Publications by authors named "Bressler J"

The relationship between mitochondrial DNA (mtDNA) heteroplasmy and nuclear DNA (nDNA) methylation (CpGs) remains to be studied. We conducted an epigenome-wide association analysis of heteroplasmy burden scores across 10,986 participants (mean age 77, 63% women, and 54% non-White races/ethnicities) from seven population-based observational cohorts. We identified 412 CpGs (FDR p < 0.

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  • There is a shared relationship between cardiovascular disease (CVD) and cancer, tied to common risk factors and biological pathways, which the study aims to explore across three diverse ethnic cohorts.
  • The researchers employed a two-stage methodology involving epigenome-wide association studies and targeted analysis of differentially methylated positions (DMPs), unveiling significant epigenetic markers for CVD and cancer.
  • The findings indicate interconnected biological pathways for CVD and cancer, suggesting potential for precision prevention strategies, including screening based on epigenetic signatures to identify at-risk patients in early diagnosis stages.
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This study describes associations between immune cell types and cancer risk in a Black population; elevated regulatory T-cell proportions that were associated with increased overall cancer and lung cancer risk, and elevated memory B-cell proportions that were associated with increased prostate and all cancer risk.

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Obesity and poverty disproportionally affect African American persons. Epigenetic mechanisms could partially explain the association between socioeconomic disadvantage and body mass index (BMI). We examined the extent to which epigenetic mechanisms mediate the effect of socioeconomic status (SES) on BMI.

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With age, hematopoietic stem cells can acquire somatic mutations in leukemogenic genes that confer a proliferative advantage in a phenomenon termed "clonal hematopoiesis of indeterminate potential" (CHIP). How these mutations confer a proliferative advantage and result in increased risk for numerous age-related diseases remains poorly understood. We conducted a multiracial meta-analysis of epigenome-wide association studies (EWAS) of CHIP and its subtypes in four cohorts (N=8196) to elucidate the molecular mechanisms underlying CHIP and illuminate how these changes influence cardiovascular disease risk.

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  • - Autism spectrum disorder (ASD) is a complex condition influenced by genetic and environmental factors, but its connection with metabolic changes is not well understood.
  • - A study analyzed plasma samples from 200 children with ASD and 200 typically developing controls to discover specific metabolites that could serve as biomarkers for the disorder.
  • - The research found distinct metabolic patterns in ASD children, identifying four significant metabolites, including three fatty acids and the amino acid sarcosine, which may inform future interventions for ASD.
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  • - We conducted a study on 7,140 Hispanic and Latino adults to identify genetic regions linked to cognitive abilities through admixture and fine-mapping analyses.
  • - We found nine regions in the genome associated with cognitive function, and three of these regions showed strong statistical evidence for supporting genes related to cognitive functioning and dementia.
  • - Our findings enhance the understanding of how ancestry influences cognitive abilities, showcasing the effectiveness of admixture mapping in identifying unique genetic variants relevant to cognitive function.
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Background: Naltrexone is a medication used to treat both opioid and alcohol use disorder with limited experience in pregnant individuals, particularly in comparison to more commonly utilized treatments such as buprenorphine-naloxone. The long-term outcomes of infants exposed to naltrexone has not been previously examined.

Aims: To compare the neurobehavioral outcomes of naltrexone versus buprenorphine-naloxone exposed infants.

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Prior cohort studies assessing cancer risk based on immune cell subtype profiles have predominantly focused on White populations. This limitation obscures vital insights into how cancer risk varies across race. Immune cell subtype proportions were estimated using deconvolution based on leukocyte DNA methylation markers from blood samples collected at baseline on participants without cancer in the Atherosclerosis Risk in Communities (ARIC) Study.

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  • Autism Spectrum Disorder (ASD) is linked to genetic and environmental factors, but the specific metabolic changes associated with it are not well understood.
  • A study compared metabolite profiles between children with ASD and typically developing (TD) controls, identifying four distinct metabolites, including three fatty acids and the amino acid sarcosine, that were associated with ASD.
  • The results suggest that these metabolic alterations could offer insights into the biological underpinnings of ASD and open up new avenues for research and potential biomarkers.
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Objective: There is a lack of knowledge about the relative safety and efficacy of naltrexone for the treatment of pregnant individuals with opioid and/or alcohol use disorder, including the range of outcomes, in both the pregnant individual and the infant, over the course of peripartum period. Our objective was to describe these outcomes in a cohort of pregnant individuals on naltrexone.

Methods: In this prospective case series, 7 pregnant individuals with opioid use disorder (OUD) or alcohol use disorder (AUD) treated with naltrexone were followed from pregnancy through 12 months after delivery.

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  • Research on verbal declarative memory (VDM) aims to understand the genetic factors that influence memory decline and dementia in older adults to develop potential interventions.
  • The study analyzed data from over 29,000 older, non-demented Europeans to explore relationships between genetic variants, gene expression, and brain tissues, finding significant associations across various pathways.
  • Results indicated that genetic variations linked to VDM are regulated by genes, transcription factors, and immune-related pathways, highlighting their importance in cognitive performance among older individuals.
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  • - Jamaican children are exposed to mercury (Hg) primarily through their diet, particularly from consuming saltwater and canned fish, which can negatively affect neurodevelopment.
  • - The study examined the relationship between environmental Hg exposure, specific GST genes (GSTT1, GSTM1, GSTP1), and blood mercury concentrations in a sample of 375 children aged 2-8.
  • - Results showed that the impact of consuming canned fish on blood Hg levels is stronger in children with specific GSTP1 genotypes, emphasizing the need for further research in other populations.
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Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.

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Ethyl Maltol (EM) is a commonly used flavoring compound and has been reported to bind iron and facilitate iron transport. Since EM is membrane permeable, the potential that it disrupts intracellular iron homeostasis was investigated. EM increased the labile iron pool in SH-SY5Y cells and increased iron-responsive protein activity using a reporter assay in the HEK293 cells.

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Aim: To investigate individual susceptibility to periodontitis by conducting an epigenome-wide association study using peripheral blood.

Materials And Methods: We included 1077 African American and 457 European American participants of the Atherosclerosis Risk in Communities (ARIC) study who had completed a dental examination or reported being edentulous at Visit 4 and had available data on DNA methylation from Visit 2 or 3. DNA methylation levels were compared by periodontal disease severity and edentulism through discovery analyses and subsequent testing of individual CpGs.

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Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the 'pleiotropy-informed' multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993).

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  • Previous research indicates a link between lower mitochondrial DNA (mtDNA) copy number and neurodegenerative diseases, prompting investigation into the relationship between mtDNA CN in blood and Alzheimer disease endophenotypes.
  • The study involved dementia-free individuals from various community cohorts, measuring mtDNA CN and analyzing its association with cognitive function and brain MRI markers over specified timeframes.
  • Findings showed that higher mtDNA CN correlates with better cognitive performance, independent of several confounding factors, with consistent results observed in both cross-sectional and prospective analyses, although the latter showed a weaker association.
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  • Fibrinogen is crucial for blood clotting and inflammation, and its circulating levels may be influenced by differences in DNA methylation at specific CpG sites.
  • An epigenome-wide association study analyzed blood DNA methylation and fibrinogen levels in over 18,000 diverse participants, revealing significant associations through advanced statistical models.
  • The study identified a total of 83 replicated CpG sites linked to fibrinogen, highlighting genes involved in inflammation, with many associations being affected but still significant after adjusting for C-reactive protein (CRP) levels.
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  • - The study explored the link between food allergies and specific glutathione S-transferase (GST) genes concerning Autism Spectrum Disorder (ASD) and its severity in a sample of Jamaican children.
  • - Researchers used data from 344 children and employed statistical models to assess associations, finding no significant connections between food allergies and ASD overall.
  • - However, they noted that children with food allergies (particularly to non-dairy and dairy) showed increased severity in ASD symptoms based on certain GST gene variations, indicating a potential interaction that needs further investigation in other populations.
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  • Aluminum can be toxic, especially from high dietary intake in children, and this study focused on 366 Jamaican children aged 2–8 to analyze factors contributing to detectable blood aluminum levels.
  • The research found that eating string beans was linked to higher odds of detectable blood aluminum, while higher parental education was associated with lower odds.
  • An interaction was noted between the consumption of saltwater fish and a specific GSTP1 genotype, indicating that children with a certain genetic makeup who ate saltwater fish showed significantly higher odds of having detectable blood aluminum levels.
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Introduction: We studied the replication and generalization of previously identified metabolites potentially associated with global cognitive function in multiple race/ethnicities and assessed the contribution of diet to these associations.

Methods: We tested metabolite-cognitive function associations in U.S.

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  • Age-related changes in DNA methylation patterns in blood are linked to health issues like blood cancer and coronary artery disease (CAD), particularly through a condition called clonal hematopoiesis of indeterminate potential (CHIP).
  • The study focused on two frequently mutated genes associated with CHIP, DNMT3A and TET2, which exhibit opposite patterns of DNA methylation despite both supporting the self-renewal of hematopoietic stem cells.
  • Findings suggest that certain methylation changes connected to DNMT3A and TET2 could increase the risk for coronary artery disease, as verified by analyses in two different participant groups.
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  • Understanding the genetic basis of memory could help address neurodegenerative disorders, and a study examined this in a large group of adults without dementia or stroke (N=53,637).
  • Researchers identified new genetic locations associated with verbal short-term memory and learning, particularly in the genes CDH18 and APOE/APOC1/TOMM40, with results verified in a separate sample.
  • Analysis showed that a genetic score for verbal learning correlated with brain activity during memory tasks and linked memory traits to various cognitive and health outcomes.
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  • Glutathione S-transferases (GST) play a key role in detoxifying harmful substances like lead, and this study explored their interaction with autism spectrum disorder (ASD) in Jamaican children.
  • Researchers analyzed blood lead concentrations in 344 pairs of ASD cases and typically developing controls, finding that ASD cases had significantly lower lead levels.
  • Genetic variations in GST genes were linked to these differences, suggesting that certain genotypes may enhance lead detoxification in children with and without ASD.
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