Publications by authors named "Anh N Do"

Article Synopsis
  • The Knight-Alzheimer Disease Research Center at Washington University has been at the forefront of Alzheimer disease research for over 40 years, significantly enhancing our understanding through various studies on cognitive and molecular aspects.
  • Over 26,000 biological samples have been collected from participants, including DNA, RNA, plasma, and cerebrospinal fluid, to support extensive research on dementia and aging.
  • The Genetics and High Throughput -Omics core has conducted in-depth molecular profiling to discover new risk factors, biomarkers, and potential treatment targets for Alzheimer disease.
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In Alzheimer's disease (AD), the most common cause of dementia, females have higher prevalence and faster progression, but sex-specific molecular findings in AD are limited. Here, we comprehensively examined and validated 7,006 aptamers targeting 6,162 proteins in cerebral spinal fluid (CSF) from 2,077 amyloid/tau positive cases and controls to identify sex-specific proteomic signatures of AD. In discovery (N=1,766), we identified 330 male-specific and 121 female-specific proteomic alternations in CSF (FDR <0.

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Background: The COVID-19 pandemic caused by SARS-CoV-2 remains public health burdens and many unresolved issues worldwide. Molecular assays based on real-time RT-PCR are critical for the detection of SARS-CoV-2 in clinical specimens from patients suspected of COVID-19.

Objective: We aimed to establish and validate an in-house real-time RT-PCR for the detection of SARS-CoV-2.

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Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies.

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Although clinical and laboratory data have long been used to guide medical practice, this information is rarely integrated with multi-omic data to identify endotypes. We present Merged Affinity Network Association Clustering (MANAclust), a coding-free, automated pipeline enabling integration of categorical and numeric data spanning clinical and multi-omic profiles for unsupervised clustering to identify disease subsets. Using simulations and real-world data from The Cancer Genome Atlas, we demonstrate that MANAclust's feature selection algorithms are accurate and outperform competitors.

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: Indices of left ventricular (LV) structure and geometry represent useful intermediate phenotypes related to LV hypertrophy (LVH), a predictor of cardiovascular (CV) disease (CVD) outcomes. We conducted an exome-wide association study of LV mass (LVM) adjusted to height, LV internal diastolic dimension (LVIDD), and relative wall thickness (RWT) among 1,364 participants of African ancestry (AAs) in the Hypertension Genetic Epidemiology Network (HyperGEN). Both single-variant and gene-based sequence kernel association tests were performed to examine whether common and rare coding variants contribute to variation in echocardiographic traits in AAs.

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Background: Nasal transcriptomics can provide an accessible window into asthma pathobiology.

Objective: Our goal was to move beyond gene signatures of asthma to identify master regulator genes that causally regulate genes associated with asthma phenotypes.

Methods: We recruited 156 children with severe persistent asthma and controls for nasal transcriptome profiling and applied network-based and probabilistic causal methods to identify severe asthma genes and their master regulators.

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Background: Unexpected allergic reactions to peanut are the most common cause of fatal food-related anaphylaxis. Mechanisms underlying the variable severity of peanut-allergic reactions remain unclear.

Objectives: We sought to expand mechanistic understanding of reaction severity in peanut allergy.

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Background: Household endotoxin levels have been variably associated with risk for asthma and atopy.

Methods: We studied participants from the 2005-2006 National Health and Nutrition Examination Survey (NHANES, n = 6963), a large cohort representative of the US population (aged 1-84 years). We built logistic regression models to test for associations between house dust endotoxin and sensitization to specific foods (milk, egg, and peanut).

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and minute intestinal flukes (MIF) such as are fish-borne trematodes (FBT) that may coexist in regions where local people have a habit of eating raw fish like Vietnam. Responses to FBT should be verified according to the data on the distribution of these flukes. This study aims to explore the prevalence of different species of FBT and related factors among local people in a northern province of Vietnam.

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Background: Left ventricular (LV) hypertrophy affects up to 43% of African Americans (AAs). Antihypertensive treatment reduces LV mass (LVM). However, interindividual variation in LV traits in response to antihypertensive treatments exists.

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Background: Folate and vitamin B-12 are essential micronutrients involved in the donation of methyl groups in cellular metabolism. However, associations between intake of these nutrients and genome-wide DNA methylation levels have not been studied comprehensively in humans.

Objective: The aim of this study was to assess whether folate and/or vitamin B-12 intake are asssociated with genome-wide changes in DNA methylation in leukocytes.

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Background: The high prevalence of obesity among US adults has resulted in significant increases in associated metabolic disorders such as diabetes, dyslipidemia, and high blood pressure. Together, these disorders constitute metabolic syndrome, a clinically defined condition highly prevalent among African-Americans. Identifying epigenetic alterations associated with metabolic syndrome may provide additional information regarding etiology beyond current evidence from genome-wide association studies.

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Importance: Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine with manifold consequences for mammalian pathophysiology, including cardiovascular disease. A deeper understanding of TNF-α biology may enhance treatment precision.

Objective: To conduct an epigenome-wide analysis of blood-derived DNA methylation and TNF-α levels and to assess the clinical relevance of findings.

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Background: Tapeworms of the genus Spirometra include species whose larval stages can infect humans, causing a disease called sparganosis. Cases of human infection with adult worms are very rare and have been reported in Korea and China. Here we report the first case of human infection with an adult of Spirometra erinaceieuropaei in Vietnam.

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Left ventricular (LV) hypertrophy, highest in prevalence among African Americans, is an established risk factor heart failure. Several genome wide association studies have identified common variants associated with LV-related quantitative-traits in African Americans. To date, however, the effect of rare variants on these traits has not been extensively studied, especially in minority groups.

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In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models.

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Previous studies have reported that risk of cardiovascular morbidity and mortality substantially increases in hypertensive patients, especially among those with inadequate blood pressure control. Two common antihypertensive drug classes including thiazide diuretics and angiotensin-converting enzyme (ACE) inhibitors affect different enzymes in the renin-angiotensin-aldosterone system (RAAS). In the RAAS, angiotensinogen is converted into angiotensin II which increases blood pressure through vasoconstriction.

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