Publications by authors named "Kelly Cho"

Atrial fibrillation (AF) is the most common heart rhythm abnormality and is a leading cause of heart failure and stroke. This large-scale meta-analysis of genome-wide association studies increased the power to detect single-nucleotide variant associations and found more than 350 AF-associated genetic loci. We identified candidate genes related to muscle contractility, cardiac muscle development and cell-cell communication at 139 loci.

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Genome-wide association studies (GWAS) identified multiple loci for cardiovascular disease, but their relevance to individuals with chronic kidney disease (CKD), who are at higher risk of cardiovascular disease, is unknown. In this study, we performed GWAS analyses of coronary heart disease (CHD) or all-cause stroke in African (AFR) and European (EUR) American participants with CKD of the Chronic Renal Insufficiency Cohort (CRIC). Mixed- effect logistic regression models were race-stratified and adjusted for age, sex, site of recruitment, estimated glomerular filtration rate (eGFR), and principal components, followed by meta-analysis.

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Background: Coronary artery disease is a leading cause of morbidity and mortality in the United States. Coronary artery disease can lead to major complications including myocardial infarction (MI). The association of dietary cholesterol with coronary artery disease remains inconsistent.

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Heart failure (HF) has limited therapeutic options. In this study, we differentiated the pathophysiological underpinnings of the HF subtypes-HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF)-and uncovered subtype-specific therapeutic strategies. We investigated the causal roles of the human proteome and transcriptome using Mendelian randomization on more than 420,000 participants from the Million Veteran Program (27,799 HFrEF and 27,579 HFpEF cases).

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Background: The development and approval of novel drugs are typically time-intensive and expensive. Leveraging a computational drug repurposing framework that integrates disease-relevant genetically regulated gene expression (GReX) and large longitudinal electronic medical record (EMR) databases can expedite the repositioning of existing medications. However, validating computational predictions of the drug repurposing framework remains a challenge.

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Objective: Electronic health record (EHR) systems contain a wealth of clinical data stored as both codified data and free-text narrative notes (NLP). The complexity of EHR presents challenges in feature representation, information extraction, and uncertainty quantification. To address these challenges, we proposed an efficient Aggregated naRrative Codified Health (ARCH) records analysis to generate a large-scale knowledge graph (KG) for a comprehensive set of EHR codified and narrative features.

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Strong sex differences exist in sleep phenotypes and also cardiovascular diseases (CVDs). However, sex-specific causal effects of sleep phenotypes on CVD-related outcomes have not been thoroughly examined. Mendelian randomization (MR) analysis is a useful approach for estimating the causal effect of a risk factor on an outcome of interest when interventional studies are not available.

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Prior research suggests metformin has anti-cancer effects, yet data are limited. We examined the association between diabetes treatment (metformin versus sulfonylurea) and risk of incident diabetes-related and non- diabetes-related cancers in US veterans. This retrospective cohort study included US veterans, without cancer, aged ≥ 55 years, who were new users of metformin or sulfonylureas for diabetes between 2001 to 2012.

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Motivation: The increasing availability of Electronic Health Record (EHR) systems has created enormous potential for translational research. Recent developments in representation learning techniques have led to effective large-scale representations of EHR concepts along with knowledge graphs that empower downstream EHR studies. However, most existing methods require training with patient-level data, limiting their abilities to expand the training with multi-institutional EHR data.

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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.

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Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported.

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Importance: The American Heart Association proposed Life's Essential 8 (LE8) as an enhanced measurement tool for cardiovascular health.

Objective: To examine the association of LE8 with risk of atherosclerotic cardiovascular disease (ASCVD) incidence and prognosis in veterans.

Design, Setting, And Participants: This was a prospective cohort study of US veterans enrolled in the Department of Veterans Affairs (VA) Million Veteran Program (MVP) between 2011 and 2022.

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Objectives: In 2016, the Department of Veterans Affairs (VA) and the Department of Energy (DOE) established an Interagency Agreement (IAA), the Million Veteran Program-Computational Health Analytics for Medical Precision to Improve Outcomes Now (MVP-CHAMPION) research collaboration.

Materials And Methods: Oversight fell under the VA Office of Research Development (VA ORD) and DOE headquarters. An Executive Committee and 2 senior scientific liaisons work with VA and DOE leadership to optimize efforts in the service of shared scientific goals.

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Background: Dietary quality plays an important role in disease development and prognosis, and diet is also a key contributor to disparities in many chronic diseases and health conditions.

Objectives: This study aimed to assess racial and ethnic disparities experienced by veterans; we examined food intake and dietary quality across different racial and ethnic groups of United States veterans.

Methods: The study included 420,730 males and females aged 19-107 y (91.

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Article Synopsis
  • This study examines how glucagon-like peptide 1 receptor agonists (GLP-1RAs) may help protect kidneys, in addition to aiding in weight loss and blood sugar control.
  • Researchers analyzed data from over 353,000 veterans to see if genetic variations related to GLP-1R gene expression were linked to kidney disease progression.
  • The findings indicated that higher levels of genetic GLP-1R expression were associated with a reduced risk of kidney disease progression, suggesting potential nephroprotective benefits of GLP-1RAs.
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  • 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.
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  • The study focused on identifying self-reported military and occupational exposures among Veterans, such as Agent Orange and chemical warfare agents, through the Million Veteran Program, which gathers health data from over a million US Veterans.
  • Over 500,000 participants detailed their military experiences, revealing significant differences in reported exposures based on factors like service era, combat deployment, and occupation, with Vietnam-era Veterans primarily reporting Agent Orange exposure.
  • The findings indicate that exposure patterns varied notably by demographics, with combat-related occupations showing higher exposure reports compared to healthcare roles, aligning with previous research on US military Veterans.
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Polygenic scores (PGSs) are a promising tool for estimating individual-level genetic risk of disease based on the results of genome-wide association studies (GWASs). However, their promise has yet to be fully realized because most currently available PGSs were built with genetic data from predominantly European-ancestry populations, and PGS performance declines when scores are applied to target populations different from the populations from which they were derived. Thus, there is a great need to improve PGS performance in currently under-studied populations.

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  • * We found 17 genetic loci associated with sleep duration impacting lipid levels, with 10 of them being newly identified and linked to sleep-related disturbances in lipid metabolism.
  • * The research points to potential drug targets that could lead to new treatments for lipid-related issues in individuals with sleep problems, highlighting the connection between sleep patterns and cardiovascular health.
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  • The study focused on understanding how various environmental factors contribute to the risk of colorectal cancer (CRC) and aimed to enhance screening methods by recalibrating an environmental risk score (e-Score) among U.S. Veterans.
  • Data was collected from over 227,000 male participants from the Million Veteran Program, with significant relationships found between CRC risk and factors like age, education, lifestyle, and medication use.
  • The new e-Score model outperformed the original one in predicting CRC risk, suggesting it could improve personalized screening and prevention efforts for colorectal cancer among veterans.
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  • Genetic studies have highlighted the need for more diverse research on plasma fibrinogen levels, as previous studies largely focused on Europeans, leading to gaps in understanding and missing heritability.
  • By analyzing data from whole-genome sequencing and genotype data from large cohorts, researchers identified 18 genetic loci related to fibrinogen levels, some of which are more common in African populations and include variants that may impact protein function.
  • The study's findings indicate a connection between fibrinogen levels and various health conditions, emphasizing the importance of whole-genome sequencing in discovering genetic factors in diverse populations and enhancing knowledge about fibrinogen regulation.
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  • Frailty is linked to increased cardiovascular disease (CVD) risk and mortality among US veterans, highlighting the importance of identifying frailty for better health outcomes.
  • In a study of nearly 190,688 veterans aged 50 and older, frailty was assessed using three different scoring systems, revealing a significant correlation between frailty and higher mortality rates from all causes and CVD.
  • The results suggest that regardless of the method used to measure frailty, it consistently indicates a greater risk for negative health events, indicating a need for more research specifically focusing on younger veterans under 60.
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Background: Individuals who have experienced a stroke, or transient ischemic attack, face a heightened risk of future cardiovascular events. Identification of genetic and molecular risk factors for subsequent cardiovascular outcomes may identify effective therapeutic targets to improve prognosis after an incident stroke.

Methods: We performed genome-wide association studies for subsequent major adverse cardiovascular events (MACE; n=51 929; n=39 980) and subsequent arterial ischemic stroke (AIS; n=45 120; n=46 789) after the first incident stroke within the Million Veteran Program and UK Biobank.

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Article Synopsis
  • Human genetic studies often lack diversity, which limits understanding of disease causes and health disparities.
  • The Department of Veterans Affairs Million Veteran Program analyzed data from a diverse group of 635,969 veterans, revealing 13,672 genomic risk loci, with significant findings particularly from non-European populations.
  • The research identified causal variants across 613 traits, showing that genetic similarities exist across populations and emphasizing the importance of including underrepresented groups in genetic research.
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