Publications by authors named "Amber A Burt"

Article Synopsis
  • * A study analyzed DNA methylation patterns in buccal cells from VPT infants to see how their gestational age (GA) and age since conception (post-menstrual age, PMA) affect their development.
  • * Researchers found thousands of DNA sites linked to GA and PMA, with pathways related to brain development and growth significantly affected, indicating that early life epigenetic changes are vital for neurodevelopment in preterm infants.
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  • 5-hydroxymethylcystosine (5hmC) is a significant epigenetic modification linked to DNA demethylation, and our study focused on mapping its distribution in the placenta using advanced bisulphite techniques and RNA-sequencing data.
  • We discovered approximately 47,000 sites with elevated 5hmC levels, noting that it was more common in 'open sea' regions and less so in CpG islands, with different abundances in enhancer regions and transcription start sites.
  • Our findings also highlighted 499 specific gene sites where 5hmC levels correlated with gene expression, revealing 107 differentially hydroxymethylated regions that could impact gene regulation in the placenta.
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  • Bronchopulmonary dysplasia (BPD) in very preterm infants is linked to long-term health issues and might be influenced by changes in glucocorticoid (GC) activity, affecting the hypothalamic-pituitary-adrenal (HPA) axis and its genetics.
  • * DNA methylation (DNAm) of HPA genes was studied using samples from infant tissues, revealing that antenatal steroid exposure correlated with changes in sex-specific methylation, particularly within genes like FKBP5 and POMC related to stress response.
  • * The results indicate that while BPD severity doesn't directly relate to these epigenetic changes, antenatal steroids do, suggesting potential pathways for understanding how preterm birth impacts infant development
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  • - Children born preterm face higher risks of neurodevelopmental issues like Autism Spectrum Disorder (ASD), and the placenta may play a crucial role in these developments due to its regulatory functions.
  • - A study analyzed the placental gene expression, DNA methylation, and microRNA levels in preterm children to find links to ASD by comparing 368 individuals, revealing that 111 genes are associated with the condition.
  • - Specific genes such as EWSR1 and BAZ2A showed strong associations with ASD, while factors like CpG methylation and miRNA regulation affected genes critical for immune response, indicating potential targets for future ASD interventions.
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  • The placenta adapts to the changing requirements of the developing fetus throughout pregnancy, showing distinct developmental patterns between male and female fetuses.
  • Research from the NIH ECHO Programme analyzed placental DNA methylation across 355 females and 419 males, identifying significant associations with gestational age in 407 CpGs for females and 794 for males.
  • The study found that while females' placental methylation changes are mainly linked to differences in cell composition, males exhibit direct changes in methylation as gestational age increases, highlighting sex-specific biological processes.
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  • Chronodisruption, an overlooked environmental factor, may affect fetal development by altering circadian signals via the placenta.
  • In a study with C57BL/6J mice, chronodisruption didn’t change embryo count, placental weight, or fetal sex ratio, but it did modify placental gene expression.
  • Exposure to chronodisruption led to increased markers of immune cells in the placenta, indicating a possible shift toward a pro-inflammatory state in fetal development.
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  • Preterm birth increases the likelihood of long-term behavioral and cognitive issues in infants, necessitating better prediction tools for developmental delays through biobehavioral measures and molecular biomarkers.
  • The study involved recording cries and collecting DNA samples from very preterm infants to analyze the relationship between cry characteristics and DNA methylation using advanced genomic techniques.
  • Results revealed a significant association between specific genomic markers and cry features, suggesting that acoustic properties of cries in preterm infants may reflect underlying epigenetic variations, which can aid in understanding their long-term health outcomes.*
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  • Seasonal exposure affects human health and development, with the placenta serving as a key link between maternal and fetal systems that can shed light on how season of birth relates to later health outcomes.
  • A differential expression analysis of full-term human placental tissue revealed 583 transcripts that differed significantly between summer and winter births, indicating that seasonal factors may influence placental gene expression.
  • The study identified increased expression of specific genes in winter births and highlighted rhythmic patterns in gene expression, suggesting the placenta functions as a peripheral clock that could explain connections between birth season and health later in life.
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Circadian disruption is a common environmental and occupational exposure with public health consequences, but not much is known about whether circadian disruption affects in utero development. We investigated whether maternal circadian disruption, using night shift work as a proxy, is associated with variations in DNA methylation patterns of placental tissue in an epigenome-wide association study (EWAS) of night shift work. Here, we compared cytosine-guanosine dinucleotide (CpG) specific methylation genome-wide of placental tissue (measured with the Illumina 450K array) from participants (n = 237) in the Rhode Island Child Health Study (RICHS) who did (n = 53) and did not (n = 184) report working the night shift, using robust linear modeling and adjusting for maternal age, pre-pregnancy smoking, infant sex, maternal adversity, and putative cell mixture.

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Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants.

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In the version of this article originally published, one of the two authors with the name Wei Zhao was omitted from the author list and the affiliations for both authors were assigned to the single Wei Zhao in the author list. In addition, the ORCID for Wei Zhao (Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA) was incorrectly assigned to author Wei Zhou. The errors have been corrected in the HTML and PDF versions of the article.

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In the published version of this paper, the name of author Emanuele Di Angelantonio was misspelled. This error has now been corrected in the HTML and PDF versions of the article.

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Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI.

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Background: We have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival.

Methods: This study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass.

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Attention-Deficit Hyperactivity Disorder (ADHD) has high heritability; however, studies of common variation account for <5% of ADHD variance. Using data from affected participants without a family history of ADHD, we sought to identify de novo variants that could account for sporadic ADHD. Considering a total of 128 families, two analyses were conducted in parallel: first, in 11 unaffected parent/affected proband trios (or quads with the addition of an unaffected sibling) we completed exome sequencing.

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Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.

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Neutrophils are a key component of innate immunity. Individuals with low neutrophil count are susceptible to frequent infections. Linkage and association between congenital neutropenia and a single rare missense variant in TCIRG1 have been reported in a single family.

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Background: Recent studies have failed to establish a causal relationship between high-density lipoprotein cholesterol levels (HDL-C) and cardiovascular disease (CVD), shifting focus to other HDL measures. We previously reported that smaller/denser HDL levels are protective against cerebrovascular disease. This study sought to determine which of small+medium HDL particle concentration (HDL-P) or large HDL-P was more strongly associated with carotid intima-media thickening (cIMT) in an ethnically diverse cohort.

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Objectives: Copy number variants (CNVs) are duplications or deletions of genomic regions. Large CNVs are potentially pathogenic and are overrepresented in children with congenital heart disease (CHD). We sought to determine the frequency of large CNVs in children with isolated CHD, and to evaluate the relationship of these potentially pathogenic CNVs with transplant-free survival.

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Recent studies have failed to demonstrate a causal cardioprotective effect of HDL cholesterol levels, shifting focus to the functional aspects of HDL. Phospholipid transfer protein (PLTP) is an HDL-associated protein involved in reverse cholesterol transport. This study sought to determine the genetic and nongenetic predictors of plasma PLTP activity (PLTPa), and separately, to determine whether PLTPa predicted carotid artery disease (CAAD).

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Objective: Apolipoprotein E (APOE) genotype is a determinant of neurologic recovery after brain ischemia and traumatic brain injury. The APOE ε2 allele has been associated with worse neurodevelopmental (ND) outcome after repair of congenital heart defects (CHD) in infancy. Replication of this finding in an independent cohort is essential to validate the observed genotype-phenotype association.

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To determine which genomic features promote homologous recombination, we created a genome-wide map of gene targeting sites. We used an adeno-associated virus vector to target identical loci introduced as transcriptionally active retroviral vectors. A comparison of ~2,000 targeted and untargeted sites showed that targeting occurred throughout the human genome and was not influenced by the presence of nearby CpG islands, sequence repeats or DNase I-hypersensitive sites.

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Background: Recent data suggest that an increased level of high-density lipoprotein cholesterol (HDL-C) is not causally protective against heart disease, shifting focus to other sub-phenotypes of HDL. Prior work on the effects of dietary intakes has focused largely on HDL-C. The goal of this study was to identify the dietary intakes that affect HDL-related measures: HDL-C, HDL-2, HDL-3, and apoA1 using data from a carotid artery disease case-control cohort.

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Background: Recent data suggest that high-density lipoprotein cholesterol (HDL-C) levels are likely not in the causative pathway of atheroprotection, shifting focus from HDL-C to its subfractions and associated proteins. This study's goal was to determine which HDL phenotype was the better predictor of carotid artery disease (CAAD).

Methods And Results: HDL-2 and HDL-3 were measured in 1725 participants of European ancestry in a prevalent case-control cohort study of CAAD.

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