Browsing by Author "Miranda, Marie Lynn"
Now showing 1 - 12 of 12
Results Per Page
Sort Options
Item A genome-wide trans-ethnic interaction study links theﾠPIGR-FCAMRﾠlocus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic(Public Library of Science, 2017) Ward-Caviness, Cavin K.; Neas, Lucas M.; Blach, Colette; Haynes, Carol S.; LaRocque-Abramson, Karen; Grass, Elizabeth; Dowdy, Z. Elaine; Devlin, Robert B.; Diaz-Sanchez, David; Cascio, Wayne E.; Miranda, Marie Lynn; Gregory, Simon G.; Shah, Svati H.; Kraus, William E.; Hauser, Elizabeth R.Air pollution is a worldwide contributor to cardiovascular disease mortality and morbidity. Traffic-related air pollution is a widespread environmental exposure and is associated with multiple cardiovascular outcomes such as coronary atherosclerosis, peripheral arterial disease, and myocardial infarction. Despite the recognition of the importance of both genetic and environmental exposures to the pathogenesis of cardiovascular disease, studies of how these two contributors operate jointly are rare. We performed a genome-wide interaction study (GWIS) to examine gene-traffic exposure interactions associated with coronary atherosclerosis. Using race-stratified cohorts of 538 African-Americans (AA) and 1562 European-Americans (EA) from a cardiac catheterization cohort (CATHGEN), we identify gene-by-traffic exposure interactions associated with the number of significantly diseased coronary vessels as a measure of chronic atherosclerosis. We found five suggestive (P<1x10-5) interactions in the AA GWIS, of which two (rs1856746 and rs2791713) replicated in the EA cohort (P < 0.05). Both SNPs are in the PIGR-FCAMR locus and are eQTLs in lymphocytes. The protein products of both PIGR and FCAMR are implicated in inflammatory processes. In the EA GWIS, there were three suggestive interactions; none of these replicated in the AA GWIS. All three were intergenic; the most significant interaction was in a regulatory region associated with SAMSN1, a gene previously associated with atherosclerosis and B cell activation. In conclusion, we have uncovered several novel genes associated with coronary atherosclerosis in individuals chronically exposed to increased ambient concentrations of traffic air pollution. These genes point towards inflammatory pathways that may modify the effects of air pollution on cardiovascular disease risk.Item Associations Between Residential Proximity to Traffic and Vascular Disease in a Cardiac Catheterization Cohort(American Heart Association, Inc, 2018) Ward-Caviness, Cavin K.; Kraus, William E.; Blach, Colette; Haynes, Carol S.; Dowdy, Elaine; Miranda, Marie Lynn; Devlin, Robert; Diaz-Sanchez, David; Cascio, Wayne E.; Mukerjee, Shaibal; Stallings, Casson; Smith, Luther A.; Gregory, Simon G.; Shah, Svati H.; Neas, Lucas M.; Hauser, Elizabeth R.Objective—Exposure to mobile source emissions is nearly ubiquitous in developed nations and is associated with multiple adverse health outcomes. There is an ongoing need to understand the specificity of traffic exposure associations with vascular outcomes, particularly in individuals with cardiovascular disease. Approach and Results—We performed a cross-sectional study using 2124 individuals residing in North Carolina, United States, who received a cardiac catheterization at the Duke University Medical Center. Traffic-related exposure was assessed via 2 metrics: (1) the distance between the primary residence and the nearest major roadway; and (2) location of the primary residence in regions defined based on local traffic patterns. We examined 4 cardiovascular disease outcomes: hypertension, peripheral arterial disease, the number of diseased coronary vessels, and recent myocardial infarction. Statistical models were adjusted for race, sex, smoking, type 2 diabetes mellitus, body mass index, hyperlipidemia, and home value. Results are expressed in terms of the odds ratio (OR). A 23% decrease in residential distance to major roadways was associated with higher prevalence of peripheral arterial disease (OR=1.29; 95% confidence interval, 1.08–1.55) and hypertension (OR=1.15; 95% confidence interval, 1.01–1.31). Associations with peripheral arterial disease were strongest in men (OR=1.42; 95% confidence interval, 1.17–1.74) while associations with hypertension were strongest in women (OR=1.21; 95% confidence interval, 0.99–1.49). Neither myocardial infarction nor the number of diseased coronary vessels were associated with traffic exposure. Conclusions—Traffic-related exposure is associated with peripheral arterial disease and hypertension while no associations are observed for 2 coronary-specific vascular outcomes.Item Concentrations of polybrominated diphenyl ethers (PBDEs) and 2,4,6-tribromophenol in human placental tissues(Elsevier, 2016) Leonetti, Christopher; Butt, Craig M.; Hoffman, Kate; Miranda, Marie Lynn; Stapleton, Heather M.Legacy environmental contaminants such as polybrominated diphenyl ethers (PBDEs) are widely detected in human tissues. However, few studies have measured PBDEs in placental tissues, and there are no reported measurements of 2,4,6-tribromophenol (2,4,6-TBP) in placental tissues. Measurements of these contaminants are important for understanding potential fetal exposures, as these compounds have been shown to alter thyroid hormone regulation in vitro and in vivo. In this study, we measured a suite of PBDEs and 2,4,6-TBP in 102 human placental tissues collected between 2010 and 2011 in Durham County, North Carolina, USA. The most abundant PBDE congener detected was BDE-47, with a mean concentration of 5.09 ng/g lipid (range: 0.12–141 ng/g lipid; detection frequency 91%); however, 2,4,6-TBP was ubiquitously detected and present at higher concentrations with a mean concentration of 15.4 ng/g lipid (range:1.31–316 ng/g lipid; detection frequency 100%). BDE-209 was also detected in more than 50% of the samples, and was significantly associated with 2,4,6-TBP in placental tissues, suggesting they may have a similar source, or that 2,4,6-TBP may be a degradation product of BDE-209. Interestingly, BDE-209 and 2,4,6-TBP were negatively associated with age (rs = − 0.16; p = 0.10 and rs = − 0.17; p = 0.08, respectively). The results of this work indicate that PBDEs and 2,4,6-TBP bioaccumulate in human placenta tissue and likely contribute to prenatal exposures to these environmental contaminants. Future studies are needed to determine if these joint exposures are associated with any adverse health measures in infants and children.Item Development of an analytical method to quantify PBDEs, OH-BDEs, HBCDs, 2,4,6-TBP, EH-TBB, and BEH-TEBP in human serum(Springer, 2016) Butt, Craig M.; Miranda, Marie Lynn; Stapleton, Heather M.Polybrominated diphenyl ethers (PBDEs) flame retardants (FRs) were phased-out in the mid-2000s (penta- and octaBDE) and 2013 (decaBDE); however, their hydroxylated metabolites (OH-BDEs) are still commonly detected in human serum. Today, novel FRs such as Firemaster® 550, a mixture that contains two brominated compounds, EH-TBB and BEH-TEBP are used as replacements for PBDEs in some applications, and there is a need to develop a comprehensive analytical method to assess exposure to both legacy PBDEs and novel FRs. This study developed a solid-phase extraction (SPE)-based method to analyze PBDEs, OH-BDEs, 2,4,6-tribromophenol (TBP), hexabromocylcododecane isomers (HBCDs), EH-TBB, and BEH-TEBP in human serum. Briefly, serum proteins were first denatured with formic acid, and then the target analytes were isolated using a SPE column. Finally, the extract was cleaned and fractioned using a silica SPE column. Method performance was assessed by spiking fetal bovine serum with 1–2 ng of the target analytes, and method accuracy was quantified by comparison to a serum Standard Reference Material (SRM). The developed method showed good recovery and accuracy for all target analytes with the exception of the very low and very high molecular weight PBDE congeners. Using this method, 43 serum samples collected from the Healthy Pregnancy, Healthy Baby Study (HPHB) cohort in Durham, NC, USA were analyzed for FRs. A novel finding was the ubiquitous detection of 2,4,6-TBP, at levels greater than the individual PBDE congeners. Furthermore, 2,4,6-TBP was positively correlated with PBDEs, suggesting that they may have a similar source of exposure, or that 2,4,6-TBP may result from metabolism of PBDEs in vivo.Item Disparities in air quality downscaler model uncertainty across socioeconomic and demographic indicators in North Carolina(Elsevier, 2022) Zhou, Shan; Griffin, Robert J.; Bui, Alexander; Lilienfeld Asbun, Aaron; Bravo, Mercedes A.; Osgood, Claire; Miranda, Marie LynnStudies increasingly use output from the Environmental Protection Agency's Fused Air Quality Surface Downscaler (“downscaler”) model, which provides spatial predictions of daily concentrations of fine particulate matter (PM2.5) and ozone (O3) at the census tract level, to study the health and societal impacts of exposure to air pollution. Downscaler outputs have been used to show that lower income and higher minority neighborhoods are exposed to higher levels of PM2.5 and lower levels of O3. However, the uncertainty of the downscaler estimates remains poorly characterized, and it is not known if all subpopulations are benefiting equally from reliable predictions. We examined how the percent errors (PEs) of daily concentrations of PM2.5 and O3 between 2002 and 2016 at the 2010 census tract centroids across North Carolina were associated with measures of racial and educational isolation, neighborhood disadvantage, and urbanicity. Results suggest that there were socioeconomic and demographic disparities in surface concentrations of PM2.5 and O3, as well as their prediction uncertainties. Neighborhoods characterized by less reliable downscaler predictions (i.e., higher PEPM2.5 and PEO3) exhibited greater levels of aerial deprivation as well as educational isolation, and were often non-urban areas (i.e., suburban, or rural). Between 2002 and 2016, predicted PM2.5 and O3 levels decreased and O3 predictions became more reliable. However, the predictive uncertainty for PM2.5 has increased since 2010. Substantial spatial variability was observed in the temporal changes in the predictive uncertainties; educational isolation and neighborhood deprivation levels were associated with smaller increases in predictive uncertainty of PM2.5. In contrast, racial isolation was associated with a greater decline in the reliability of PM2.5 predictions between 2002 and 2016; it was associated with a greater improvement in the predictive reliability of O3 within the same time frame.Item Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease(Public Library of Science, 2016) Ward-Caviness, Cavin K.; Neas, Lucas M.; Blach, Colette; Haynes, Carol S.; LaRocque-Abramson, Karen; Grass, Elizabeth; Dowdy, Elaine; Devlin, Robert B.; Diaz-Sanchez, David; Cascio, Wayne E.; Miranda, Marie Lynn; Gregory, Simon G.; Shah, Svati H.; Kraus, William E.; Hauser, Elizabeth R.; National Center for Geospatial MedicineThere is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been rarely performed particularly in the case of air pollution exposures. We performed race-stratified genome-wide gene-environment interaction association studies on European-American (EA, N = 1623) and African-American (AA, N = 554) cohorts to investigate the joint influence of common single nucleotide polymorphisms (SNPs) and residential exposure to traffic (“traffic exposure”)—a recognized vascular disease risk factor—on peripheral arterial disease (PAD). Traffic exposure was estimated via the distance from the primary residence to the nearest major roadway, defined as the nearest limited access highways or major arterial. The rs755249-traffic exposure interaction was associated with PAD at a genome-wide significant level (P = 2.29x10-8) in European-Americans. Rs755249 is located in the 3’ untranslated region of BMP8A, a member of the bone morphogenic protein (BMP) gene family. Further investigation revealed several variants in BMP genes associated with PAD via an interaction with traffic exposure in both the EA and AA cohorts; this included interactions with non-synonymous variants in BMP2, which is regulated by air pollution exposure. The BMP family of genes is linked to vascular growth and calcification and is a novel gene family for the study of PAD pathophysiology. Further investigation of BMP8A using the Genotype Tissue Expression Database revealed multiple variants with nominally significant (P < 0.05) interaction P-values in our EA cohort were significant BMP8A eQTLs in tissue types highlight relevant for PAD such as rs755249 (tibial nerve, eQTL P = 3.6x10-6) and rs1180341 (tibial artery, eQTL P = 5.3x10-6). Together these results reveal a novel gene, and possibly gene family, associated with PAD via an interaction with traffic air pollution exposure. These results also highlight the potential for interactions studies, particularly at the genome scale, to reveal novel biology linking environmental exposures to clinical outcomes.Item Powering Research through Innovative Methods for Mixtures in Epidemiology (PRIME) Program: Novel and Expanded Statistical Methods(MDPI, 2022) Joubert, Bonnie R.; Kioumourtzoglou, Marianthi-Anna; Chamberlain, Toccara; Chen, Hua Yun; Gennings, Chris; Turyk, Mary E.; Miranda, Marie Lynn; Webster, Thomas F.; Ensor, Katherine B.; Dunson, David B.; Coull, Brent A.Humans are exposed to a diverse mixture of chemical and non-chemical exposures across their lifetimes. Well-designed epidemiology studies as well as sophisticated exposure science and related technologies enable the investigation of the health impacts of mixtures. While existing statistical methods can address the most basic questions related to the association between environmental mixtures and health endpoints, there were gaps in our ability to learn from mixtures data in several common epidemiologic scenarios, including high correlation among health and exposure measures in space and/or time, the presence of missing observations, the violation of important modeling assumptions, and the presence of computational challenges incurred by current implementations. To address these and other challenges, NIEHS initiated the Powering Research through Innovative methods for Mixtures in Epidemiology (PRIME) program, to support work on the development and expansion of statistical methods for mixtures. Six independent projects supported by PRIME have been highly productive but their methods have not yet been described collectively in a way that would inform application. We review 37 new methods from PRIME projects and summarize the work across previously published research questions, to inform methods selection and increase awareness of these new methods. We highlight important statistical advancements considering data science strategies, exposure-response estimation, timing of exposures, epidemiological methods, the incorporation of toxicity/chemical information, spatiotemporal data, risk assessment, and model performance, efficiency, and interpretation. Importantly, we link to software to encourage application and testing on other datasets. This review can enable more informed analyses of environmental mixtures. We stress training for early career scientists as well as innovation in statistical methodology as an ongoing need. Ultimately, we direct efforts to the common goal of reducing harmful exposures to improve public health.Item Prenatal exposure to cadmium and cotinine and CpG island DNA methylation in mother-infant pairs(Elsevier, 2015) Gona, Saideep; Sanders, Alison P.; Miranda, Marie Lynn; Fry, Rebecca C.A precise biological mechanism by which cadmium acts as a developmental toxicant is unknown but is suggested to include an epigenetic basis. In prior work, we analyzed CpG island methylation levels within gene promoters (nﾠ=ﾠ16,421) in leukocytes collected from mothers and their infants from a pregnancy cohort in Durham County, North Carolina. The CpG methylation levels were examined in relationship to prenatal exposure to cadmium and/or cotinine to identify genes and pathways influenced by in utero exposure. In the present article, we provide an enhanced description of the data collection and processing to facilitate cross-study comparisons. Data are available within the Gene Expression Omnibus database (GSE67976).Item Racial residential segregation shapes the relationship between early childhood lead exposure and fourth-grade standardized test scores(National Academy of Sciences, 2022) Bravo, Mercedes A.; Zephyr, Dominique; Kowal, Daniel; Ensor, Katherine; Miranda, Marie LynnRacial/ethnic disparities in academic performance may result from a confluence of adverse exposures that arise from structural racism and accrue to specific subpopulations. This study investigates childhood lead exposure, racial residential segregation, and early educational outcomes. Geocoded North Carolina birth data is linked to blood lead surveillance data and fourth-grade standardized test scores (n = 25,699). We constructed a census tract-level measure of racial isolation (RI) of the non-Hispanic Black (NHB) population. We fit generalized additive models of reading and mathematics test scores regressed on individual-level blood lead level (BLL) and neighborhood RI of NHB (RINHB). Models included an interaction term between BLL and RINHB. BLL and RINHB were associated with lower reading scores; among NHB children, an interaction was observed between BLL and RINHB. Reading scores for NHB children with BLLs of 1 to 3 µg/dL were similar across the range of RINHB values. For NHB children with BLLs of 4 µg/dL, reading scores were similar to those of NHB children with BLLs of 1 to 3 µg/dL at lower RINHB values (less racial isolation/segregation). At higher RINHB levels (greater racial isolation/segregation), children with BLLs of 4 µg/dL had lower reading scores than children with BLLs of 1 to 3 µg/dL. This pattern becomes more marked at higher BLLs. Higher BLL was associated with lower mathematics test scores among NHB and non-Hispanic White (NHW) children, but there was no evidence of an interaction. In conclusion, NHB children with high BLLs residing in high RINHB neighborhoods had worse reading scores.Item Spatial Variability in Relationships between Early Childhood Lead Exposure and Standardized Test Scores in Fourth Grade North Carolina Public School Students (2013–2016)(National Institute of Environmental Health Sciences, National Institutes of Health, 2024) Bravo, Mercedes A.; Kowal, Daniel R.; Zephyr, Dominique; Feldman, Joseph; Ensor, Katherine; Miranda, Marie LynnBackground:Exposure to lead during childhood is detrimental to children’s health. The extent to which the association between lead exposure and elementary school academic outcomes varies across geography is not known.Objective:Estimate associations between blood lead levels (BLLs) and fourth grade standardized test scores in reading and mathematics in North Carolina using models that allow associations between BLL and test scores to vary spatially across communities.Methods:We link geocoded, individual-level, standardized test score data for North Carolina public school students in fourth grade (2013–2016) with detailed birth records and blood lead testing data retrieved from the North Carolina childhood blood lead state registry on samples typically collected at 1–6 y of age. BLLs were categorized as: 1μg/dL (reference), 2μg/dL, 3–4μg/dL and ≥5μg/dL. We then fit spatially varying coefficient models that incorporate information sharing (smoothness), across neighboring communities via a Gaussian Markov random field to provide a global estimate of the association between BLL and test scores, as well as census tract–specific estimates (i.e., spatial coefficients). Models adjusted for maternal- and child-level covariates and were fit separately for reading and math.Results:The average BLL across the 91,706 individuals in the analysis dataset was 2.84μg/dL. Individuals were distributed across 2,002 (out of 2,195) census tracts in North Carolina. In models adjusting for child sex, birth weight percentile for gestational age, and Medicaid participation as well as maternal race/ethnicity, educational attainment, marital status, and tobacco use, BLLs of 2μg/dL, 3–4μg/dL and ≥5μg/dL were associated with overall lower reading test scores of −0.28 [95% confidence interval (CI): −0.43, −0.12], −0.53 (−0.69, −0.38), and −0.79 (−0.99, −0.604), respectively. For BLLs of 1μg/dL, 2μg/dL, 3–4μg/dL and ≥5μg/dL, spatial coefficients—that is, tract-specific adjustments in reading test score relative to the “global” coefficient—ranged from −9.70 to 2.52, −3.19 to 3.90, −11.14 to 7.85, and −4.73 to 4.33, respectively. Results for mathematics were similar to those for reading.Conclusion:The association between lead exposure and reading and mathematics test scores exhibits considerable heterogeneity across North Carolina communities. These results emphasize the need for prevention and mitigation efforts with respect to lead exposures everywhere, with special attention to locations where the cognitive impact is elevated. https://doi.org/10.1289/EHP13898Item The Texas flood registry: a flexible tool for environmental and public health practitioners and researchers(Springer Nature, 2021) Miranda, Marie Lynn; Callender, Rashida; Canales, Joally M.; Craft, Elena; Ensor, Katherine B.; Grossman, Max; Hopkins, Loren; Johnston, Jocelyn; Shah, Umair; Tootoo, JoshuaBackground: Making landfall in Rockport, Texas in August 2017, Hurricane Harvey resulted in unprecedented flooding, displacing tens of thousands of people, and creating environmental hazards and exposures for many more. Objective: We describe a collaborative project to establish the Texas Flood Registry to track the health and housing impacts of major flooding events. Methods: Those who enroll in the registry answer retrospective questions regarding the impact of storms on their health and housing status. We recruit both those who did and did not flood during storm events to enable key comparisons. We leverage partnerships with multiple local health departments, community groups, and media outlets to recruit broadly. We performed a preliminary analysis using multivariable logistic regression and a binomial Bayesian conditional autoregressive (CAR) spatial model. Results: We find that those whose homes flooded, or who came into direct skin contact with flood water, are more likely to experience a series of self-reported health effects. Median household income is inversely related to adverse health effects, and spatial analysis provides important insights within the modeling approach. Significance: Global climate change is likely to increase the number and intensity of rainfall events, resulting in additional health burdens. Population-level data on the health and housing impacts of major flooding events is imperative in preparing for our planet’s future.Item Toll-like Receptor 4 Pathway Polymorphisms Interact with Pollution to Influence Asthma Diagnosis and Severity(Springer Nature, 2018) Schurman, Shepherd H.; Bravo, Mercedes A.; Innes, Cynthia L.; Jackson, W. Braxton II; McGrath, John A.; Miranda, Marie Lynn; Garantziotis, StavrosAsthma is a common chronic lung disease, the incidence and severity of which may be influenced by gene-environment interactions. Our objective was to examine associations between single nucleotide polymorphisms (SNPs) and combinations of SNPs in the toll-like receptor 4 (TLR4) pathway, residential distance to roadway as a proxy for traffic-related air pollution exposure, and asthma diagnosis and exacerbations. We obtained individual-level data on genotype, residential address, and asthma diagnosis and exacerbations from the Environmental Polymorphisms Registry. Subjects (n = 2,704) were divided into three groups (hyper-responders, hypo-responders, and neither) based on SNP combinations in genes along the TLR4 pathway. We geocoded subjects and calculated distance, classified as <250 m or ≥250 m, between residence and nearest major road. Relationships between genotype, distance to road, and odds of asthma diagnosis and exacerbations were examined using logistic regression. Odds of an asthma diagnosis among hyper-responders <250 m from a major road was 2.37(0.97, 6.01) compared to the reference group (p < 0.10). Hypo-responders ≥250 m from the nearest road had lower odds of activity limitations (0.46 [0.21, 0.95]) and sleeplessness (0.36 [0.12, 0.91]) compared to neither-responders (p < 0.05). Specific genotype combinations when combined with an individual's proximity to roadways, possibly due to traffic-related air pollution exposure, may affect the likelihood of asthma diagnosis and exacerbations.