Biomedical subjects

Fuu-Jen Tsai

Publications and source records attributed to Fuu-Jen Tsai.

3 recordsLinked to original sources

PubMed2026

Evaluation of population-specific polygenic risk scores for blood lipids: insights from Taiwanese cohorts and multiancestry meta-analysis.

BACKGROUND: Blood lipids are heritable risk factors for cardiovascular disease (CVD), a leading cause of mortality worldwide. However, the genetic architecture of lipid traits and the performance of polygenic risk scores (PRSs) remain underexplored in East Asian (EAS) populations, including Taiwanese Han individuals. METHODS: We conducted genome-wide association studies and PRS analyses for five lipid traits: total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and the ratio of low-density lipoprotein cholesterol to total cholesterol. Lipid profile data were obtained from the China Medical University Hospital cohort. PRSs were evaluated on the basis of their correlations with measured lipid levels. To evaluate trans-ancestry PRS transferability, localized models were systematically compared against models derived from discovery-stage GWAS meta-analyses incorporating five ancestry groups from the Global Lipids Genetics Consortium. The performance of the PRS models in predicting lipid-related diseases was evaluated through receiver operating characteristic curve analyses. RESULTS: The population-specific PRS models explained 11%-40% of the variance in lipid levels within the target cohort. Models leveraging global multiancestry GWAS meta-analysis weights revealed limited predictive performance (r 2 = 0.04-0.19), whereas analyses incorporating EAS-specific data yielded higher correlations (r 2 = 0.13-0.30), although these correlations did not exceed those derived from the hospital-based cohort alone. When combined with age and sex, the PRS models demonstrated strong predictive performance for coronary artery disease, atherosclerosis, and ischemic stroke, with area under the curve values of 0.910, 0.926, and 0.854, respectively. CONCLUSION: Population-specific PRS models derived from a Taiwanese population outperformed meta-analysis-derived frameworks in predicting lipid levels and demonstrated substantial potential for predicting CVD risk, indicating the importance of ancestry-matched genetic studies in precision medicine.

LDL-C/TC ratio↗

PubMed2025

Blood Pressure Genetics in Han Taiwanese With Cross-Trait Analysis in East Asians: Insights Into Comorbidities, All-Cause Mortality, and Cardiovascular Mortality.

BACKGROUND: Hypertension is a major health burden in East Asia. However, the genetic architecture and clinical implications of blood pressure (BP) traits remain underexplored beyond European-focused studies. This large-scale study aimed to investigate hypertension, systolic BP, and diastolic BP, to uncover genetic links to comorbidities and mortality in Han Taiwanese individuals. METHODS: This large-scale study used China Medical University Hospital biobank data and conducted genome-wide association studies on 25 523 hypertension cases and 47 522 controls, plus 66 236 individuals for systolic BP and 66 152 for diastolic BP. Cross-trait genetic correlations were assessed across 5 East Asian biobanks. Mendelian randomization and polygenic risk scores were applied to assess causality and predict clinical outcomes. RESULTS: We identified 8 loci and 36 genes for hypertension, 7 loci and 17 genes for systolic BP, and 9 loci and 26 genes for diastolic BP. ATP2B1 and FGF5 were common to all BP traits, implicating calcium signaling and vascular remodeling pathways. Cross-trait analyses showed shared genetic liability between BP traits and cardiovascular and metabolic comorbidities. Phenome-wide association studies confirmed strong associations with circulatory diseases. Mendelian randomization analyses demonstrated that elevated BP causally increases the risk of unstable angina pectoris. Polygenic risk scores predicted significantly higher risks and earlier onset of unstable angina pectoris, all-cause mortality, and cardiovascular mortality among individuals in the top polygenic risk score quintiles. CONCLUSIONS: Our findings highlight the genetic basis of BP and comorbidities in East Asians, suggesting that BP genetic risk may inform future approaches to early risk assessment and prevention.

Aged↗

PubMed2024

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

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.

Adolescent↗