Biomedical subjects

Yan V Sun

Publications and source records attributed to Yan V Sun.

5 recordsLinked to original sources

PubMed2026

Multi-ancestry genetic architecture of heart failure subtypes.

Heart failure (HF) affects 6.7 million people in the US and includes two major subtypes, HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), with distinct genetic architectures. We meta-analyze genome-wide association studies (GWAS) of 38,781 HFrEF cases, 38,163 HFpEF cases, and 526,135 controls across European, African, Hispanic, and Asian ancestries using the Million Veteran Program and Vanderbilt University DNA Databank (BioVU). We identify 46 genome-wide significant loci for HFrEF (9 novel) and 3 loci for HFpEF (1 novel). Four HFrEF loci are detected in African ancestry participants near CD36, SPI1, TRIM48, and SPNS3, with lead SNPs showing low risk-allele frequencies in European populations. In the all-cause HF meta-analysis (200,070 cases, 2,076,466 controls), we identify 136 loci (12 novel). Gene-based tests, tissue enrichment, transcriptome-wide association, and fine-mapping implicate vascular, metabolic, and TGF-β/Smad signaling pathways and nominate candidate causal genes, clarifying shared and subtype-specific risk across ancestries.

Humans↗

PubMed2026

Proteomics-Based Soluble Urokinase Plasminogen Activator Receptor Levels Are Associated With Adverse Cardiovascular Outcomes in the General Population: Insights From the UK Biobank.

BACKGROUND: Elevated soluble urokinase plasminogen activator receptor (suPAR) levels are associated with inflammation, immune activation, and major adverse cardiovascular events in coronary artery disease. Encoded by the PLAUR gene, suPAR levels are influenced by the rs4760 genetic variant. Whether proteomics-based suPAR levels predict adverse outcomes in the general population remains unknown. METHODS: Proteomics-based suPAR levels were measured using the Olink Immunoassay in 33 963 UK Biobank participants without known coronary artery disease. Fine-Gray and Cox proportional hazards models assessed associations between suPAR and major adverse cardiovascular events (primary outcome: cardiovascular mortality, nonfatal myocardial infarction, or stroke), cardiovascular mortality, and all-cause mortality (secondary outcomes), after adjustment for demographic and clinical risk factors, hs-CRP (high-sensitivity C-reactive protein), and the rs4760 variant. Incremental discrimination was evaluated using C-statistics. RESULTS: Participants were aged 56.4 (SD, 8.2) years; 45% were men, and 93.4% were White. Over a median follow-up of 14 years (476 177 person-years), 10.7% experienced major adverse cardiovascular events, 2.6% experienced cardiovascular mortality, and 9.4% experienced all-cause mortality. Each 1-SD increment in proteomics-based suPAR was associated with significantly higher risk of major adverse cardiovascular events (hazard ratio [HR], 3.2 [95% CI, 2.9-4.5]), cardiovascular mortality (HR, 5.9 [95% CI, 5.1-6.9]), and all-cause mortality (HR, 5.0 [95% CI, 4.6-5.5]), independent of clinical risk factors and hs-CRP. Additional adjustment for rs4760 did not attenuate these associations. Proteomics-based suPAR significantly improved discrimination beyond clinical risk factors (C-statistic: 0.719 versus 0.732; P<0.001). CONCLUSIONS: Proteomics-based suPAR independently predicts adverse cardiovascular outcomes in the general population, beyond conventional risk factors, hs-CRP, and genetic predisposition to elevated suPAR levels.

Humans↗

PubMed2025

Novel approaches and applications in identifying DNA methylation markers of cardio-kidney-metabolic disease.

Cardio-kidney-metabolic (CKM) diseases represent a major public health challenge, accounting for a large proportion of global burden of morbidity and mortality. These conditions share risk factors, including genetic predisposition, environmental exposures, and lifestyle influences, which collectively drive disease development and progression. Epigenetic modifications, particularly DNA methylation (DNAm), serve as key mediators and biomarkers between these risk factors and disease phenotypes by regulating gene expression without altering the DNA sequence. Epigenome-wide association studies have identified DNAm markers associated with CKM diseases and related phenotypes, highlighting both shared pathways and disease-specific epigenetic signatures in inflammation, metabolic dysfunction, and aging-related processes. Longitudinal studies further demonstrate the dynamic nature of DNAm changes over time, offering insights into disease trajectories. Additionally, methylation risk scores integrating multiple epigenetic markers show promise in improving disease prediction and risk stratification beyond traditional clinical factors. To synthesize the current evidence, we conducted a targeted literature search in PubMed for English-language, peer-reviewed articles published between 2014 and the present. Future research leveraging large, well-phenotyped cohorts, advanced statistical methods, and innovative study designs will be critical for uncovering novel biomarkers, refining risk prediction models, and developing targeted epigenetic therapies to mitigate the global burden.

Humans↗

PubMed2025

Primary care providers' perspectives on receiving opportunistic genomic results from a national study: The Million Veteran Program Return Of Actionable Results (MVP-ROAR) Study.

PURPOSE: Patients are increasingly obtaining genetic health information and integrating it into their care with the help of their primary care provider (PCP). However, PCPs may not be adequately prepared to effectively utilize genetic results. Across the Veterans Health Administration health system, the Million Veteran Program Return Of Actionable Results-Familial Hypercholesterolemia (MVP-ROAR-FH) Study clinically confirms and returns genetic results associated with familial hypercholesterolemia (FH), identified in a national biobank program. METHODS: PCPs who received their patient's genetic results through the MVP-ROAR-FH study were invited to participate in semistructured interviews, which explored PCPs' familiarity with FH, how the results affected medical management, and suggestions for process improvement. Interviews were transcribed and analyzed using directed content analysis and constant comparison methods to identify key themes. RESULTS: Interviews with 9 PCPs revealed varied levels of familiarity with genetic testing and FH. Most PCPs did not distinguish FH from common high cholesterol issues and already used similar treatment approaches. Many PCPs did not recall receiving results from the MVP-ROAR-FH study. Alerts in medical records were deemed effective for communicating results. PCPs valued genetics in informing patient care and identifying at-risk family members but noted several implementation barriers, such as additional workload and unclear medical management benefits. Recommendations for improving results disclosure included simplifying the genetic testing report and associated support documents. CONCLUSION: The study represents the first investigation into PCPs' experiences with receiving genetic test results from a biobank linked to a national healthcare system. Results suggest that PCPs generally view genetic testing as beneficial, although they may not significantly alter medical management. PCPs expressed that integrating genetics into routine care may be burdensome and require additional training, which may not be practical. The study underscores the need for accessible genetic information, which could be aided by specialized support roles or different clinical specialties assisting with incorporating genetic results into patient care.

Humans↗

PubMed2025

The impact of common and rare genetic variants on bradyarrhythmia development.

To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively. Four well-known loci (SCN5A/SCN10A, CCDC141, TBX20 and CAMK2D) were shared for SND and DCD, while others were more specific for SND or DCD. SND and DCD showed a moderate genetic correlation (rg = 0.63). Cardiomyocyte-expressed genes were enriched for contributions to DCD heritability. Rare-variant analyses implicated LMNA for all bradyarrhythmia phenotypes, SMAD6 and SCN5A for DCD and TTN, MYBPC3 and SCN5A for PM. These results show that variation in multiple genetic pathways (for example, ion channel function, cardiac developmental programs, sarcomeric structure and cellular homeostasis) appear critical to the development of bradyarrhythmias.

Humans↗