Publications by authors named "John Dou"

Steroid hormones are integral to pregnancy and fetal development, regulating processes such as metabolism, inflammation, and immune responses. Excessive prenatal steroid exposure, through lifestyle choices or environmental chemicals, can lead to metabolic dysfunctions in offspring. The research focuses on how exposure to testosterone (T) and bisphenol A (BPA) affects the liver's DNA methylome, a key component of the epigenome influencing long-term health.

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Trichloroethylene (TCE) is a volatile synthetic chemical used in various industrial processes like metal degreasing. Large amounts of TCE have been released into the environment. Exposure to TCE can occur through routes, such as inhalation for workers using TCE or ingestion of drinking water in contaminated areas.

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Our study tests residential segregation as an explanation for biological aging disparities between Black and White Americans. We analyze data from 288 Black and White older-age adults who participated in Wave 6 (2019) of the Americans' Changing Lives study, a nationally representative cohort of adults in the contiguous United States. Our outcome of interest is epigenetic age acceleration assessed via five epigenetic clocks: GrimAge, PhenoAge, SkinBloodAge, HannumAge, and HorvathAge.

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Cognitive impairment among older adults is a growing public health challenge and environmental chemicals may be modifiable risk factors. A wide array of chemicals has not yet been tested for association with cognition in an environment-wide association framework. In the US National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2011-2014 cross-sectional cycles, cognition was assessed using the Digit Symbol Substitution Test (DSST, scores 0-117) among participants aged 60 years and older.

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To distinguish DNA methylation (DNAm) from cell proportion changes in whole placental villous tissue research, we developed a robust cell type-specific DNAm reference to estimate cell composition. We collated new and existing cell type DNAm profiles quantified via Illumina EPIC or 450k microarrays. To estimate cell composition, we deconvoluted whole placental samples ( = 36) with robust partial correlation based on the top 30 hyper- and hypomethylated sites identified per cell type.

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Major depressive disorder accelerates DNA methylation age, a biological aging marker. Subclinical depressive symptoms are common, but their link to DNA methylation aging in older adults remains unexplored. This study analyzed the cross-sectional relationship between depressive symptoms and accelerated DNA methylation aging, considering gender and race/ethnicity in U.

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  • Amyotrophic lateral sclerosis (ALS) is associated with age and various risk factors, and this study explored the role of epigenetic age acceleration (EAA) in ALS patients versus controls.
  • Researchers analyzed blood samples from 428 ALS patients and 288 controls to assess EAA using the GrimAge method, which can indicate how much faster a person's biological age is compared to their chronological age.
  • The study found that ALS patients experienced significantly higher EAA and that those with rapid ageing had a greater risk of shorter survival, with strong associations to specific occupational exposures and changes in immune cell types, particularly in males.
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  • This study explores how metal levels in plasma and urine relate to the risk and survival of amyotrophic lateral sclerosis (ALS), focusing on both genetic and environmental influences.
  • In the analysis of samples from 454 ALS patients and 294 control subjects, higher levels of metals like copper, selenium, and zinc were linked to increased ALS risk and lower survival rates.
  • The findings emphasize the importance of both occupational and non-occupational metal exposure in contributing to ALS progression, independent of genetic predispositions.
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Cognitive impairment among older adults is a growing public health challenge and environmental chemicals may be modifiable risk factors. A wide array of chemicals has not yet been tested for association with cognition in an environment-wide association framework. In the US National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2011-2014 cross-sectional cycles, cognition was assessed using the Digit Symbol Substitution Test (DSST, scores 0-117) among participants aged 60 years and older.

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  • Autism spectrum disorder (ASD) is a common and diverse neurodevelopmental condition influenced by genetic and environmental factors, particularly during pregnancy.
  • A study analyzed urinary metal concentrations (cadmium and cesium) from two pregnancy cohorts and found that higher levels were linked to increased risks of ASD and non-neurotypical development in children.
  • Results indicated that elevated cadmium levels in early pregnancy were significantly associated with a higher risk of ASD, while cesium levels showed a marginally increased risk, highlighting the potential impact of these environmental agents on child development.
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Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals.

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To distinguish DNA methylation (DNAm) from cell proportion changes in whole placental tissue research, we developed a robust cell type-specific DNAm reference to estimate cell composition. We collated newly collected and existing cell type DNAm profiles quantified via Illumina EPIC or 450k microarrays. To estimate cell composition, we deconvoluted whole placental samples (n=36) with robust partial correlation based on the top 50 hyper- and hypomethylated sites per cell type.

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Environmental chemical exposures influence immune system functions, and humans are exposed to a wide range of chemicals, termed the chemical "exposome". A comprehensive, discovery analysis of the associations of multiple chemical families with immune biomarkers is needed. In this study, we tested the associations between environmental chemical concentrations and immune biomarkers.

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Background: The pathogenesis of amyotrophic lateral sclerosis (ALS) involves both genetic and environmental factors. This study investigates associations between metal measures in plasma and urine, ALS risk and survival, and exposure sources.

Methods: Participants with and without ALS from Michigan provided plasma and urine samples for metal measurement via inductively coupled plasma mass spectrometry.

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  • Prenatal exposure to metals like lead, mercury, manganese, and selenium was studied for potential links to autism by analyzing urine samples from mothers during pregnancy.
  • The research used data from two autism-risk cohorts (EARLI and MARBLES), employing complex statistical methods to assess the relationships between metal levels and child social responsiveness scores.
  • Results showed no consistent associations between overall metal exposure or individual metals and the social responsiveness scores at 36 months, suggesting the effects could vary based on child sex and study cohort.
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Introduction: Hematopoietic stem cells are cells that differentiate into blood cell types. Although the placenta secretes hormones, proteins and other factors important for maternal/fetal health, cross-talk between placental and hematopoietic stem cells is poorly understood. Moreover, toxicant impacts on placental-hematopoietic stem cell communication is understudied.

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  • * A meta-analysis of 37 studies revealed that higher MEA is linked to different DNA methylation patterns in offspring at birth, childhood, and adolescence, with significant findings at 473 specific sites associated with maternal factors like smoking and nutrition.
  • * The research underscores the connection between socio-economic status and biological processes, enhancing our understanding of how maternal education impacts health through genetic mechanisms and emphasizing the role of social determinants in health disparities.
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  • Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder influenced by genetic and environmental factors, particularly through maternal exposure to specific metals during pregnancy.
  • A study involving two pregnancy cohorts found significant associations between elevated levels of cadmium and cesium in maternal urine and an increased risk of children developing ASD or other non-typical developmental disorders.
  • Results indicate that higher concentrations of these metals during early pregnancy may contribute to neurodevelopmental risks, highlighting the importance of monitoring environmental exposures in expecting mothers.
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Importance: Neighborhood segregation and poverty may be important drivers of health inequities. Epigenomic factors, including DNA methylation clocks that may mark underlying biological aging, have been implicated in the link between social factors and health.

Objective: To examine the associations of neighborhood segregation and poverty with 4 DNA methylation clocks trained to capture either chronological age or physiological dysregulation.

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  • Seasonal variations at birth can influence DNA methylation, which may affect health outcomes over a person’s lifetime.
  • A study involving multiple cohorts discovered specific DNA methylation patterns linked to different birth seasons, revealing 26 differentially methylated regions (DMRs) at birth and 32 in childhood.
  • Results suggested that geographic latitude plays a role in these associations, linking certain genes to conditions like schizophrenia and asthma, particularly in infants born in higher latitudes (≥50°N).
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  • * Researchers analyzed saliva samples from 796 children at ages 9 and 15 and found 8,430 sites on autosomal chromosomes where DNA methylation levels differed by sex, with a significant 76.2% showing higher levels in females.
  • * The consistent results between ages 9 and 15 suggest that these sex-differential DNA methylation patterns are stable over time, contributing to our understanding of why some diseases show differing prevalence based on sex.
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Background And Objectives: Most patients with amyotrophic lateral sclerosis (ALS) lack a monogenic mutation. This study evaluates ALS cumulative genetic risk in an independent Michigan and Spanish replication cohort using polygenic scores.

Methods: Participant samples from University of Michigan were genotyped and assayed for the chromosome 9 open reading frame 72 hexanucleotide expansion.

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Background: Major depressive disorder affects mental well-being and accelerates DNA methylation age, a marker of biological aging. Subclinical depressive symptoms and DNA methylation aging have not been explored.

Objective: To assess the cross-sectional association between depressive symptoms and accelerated DNA methylation aging among United States adults over age 50.

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Circulating vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy ( = 2,420) or cord blood ( = 1,029), with cord blood DNA methylation.

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