Publications by authors named "Hornsby W"
Sharing diverse genomic and other biomedical datasets is critical to advance scientific discoveries and their equitable translation to improve human health. However, data sharing remains challenging in the context of legacy datasets, evolving policies, multi-institutional consortium science, and international stakeholders. The NIH-funded Polygenic Risk Methods in Diverse Populations (PRIMED) Consortium was established to improve the performance of polygenic risk estimates for a broad range of health and disease outcomes with global impacts.
View Article and Find Full Text PDFSpecial Issue "Applied Sport Physiology and Performance-3rd Edition".
J Funct Morphol Kinesiol
February 2025
This Special Issue, "Applied Sport Physiology and Performance-3rd edition", is a follow up to the previous two iterations (i [...
View Article and Find Full Text PDFBackground: Cardiovascular disease (CVD) risk differs across Asian subgroups, possibly due to differences in hypertension burden. We characterized lifetime blood pressure (BP) trajectories for East and South Asian individuals and compared their associations with CVD risk.
Methods: Among 148 872 UK Biobank participants with primary care utilization data, life course BP trajectories were fitted as a function of age by sex according to self-identified ethnicity.
The relatively low representation of admixed populations in both discovery and fine-tuning individual-level datasets limits polygenic risk score (PRS) development and equitable clinical translation for admixed populations. Under the assumption that the most informative PRS weight for a homogeneous sample varies linearly in an ancestry continuum space, we introduce a Genetic tance-assisted PRS mbination Pipeline for erse Genetic ncestrie () to interpolate a harmonized PRS for diverse, especially admixed, ancestries, leveraging multiple PRS weights fine-tuned within single-ancestry samples and genetic distance. DiscoDivas treats ancestry as a continuous variable and does not require shifting between different models when calculating PRS for different ancestries.
View Article and Find Full Text PDFBackground: Earlier identification of high coronary artery disease (CAD) risk individuals may enable more effective prevention strategies. However, existing 10-year risk frameworks are ineffective at earlier identification. We sought to understand how the variable importance of genomic and clinical factors across life stages may significantly improve lifelong CAD event prediction.
View Article and Find Full Text PDFImportance: Treatment to lower high levels of low-density lipoprotein cholesterol (LDL-C) reduces incident coronary artery disease (CAD) risk but modestly increases the risk for incident type 2 diabetes (T2D). The extent to which genetic factors across the cholesterol spectrum are associated with incident T2D is not well understood.
Objective: To investigate the association of genetic predisposition to increased LDL-C levels with incident T2D risk.
Cardiac diseases represent common highly morbid conditions for which molecular mechanisms remain incompletely understood. Here we report the analysis of 1,459 protein measurements in 44,313 UK Biobank participants to characterize the circulating proteome associated with incident coronary artery disease, heart failure, atrial fibrillation and aortic stenosis. Multivariable-adjusted Cox regression identified 820 protein-disease associations-including 441 proteins-at Bonferroni-adjusted P < 8.
View Article and Find Full Text PDFEarly identification of high-risk individuals through the analysis of their unique disease trajectories has a strong potential to support efficient prevention and clinical management across a range of chronic conditions. In this paper we present a novel approach for dynamic modeling of the evolution of chronic disease risks over time, incorporating individual genetic predispositions. Our approach uses a hierarchical Bayesian topic model including Gaussian Processes to capture age effects.
View Article and Find Full Text PDFArticle Synopsis
- Polygenic risk scores (PRSs) could enhance disease risk prediction, but their current effectiveness is compromised for non-European populations, creating potential health disparities.
- The PRIMED Consortium aims to improve PRS performance by aggregating diverse genetic data on a cloud platform and evaluating ethical implications related to its implementation.
- Focused on cardiometabolic diseases and cancer, PRIMED seeks to promote equity in polygenic risk assessment through collaboration across multiple research sites and organizations.
Article Synopsis
- Researchers studied plasma proteomic profiles linked to subclinical mutations in blood cells, particularly focusing on clonal hematopoiesis of indeterminate potential (CHIP) and its connection to various health outcomes, including coronary artery disease (CAD).
- The study involved a large, diverse group of participants and identified a significant number of unique proteins associated with key driver genes, showing differences based on genetics, sex, and race.
- Methods like Mendelian randomization and mouse model tests helped clarify the causal effects of these proteins, revealing shared plasma proteins between CHIP and CAD that could inform future clinical insights.
Article Synopsis
- This study identifies and characterizes rare coding alleles linked to genetic dyslipidemia, a major risk factor for coronary artery disease, using data from over 1.1 million individuals across various ancestries.
- It discovered 800 significant variants across 209 genes, with a notable focus on non-European populations, and included a diverse cohort of participants to enhance genetic understanding.
- The findings highlight potential therapeutic targets, particularly new genes that may help lower LDL cholesterol levels, providing valuable insights for future genetic disease research and drug development.
Background: Atherosclerotic cardiovascular disease (ASCVD) risk estimation based on the pooled cohort equation (PCE) overestimates in population-based cohorts. Whether it performs equally across disaggregated demographics in health care populations is less known.
Objectives: The purpose of the study was to recalibrate PCE and rederive prevention thresholds in a contemporary health care system and evaluate its performance across sociodemographics.
Clonal hematopoiesis of indeterminate potential (CHIP) is linked to diverse aging-related diseases, including hematologic malignancy and atherosclerotic cardiovascular disease (ASCVD). While CHIP is common among older adults, the underlying factors driving its development are largely unknown. To address this, we performed whole-exome sequencing on 8,374 blood DNA samples collected from 4,187 Atherosclerosis Risk in Communities Study (ARIC) participants over a median follow-up of 21 years.
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- - The study investigates the role of genetics in postoperative nausea and vomiting (PONV), which impacts patient satisfaction and results in unplanned hospital admissions after surgery, hypothesizing that genetic factors might explain some of the variability in risk that traditional factors do not cover.
- - Researchers conducted a genome-wide association study using data from patients at Michigan Medicine and Vanderbilt University Medical Center, identifying 46 genetic variants associated with PONV and developing a polygenic risk score to better predict occurrences in different patient cohorts.
- - Findings showed that higher polygenic risk scores corresponded with increased risk for developing PONV, suggesting that genetic predisposition combined with known clinical risks can improve understanding and prediction of this complication in surgical patients.
Article Synopsis
- Despite improvements in managing traditional risk factors, coronary artery disease (CAD) continues to be a leading cause of death, highlighting the need to understand new risk factors, including the role of the spleen.* -
- Researchers employed deep learning and radiomics techniques on MRI data from 42,059 UK Biobank participants to identify splenic features linked to CAD, uncovering 10 relevant features and 219 genetic loci associated with these features.* -
- The study suggests a genetic connection between the spleen and CAD, particularly with the 9p21 variant, and demonstrates how integrating deep learning with genomics can enhance our understanding of CAD mechanisms.*
Integrative Metabolomics Differentiate Coronary Artery Disease, Peripheral Artery Disease, and Venous Thromboembolism Risks.
Arterioscler Thromb Vasc Biol
September 2024
Background: Arterial and venous cardiovascular conditions, such as coronary artery disease (CAD), peripheral artery disease (PAD), and venous thromboembolism (VTE), are genetically correlated. Interrogating underlying mechanisms may shed light on disease mechanisms. In this study, we aimed to identify (1) epidemiological and (2) causal, genetic relationships between metabolites and CAD, PAD, and VTE.
View Article and Find Full Text PDFBackground: The extent to which the relationships between clinical risk factors and coronary artery disease (CAD) are altered by CAD polygenic risk score (PRS) is not well understood. Here, we determine whether the interactions between clinical risk factors and CAD PRS further explain risk for incident CAD.
Methods: Participants were of European ancestry from the UK Biobank without prevalent CAD.
Background: Coronary artery disease (CAD) is a leading cause of death among the 38.4 million people with HIV globally. The extent to which cardiovascular polygenic risk scores (PRSs) derived in non-HIV populations generalize to people with HIV is not well understood.
View Article and Find Full Text PDFPolygenic risk scores (PRSs) are an emerging tool to predict the clinical phenotypes and outcomes of individuals. We propose PRSmix, a framework that leverages the PRS corpus of a target trait to improve prediction accuracy, and PRSmix+, which incorporates genetically correlated traits to better capture the human genetic architecture for 47 and 32 diseases/traits in European and South Asian ancestries, respectively. PRSmix demonstrated a mean prediction accuracy improvement of 1.
View Article and Find Full Text PDFClonal hematopoiesis of indeterminate potential (CHIP), the clonal expansion of myeloid cells with leukemogenic mutations, results in increased coronary artery disease (CAD) risk. CHIP is more prevalent among people with HIV (PWH), but the risk factors are unknown. CHIP was identified among PWH in REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) using whole-exome sequencing.
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- Scientists studied blood proteins in over 44,000 people to understand heart diseases better.
- They found 820 important protein links to conditions like heart failure and aortic stenosis, which could help create new treatments.
- Their research showed that looking at these proteins can improve predictions for heart diseases more than just using regular health information.
Article Synopsis
- Hypertensive disorders of pregnancy (HDPs), such as gestational hypertension and preeclampsia, significantly increase risks of maternal health issues and long-term cardiovascular disease across the globe.
- The study aimed to link specific proteins in the blood to HDPs using genetic data, employing two-sample mendelian randomization for analysis.
- Findings involved a broad dataset, including over 393,000 women for gestational hypertension and nearly 607,000 for preeclampsia, uncovering associations between 90 candidate cardiovascular-related proteins and these hypertensive disorders.
Background: The clinical significance of isolated diastolic hypertension defined by the 2017 American College of Cardiology/American Heart Association blood pressure (BP) guidelines remains inconsistent. We examined whether long-term diastolic burden predicts the first major adverse cardiovascular event in participants with sustained and untreated normal systolic BP.
Methods: The Mass General Brigham Biobank is a New England health care-based cohort recruited between 2010 and 2021.