharmacogenetics: A Real-world Investigation Among Han Taiwanese

Cited by 7 publications

References 44 publications

Identification of 13 Novel Loci in a Genome-Wide Association Study on Taiwanese with Hepatocellular Carcinoma

Identification of 13 Novel Loci in a Genome-Wide Association Study on Taiwanese with Hepatocellular Carcinoma

Increased risk of hearing loss associated with MT-RNR1 gene mutations: a real-world investigation among Han Taiwanese Population

QPGx‐CARES: Qatar pharmacogenetics clinical applications and research enhancement strategies

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