Associations of mid-childhood per- and polyfluoroalkyl substances and early childhood metals with mid-childhood antibody titers

Environmental Epidemiology · 2026-03-13

Background: Per- and polyfluoroalkyl substances (PFAS) and nonessential metals impair immune responses, while essential metals promote immune maintenance. We evaluated associations of childhood PFAS and metal mixtures with measles, mumps, rubella (MMR), pertussis, diphtheria, and tetanus antibody titers. Methods: We measured mid-childhood (age 7.7 years, interquartile range 7.4, 8.4) plasma PFAS (perfluorooctanoate, perfluorooctane sulfonate, perfluorodecanoate, perfluorohexane sulfonate, 2-(N-methyl-perfluorooctane sulfonamide) acetate, and perfluorononanoate) and early childhood (3.2 years, interquartile range 3.0, 3.5) blood levels of nonessential (arsenic, barium, cadmium, cesium, lead, mercury, strontium, and tin), and essential (cobalt, copper, magnesium, manganese, molybdenum, selenium, and zinc) metals in children from the Project Viva cohort, recruited prenatally between 1999 and 2000 in Massachusetts, United States. We measured plasma MMR, pertussis, diphtheria, and tetanus titers, and the analytical sample of children with all measurements ranged from n = 493-507 for PFAS and n = 179-185 for metals analyses. We used adjusted quantile g-computation and regression models to estimate mixture- and individual PFAS or metal associations, respectively. Results: Approximately 48% of the children were female, and children received their last MMR or diphtheria, tetanus, pertussis vaccination dose about 3 years before blood antibody titer collection. Contrary to our hypothesis, a one-quartile increase in the mid-childhood PFAS mixture was associated with higher mid-childhood measles [β = 0.06 antibody (Ab) index, 95% confidence interval (CI): 0.02, 0.1], rubella (β = 2.6 IU/mL, 95% CI: 0.5, 4.8), pertussis (log-β = 0.2 IU/mL, 95% CI: 0.2, 0.5), and tetanus (log-β = 0.2 IU/mL, 95% CI: 0.04, 0.4) antibody titers. A one-quartile increase in the early childhood essential metals mixture was associated with lower mid-childhood rubella antibody titers (β = -4.9 IU/mL, 95% CI: -9.0, -0.8). Individual PFAS and metals were associated with pertussis, diphtheria, and tetanus antibody titers in directions contrary to our initial hypotheses. Conclusions: Our results suggest that mid-childhood blood PFAS and early childhood metals may influence antibody titers, although additional prospective studies are needed.

Multi-Ancestry Epigenome-Wide Meta-Analysis Identifies Novel Bulk and Cell-Type-Specific Epigenetic Markers of Asthma with Severe Exacerbations

medRxiv · 2026-04-18

Background: Extreme-phenotype comparisons allowed the discovery of novel asthma genetic risk loci. However, this approach remains unexplored in epigenome-wide association studies (EWAS). We aimed to identify bulk and cell-specific methylation markers of asthma with severe exacerbations across diverse ancestry groups. Methods: We conducted a meta-EWAS of 739,543 CpGs in whole blood among 1,192 African American and Latino pediatric populations, comparing non-asthmatics and asthma exacerbators. Genome-wide CpGs were followed up for replication in a meta-analysis across 1,516 ethnically diverse participants and in a cross-tissue evaluation of 393 nasal samples. We conducted differentially methylated region (DMRs), cell-type-deconvoluted, and quantitative trait loci analyses (whole-genome sequencing n=1,668; RNA-seq n=1,209). We examined enrichment in traits, pathways, and druggable genes, and analyzed DNAm predictors of plasma proteins and aging. Results: , λ=1.05). We replicated 25 CpGs in blood cells, cross-validated 7 in nasal samples, and detected 42 cell-specific DNAm markers mainly driven by T cells. DNAm at 134 CpGs was associated with gene expression in whole blood, including 118 associations with T-cell receptor genes, and 446 CpGs were regulated by > 1 genetic variant. We found enrichment for previous associations with environmental exposures, immune disorders, immune and inflammatory pathways, and druggable genes by developmental drugs. 21 methylation-predicted plasma proteins, involved in host defense, and one lung aging clock were associated with asthma exacerbations. Conclusions: The first meta-EWAS of extreme asthma phenotypes identified hundreds of novel DNAm markers, suggesting novel methylation biomarkers and candidate drugs for asthma and supporting the role of T cells.

One-carbon metabolism-related compounds are associated with epigenetic aging biomarkers: results from the cross-sectional National Health and Nutrition Examination Survey 1999–2002

American Journal of Clinical Nutrition · 2025-05-31 · 10 citations

Associations of Metal Mixtures During Early Pregnancy With Midlife Obesity and Body Composition: A Prospective Study

Obesity · 2025-08-26

OBJECTIVE: To examine the prospective associations of metal mixtures during pregnancy with midlife adiposity and explore metal-folate interactions. METHODS: In 500 participants from Project Viva, we measured six non-essential metals (arsenic, barium, cadmium, cesium, mercury, and lead) and five essential metals (copper, magnesium, manganese, selenium, and zinc) in red blood cells and folate in plasma collected during early pregnancy (mean gestational age: 10.0 weeks; mean age: 32.9 years). We assessed midlife (mean age: 51.2 years) adiposity using BMI and dual-energy X-ray absorptiometry (DXA) measures. We used multivariable-adjusted linear and multinomial logistic regression models to analyze individual exposures and Bayesian kernel machine regression to examine exposure mixtures. RESULTS: Higher arsenic, cesium, and mercury levels were associated with lower midlife DXA percentage fat, total fat mass index, and/or trunk fat mass index, even after adjustments for diet in pregnancy. We observed an antagonistic interaction between folate and arsenic: arsenic was associated with higher obesity risk at lower folate levels but lower obesity risk at higher folate levels. The essential metal mixture tended to be associated with lower midlife BMI and obesity risk. CONCLUSIONS: Higher pregnancy levels of arsenic, cesium, mercury, and the mixture of essential metals were associated with lower midlife adiposity.

Physical fitness is associated with slower epigenetic aging in US adults: evidence from the National Health and Nutrition Examination Survey

AJE Advances Research in Epidemiology · 2025-10-01 · 1 citations

Abstract Regular engagement in physical activity is a vital component of healthy aging, and epigenetic clocks are powerful biomarkers of biological aging. However, the extent to which physical activity and fitness influence epigenetic aging in diverse populations remains unclear. We harnessed 2346 participants (50-84 years of age) from the National Health and Nutrition Examination Survey 1999-2000 and 2001-2002 cycles. We examined associations of self-reported physical activity (moderate, vigorous, and muscle strengthening), metabolic equivalent time, walking speed, and knee extensor strength with epigenetic age acceleration (EAA) measures from 6 epigenetic clocks using adjusted survey-weighted generalized linear regression. A 40 N-m increase in peak knee extension torque was associated with lower EAA for PhenoAge (−1.09 years; 95% CI, −1.74 to −0.44), GrimAge2 (−0.72 years; 95% CI, −1.14 to −0.30), and DunedinPoAm (−0.015; 95% CI, −0.023 to −0.007) in fully adjusted models. Shorter time to complete a 20-ft walk and self-reported physical activity were also associated with lower EAA across several clocks, although these associations attenuated after adjusting for smoking, self-reported health, height, and waist circumference. Greater knee extensor strength is associated with reduced epigenetic aging across several next-generation clocks in the general US population, while associations related to self-reported physical activity tended to attenuate after adjusting for health and behavioral factors.

Autoimmune encephalitis in an underrepresented population: A case series from 2018 to 2023 in Bogotá, Colombia

Neuroscience · 2025-07-02 · 1 citations

Autoimmune encephalitis (AE) is a challenging neurological disorder with varying clinical presentations and outcomes, yet it remains underreported in Latin America. This study describes the clinical and paraclinical characteristics of patients diagnosed with AE at a tertiary center in Bogotá, Colombia, from 2018 to 2023. A total of 43 patients were included; the most common antibodies were anti-NMDAR, anti-GAD65, and anti-SOX. Notably, we observed a high occurrence of seronegative AE, often associated with neoplasms. Cerebellar ataxia, behavioral changes, and seizures were frequent clinical presentations. Our findings highlight the variability in antibody frequency, the significance of seronegative AE, and the potential association with neoplasms in our cohort, underscoring the need for increased awareness, improved diagnostic capabilities, and further research to address the knowledge gaps and improve healthcare outcomes for AE patients in Latin America.

The Nasal Microbiome and Associations With Environmental Exposures and Respiratory Health

Allergy · 2025-10-11 · 3 citations

ABSTRACT Background The nasal microbiome is directly in contact with the external environment and may play a role in respiratory health. This study aimed to evaluate the association of the nasal microbiome with air pollutants, meteorological conditions, and respiratory health in adolescents. Methods We analyzed the nasal microbiome in 416 adolescents from the Project Viva cohort (mean age 13 years and 52% female). We tested for the association of alpha diversity, nasotypes, and bacterial genera abundance with environmental exposures from the past 2 days to the past year (PM 2.5 , NO 2 , O 3 , temperature, humidity, residential greenness) and respiratory outcomes (asthma, hay fever, wheezing, IgE, aeroallergen sensitization, FeNO, lung function) through regression models adjusted for confounders and corrected using a false discovery rate (FDR) < 5%. Results Bacterial diversity was positively associated with hay fever and short‐term exposure to NO 2 , while it was negatively correlated with temperature (FDR < 0.05). Adolescents whose nasal microbiome was dominated by Moraxella were exposed in the past week to lower O 3 levels (ORs: 0.73–0.76) and higher temperature and humidity (ORs: 1.19–1.26). Staphylococcus dominance was positively associated with aeroallergen sensitization compared to Propionibacterium dominance (OR: 4.48, FDR = 0.03). Thirteen and eight bacterial genera abundance were associated with short‐to‐medium‐term exposures (PM 2.5 , NO 2 , temperature) and respiratory outcomes (hay fever, wheezing, IgE, FeNO, lung function) (FDR < 0.05). Staphylococcus , Corynebacterium , Pelomonas , Lactococcus , Lachnospiraceae (unclassified) , and Faecalibacterium abundance were associated with both environmental exposures and respiratory traits. Conclusions Nasal microbiome diversity was associated with hay fever, NO 2 , and temperature exposure. Multiple short‐to‐medium‐term environmental exposures and respiratory outcomes were associated with nasotypes and bacterial genera abundance in adolescents.

Cumulative Epigenetic Aging From Birth to Young Adulthood and Prospective Associations With Cardiometabolic Health in the CHAMACOS Study

Journal of the American Heart Association · 2025-09-30 · 3 citations

BACKGROUND: Epigenetic modifications linked to biological aging, like DNA methylation (DNAm), may serve as biomarkers for future cardiometabolic disease risk. However, existing studies have focused on older adults, overlooking the early-life origins of cardiometabolic health. METHODS: Among 378 participants from the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study, we measured DNAm repeatedly from birth to age 18 years to calculate 4 epigenetic aging (EA) biomarkers: Horvath, Skin & Blood, Intrinsic epigenetic age, and DNAm Telomere Length (DNAmTL). We then developed a novel measure of cumulative EA spanning from birth to age 18 years. Using multinomial logistic and multivariable linear regression models, we examined associations between cumulative EA and several indicators of cardiometabolic health at 18 years. RESULTS: We observed an increased risk of obesity with an interquartile range increase in cumulative EA by Horvath (relative risk [RR], 2.61 [95% CI, 1.79-3.80]), Skin & Blood (RR, 2.76 [95% CI, 1.89-4.03]), and Intrinsic epigenetic age (RR, 1.61 [95% CI, 1.11-2.34]), whereas DNAm TL decreased obesity risk (RR, 0.32 [95% CI, 0.22 -0.45]). Similarly, cumulative EA was associated with higher body mass index, waist circumference, body fat percentage, systolic blood pressure, mean arterial pressure, and resting pulse/heart rate at age 18 years. CONCLUSIONS: Cumulative EA throughout childhood predicts young adult cardiometabolic health and may signal increased risk for later cardiometabolic disease, highlighting the value of life-course epigenetic clocks as biomarkers for early-life health interventions.

Associations of maternal neighborhood and trauma-related stressors with mitochondrial DNA copy number and telomere length in maternal and cord blood

Scientific Reports · 2025-08-09 · 1 citations

Neighborhood and individual-level trauma-related stressors during pregnancy can increase oxidative stress, potentially altering cellular disease pathway biomarkers such as mitochondrial DNA copy number (mtDNAcn) and telomere length (TL). However, the biological mechanisms linking early-life stressors to long-term health outcomes remain understudied. In a subset of Project Viva participants (n = 415-917), we evaluated associations of neighborhood and individual-level stressors with mean relative mtDNAcn and TL measured in first trimester maternal blood and cord blood. Neighborhood stressors during pregnancy were assessed using the Child Opportunity Index (COI) and Social Vulnerability Index (SVI). Trauma-related stressors were measured using the Personal Safety Questionnaire (PSQ), administered mid-pregnancy, and maternal Adverse Childhood Experiences (ACEs), reported during a mid-life follow-up. In multivariable linear regression analysis, residence in a very high versus very low opportunity neighborhood was associated with lower maternal mtDNAcn ([Formula: see text]= - 0.09, 95% confidence interval (CI) - 0.17, - 0.02), while residence in a very high versus very low vulnerability area was associated with higher maternal mtDNAcn ([Formula: see text]= 0.06, 95% CI 0.01, 0.12). Additionally, residence in moderate versus very low opportunity neighborhoods was associated with longer cord blood TL ([Formula: see text]= 0.39, 95% CI 0.0002, 0.78), but associations were attenuated after cell-type adjustment. Our findings suggest that prenatal neighborhood stressors are associated with increased maternal mtDNAcn and neighborhood opportunity is associated with longer fetal TL, indicating possible links to biological pathways related to oxidative stress and cellular aging.

DNA methylation age deviation and cognitive status among older adults in the US, NHANES 1999-2002

medRxiv · 2025-09-18

Abstract Biological aging, measured using DNA methylation, is a potential biomarker for cognitive health outcomes. We evaluated associations between DNA methylation measures of aging and cognition in a nationally representative sample of adults aged 60+ in the National Health and Nutrition Examination Survey (NHANES), 1999-2002. Genome-wide DNA methylation data were used to create 13 measures of biological aging trained on different aging phenotypes. Cognition was assessed with the Digit Symbol Substitution Test (DSST). To evaluate associations between each DNA methylation measure and DSST score, survey-weighted linear regression models adjusted for age, sex, race/ethnicity, education, smoking, serum cotinine, and BMI were run. We assessed effect modification by sex, education, and race and ethnicity. Included participants (N=1,463) were an average of 70.5 years old and 82.7% non-Hispanic White. The average DSST score was 46.9 (SD 17.6). Ten of 13 DNA methylation measures were associated with DSST (adjusted p<0.05). One year of GrimAge2 accelerated aging was associated with –0.41 points lower DSST score (95% CI: –0.61, –0.21; adjusted p=5x10 -4 ). In stratified analyses, higher magnitudes of association were observed among male and non-Hispanic White participants across multiple aging measures. DNA methylation may be a useful biomarker of cognitive status among older adults.