Publications by authors named "Kyong-Mi Chang"
Article Synopsis
- * A large study involving nearly 10,000 DCM cases and close to a million controls identified 70 significant genetic locations linked to the disease, revealing the importance of heart muscle cells in its development.
- * The research also indicates that factors like higher body weight and blood pressure may contribute to DCM, and genetic risk scores can help predict the condition across different populations.
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: Fibrosis-4 (FIB4) is a recommended noninvasive test to assess hepatic fibrosis among patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we used FIB4 trajectory over time (ie, "slope" of FIB4) as a surrogate marker of liver fibrosis progression and examined if FIB4 slope is associated with clinical and genetic factors among individuals with clinically defined MASLD within the Million Veteran Program Cohort.
Methods: In this retrospective cohort study, FIB4 slopes were estimated through linear regression for participants with clinically defined MASLD and FIB4 <2.
We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) and γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals with liver function tests and a validation cohort of 21,689 cases and 617,729 controls, we identify and validate 14 risk associations for cirrhosis. Many variants are located near genes involved in hepatic lipid metabolism.
View Article and Find Full Text PDFBackground: Predictive performance of polygenic risk scores (PRS) varies across populations. To facilitate equitable clinical use, we developed PRS for coronary heart disease (CHD; PRS) for 5 genetic ancestry groups.
Methods: We derived ancestry-specific and multi-ancestry PRS based on pruning and thresholding (PRS) and ancestry-based continuous shrinkage priors (PRS) applied to summary statistics from the largest multi-ancestry genome-wide association study meta-analysis for CHD to date, including 1.
Article Synopsis
- Type 2 diabetes (T2D) is a complex disease influenced by various genetic factors and molecular mechanisms that vary by cell type and ancestry.
- In a large study involving over 2.5 million individuals, researchers identified 1,289 significant genetic associations linked to T2D, including 145 new loci not previously reported.
- The study categorized T2D signals into eight distinct clusters based on their connections to cardiometabolic traits and showed that these genetic profiles are linked to vascular complications, emphasizing the role of obesity-related processes across different ancestry groups.
Clopidogrel, an anti-platelet drug, used to prevent thrombosis after percutaneous coronary intervention. Clopidogrel resistance results in recurring ischemic episodes, with African Americans suffering disproportionately. The aim of this study was to identify biomarkers of clopidogrel resistance in African American patients.
View Article and Find Full Text PDFBackground & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 25% of the population and currently has no effective treatments. Plasma proteins with causal evidence may represent promising drug targets. We aimed to identify plasma proteins in the causal pathway of MASLD and explore their interaction with obesity.
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- Non-alcoholic fatty liver disease (NAFLD) involves fat buildup in liver cells, with Perilipin 2 (PLIN2) playing a key role; a variant known as Ser251Pro was linked to this condition.
- In a study using genetically modified mice, those expressing the Pro251 variant showed reduced liver fat and lower levels of certain enzymes compared to mice with the wild-type variant after being fed a fatty diet.
- Although the Pro251 variant showed potential for less liver fat in human subjects, it wasn't significantly associated with NAFLD in larger human data sets, indicating its impact may be limited in clinical settings.
Article Synopsis
- The study investigates the branching pattern of coronary arteries in humans, known as coronary dominance, and aims to understand its genetic regulation, which has been poorly understood due to challenges in studying human heart development.
- By analyzing data from 61,043 participants in the VA Million Veteran Program, researchers identified a moderate heritability of 27.7% for coronary dominance and discovered ten significant genetic loci, particularly near a chemokine-related region.
- The findings suggest that the gene in question plays a crucial role in the development of coronary artery patterns, as experiments in mice showed altered artery development when this gene was reduced, indicating potential targets for future medical treatments related to coronary artery conditions.
Article Synopsis
- Loss-of-function (LOF) alleles may reduce the effectiveness of clopidogrel, a medication used after PCI in patients with acute coronary syndrome (ACS) or stable ischemic heart disease (SIHD), but their impact on these conditions remains uncertain.
- A study involving 4,461 Veterans indicated that while LOF allele carriers had a slightly higher risk of major adverse cardiac events (MACE) after PCI for ACS, the difference wasn't statistically significant; the risk for SIHD patients with LOF alleles remained unchanged.
- The findings suggest that while LOF allele carriers with ACS treated with clopidogrel may face increased MACE risk, this genetic factor does not appear to
Hyperinsulinemia is a complex and heterogeneous phenotype that characterizes molecular alterations that precede the development of type 2 diabetes (T2D). It results from a complex combination of molecular processes, including insulin secretion and insulin sensitivity, that differ between individuals. To better understand the physiology of hyperinsulinemia and ultimately T2D, we implemented a genetic approach grouping fasting insulin (FI)-associated genetic variants based on their molecular and phenotypic similarities.
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- Obesity poses a significant public health challenge and is linked to high mortality rates, with prior studies focusing mostly on European populations.
- This research utilized whole-genome sequencing data from a diverse group of 88,873 individuals, finding 18 new signals associated with body mass index (BMI) and highlighting a novel SNP prevalent among people of African descent.
- The study emphasizes the importance of diverse genetic data in identifying new obesity-related variants, moving us closer to personalized medical interventions for this crisis.
Background: Predictive performance of polygenic risk scores (PRS) varies across populations. To facilitate equitable clinical use, we developed PRS for coronary heart disease (PRS) for 5 genetic ancestry groups.
Methods: We derived ancestry-specific and multi-ancestry PRS based on pruning and thresholding (PRS) and continuous shrinkage priors (PRS) applied on summary statistics from the largest multi-ancestry genome-wide meta-analysis for CHD to date, including 1.
Background: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity in people with and without diabetes, but it is underdiagnosed, posing challenges for research and clinical management. Here, we determine if natural language processing (NLP) of data in the electronic health record (EHR) could identify undiagnosed patients with hepatic steatosis based on pathology and radiology reports.
Methods: A rule-based NLP algorithm was built using a Linguamatics literature text mining tool to search 2.
In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma (HCC) risk after viral clearance is an important consideration when evaluating the CHIM. We estimate HCC risk in spontaneously cleared HCV and in noncirrhosis after sustained virological response (SVR) to HCV treatment in a systematic review and using data from 3 cohorts: German anti-D, Taiwan, and US Veterans Affairs (VA).
View Article and Find Full Text PDFBackground: Over 870 000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have occurred among Veterans Health Administration users, and 24 000 have resulted in death. We examined early outcomes of SARS-CoV-2 infection in hospitalized veterans.
Methods: In an ongoing, prospective cohort study, we enrolled veterans age ≥18 tested for SARS-CoV-2 and hospitalized at 15 Department of Veterans Affairs medical centers between February 2021 and June 2022.
Aims/hypothesis: Epidemiological studies have generated conflicting findings on the relationship between glucose-lowering medication use and cancer risk. Naturally occurring variation in genes encoding glucose-lowering drug targets can be used to investigate the effect of their pharmacological perturbation on cancer risk.
Methods: We developed genetic instruments for three glucose-lowering drug targets (peroxisome proliferator activated receptor γ [PPARG]; sulfonylurea receptor 1 [ATP binding cassette subfamily C member 8 (ABCC8)]; glucagon-like peptide 1 receptor [GLP1R]) using summary genetic association data from a genome-wide association study of type 2 diabetes in 148,726 cases and 965,732 controls in the Million Veteran Program.
Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases.
View Article and Find Full Text PDFObjective: To investigate the effects of metabolic traits, lifestyle factors, and drug interventions on liver fat using the mendelian randomisation paradigm.
Design: Mendelian randomisation study.
Setting: Publicly available summary level data from genome-wide association studies.
Elevated body mass index (BMI) is heritable and associated with many health conditions that impact morbidity and mortality. The study of the genetic association of BMI across a broad range of common disease conditions offers the opportunity to extend current knowledge regarding the breadth and depth of adiposity-related diseases. We identify 906 (364 novel) and 41 (6 novel) genome-wide significant loci for BMI among participants of European (N~1.
View Article and Find Full Text PDFBackground: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.
Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches.