Joel Schwartz
Harvard School of Public Health, Environmental Health, Faculty Member
Research Interests:
Research Interests: Inflammation and Medicine
Research Interests:
Research Interests:
Research Interests:
ABSTRACT Funding: 5 T32 ES07069-22, NIEHS ES00002, EPAR827353, 5P01ES09825 Epidemiological studies of airborne particles and mortality and hospital admission have shown that people with diabetes are a vulnerable group, especially with... more
ABSTRACT Funding: 5 T32 ES07069-22, NIEHS ES00002, EPAR827353, 5P01ES09825 Epidemiological studies of airborne particles and mortality and hospital admission have shown that people with diabetes are a vulnerable group, especially with regard to cardiovascular outcomes. Research examining whether intermediate markers of cardiovascular risk are associated with air pollution exposure in diabetic populations is necessary to explore possible mechanisms. We evaluated associations between air pollution and various physiological measurements of cardiovascular health taken at baseline visits from 342 Boston-area residents participating in clinical trials. Air pollutants (PM2.5, particle number (PN), balck carbon (BC), and sulfates (SO4) were measured at a facility approximately 1 km from where patients were seen. Pollutant concentrations for the day of examination, one day previous, and moving averages from 3 and 5 days previous were evaluated for associations with a variety of clinical and laboratory parameters. These included: inflammatory markers in the blood (C reactive protein (CRP), TNF-alpha, ICAM, VCAM, endothelin-1), blood pressure, liver function tests, serum lipids, platelets, hemoglobin and HbA 1c, an indicator of longer-term glycemic control. These variables were log-transformed where necessary to achieve normal distributions. Linear regression analysis was performed for each of the clinical outcomes, including as predictors the pollutant index of interest and the subject's age, race, gender, smoking history, and body mass index (BMI). We express results as percent change in the clinical outcome per interquartile range (IQR) increase in the pollutant, which were, for lag 0 values: PM2.5: 7.6 ug/m3, BC: 0.61 ug/m3, PN:20,993 #/cc, SO4: 2.1 ug/m3. Increases in pollution exposure were associated with increased levels of three of the inflammatory markers (CRP, ICAM, and VCAM). CRP increases were associated with BC lag 0 (52% increase in CRP per IQR of BC, 95% confidence interval (CI): (0.3%, 130%)). CRP was also marginally associated with PM2.5 3 day average (45% increase per IQR, 95% CI: -7%, 127%). PN and SO4 were significantly associated with increased ICAM, and SO4 with increased levels of VCAM. The associations with inflammatory blood markers are consistent with previous studies showing that air pollution exposure can increase inflammation and potentially change risk profiles for cardiac events or disease progression. Results with other outcomes were less consistent and suggest the need for further testing of model specifications. The opportunity to examine air pollution associations with risk factors for cardiovascular events in a population of people with diabetes may contribute to understanding of mechanisms for previously observed epidemiological associations.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Air pollution and social characteristics have been shown to affect indicators of health. While use of spatial methods to estimate exposure to air pollution has increased the power to detect effects, questions have been raised about... more
Air pollution and social characteristics have been shown to affect indicators of health. While use of spatial methods to estimate exposure to air pollution has increased the power to detect effects, questions have been raised about potential for confounding by social factors. A study of singleton births in Eastern Massachusetts was conducted between 1996 and 2002 to examine the association between indicators of traffic, land use, individual and area-based socioeconomic measures (SEM), and birth outcomes (birth weight, small for gestational age and preterm births), in a two-level hierarchical model. We found effects of both individual (education, race, prenatal care index) and area-based (median household income) SEM with all birth outcomes. The associations for traffic and land use variables were mainly seen with birth weight, with an exception for an effect of cumulative traffic density on small for gestational age. Race/ethnicity of mother was an important predictor of birth outco...
Research Interests: Demography, Environmental Health, Air pollution, Air Pollution and Health Effects, Adolescent, and 15 moreBirth Weight, Humans, Low Birth Weight, Female, Land Use, Adult, Determinants of Health, Birthweight, Household Income, Environmental Exposure, Air Pollutants, Cumulant, confounding, Hierarchical Model, and Infant Premature
Rationale: Few studies have examined associations between long-term exposure to fine particulate matter (PM2.5) and lung function decline in adults. Objectives: To determine if exposure to traffic and PM2.5 are associated with... more
Rationale: Few studies have examined associations between long-term exposure to fine particulate matter (PM2.5) and lung function decline in adults. Objectives: To determine if exposure to traffic and PM2.5 are associated with longitudinal changes in lung function in a population-based cohort in the Northeastern U.S., where pollution levels are relatively low. Methods: FEV1 and FVC were measured up to 2 times between 1995-2011 among 6,339 participants of the Framingham Offspring or Third Generation studies. We tested associations between residential proximity to a major roadway and PM2.5 exposure in 2001 (estimated by a land-use model using satellite measurements of aerosol optical thickness) and lung function. We examined differences in average lung function using mixed effects models and differences in lung function decline using linear regression models. Current smokers were excluded. Models were adjusted for age, sex, height, weight, pack-years, socioeconomic status indicators, ...
Research Interests:
The 80,000 inhabitants of the lower part of Le Havre obtain their water supply from two karstic springs, Radicatel and Saint-Laurent. Until 2000, the Radicatel water was settled when turbidity exceeded 3 NTU, then filtered and... more
The 80,000 inhabitants of the lower part of Le Havre obtain their water supply from two karstic springs, Radicatel and Saint-Laurent. Until 2000, the Radicatel water was settled when turbidity exceeded 3 NTU, then filtered and chlorinated, whereas the Saint-Laurent water was simply chlorinated. Our study aimed to characterize the link between water turbidity and the incidence of acute gastroenteritis (AGE). Records on drug sales used for the treatment of AGE were collected from January 1994 to June 1996 (period 1) and from March 1997 to July 2000 (period 2). Daily counts of drug sales were modeled using a Poisson Regression. We used data set 2 as a discovery set, identifying relevant (i.e. both significant and plausible) exposure covariates and lags. We then tested this model on period 1 as a replication dataset. In period 2, the daily drug sales correlated with finished water turbidity at both resources. Settling substantially modified the risk related to turbidity of both raw and ...
Research Interests: Environmental Science, Water, Water quality, Environmental Monitoring, Water Pollution, and 15 moreMedicine, France, Multidisciplinary, Water Supply, Pharmaceutical Economics, Humans, Gastroenteritis, Poisson regression, Time Factors, Saint Petersburg, Water Quality, Turbidity, Tap Water, Epidemiological monitoring, and Drug prescriptions
Research Interests:
Research Interests:
Epidemiological studies have shown that extremes in ambient temperature are associated with short term increases in mortality. To control for seasonality, most previous time series studies used non-parametric functions of time. We... more
Epidemiological studies have shown that extremes in ambient temperature are associated with short term increases in mortality. To control for seasonality, most previous time series studies used non-parametric functions of time. We conducted a US multi-city study evaluating whether adjustment for influenza epidemics changes the exposure-response function of temperature, and whether controlling for the remaining seasonal pattern could be modeled more simply. Counts of daily cardiovascular deaths and of emergency hospital admissions of the elderly for pneumonia during 1992-2000 were obtained for 48 cities. Applying city-specific Quasi-Poisson regression models we estimated the association between daily cardiovascular mortality and temperature. Models included day-of-the-week indicators and regression splines of temperature, relative humidity, barometric pressure. In the base model a regression spline of date with five degrees of freedom (df) per year captured trend and seasonality. In the alternative model a regression spline of pneumonia admissions, a sinusoidal function of time, and a regression spline of date with ten df were included instead. Temperatures were lower in the north-east compared to the south-west and the range differed greatly. The alternative model fit the data better than the base model based on GSV-scores, capturing well the regular seasonal pattern as well as the irregular pattern of the outcome. The temperature-response function was mostly U- or J-shaped and not greatly affected by adjusting for influenza. The pooled estimated increase in risk for a temperature decrease from 0 to -5°C was 1.6% (95% confidence interval (CI) 0.9-2.4%) in the base and 1.9% (95% CI 1.2-2.6%) in the alternative model. This study on the effect of temperature on mortality shows that including epidemic data explained most of the irregular seasonal pattern, allowing more parsimonious models than when adjusting for seasonality only with smooth functions of time. The effect of cold temperature is not confounded by epidemics
Research Interests:
ABSTRACT An abstract is unavailable. This article is available as HTML full text and PDF.
Research Interests:
Research Interests: Environmental Science, Environmental Health, Drug interactions, Air pollution, Risk assessment, and 15 moreMortality, Medicine, Environmental Sciences, Humans, Carbon Monoxide, Measurement Error, Particulate Matter, Pollutant, Reproducibility of Results, Risk Assessment, Environmental Exposure, Carbon Monoxide Poisoning, Air Pollutants, Aerodynamic Diameter, and Medical and Health Sciences
Research Interests: Environmental Health, Medicine, Drug, Exposure Assessment, Environmental Sciences, and 15 moreHumans, Infrastructure, Data Collection, Environmental Research, Dose Response Relationship, Morbidity, Dosimetry, Acute Effects, Health Effect, Environmental Protection Agency, Environmental Exposure, Air Pollutants, Criteria Pollutants, Chronic effects, and Medical and Health Sciences
Research Interests: Cardiology, Epidemiology, Carbon, Environmental Health, Air pollution, and 15 moreEnvironmental Sciences, Carbon Monoxide, Ambient Air Pollution, Female, Atrial Fibrillation, Environmental Medicine, Boston, Aged, Dust, Fibrillation, Arrhythmia, Environmental Exposure, Confidence Interval, Arrhythmias, and Air Pollutants
Research Interests: Aging, Environmental Health, Research, Medicine, Environmental Sciences, and 15 moreHumans, Hypertension, Tibia, Blood Pressure, Male, Lead, Normative, Body Mass Index, Boston, Environmental Pollutants, Psychosocial Stress, Environmental Exposure, Confidence Interval, Patella, and Medical and Health Sciences
Research Interests:
Research Interests: Obesity, Aging, Medicine, Lung Function, Humans, and 15 moreInternal Medicine, Male, Regression Analysis, Body Mass Index, Clinical Sciences, Aged, Ozone, Chest, Likelihood Functions, Environmental Exposure, Confidence Interval, AIRWAY HYPERRESPONSIVENESS, Pulmonary Function Tests, confounding, and Methacholine
There is increased evidence that air pollution may be associated with cardiovascular disease. The... more
There is increased evidence that air pollution may be associated with cardiovascular disease. The authors' prior investigations on the association between air pollution exposure and stroke mortality led to the current study, which was conducted to assess the effects of ambient air pollution on ischemic cardiovascular diseases among the elderly population (i.e., males and females 64+ yr of age) in Seoul, Korea. The authors estimated the relative risks of hospitalization associated with an interquartile range (IQR) increase in pollution concentrations; a generalized additive Poisson model was used to conduct a time-series analysis of the counts. The concentrations of ambient air pollutants were lower than the current recommendations for air quality in Korea. The estimated relative risks of hospitalization associated with an IQR were 1.05 (95% confidence interval [CI] = 1.01, 1.10) for particulate matter less than or equal to 10 microm in diameter (PM10) (IQR = 40.4 microg/m3); 1.10 (95% CI = 1.05, 1.15) for ozone (IQR = 21.7 ppb); 1.08 (95% CI = 1.03, 1.14) for nitrogen dioxide (IQR = 14.6 ppb); 1.07 (95% CI = 1.01, 1.13) for carbon monoxide (IQR = 1.0 ppm); and 0.95 (95% CI = 0.90, 1.01) for sulfur dioxide (IQR = 4.4 ppb). The authors observed that sulfur dioxide was a significant risk factor for ischemic heart disease-related hospital admissions during the summer months (i.e., June, July, and August) (relative risk = 1.32; 95% CI = 1.08, 1.62). Hospital admissions for ischemic heart diseases were associated significantly with daily variations in levels of ambient air pollutants. These findings may provide new insights into the possible pathologic mechanisms involving air pollutants, and they support the hypothesis that the elderly appear to be at particular risk from the effects of air pollution, at pollutant levels lower than the standards commonly adopted by many countries.
Research Interests: Air Quality, Environmental Health, Archives, Air pollution, Cardiovascular disease, and 15 moreEnvironmental Sciences, Humans, Carbon Monoxide, Ambient Air Pollution, Hospitalization, Female, Heart, Clinical Sciences, Aged, Age Factors, Ischemic Heart Disease, Confidence Interval, Air Pollutants, Hospital Admission, and Cardiovascular medicine and haematology
In several studies, investigators have reported associations among air pollution, weather, and daily deaths, usually from all causes. In the current study, we focused on the difference in lag time between exposure to total suspended... more
In several studies, investigators have reported associations among air pollution, weather, and daily deaths, usually from all causes. In the current study, we focused on the difference in lag time between exposure to total suspended particulates or extreme weather and cause-specific mortality in an effort to understand the potential underlying mechanism. We used a robust Poisson regression in a generalized additive model to investigate the association between air pollution and daily mortality. We used a loess smooth function to model season, weather, and humidity; indicator variables for hot days were also used. To examine the relationship in a currently meaningful range, we excluded all days with a total suspended particulate concentration higher than 200 microg/m3. We found a significant association on the concurrent day, both for respiratory infection deaths (11% increase/100 microg/m3 increase in total suspended particulate; 95% confidence interval = 5, 17) and for heart-failure deaths (7% increase; 95% confidence interval = 3, 11). The associations with myocardial infarction (i.e., 10% increase; 95% confidence interval = 3, 18) and chronic obstructive pulmonary disease (12% increase, 95% confidence interval = 6, 17) were found for the means of 3 and 4 d prior to death. We observed an effect of cold weather at lag 1 for respiratory infections and an effect of hot weather at lag 0 for heart failure and myocardial infarctions. The association for all causes and cause-specific deaths was almost identical to that noted previously in Philadelphia, Pennsylvania. Smoothed functions of total suspended particulates suggested a higher slope at lower concentrations, and this finding may account for differences noted between European and U.S. studies. Given that both the dependence between weather and daily mortality and the lag between exposure and death varies by cause of death, analyses by specific causes of death would be very useful in the future.
Research Interests: Nonlinear dynamics, Air pollution, Mortality, Medicine, Italy, and 15 moreHeart Failure, Humans, Regression Analysis, Poisson regression, Confidence intervals, Generalized Additive Model, Pennsylvania, Myocardial Infarction, Public health systems and services research, Respiratory Tract Infections, Chronic obstructive pulmonary disease, Poisson Distribution, Confidence Interval, Cause of death, and Respiratory Infection
Research Interests: Air pollution, Medicine, Humans, COPD, Mathematical Sciences, and 15 moreAir Conditioning, American, Patient Admission, Meta Analysis, Aged, Ozone, Particle Size, Particulate Matter, Chronic obstructive pulmonary disease, Confidence Interval, Air Pollutants, Cumulant, Aerodynamic Diameter, Hospital Admission, and Medical and Health Sciences
The association between short-term elevations in ambient particulate air pollution and increased cardiovascular morbidity and mortality is well documented. Ambient particles may also trigger acute decompensation in patients with... more
The association between short-term elevations in ambient particulate air pollution and increased cardiovascular morbidity and mortality is well documented. Ambient particles may also trigger acute decompensation in patients with congestive heart failure (CHF), but this hypothesis has not been evaluated in a systematic manner. This study evaluated the association between daily levels of respirable particulate matter of aerodynamic diameters < or =10 microm (PM10) and the rate of hospitalization from the emergency room for CHF in Medicare recipients (age > or = 65 years) in 7 United States cities from 1986 and 1999. The time-stratified case-crossover design was used to separately estimate the effect of a 10 microg/m3 increase in PM10 in each city. A combined random-effects estimate was then obtained from the city-specific effect estimates. There were 292,918 admissions with primary diagnoses of CHF during the observation period. Overall, a 10 microg/m3 increase in PM10 was associated with a 0.72% (95% confidence interval 0.35% to 1.10%) increase in the rate of admission for CHF on the same day. The effect of PM10 appeared to be less in patients with secondary diagnoses of hypertension. There was no consistent effect modification by age, gender, race, or any other secondary diagnosis evaluated. In conclusion, these results support the hypothesis that elevated levels of particulate air pollution, below the current limits set by the United States Environmental Protection Agency, are associated with an increase in the rate of hospital admission for exacerbation of CHF.
Research Interests: Cardiology, Air pollution, Medicine, Heart Failure, Humans, and 15 moreCongestive Heart Failure, Hospitalization, United States, Female, Male, Airborne Particulates, Aged, Particulate Air Pollution, Confidence Interval, Air Pollutants, The American, Hospital Admission, Exacerbation, Medical and Health Sciences, and Cardiovascular medicine and haematology
Research Interests: Demography, Epidemiology, Environmental Monitoring, Cities, Environmental Sciences, and 15 moreHumans, Female, Male, Air Conditioning, Exposure, CHEMICAL SCIENCES, Aged, Exposure science, And, Cardiovascular Diseases, Environmental, Air Pollutants, effect modification, Cause of death, and Medical and Health Sciences
Research Interests: Demography, Aging, Environmental Health, Environmental Monitoring, Air pollution, and 15 moreLinear models, Cardiovascular Physiology, Environmental Sciences, Humans, Male, Aged, Cardiovascular Diseases, Biological markers, Black Carbon, Environmental Exposure, Confidence Interval, Air Pollutants, confounding, Medical and Health Sciences, and Epidemiological monitoring
Air pollution is associated with adverse human health, but mechanisms through which pollution exerts effects remain to be clarified. One suggested pathway is that pollution causes oxidative stress. If so, oxidative stress-related... more
Air pollution is associated with adverse human health, but mechanisms through which pollution exerts effects remain to be clarified. One suggested pathway is that pollution causes oxidative stress. If so, oxidative stress-related genotypes may modify the oxidative response defenses to pollution exposure. We explored the potential pathway by examining whether an array of oxidative stress-related genes (twenty single nucleotide polymorphisms, SNPs in nine genes) modified associations of pollutants (organic carbon (OC), ozone and sulfate) with urinary 8-hydroxy-2-deoxygunosine (8-OHdG), a biomarker of oxidative stress among the 320 aging men. We used a Multiple Testing Procedure in R modified by our team to identify the significance of the candidate genes adjusting for a priori covariates. We found that glutathione S-tranferase P1 (GSTP1, rs1799811), M1 and catalase (rs2284367) and group-specific component (GC, rs2282679, rs1155563) significantly or marginally significantly modified ef...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Acute exacerbations and worsening of idiopathic pulmonary fibrosis (IPF) have been associated with exposure to ozone (O), nitrogen dioxide (NO) and particulate matter, but chronic exposure to air pollution might also affect the incidence... more
Acute exacerbations and worsening of idiopathic pulmonary fibrosis (IPF) have been associated with exposure to ozone (O), nitrogen dioxide (NO) and particulate matter, but chronic exposure to air pollution might also affect the incidence of IPF. We investigated the association between chronic exposure to NO, O and particulate matter with an aerodynamic diameter <10 μm (PM) and IPF incidence in Northern Italy between 2005 and 2010.Daily predictions of PM concentrations were obtained from spatiotemporal models, and NO and O hourly concentrations from fixed monitoring stations. We identified areas with homogenous exposure to each pollutant. We built negative binomial models to assess the association between area-specific IPF incidence rate, estimated through administrative databases, and average overall and seasonal PM, NO, and 8-hour maximum O concentrations.Using unadjusted models, an increment of 10 µg·m in NO concentration was associated with an increase between 7.93% (95% CI 0....
Research Interests: Geography, Incidence Geometry, Environmental Monitoring, Air pollution, Medicine, and 15 moreItaly, Humans, Female, Male, Incidence, Middle Aged, Adult, Idiopathic Pulmonary Fibrosis, Nitrogen Dioxide, Environmental Exposure, Confidence Interval, Air Pollutants, Aerodynamic Diameter, confounding, and Medical and Health Sciences
Particulate matter < 2.5 μm in diameter (PM) and heat are strong predictors of morbidity, yet few studies have examined the effects of long-term exposures on non-fatal events, or assessed the short and long-term effect on health... more
Particulate matter < 2.5 μm in diameter (PM) and heat are strong predictors of morbidity, yet few studies have examined the effects of long-term exposures on non-fatal events, or assessed the short and long-term effect on health simultaneously. We jointly investigated the association of short and long-term exposures to PM and temperature with hospital admissions, and explored the modification of the associations with the short-term exposures by one another and by temperature variability. Daily ZIP code counts of respiratory, cardiac and stroke admissions of adults ≥65 (N = 2,015,660) were constructed across New-England (2001-2011). Daily PM and temperature exposure estimates were obtained from satellite-based spatio-temporally resolved models. For each admission cause, a Poisson regression was fit on short and long-term exposures, with a random intercept for ZIP code. Modifications of the short-term effects were tested by adding interaction terms with temperature, PM and temperat...
Research Interests:
Mounting evidence suggests that the natural and built environment can affect human health, but relatively few studies have considered links between features of the residential natural and built environment other than air pollution and... more
Mounting evidence suggests that the natural and built environment can affect human health, but relatively few studies have considered links between features of the residential natural and built environment other than air pollution and complications of pregnancy. To quantify the impact of features of the maternal residential natural and built environments on risk of gestational diabetes mellitus (GDM), gestational hypertension and preeclampsia among 61,640 women who delivered at a single hospital in Rhode Island between 2002 and 2012. We estimated residential levels of ambient fine particulate matter (PM) and black carbon (BC) using spatiotemporal models, neighborhood green space using remote sensing and proximity to recreational facilities, and neighborhood blue space using distance to coastal and fresh water. We used logistic regression to separately estimate the association between each feature and GDM, gestational hypertension, and preeclampsia, adjusting for individual and neigh...
Research Interests:
Decay products of radioactive materials may attach to ambient fine particles and form radioactive aerosol. Internal ionizing radiation source from inhaled radioactive aerosol may contribute to the fine particulate matter (PM)-inflammation... more
Decay products of radioactive materials may attach to ambient fine particles and form radioactive aerosol. Internal ionizing radiation source from inhaled radioactive aerosol may contribute to the fine particulate matter (PM)-inflammation pathway. However, few studies in humans have examined the associations. To examine the associations between particle radioactivity and biomarkers of oxidative stress and inflammation among participants from the Framingham Offspring and Third Generation cohorts. We included 3996 participants who were not current smokers and lived within 50 km from our central air pollution monitoring station. We estimated regional mean gross beta radioactivity from monitors in the northeastern U.S. as a surrogate for ambient radioactive particles, and calculated the 1- to 28-day moving averages. We used linear regression models for fibrinogen, tumor necrosis factor α, interleukin-6, and myeloperoxidase which were measured once, and linear mixed effect models for 8-e...
Research Interests:
Research Interests:
To examine associations of proximity to major roadways, sustained exposure to fine particulate matter (PM), and acute exposure to ambient air pollutants with adipokines and measures of glucose homeostasis among participants living in the... more
To examine associations of proximity to major roadways, sustained exposure to fine particulate matter (PM), and acute exposure to ambient air pollutants with adipokines and measures of glucose homeostasis among participants living in the northeastern United States. We included 5958 participants from the Framingham Offspring cohort examination cycle 7 (1998-2001) and 8 (2005-2008) and Third Generation cohort examination cycle 1 (2002-2005) and 2 (2008-2011), who did not have type 2 diabetes at the time of examination visit. We calculated 2003 annual average PM at participants' home address, residential distance to the nearest major roadway, and daily PM, black carbon (BC), sulfate, nitrogen oxides (NO), and ozone concentrations. We used linear mixed effects models for fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) which were measured up to twice, and used linear regression models for adiponectin, resistin, leptin, and hemoglobin A1c (Hb...
Research Interests:
Natural vegetation, or greenness, may benefit maternal health and consequently, fetal growth, by providing opportunities for physical activity and psychological restoration, and decreasing detrimental environmental exposures. We retrieved... more
Natural vegetation, or greenness, may benefit maternal health and consequently, fetal growth, by providing opportunities for physical activity and psychological restoration, and decreasing detrimental environmental exposures. We retrieved Massachusetts Birth Registry data from 2001⁻2013 and investigated the association between residential greenness and birthweight in full-term births (≥37 weeks gestation). We calculated average residential greenness during pregnancy using 250 m normalized difference vegetation index (NDVI) from satellites. We estimated associations between greenness and continuous birthweight, term low birthweight (TLBW: <2500 g), and small for gestational age (SGA: <10th percentile of birthweight stratified by sex and gestational age) adjusted for individual and neighborhood covariates and considered nonlinearity and effect modification. Higher greenness exposure was associated with higher birthweight with stronger associations in the lower than higher ran...
Research Interests:
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. To conduct... more
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. To conduct an epigenome-wide analysis of blood-derived DNA methylation and TNF-α levels and to assess the clinical relevance of findings. This meta-analysis assessed epigenome-wide associations in circulating TNF-α concentrations from 5 cohort studies and 1 interventional trial, with replication in 3 additional cohort studies. Follow-up analyses investigated associations of identified methylation loci with gene expression and incident coronary heart disease; this meta-analysis included 11 461 participants who experienced 1895 coronary events. Circulating TNF-α concentration. DNA methylation at approximately 450 000 loci, neighboring DNA sequence variation, gene expression, and incident coronary heart disease. The discovery cohort included 4794 participants, an...
Research Interests:
The US Environmental Protection Agency is required to reexamine its National Ambient Air Quality Standards (NAAQS) every 5 years, but evidence of mortality risk is lacking at air pollution levels below the current daily NAAQS in... more
The US Environmental Protection Agency is required to reexamine its National Ambient Air Quality Standards (NAAQS) every 5 years, but evidence of mortality risk is lacking at air pollution levels below the current daily NAAQS in unmonitored areas and for sensitive subgroups. To estimate the association between short-term exposures to ambient fine particulate matter (PM2.5) and ozone, and at levels below the current daily NAAQS, and mortality in the continental United States. Case-crossover design and conditional logistic regression to estimate the association between short-term exposures to PM2.5 and ozone (mean of daily exposure on the same day of death and 1 day prior) and mortality in 2-pollutant models. The study included the entire Medicare population from January 1, 2000, to December 31, 2012, residing in 39 182 zip codes. Daily PM2.5 and ozone levels in a 1-km × 1-km grid were estimated using published and validated air pollution prediction models based on land use, chemical ...
Research Interests:
Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression... more
Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry. Of 31 discovery-stage cytosine-phosphate-guanine (CpG) dinucleotides, 13 replicated after Bonferroni correction (discovery: N = 9,828, p < 1.0 × 10-7; replication: N = 7,182, p < 1.6 × 10-3). The replicated methylation sites are heritable (h2 > 30%) and independent of known BP genetic variants, explaining an additional 1.4% and 2.0% of the interindividual variation in systol...
Research Interests:
We tested whether genetic variation in miRNA processing genes modified the association of PM2.5 with DNA methylation (DNAm) age. We conducted a repeated measures study based on 552 participants from the Normative Aging Study with multiple... more
We tested whether genetic variation in miRNA processing genes modified the association of PM2.5 with DNA methylation (DNAm) age. We conducted a repeated measures study based on 552 participants from the Normative Aging Study with multiple visits between 2000 and 2011 (n = 940 visits). Address-level 1-year PM2.5 exposures were estimated using the GEOS-chem model. DNAm-age and a panel of 14 SNPs in miRNA processing genes were measured from participant blood samples. In fully adjusted linear mixed-effects models, having at least one copy of the minor rs4961280 [AGO2] allele was associated with a lower DNAm-age (β = -1.13; 95% CI: -2.26 to -0.002). However, the association of PM2.5 with DNAm-age was significantly (Pinteraction = 0.01) weaker in homozygous carriers of the major rs4961280 [AGO2] allele (β = 0.38; 95% CI: -0.20 to 0.96) when compared with all other participants (β = 1.58; 95% CI: 0.76 to 2.39). Our results suggest that miRNA processing impacts DNAm-age relationships. Grap...
Research Interests:
Research Interests:
Research Interests:
Objective— The objective of this study is to examine associations between short-term exposure to ambient air pollution and circulating biomarkers of systemic inflammation in participants from the Framingham Offspring and Third Generation... more
Objective— The objective of this study is to examine associations between short-term exposure to ambient air pollution and circulating biomarkers of systemic inflammation in participants from the Framingham Offspring and Third Generation cohorts in the greater Boston area. Approach and Results— We included 3996 noncurrent smoking participants (mean age, 53.6 years; 54% women) who lived within 50 km from a central air pollution monitoring site in Boston, MA, and calculated the 1- to 7-day moving averages of fine particulate matter (diameter<2.5 µm), black carbon, sulfate, nitrogen oxides, and ozone before the examination visits. We used linear mixed effects models for C-reactive protein and tumor necrosis factor receptor 2, which were measured up to twice for each participant; we used linear regression models for interleukin-6, fibrinogen, and tumor necrosis factor α, which were measured once. We adjusted for demographics, socioeconomic position, lifestyle, time, and weather. The ...