Biomedical subjects

Peter Ganz

Publications and source records attributed to Peter Ganz.

4 recordsLinked to original sources

PubMed2026

Plasma proteomics and coronary artery calcium score: synergistic, concordant and contrasting predictions of cardiovascular outcomes in The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Coronary artery calcium (CAC) scores inform subclinical atherosclerotic cardiovascular disease (ASCVD) burden, helping guide preventative treatments. However, prediction of cardiovascular (CV) events by CAC is largely limited to ASCVD outcomes. This study investigated whether a previously validated proteomic test for predicting a broad composite of four-year CV events could enhance the prognostic utility of CAC. METHODS: We used a 27-protein CV risk score (Prot-CVR), derived from ~5,000 SomaScan™ Assay plasma protein measurements, to predict four-year risk of a composite CV and mortality outcome (myocardial infarction, stroke/TIA, heart failure hospitalization, death) in 2,122 participants with ≥1 CV risk factors from the Multi-Ethnic Study of Atherosclerosis (MESA) observational cohort at exam 5 and compared predictions to CAC Agatston scores. Discriminatory performance was assessed using C-Index and 4-year area under the curve (AUC). Cox Proportional Hazard (CoxPH) ratios were calculated for the composite outcome, ASCVD outcome (myocardial infarction, resuscitated cardiac arrest, stroke, coronary heart disease death), and individual events. Changes in Prot-CVR and CAC scores from baseline to MESA exam 5 (+10-years) in CV event versus event-free participants were assessed using 2-tailed paired t-tests. CoxPH regression models of CV event status distributed by Prot-CVR, CAC, and relevant co-variates were evaluated for performance relative to individual models. RESULTS: Individual Prot-CVR and CAC models predicting the composite outcome had comparable 4-year AUCs, but Prot-CVR had a higher C-index (0.68 (0.65-0.70) versus 0.63 (0.60-0.65), p=0.001) and greater hazard ratios for the composite outcome (p<0.001), death (p<0.001), and heart failure (p=0.015). A combined CoxPH model of Prot-CVR + CAC + Age had a higher 4-year AUC (0.72, p<0.05) and C-Index (0.71, p<0.05) than Prot-CVR or CAC alone. Both Prot-CVR and CAC scores detected an increase in risk prior to an approaching CV event in ~10-year sensitivity-to-change analysis. For 49.6% of MESA population with CAC=0 at baseline, Prot-CVR was greater in composite event versus event free participants at 4 years (0.23 versus 0.15, p=0.006) and full follow-up (0.18 versus 0.13, p<0.001). CONCLUSION: Protein testing complements CAC for CV risk assessment although the improvement is modest. Prot-CVR may resolve which patients with CAC=0 are at heightened CV risk.

Journal Article↗

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

Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study.

BACKGROUND: Pulmonary emphysema occurs frequently in older adults, often without airflow limitation. Its presence predicts symptoms, respiratory hospitalizations and deaths, and all-cause mortality. Proteomics may provide further insights into emphysema pathogenesis and inform therapeutic targets. OBJECTIVE: We performed a proteomic discovery analysis of percent emphysema on computed tomography (CT) in a population-based, multiethnic sample from the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study. Replication was performed in two chronic obstructive pulmonary disease (COPD)-based studies, the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) and the Genetic Epidemiology of COPD (COPDGene) Study. METHODS: MESA recruited participants from the general population in 2000-02. The MESA Lung Study performed full-lung CT scans in 2010-12. Percent emphysema was defined as the percentage of lung voxels < -950 Hounsfield units. Over 7,200 plasma aptamers were measured via SomaScan. Cross-sectional linear and least absolute shrinkage and selection operator (LASSO) regression models were adjusted for demographics, anthropometrics, smoking, renal function, and scanner parameters. Statistical significance was defined as a false discovery rate p-value < 0.05. Gene Ontology (GO)/Reactome enrichment analyses were performed. LASSO-selected proteins' predictive performance was evaluated. RESULTS: Among 2,504 participants in the MESA Lung Study, mean age was 69.4 years, 1,291 had ever smoked, and median percent emphysema-like lung was 1.4%. In total, 1,234 aptamers were significantly associated with percent emphysema in the MESA Lung Study, and 35 replicated in the SPIROMICS and COPDGene Studies. Novel associations included protein family with sequence similarity (FAM) 177A1, syntenin-2, ubiquitin carboxyl-terminal hydrolase 25, and uncharacterized protein C20orf173. Previously identified emphysema-associated proteins included soluble advanced glycosylation end product-specific receptor (sRAGE), protein S100-A12, high mobility group protein B1, and roundabout homolog 2. Enrichment analyses identified 40 GO biological processes, including chemokine production and regulation and cell-cell adhesion and regulation, and two Reactome pathways, including RAGE signaling. In tenfold cross-validation, novel proteins were largely retained by LASSO (R2 = 5.4%), improved overall model performance (R2 = 24.8%), and uniquely explained greater variance in percent emphysema. CONCLUSIONS: This analysis in a general population sample identified novel and previously characterized proteins whose functional roles were validated by GO/Reactome enriched pathways, offering new insights into emphysema pathophysiology and therapeutics.

Humans↗

PubMed2025

Associations of High Attenuation Area-Related Proteomic Biomarkers with Fibrotic or Subpleural Interstitial Lung Abnormalities.

Rationale: High-attenuation area (HAA) is a computed tomography (CT) tool that correlates with lung inflammation and fibrosis. Systemic molecular correlates of HAA (e.g., plasma proteins) may inform biological processes involved in interstitial lung disease. Objectives: To identify plasma proteins that associate with HAA and correlate with a higher probability of developing new-onset fibrotic or subpleural interstitial lung abnormalities (ILAs). Methods: Plasma protein levels were measured using a semiquantitative aptamer-based platform in MESA (the Multi-Ethnic Study of Atherosclerosis; N = 5,486) and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study; N = 1,781). Linear regression models identified HAA-associated proteins after adjustment for demographic and socioeconomic factors, CT scanner parameters, study center, and batch. Associations of HAA-related proteins with new-onset fibrotic or subpleural ILAs were examined in MESA participants with ILA assessments on full-lung CT 10 years later. Immunohistochemical staining of select proteins was performed in lung tissue from pulmonary fibrosis cases. Measurements and Main Results: There were 75 proteins detected that were significantly associated with HAA in MESA and SPIROMICS. Gene Ontology analysis of these proteins identified processes involved in immune cell chemotaxis and cellular growth and apoptosis. Seven proteins were associated with a higher probability of new-onset fibrotic or subpleural ILAs in MESA, and two of these, junctional adhesion molecule-like protein and GTP cyclohydrolase 1 feedback regulatory protein, stained in areas of fibrosis in lung tissue from patients with interstitial lung disease. Conclusions: Plasma proteins associated with more HAA are involved in immune and cellular processes and associate with new-onset fibrotic-subpleural ILA.

Humans↗