Biomedical subjects

Henry J Lin

Publications and source records attributed to Henry J Lin.

4 recordsLinked to original sources

PubMed2026

Addition of CAD polygenic risk score to coronary artery calcium score enhances prediction of MACE.

BACKGROUND: Coronary heart disease (CHD) is prevalent in the United States, highlighting the need for accurate risk prediction to inform primary prevention strategies. While multivariate risk models like the Framingham Risk Score and ACC/AHA Pooled Cohort Equations are commonly utilized, novel risk markers, such as the coronary artery calcium score (CACS) and polygenic risk score (PRS), are increasingly gaining recognition. OBJECTIVES: This study aimed to compare the diagnostic utility of CACS and CAD PRS, both individually and in combination, for predicting major adverse cardiovascular events (MACE). METHODS: We conducted a retrospective analysis of a cohort comprising 1,380 predominantly Caucasian participants from the Sanford Health System. CAD PRS was constructed using genetic variants, while CACS was assessed via cardiac computed tomography (CT). Statistical analyses evaluated the relationship between each modality and MACE. RESULTS: Both CAD PRS and CACS were significantly associated with future MACE. Following the adjustment for covariates, the area under the curve (AUC) for both the CACS and PRS models was comparable, indicating similar predictive capabilities for MACE. However, the combination of CAD PRS with CACS significantly enhanced predictive accuracy, outperforming either modality alone. CONCLUSIONS: This study underscores the value of integrating CACS and CAD PRS in predicting MACE. The synergistic effect of CAD PRS combined with CACS markedly improves predictive power. Further research and prospective studies are necessary to validate these findings and assess their clinical implications. Investigating the interactions between PRS and CACS will be crucial for refining cardiovascular risk prediction and optimizing prevention strategies.

cardiac genetics↗

PubMed2025

Proteome-wide association study of prostate cancer risk across populations.

There is insufficient understanding of the molecular basis of prostate cancer (PCa) across different populations. We perform a large-scale proteome-wide association study (PWAS) to identify proteins with genetically regulated expression in plasma to be associated with PCa risk across populations. We develop genetic prediction models for expression of 1578, 1993, 1218, and 1390 proteins for African (n = 450), European (n = 758), Asian (n = 289), and Hispanic/Latino (n = 474) males, respectively, and evaluate associations of genetically regulated protein expression with PCa risk in 19,391 PCa cases and 61,608 controls of African population, 122,188 cases and 604,640 controls of European population, 10,809 cases and 95,790 controls of Asian population, and 3931 cases and 26,405 controls of Hispanic/Latino population. We identify three, four, 15, and 73 PCa-associated proteins in African, Hispanic/Latino, Asian, and European populations, respectively, and 83 in trans-population meta-analysis. There are both pan-population and population-specific associations. Our findings provide valuable insights into etiology of PCa.

Humans↗

PubMed2025

Genome-wide gene-sleep interaction study identifies novel lipid loci in 732,564 participants.

BACKGROUND AND AIMS: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets. METHODS: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) total sleep time were defined by the extreme 20 % of the age- and sex-standardized values within each cohort. Based on cohort-level summary statistics data, we performed meta-analyses for one-degree of freedom tests of interaction and two-degree of freedom joint tests of the SNP-main and -interaction effect on lipid levels. RESULTS: The one-degree of freedom variant-sleep interaction test identified 10 novel loci (Pint<5.0e-9), and we additionally identify 7 loci within the two-degree of freedom analyses (Pjoint<5.0e-9 in combination with Pint<6.6e-6). Multiple loci, including those mapped to APSH (target for aspartic and succinic acid) and SLC8A1 showed biological plausibility and druggability potential based on literature. CONCLUSIONS: Collectively, the 17 (9 with short and 8 with long sleep) loci provided evidence into the biomolecular mechanisms underlying sleep-associated lipid changes, including potential involvement of the vitamin D receptor pathway. Collectively, these findings may contribute developing novel interventions for treating dyslipidemia in people with sleep disturbances.

Humans↗

PubMed2025

Genome-wide association study of angiotensinogen levels and key single nucleotide polymorphism associations with blood pressure.

OBJECTIVE: The renin angiotensin aldosterone system plays a key role in circulatory homeostasis. We sought to identify genetic determinants of measured plasma angiotensinogen levels and subsequently evaluate the association of these single nucleotide polymorphisms (SNPs) with blood pressure (BP) and hypertension in a multiethnic population. METHODS: Genome-wide association study (GWAS) of plasma angiotensinogen levels, measured using an enzyme-linked immunoassay, was conducted in 4899 Multi-Ethnic Study of Atherosclerosis (MESA) participants (self-identified as White, n = 1865; Hispanic, n  = 1113; Black, n  = 1224; and Chinese, n  = 629). Linear and logistic models examined the association between SNPs with angiotensinogen and hypertension, respectively. Mediation analysis evaluated the effect of angiotensinogen on BP/hypertension through the top SNPs identified by GWAS. RESULTS: In the analysis utilizing all participants, 115 SNPs were associated with angiotensinogen ( P  < 5 × 10 -8 ), including lead SNP rs4762(G>A) in exon 2 ( P  = 1.51E -100 ) and rs5050(T>G) in the promoter region ( P  = 2.26E -69 ) of the AGT gene. Race/ethnic-specific analyses identified rs4762(G>A) as the lead SNP for White and Hispanic participants, whereas Black and Chinese participants had rs5050(T>G) and rs16852311(G>C), respectively. Both rs4762(G>A) and rs5050(T>G) indirectly increased systolic BP, diastolic BP, and the odds of hypertension through its effect of increasing angiotensinogen. CONCLUSIONS: Our findings demonstrate racial/ethnic differences in genetic effects on angiotensinogen levels across multiple SNPs. AGT rs4762(G>A) and rs5050(T>G) impact BP and hypertension through a mediated effect via angiotensinogen, though opposing direct effects may mask the overall association.

Humans↗