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Biomedical subjects

Jingyi Tan

Publications and source records attributed to Jingyi Tan.

3 recordsLinked to original sources

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

A comprehensive evaluation of candidate genetic polymorphisms in a large histologically characterized MASLD cohort using a novel framework.

BACKGROUND: There is a substantial heritable component to metabolic dysfunction-associated steatotic liver disease (MASLD), and several genetic variants that promote MASLD development or associate with its severity have been reported. These associations vary in terms of their effect size and degree of replication. METHODS: We developed a framework to classify previously identified MASLD genetic polymorphisms into 4 tiers based on effect size and extent of replication in the literature. We tested the association between "tier 1" single-nucleotide polymorphisms (OR ≥1.5, replicated in >2 independent studies) and biopsy measures of MASLD severity in a large, well-characterized histologic cohort of MASLD patients (n=3094). RESULTS: Across 19 "tier 1" variants reflecting 11 genetic loci, only those in the PNPLA3-SAMM50-PARVB locus showed significant associations with biopsy-proven fibrosis severity and NAFLD activity score; the highest risk was for the rs738409 p.I148M variant in PNPLA3. A genetic risk score based on "tier 1" variants, as well as a previously developed genetic risk score based on variants in PNPLA3, TM6SF2, and HSD17B13, were both associated with fibrosis and NAFLD activity score, but these results were driven entirely by PNPLA3 rs738409. CONCLUSIONS: Our study provides a framework to prioritize evaluation of genetic polymorphisms for future replication efforts and demonstrates that in a large case-only cohort, histologic severity of MASLD is only robustly associated with the presence of variation in PNPLA3 among known candidate genes. These findings may have implications for patient risk stratification based on the presence of PNPLA3 rs738409.

Humans

Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits.

Here, we present a multi-omics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits conducted to date in Hispanic/Latino populations (nmax = 63,184). We conduct a meta-analysis of 16 type 2 diabetes and 19 lipid trait GWAS, identifying 20 genome-wide significant loci for type 2 diabetes, including one novel locus and novel signals at two known loci, based on fine-mapping. We also identify sixty-one genome-wide significant loci across the lipid/lipoprotein traits, including nine novel loci, and novel signals at 19 known loci through fine-mapping. Next, we analyze genetically regulated expression, perform Mendelian randomization, and analyze association with transcriptomic and proteomic measure using multi-omics data from a Hispanic/Latino population. Using this approach, we identify genes linked to type 2 diabetes and lipid/lipoprotein traits, including TMEM205 and NEDD9 for HDL cholesterol, TREH for triglycerides, and ANXA4 for type 2 diabetes.

Female