2014 Progress Report: Lifecourse Exposures & Diet: Epigenetics, Maturation & Metabolic Syndrome

EPA Grant Number: R835436
Center: Lifecourse Exposures & Diet: Epigenetics, Maturation & Metabolic Syndrome
Center Director: Peterson, Karen E.
Title: Lifecourse Exposures & Diet: Epigenetics, Maturation & Metabolic Syndrome
Investigators: Peterson, Karen E. , Padmanabhan, Vasantha
Institution: University of Michigan
EPA Project Officer: Nolt-Helms, Cynthia
Project Period: June 1, 2013 through May 31, 2018 (Extended to May 31, 2019)
Project Period Covered by this Report: June 1, 2014 through May 31,2015
Project Amount: $3,651,990
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2012) RFA Text |  Recipients Lists
Research Category: Children's Health , Health

Objective:

The developmental origins hypothesis relates in utero exposures to endocrine disrupting chemicals (EDCs) to children’s physical growth and maturation and the later development of chronic diseases, including metabolic syndrome, a condition affecting up to 25% of U.S. adults and 30% of obese adolescents. Few studies have considered whether subsequent exposures during the pubertal transition may exacerbate impact of prenatal EDC mixtures on growth, maturation and the risk of metabolic syndrome. This center will test the overarching hypothesis that in utero and peripubertal exposures to mixtures of EDCs (BPA, phthalates, lead, cadmium) will, via epigenetic mechanisms, lead to changes in gene expression and alter the tempo of physical growth and maturation as well as metabolic function and increase risk of metabolic syndrome. Because nutrients may serve as agonists or antagonists of toxic effects of environmental chemicals, we further hypothesize that dietary intake will modify the impact of EDC mixtures on metabolic outcomes.

The Specific Aims of the University of Michigan Children’s Environmental Health and Disease Protection Center (UM-CEHC) are to:

  1. Assess the impact of in utero and peripubertal exposures to mixtures of EDCs (bisphenol A, phthalates, lead and cadmium) on linear growth and weight status (BMI), sexual maturation and reproductive hormones.
  2. Determine whether EDC mixtures (BPA, phthalates, lead, cadmium) via epigenetic mechanisms induce oxidative stress (tyrosine oxidation products), disrupt metabolic homeostasis (free fatty acids, amino acids, Acyl-carnitine) and lead to changes in gene transcription and metabolic function.
  3. Conduct tissue- and age-specific unbiased epigenomic analyses (DNA methylation, chromatin structure, transcriptomics) to identify a subset of tissue-independent labile genes to serve as biomarkers of exposure-induced metabolic syndrome.
  4. Examine the role of dietary intake during pregnancy and adolescence in modifying the impact of EDC mixtures on metabolic homeostasis, oxidative stress and risk of metabolic syndrome.
  5. Foster career development by assisting new investigators in the advancement of their research skills and knowledge in translational and children's environmental health research.
  6. Share current research findings on the role that environmental exposures have on children's health in an accurate, relevant way that allows community members, healthcare professionals, and policy makers to incorporate this new knowledge into practice for the protection of children's health.

Progress Summary:

Research Projects

The University of Michigan Children’s Environmental Health and Disease Prevention Center’s (CEHC) three research projects are designed to provide scientific integration across shared environmental exposures and interrelated outcomes to examine the impact of EDC mixtures (bisphenol A, phthalates, lead, cadmium) in utero and during the pubertal transition on physical growth and maturation and leading to alterations in metabolic homeostasis, oxidative stress and metabolic syndrome, using human and animal models. Projects 1 and 2 are human studies, both conducted within the Early Life Exposures in Mexico to ENvironmental Toxicants (ELEMENT) birth cohorts that have been successfully followed for nearly two decades. In addition to ELEMENT participants overseen by Drs. Meeker (Project 1) and Peterson (Project 2), the Michigan Mother Infant Pairs (MMIP) cohort, a U.S. study population established by MPI Padmanabhan, is included in Project 2 of the UM CEHC to extend findings from the ELEMENT cohort to a U.S. study population. Whereas Project 1 focuses on the impact of metals (Cd, Pb) and EDCs (BPA and phthalates) in utero and during peripuberty on children’s growth and sexual maturation (Overall Aim 1) in ELEMENT, Project 2 considers the effect of EDC exposures via epigenetic mechanisms to fetal and peripubertal alterations in metabolic homeostasis and oxidative stress and the potential modifying role of diet (Overall Aims 2, 3, and 4) in both ELEMENT and MMIP cohorts. To parallel the human studies, Project 3 utilizes a mouse model of perinatal environmental exposures to address the influence of perinatal and peripubertal exposure mixtures and diet on life course offspring metabolic status, reproductive development and epigenetic gene regulation (Aims 2, 3, and 4).

Progress for Project 1 in Year 2 included the development of a new exposure assessment of urinary concentrations of phthalate metabolites and BPA at multiple time points in pregnancy, which will allow us to assess potential windows of susceptibility to exposure related developmental effects. Archived urine samples from mothers during their third trimester in pregnancy and from children during peripubertal development also were analyzed for cadmium and a number of other metals. Protocols were finalized for the collection of new biologic and survey data on ELEMENT participants, and fieldwork began in Quarter 3. Recruitment has been faster than originally planned, and we are on track for finishing the first data collection on time or ahead of schedule. We published two papers relevant to Project 1 using our P20 CEHC data (upon which the P01 CEHC builds) on associations between in utero or peripubertal exposure to EDCs and sexual maturation. Our findings among boys were published in the journal Reproductive Toxicology (Ferguson, et al. Reproductive Toxicology 2014;47:70-76). Our findings among girls were presented by Dr. Watkins at the 2014 International Society of Environmental Epidemiology (ISEE) annual conference in Seattle, Washington, and were published in the journal Environmental Research (Watkins, et al. Environmental Research 2014;134:233-241). We also continued to utilize U.S. NHANES data to test hypotheses relevant to Project 1, and published a manuscript examining cross-sectional associations between phthalate metabolites and testosterone levels among men, women and children (Meeker and Ferguson; Journal of Clinical Endocrinology and Metabolism 2014;99(110:4346-4352). Among boys 6-12 years old, ages which overlap with boys from our study presented above, DEHP metabolites were strongly associated with a decrease in testosterone, which is consistent with new results from the ELEMENT cohort (Ferguson, et al. Reproductive Toxicology 2014;47:70-76). Dr. Peterson also presented our analysis of lead exposure at numerous developmental time periods in relation to sexual maturation in a talk at the 2014 ISEE annual conference in Seattle, Washington.

Progress for Project 2 in Year 2 included the development of a new exposure assessment of concentrations of BPA and phthalates metabolites at multiple time points in pregnancy and analysis of cadmium in archived urine samples (via Project 1). Protocols were finalized for the collection of new biologic and survey data on ELEMENT participants. Fieldwork began in Quarter 3 and recruitment has been faster than originally planned. As noted above, we have re-recruited nearly one-half of the sample and are on schedule for finishing the first data collection time point as planned, midway through Year 3. Another accomplishment in Year 2 was the optimization of DNA methylation assays for a targeted profile of 12 candidate genes related to metabolism and growth using both ELEMENT and MMIP cohorts.  Four manuscripts were published from Project 2.

MMIP Cohort: Analysis of matched samples from MMIP provided evidence of the use of maternal 3-nitrotyrosine as a biomarker for offspring health. These findings were published as part of a multi-species study in Endocrinology (Veiga-lopez, et al.). Levels of unconjugated BPA and BPA glucuronide in 80 matching MMIP samples also were studied and findings indicate that higher uBPA exposure levels during first trimester and term are associated with gender-specific reduction in birth weight and increase in gestational length, respectively. A manuscript will be submitted reporting the impact of early pregnancy BPA levels on reduction of birth weight as an adverse health outcome. Pilot funds were received to test the feasibility of genome-wide DNA methylation analyses using a subsample of 24 cord blood and 12 matched placental samples from the MMIP cohort.

ELEMENT Cohorts: ELEMENT data were used to examine relationships between exposure mixtures and metabolic outcomes, including new statistical analysis of BPA and phthalates exposures and new data and preliminary analysis of untargeted metabolomics features. Year 2 also included examination of dietary intake in relation to toxicants, maturation and obesity using ELEMENT data.  One study examined the effect modification by antioxidant intake of in utero exposure to lead on measures of metabolic syndrome risk at ages 8–15; another analyzed the effects of maternal intakes of selenium (Se), vitamin B2, calcium (Ca) and iron (Fe) on pubertal onset at ages 8–14; and a third considered whether age of introduction and cumulative sugar-sweetened beverage (SSB) consumption increases risk of obesity in children. The first two analyses were presented as posters at scientific meetings and the third is in press (Cantoral, et al. Pediatric Obesity 2015). Finally, sophisticated statistical analysis techniques were developed to correct for batch effects and increase statistical power needed to investigate associations between epigenetic modifications at candidate genes and exposures to environmental toxicants (Goodrich, et al. Epigenetics 2015). .

Project 3 is being implemented in the viable yellow agouti mouse model.  In Year 2, six cohorts of mating pairs and litters were established and followed until 10 months of age to assess whether in utero high-fat diets modify the effects of perinatal BPA exposure on metabolic, hormonal, and oxidative stress parameters throughout the life course, and to identify DNA methylation alterations underlying such effects. Data analyses of PND10 offspring and maternal (dam) tissues are underway with two papers drafted that focus on fetal programming of metabolic and oxidative stress pathways in early life. Data on weight, fertility and birth outcomes suggest differences between exposure groups. For example, offspring survival rate was the lowest among the control diet + BPA exposure group. Preliminary analyses examining oxidative stress in PND10 liver suggest that Western diet + BPA exposure results in a more oxidized intracellular environment. Preliminary shotgun lipidomics analyses in female 10 month-old offspring reveal differences in long-chain polyunsaturated fatty acids (LC-PUFAs) between mice prenatally exposed to control vs. Western diet. Additional detail is provided in the Project 3 description.  A number of abstracts detailing preliminary analyses from these cohorts have been accepted for presentation at upcoming meetings.

Data Management and Modeling Core (DMMC):  In Year 2, the DMMC not only provided data analysis to support the three research projects but also the development of grant applications, including a K99/R00 submitted by Dr. Goodrich informed by work completed for Project 2 on targeted fatty acids and DNA methylation. Dr. Peter Song, Director of the DMMC, also submitted a revised R01 application , which was ranked at the 8th percentile, to focus on the development of novel statistical methodologies and efficient algorithms to evaluate, interpret and predict environmental risk of early life exposure on child health and development outcomes. In addition to analysis, a major accomplishment of the DMMC was creation of methods for cleaning, standardizing and normalizing more than 9,000 metabolic features and for relating these to biochemical pathways impacted by Pb exposure. The DMMC has established a system to integrate the previous P20 database with the P01 database to facilitate efficient data management and analysis, that includes several types of high-dimensional data such as metabolomics, accelerometry data, etc. Research regarding the DMMC methodology of handling inter-batch heterogeneities in the analysis of metabolomics was presented and awarded top five among posters presented at ENAR, the largest biostatistics conference in the world. A data management plan also was developed in Year 2 to capture the DMMC processes and procedures for transferring, sharing, managing and storing data.

Community Outreach and Translation Core (COTC): In Year 2, our COTC worked at the local and regional level with our Community Advisory Board (CAB) in Kent County, Michigan, which includes representatives from Head Start for Kent County, the Healthy Homes Coalition, and the Kent County Health Department. These three organizations have been central to identifying children’s environmental health issues and opportunities for improvement in Kent County. In addition, our CAB has partnered with the West Michigan Environmental Action Council (WMEAC) and the Asthma Network of West Michigan through a collaborative process and a created a partnership with Grand Valley State University, to produce maps illustrating the prevalence and burden of asthma on low-income preschool-age children in Kent County. These maps are being used in presentations to community and other stakeholders to address childhood asthma in Kent County, Michigan. Advancements in CEHC outreach also were achieved through UM contributions to a CEHN white paper. Additionally, the COTC Director, Dr. Miller, and Associate Director (Seema Jolly) attended the October 2014 CEHC meeting in Boston.  In March 2015, Lindsey Mitchell, MPH, replaced Ms. Jolly as Center Manager and COTC Associate Director.  The Director and Associate Director are active participants in the COTC workgroup where best practices for disseminating education and information to the community are shared. Conference calls with the University of Illinois COTC and the Region 5 Pediatric Environmental Health Specialty Unit (PEHSU) also were held to discuss strategies for disseminating research from the CEHCs to the PEHSUs and to explore how the PEHSUs may be able to advise the creation of educational materials for our community partners. In collaboration with our fieldwork host site in Mexico, the Instituto Nacional de Salud Pública, we also are identifying ways to disseminate research to the ELEMENT cohort. This includes creation of a subcommittee to plan for and define specific methods for this outreach, development of an information sheet that thanks participants for their contributions and provides program updates, and development of a participant questionnaire to learn about the participants’ feedback from their experience in the study. This questionnaire also will help identify opportunities for improvement. In addition, the COTC also began development of a CEHC website at the end of Year 2 that includes information about the center, research projects and findings, the research team, outreach initiatives and more.

Future Activities:

Research Projects: In Year 3, we will finish the first P01 data collection on all ELEMENT subjects and will begin planning for the start of the second data collection to take place in Quarter 4, Year 3. For Project 1, we will utilize our new urinary metals data to address Aim 2 by evaluating how exposure to EDC mixtures (phthalates, BPA, lead, cadmium) during development affect sexual maturation and reproductive hormone levels. For Aim 3, we will utilize our newly available urinary phthalate metabolite and BPA data to identify potential windows of susceptibility during pregnancy and to explore interactions between in utero and peripubertal exposures and their impact on child growth, sexual maturation, and reproductive hormone levels. In addition, as new data from the first P01 visit become available we will continue to expand our analyses to include this new information, and begin to examine associations between EDC exposure and growth velocities (Aim 1).

As part of Project 2 activities related to the ELEMENT cohort, we will focus on statistical analyses, toxicant-diet interactions in relation to metabolic outcomes, and complete pilot analyses of DNA methylation. Also in Project 2, we plan to use MMIP samples to undertake untargeted metabolomics analyses on first trimester and cord blood samples, maternal urinary phthalate measures and relate changes in phthalates and BPA to metabolites and pregnancy outcomes. Bisulfite sequencing will also commence on cord blood samples and we will optimize assays for qPCR gene expression. In Year 2 (April 2015), we applied for and received an Administrative Supplement to Project 2 entitled: High-Dimensional Epigenomic and Metabolomic Responses to Metal and EDC Exposures to be implemented from July 1, 2013. The supplement will examine the effect of repeated exposures to metals and EDCs in pregnancy and adolescence on novel, high-dimensional markers of metabolic homeostasis in longitudinal subsamples from the MMIP and ELEMENT (Mexico City) projects, including lipidomics and untargeted metabolomics and the potential mediation of these associations via changes in genome-wide DNA methylation.

For Project 3, we will begin studies on phthalates mixtures and Pb and high fat diets. Also, during Year 3, the biospecimens collected for Aim 1 and in the next reporting period will be used for Aim 3 to assess epigenetic tissue specificity and time-dependent epigenetic drift using genome wide whole methylome, transcriptome, and histone mark analysis.

The DMMC will continue to provide timely and effective statistical and bioinformatics support for all projects, data management and integration of existing data into a streamlined system. In addition, the DMMC will complete the creation of a P01 database and dictionary for the variables available in the database.  Participation of the DMMC in dissemination of research findings, including writing of manuscripts and presentations, also will continue. A major focus in Year 3 will be the completion of the initial analysis of untargeted and targeted metabolites and application of advanced statistical modeling to analyze exposure to EDCs. Dr. Song has been invited to provide a presentation on statistical methods to relate toxicants to DNA methylation in epigenetics to be convened September 2-3, 2015, by the EPA.

The COTC will continue partnerships in Kent County, Michigan in Year 3 and work to actively disseminate findings from our asthma mapping project. This will include presentations at multiple upcoming local and statewide events as well as promotion through social media and articles. We also will work to create similar maps using larger state data. Additionally, we will work with the ELEMENT PI team on strategies to disseminate project findings to the community and enhance participant engagement. A new collaboration with the Healthy Environments Partnership at the University of Michigan also will be established to strengthen the effort to address child environmental health issues in Southeast Michigan. The CEHC website also will be finalized and go live in Quarter 1 of Year 3.


Journal Articles: 93 Displayed | Download in RIS Format

Other center views: All 130 publications 104 publications in selected types All 93 journal articles
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Journal Article Baek J, Sancehz BN, Berrocal VJ, Sanchez-Vaznaugh EV. Distributed lag models: examining associations between the built environment and health. Epidemiology 2016;27(1):116-124. R835436 (2016)
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  • Journal Article Baek J, Sanchez-Vaznaugh EV, Sanchez BN. Hierarchial distributed-lag models: exploring varying geographic scale and magnitude in associations between built environment and health. American Journal of Epidemiology 2016;183(6):583-592. R835436 (2016)
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  • Journal Article Breton CV, Marsit CJ, Faustman E, Nadeau K, Goodrich JM, Dolinoy DC, Herbstman J, Holland N, LaSalle JM, Schmidt R, Yousefi P, Perera F, Joubert BR, Wiemels J, Taylor M, Yang IV, Chen R, Hew KM, Freeland DM, Miller R, Murphy SK. Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children's Environmental Health Studies: The Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. Environmental Health Perspectives 2017;125(4):511-526. R835436 (Final)
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  • Journal Article Breton CV, Marsit CJ, Faustman E, Nadeau K, Goodrich JM, Dolinoy DC, Herbstman J, Holland N, LaSalle JM, Schmidt R, Yousefi P, Perera F, Joubert BR, Wiemels J, Taylor M, Yang IV, Chen R, Hew KM, Freeland DM, Miller R, Murphy SK. Small-magnitude effect sizes in epigenetic end points are important in children's environmental health studies:the Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. Environmental Health Perspectives 2017;125(4):511-526. R835436 (2017)
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  • Journal Article Cantonwine DE, Hauser R, Meeker JD. Bisphenol A and human reproductive health. Expert Review of Obstetrics & Gynecology 2013;8(4):329-335. R835436 (2014)
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  • Journal Article Cantoral A, Tellez-Rojo MM, Levy TS, Hernandez-Avila M, Schnaas L, Hu H, Peterson KE, Ettinger AS. Differential association of lead on length by zinc status in two-year old Mexican children. Environmental Health 2015;14:95 (7 pp.). R835436 (2015)
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  • Journal Article Cantoral A, Tellez-Rojo MM, Ettinger AS, Hu H, Hernandez-Avila M, Peterson K. Early introduction and cumulative consumption of sugar-sweetened beverages during the pre-school period and risk of obesity at 8-14 years of age. Pediatric Obesity 2016;11(1):68-74. R835436 (2014)
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  • Journal Article Chavarro JE, Watkins DJ, Afeiche MC, Zhang Z, Sanchez BN, Cantonwine D, Mercado-Garcia A, Blank-Goldenberg C, Meeker JD, Tellez-Rojo MM, Peterson KE. Validity of self-assessed sexual maturation against physician assessments and hormone levels. The Journal of Pediatrics 2017;186:172-178.e3. R835436 (2016)
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  • Journal Article Chen Y-H, Ferguson KK, Meeker JD, McElrath TF, Mukherjee B. Statistical methods for modeling repeated measures of maternal environmental exposure biomarkers during pregnancy in association with preterm birth. Environmental Health 2015;14(1):9 (13 pp.). R835436 (2014)
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  • Journal Article Faulk C, Liu K, Barks A, Goodrich JM, Dolinoy DC. Longitudinal epigenetic drift in mice perinatally exposed to lead. Epigenetics 2014;9(7):934-941. R835436 (2014)
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  • Journal Article Ferguson KK, Peterson KE, Lee JM, Mercado-Garcia A, Blank-Goldenberg C, Tellez-Rojo MM, Meeker JD. Prenatal and peripubertal phthalates and bisphenol A in relation to sex hormones and puberty in boys. Reproductive Toxicology 2014;47:70-76. R835436 (2014)
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  • Journal Article Ferguson KK, McElrath TF, Chen Y-H, Loch-Caruso R, Mukherjee B, Meeker JD. Repeated measures of urinary oxidative stress biomarkers during pregnancy and preterm birth. American Journal of Obstetrics & Gynecology 2015;212(2):208.e1-208.e8. R835436 (2014)
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  • Journal Article Ferguson KK, McElrath TF, Cantonwine DE, Mukherjee B, Meeker JD. Phthalate metabolites and bisphenol-A in association with circulating angiogenic biomarkers across pregnancy. Placenta 2015;36(6):699-703. R835436 (2015)
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  • Journal Article Ferguson KK, Meeker JD, Cantonwine DE, Chen Y-H, Mukherjee B, McElrath TF. Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth. Environment International 2016;94:531-537. R835436 (2016)
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  • Journal Article Fortenberry GZ, Meeker JD, Sanchez BN, Barr DB, Panuwet P, Bellinger D, Schnaas L, Solano-Gonzalez M, Ettinger AS, Hernandez-Avila M, Hu H, Tellez-Rojo MM. Urinary 3,5,6-trichloro-2-pyridinol (TCPY) in pregnant women from Mexico City:distribution, temporal variability, and relationship with child attention and hyperactivity. International Journal of Hygiene and Environmental Health 2014; 217(2-3):405-412. R835436 (2014)
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  • Journal Article Goodrich JM, Sanchez BN, Dolinoy DC, Zhang Z, Hernandez-Avila M, Hu H, Peterson KE, Tellez-Rojo MM. Quality control and statistical modeling for environmental epigenetics: a study on in utero lead exposure and DNA methylation at birth. Epigenetics 2015;10(1):19-30. R835436 (2014)
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  • Journal Article Goodrich JM, Dolinoy DC, Sanchez BN, Zhang Z, Meeker JD, Mercado-Garcia A, Solano-Gonzalez M, Hu H, Tellez-Rojo MM, Peterson KE. Adolescent epigenetic profiles and environmental exposures from early life through peri-adolescence. Environmental Epigenetics 2016;2(3):dvw018 (11 pp.). R835436 (2016)
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  • Journal Article Goodrich JM, Chou HN, Gruninger SE, Fraznblau A, Baus N. Exposures of dental professionals to elemental mercury and methylmercury. Journal of Exposure Science and Environmental Epidemiology 2016;26(1):78-85. R835436 (2016)
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  • Journal Article Huang S, Hu H, Sanchez BN, Peterson KE, Ettinger AS, Lamadrid-Figueroa H, Schnaas L, Mercado-Garcia A, Wright RO, Basu N, Cantonwine DE, Hernandez-Avila M, Tellez-Rojo MM. Childhood blood lead levels and symptoms of attention deficit hyperactivity disorder (ADHD):a cross-sectional study of Mexican children. Environmental Health Perspectives 2016;124(6):868-874. R835436 (2016)
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  • Journal Article Jansen EC, Zhou L, Song PXK, Sanchez BN, Mercado A, Hu H, Solano M, Peterson KE, Tellez-Rojo MM. Prenatal lead exposure in relation to age at menarche: results from a longitudinal study in Mexico City. Journal of Developmental Origins of Health and Disease 2018;9(4):467-472. R835436 (2017)
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  • Journal Article Jansen EC, Zhou L, Perng W, Song PXK, Tellez-Rojo MM, Mercado A, Peterson KE, Cantoral A. Vegetables and lean proteins-based and processed meats and refined grains-based dietary patterns in early childhood are associated with pubertal timing in a sex-specific manner: a prospective study of children from Mexico City. Nutrition Research 2018;56:41-50. R835436 (2017)
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  • Journal Article Kasper N, Peterson KE, Zhang Z, Ferguson KK, Sanchez BN, Cantoral A, Meeker JD, Tellez-Rojo MM, Pawlowski CM, Ettinger AS. Association of bisphenol A exposure with breastfeeding and perceived insufficient milk supply in Mexican women. Maternal and Child Health Journal 2016;20(8):1713-1719. R835436 (2015)
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  • Journal Article Kochmanski JJ, Marchlewicz EH, Cavalcante RG, Perera BPU, Sartor MA, Dolinoy DC. Longitudinal effects of developmental bisphenol A exposure on epigenome-wide DNA hydroxymethylation at imprinted loci in mouse blood. Environmental Health Perspectives 2018;126(7):077006 (16 pp.). R835436 (2017)
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  • Journal Article Kochmanski J, Montrose L, Goodrich JM, Dolinoy DC. Environmental deflection: the impact of toxicant exposures on the aging epigenome. Toxicological Sciences 2017;156(2):325-335. R835436 (2016)
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  • Journal Article Kochmanski J, Marchlewicz EH, Savidge M, Montrose L, Faulk C, Dolinoy DC. Longitudinal effects of perinatal bisphenol A and variable diet exposures on epigenetic drift in mice. Reproductive Toxicology 2017;68:154-163. R835436 (2016)
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  • Journal Article Kochmanski J, Marchlewicz EH, Dolinoy DC. Longitudinal effects of developmental bisphenol A, variable diet, and physical activity on age-related methylation in blood. Environmental Epigenetics 2018;4(3):dvy017 (10 pp.). R835436 (2017)
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  • Journal Article Lewis RC, Meeker JD. Biomarkers of exposure to molybdenum and other metals in relation to testosterone among men from the United States National Health and Nutrition Examination Survey 2011-2012. Fertility and Sterility 2015;103(1):172-178. R835436 (2014)
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  • Journal Article Lewis RC, Johns LE, Meeker JD. Serum biomarkers of exposure to perfluoroalkyl substances in relation to serum testosterone and measures of thyroid function among adults and adolescents from NHANES 2011-2012. International Journal of Environmental Research and Public Health 2015;12(6):6098-6114. R835436 (2014)
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  • Journal Article Lewis RC, Johns LE, Meeker JD. Exploratory analysis of the potential relationship between urinary molybdenum and bone mineral density among adult men and women from NHANES 2007-2010. Chemosphere 2016;164:677-682. R835436 (2016)
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  • Journal Article Liu Y, Peterson KE. Maternal exposure to synthetic chemicals and obesity in the offspring: recent findings. Current Environmental Health Reports 2015;2(4):339-347. R835436 (2015)
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  • Journal Article Marchlewicz EH, Dolinoy DC, Tang L, Milewski S, Jones TR, Goodrich JM, Soni T, Domino SE, Song PXK, Burant C, Padmanabhan V. Lipid metabolism is associated with developmental epigenetic programming. Scientific Reports 2016;6:34857 (13 pp.). R835436 (2016)
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  • Journal Article Meeker JD, Ferguson KK. Urinary phthalate metabolites are associated with decreased serum testosterone in men, women, and children from NHANES 2011-2012. The Journal of Clinical Endocrinology and Metabolism 2014;99(11):4346-4352. R835436 (2014)
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  • Journal Article Montrose L, Padmanabhan V, Goodrich JM, Domino SE, Treadwell MC, Meeker JD, Watkins DJ, Dolinoy DC. Maternal levels of endocrine disrupting chemicals in the first trimester of pregnancy are associated with infant cord blood DNA methylation. Epigenetics 2018;13(3):301-309. R835436 (2017)
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  • Journal Article Moynihan M, Peterson KE, Cantoral A, Song PXK, Jones A, Solano-Gonzalez M, Meeker JD, Basu N, Tellez-Rojo MM. Dietary predictors of urinary cadmium among pregnant women and children. Science of the Total Environment 2017;575:1255-1262. R835436 (2016)
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  • Journal Article Neier K, Marchlewicz EH, Dolinoy DC, Padmanabhan V. Assessing human health risk to endocrine disrupting chemicals: a focus on prenatal exposures and oxidative stress. Endocrine Disruptors (Austin);2015;3(1):e1069916 (8 pp.). R835436 (2015)
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  • Journal Article Omoike OE, Lewis RC, Meeker JD. Association between urinary biomarkers of exposure to organophosphate insecticides and serum reproductive hormones in men from NHANES 1999-2002. Reproductive Toxicology 2015;53:99-104. R835436 (2015)
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  • Journal Article Peretz J, Vrooman L, Ricke WA, Hunt PA, Ehrlich S, Hauser R, Padmanabhan V, Taylor HS, Swan SH, VandeVoort CA, Flaws JA. Bisphenol A and reproductive health: update of experimental and human evidence, 2007-2013. Environmental Health Perspectives 2014;122(8):775-786. R835436 (2014)
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  • Journal Article Perng W, Watkins DJ, Cantoral A, Mercado-Garcia A, Meeker JD, Tellez-Rojo MM, Peterson KE. Exposure to phthalates is associated with lipid profile in peripubertal Mexican youth. Environmental Research 2017;154:311-317. R835436 (2016)
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  • Journal Article Perng W, Fernandez C, Peterson KE, Zhang Z, Cantoral A, Sanchez BN, Solano-Gonzalez M, Tellez-Rojo MM, Baylin A. Dietary patterns exhibit sex-specific associations with adiposity and metabolic risk in a cross-sectional study in urban Mexican adolescents. The Journal of Nutrition 2017;147(10):1977-1985. R835436 (2017)
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  • Journal Article Perng W, Hector EC, Song PXK, Tellez Rojo MM, Raskind S, Kachman M, Cantoral A, Burant CF, Peterson KE. Metabolomic determinants of metabolic risk in Mexican adolescents. Obesity (Silver Spring) 2017;25(9):1594-1602. R835436 (2017)
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  • Journal Article Sanchez-Vaznaugh EV, Sanchez BN, Crawford PB, Egerter S. Association between competitive food and beverage policies in elementary schools and childhood overweight/obesity trends: differences by neighborhood socioeconomic resources. JAMA Pediatrics 2015;169(5):e150781 (17 pp.). R835436 (2014)
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  • Journal Article Silver MK, Lozoff B, Meeker JD. Blood cadmium is elevated in iron deficient U.S. children: a cross-sectional study. Environmental Health 2013;12(1):117 (9 pp.). R835436 (2014)
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  • Journal Article Somers EC, Monrad SU, Warren JS, Solano M, Schnaas L, Hernandez-Avila M, Tellez-Rojo MM, Hu H. Antinuclear antibody prevalence in a general pediatric cohort from Mexico City: discordance between immunofluorescence and multiplex assays. Clinical Epidemiology 2017;9:1-8. R835436 (2016)
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  • Journal Article Sun Z, Tao Y, Li S, Ferguson KK, Meeker JD, Park SK, Batterman SA, Mukherjee B. Statistical strategies for constructing health risk models with multiple pollutants and their interactions: possible choices and comparisons. Environmental Health 2013;12(1):85 (19 pp.). R835436 (2014)
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  • Journal Article Tao Y, Sanchez BN, Mukherjee B. Latent variable models for gene-environment interactions in longitudinal studies with multiple correlated exposures. Statistics in Medicine 2015;34(7):1227-1241. R835436 (2014)
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  • Journal Article Trentacosta CJ, Davis-Kean P, Mitchell C, Hyde L, Dolinoy D. Environmental contaminants and child development. Child Developmental Perspectives 2016;10(4):228-233. R835436 (2016)
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  • Journal Article Vandenberg LN, Gerona RR, Kannan K, Taylor JA, van Breemen RB, Dickenson CA, Liao C, Yuan Y, Newbold RR, Padmanabhan V, vom Saal FS, Woodruff TJ. A round robin approach to the analysis of bisphenol A (BPA) in human blood samples. Environmental Health 2014;13(1):25 (20 pp.). R835436 (2014)
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  • Journal Article Veiga-Lopez A, Pennathur S, Kannan K, Patisaul HB, Dolinoy DC, Zeng L, Padmanabhan V. Impact of gestational bisphenol A on oxidative stress and free fatty acids: human association and interspecies animal testing studies. Endocrinology 2015;156(3):911-922. R835436 (2014)
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  • Journal Article Veiga-Lopez A, Kannan K, Liao C, Ye W, Domino S, Padmanabhan V. Gender-specific effects on gestational length and birth weight by early pregnancy BPA exposure. Journal of Clinical Endocrinology and Metabolism 2015;100(11):E1394-E1403. R835436 (2015)
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  • Journal Article Watkins DJ, Tellez-Rojo MM, Ferguson KK, Lee JM, Solano-Gonzalez M, Blank-Goldenberg C, Peterson KE, Meeker JD. In utero and peripubertal exposure to phthalates and BPA in relation to female sexual maturation. Environmental Research 2014;134:233-241. R835436 (2014)
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  • Journal Article Watkins DJ, Peterson KE, Ferguson KK, Mercado-Garcia A, Tamayo y Ortiz M, Cantoral A, Meeker JD, Tellez-Rojo MM. Relating phthalate and BPA exposure to metabolism in peripubescence: the role of exposure timing, sex, and puberty. Journal of Clinical Endocrinology & Metabolism 2016;101(1):79-88. R835436 (2015)
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  • Journal Article Watkins DJ, Fortenberry GZ, Sanchez BN, Barr DB, Panuwet P, Schnaas L, Osorio-Valencia E, Solano-Gonzalez M, Ettinger AS, Hernandez-Avila M, Hu H, Tellez-Rojo MM, Meeker JD. Urinary 3-phenoxybenzoic acid (3-PBA) levels among pregnant women in Mexico City: distribution and relationships with child neurodevelopment. Environmental Research 2016;147:307-313. R835436 (2015)
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  • Journal Article Watkins DJ, Milewski S, Domino SE, Meeker JD, Padmanabhan V. Maternal phthalate exposure during early pregnancy and at delivery in relation to gestational age and size at birth: a preliminary analysis. Reproductive Toxicology 2016;65:59-66. R835436 (2016)
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  • Journal Article Watkins DJ, Sanchez BN, Tellez-Rojo MM, Lee JM, Mercado-Garcia A, Blank-Goldenberg C, Peterson KE, Meeker JD. Impact of phthalate and BPA exposure during the in utero windows of susceptibility on reproductive hormones and sexual maturation in peripubertal males. Environmental Health 2017;16(1):69 (10 pp.). R835436 (2016)
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  • Journal Article Watkins DJ, Sanchez BN, Tellez-Rojo MM, Lee JM, Mercado-Garcia A, Blank-Goldenberg C, Peterson KE, Meeker JD. Phthalate and bisphenol A exposure during in utero windows of susceptibility in relation to reproductive hormones and pubertal development in girls. Environmental Research 2017;159:143-151. R835436 (2017)
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  • Journal Article Wu J, Wen XW, Faulk C, Boehnke K, Zhang H, Dolinoy DC, Xi C. Perinatal lead exposure alters gut microbiota composition and results in sex-specific body weight increases in adult mice. Toxicological Sciences 2016;151(2):324-333. R835436 (2016)
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  • Journal Article Yang TC, Peterson KE, Meeker JD, Sanchez BN, Zhang Z, Cantoral A, Solano M, Tellez-Rojo MM. Bisphenol A and phthalates in utero and in childhood: association with child BMI z-score and adiposity. Environmental Research 2017;156:326-333. R835436 (2016)
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  • Journal Article Yang TC, Peterson KE, Meeker JD, Sanchez BN, Zhang Z, Cantoral A, Solano M, Tellez-Rojo MM. Exposure to bisphenol A and phthalates metabolites in the third trimester and BMI trajectories. Pediatric Obesity 2018;13(9):550-557. R835436 (2017)
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  • Journal Article Zhang Z, O’Neill MS, Sanchez BN. Using a latent variable model with non-constant factor loadings to examing PM2.5 constituents related to secondary inorganic aerosols. Statistical Modeling 2016;16(2):91-113. R835436 (2016)
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  • Journal Article Zhou Y, Wang P, Wang X, Zhu J, Song PX. Sparse multivariate factor analysis regression models and its applications to integrative genomics analysis. Genetic Epidemiology 2017;41(1):70-80. R835436 (2016)
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  • Journal Article Shimpi PC, More VR, Paranjpe M, Donepudi AC, Goodrich JM, Dolinoy DC, Rubin B, Slitt AL. Hepatic lipid accumulation and Nrf2 expression following perinatal and peripubertal exposure to bisphenol A in a mouse model of nonalcoholic liver disease. Environmental health perspectives 2017;125(8):087005. R835436 (Final)
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  • Journal Article McCabe C, Anderson OS, Montrose L, Neier K, Dolinoy DC. Sexually dimorphic effects of early-life exposures to endocrine disruptors:sex-specific epigenetic reprogramming as a potential mechanism. Current environmental health reports 2017;4(4):426-38. R835436 (Final)
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  • Journal Article Banu SK, Stanley JA, Taylor RJ, Sivakumar KK, Arosh JA, Zeng L, Pennathur S, Padmanabhan V. Sexually dimorphic impact of chromium accumulation on human placental oxidative stress and apoptosis. Toxicological Sciences 2017;161(2):375-87. R835436 (Final)
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  • Journal Article Jansen EC, Dunietz GL, Chervin RD, Baylin A, Baek J, Banker M, Song PX, Cantoral A, Rojo MM, Peterson KE. Adiposity in adolescents:the interplay of sleep duration and sleep variability. The Journal of pediatrics 2018;203:309-16. R835436 (Final)
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  • Journal Article Kochmanski J, Marchlewicz EH, Cavalcante RG, Sartor MA, Dolinoy DC. Age-related epigenome-wide DNA methylation and hydroxymethylation in longitudinal mouse blood. Epigenetics 2018;13(7):779-92. R835436 (Final)
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  • Journal Article Wu Y, Peterson KE, Sánchez BN, Dolinoy DC, Mercado-Garcia A, Téllez-Rojo MM, Goodrich JM. Association of blood leukocyte DNA methylation at LINE-1 and growth-related candidate genes with pubertal onset and progression. Epigenetics 2018;13(12):1222-33. R835436 (Final)
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  • Journal Article Banu SK. Chromium Burden in Human Placenta:Author (s) Responses to Thompson et al. Toxicological Sciences 2018;165(2):270-1. R835436 (Final)
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  • Journal Article Axson EL, Peterson KE, Tellez-Rojo MM, Goodrich JM, Meeker J, Mercado-García A, Solano M, Needham BL. Sex differences in telomere length are not mediated by sex steroid hormones or body size in early adolescence. Gender and the Genome 2018;2(3):68-75. R835436 (Final)
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  • Journal Article Wang T, Pehrsson EC, Purushotham D, Li D, Zhuo X, Zhang B, Lawson HA, Province MA, Krapp C, Lan Y, Coarfa C. The NIEHS TaRGET II Consortium and environmental epigenomics. Nature biotechnology 2018;36(3):225. R835436 (Final)
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  • Journal Article Lewis RC, Meeker JD, Basu N, Gauthier AM, Cantoral A, Mercado-García A, Peterson KE, Téllez-Rojo MM, Watkins DJ. Urinary metal concentrations among mothers and children in a Mexico City birth cohort study. International journal of hygiene and environmental health. 2018;221(4):609-15. R835436 (Final)
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  • Journal Article Neier K, Marchlewicz EM, Bedrosian LD, Dolinoy DC, Harris C. Characterization of the mouse white adipose tissue redox environment and associations with perinatal environmental exposures to bisphenol A and high-fat diets. The Journal of nutritional biochemistry 2019;1(66):86-97. R835436 (Final)
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  • Journal Article Wu Y, Sánchez BN, Goodrich JM, Dolinoy DC, Cantoral A, Mercado-Garcia A, Ruiz-Narváez EA, Téllez-Rojo MM, Peterson KE. Dietary exposures, epigenetics and pubertal tempo. Environmental Epigenetics 2019;5(1):dvz002. R835436 (Final)
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  • Journal Article Perng W, Tamayo-Ortiz M, Tang L, Sánchez BN, Cantoral A, Meeker JD, Dolinoy DC, Roberts EF, Martinez-Mier EA, Lamadrid-Figueroa H, Song PX. Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) Project. BMJ open 2019;9(8):e030427. R835436 (Final)
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  • Journal Article Liu Y, Téllez-Rojo MM, Sánchez BN, Zhang Z, Afeiche MC, Mercado-García A, Hu H, Meeker JD, Peterson KE. Early lead exposure and pubertal development in a Mexico City population. Environment international. 2019;125:445-51. R835436 (Final)
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  • Journal Article Kelley AS, Banker M, Goodrich JM, Dolinoy DC, Burant C, Domino SE, Smith YR, Song PX, Padmanabhan V. Early pregnancy exposure to endocrine disrupting chemical mixtures are associated with inflammatory changes in maternal and neonatal circulation. Scientific reports 2019;9(1):5422. R835436 (Final)
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  • Journal Article Neier K, Cheatham D, Bedrosian LD, Gregg BE, Song PXK, Dolinoy DC. Longitudinal metabolic impacts of perinatal exposure to phthalates and phthalate mixtures in mice." Endocrinology 2019;160(7):1613-1630. R835436 (Final)
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  • Journal Article Perng W, Tang L, Song PX, Tellez-Rojo MM, Cantoral A, Peterson KE. Metabolomic profiles and development of metabolic risk during the pubertal transition:a prospective study in the ELEMENT Project. Pediatric research 2019;85(3):262. R835436 (Final)
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  • Journal Article Neier K, Cheatham D, Bedrosian LD, Dolinoy DC. Perinatal exposures to phthalates and phthalate mixtures result in sex-specific effects on body weight, organ weights and intracisternal A-particle (IAP) DNA methylation in weanling mice. Journal of developmental origins of health and disease 2019;10(2):176-87. R835436 (Final)
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  • Journal Article Rodríguez-Carmona Y, Cantoral A, Trejo-Valdivia B, Téllez-Rojo MM, Svensson K, Peterson KE, Meeker JD, Schnaas L, Solano M, Watkins DJ. Phthalate exposure during pregnancy and long-term weight gain in women. Environmental research 2019;169:26-32. R835436 (Final)
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  • Journal Article Moynihan M, Telléz-Rojo MM, Colacino J, Jones AD, Song PX, Cantoral A, Mercado-Garcia A, Peterson K. Prenatal cadmium exposure is negatively associated with adiposity in girls not boys during adolescence. Frontiers in Public Health 2019;7:61. R835436 (Final)
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  • Journal Article Wu Y, Jansen EC, Peterson KE, Foxman B, Goodrich JM, Hu H, Solano-González M, Cantoral A, Téllez-Rojo MM, Martinez-Mier EA. The associations between lead exposure at multiple sensitive life periods and dental caries risks in permanent teeth. Science of the Total Environment 2019;654:1048-55. R835436 (Final)
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  • Journal Article Perng W, Tang L, Song PX, Goran M, Tellez Rojo MM, Cantoral A, Peterson KE. Urate and Nonanoate Mark the Relationship between Sugar-Sweetened Beverage Intake and Blood Pressure in Adolescent Girls:A Metabolomics Analysis in the ELEMENT Cohort. Metabolites 2019;9(5):100. R835436 (Final)
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  • Journal Article Jansen EC, Dunietz GL, Dababneh A, Peterson KE, Chervin RD, Baek J, O'Brien L, Song PX, Cantoral A, Hu H, Téllez-Rojo MM. Cumulative Childhood Lead Levels in Relation to Sleep During Adolescence. Journal of clinical sleep medicine:JCSM:official publication of the American Academy of Sleep Medicine 2019. R835436 (Final)
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  • Journal Article Goodrich JM, Ingle ME, Domino SE, Treadwell MC, Dolinoy DC, Burant C, Meeker JD, Padmanabhan V. First trimester maternal exposures to endocrine disrupting chemicals and metals and fetal size in the Michigan Mother–Infant Pairs study. Journal of developmental origins of health and disease 2019:1-2. R835436 (Final)
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  • Journal Article Perera BP, Svoboda L, Dolinoy DC. Genomic tools for environmental epigenetics and implications for public health. Current Opinion in Toxicology 2019. R835436 (Final)
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  • Journal Article Marchlewicz E, Djuric Z, Sanchez B, Peterson K, Dolinoy D. Impact of Prenatal Exposure to Humanized High Fat Diets on Murine Metabolic Phenotype. The FASEB Journal. 2015;29(1):754-3. R835436 (Final)
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  • Journal Article Ashrap, Pahriya, Sánchez BN, Martha M, Téllez-Rojo, Niladri Basu, Tamayo-Ortiz M, Peterson KE, Meeker JD, and Watkins DJ. In utero and peripubertal metals exposure in relation to reproductive hormones and sexual maturation and progression among girls in Mexico City. Environmental research (2019):108630, https://www.sciencedirect.com/science/article/pii/S001393511930427X. R835436 (Final)
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  • Journal Article Anderson OS, Kim JH, Peterson KE, Sanchez BN, Sant KE, Sartor MA, Weinhouse C, Dolinoy DC. Novel epigenetic biomarkers mediating bisphenol A exposure and metabolic phenotypes in female mice. Endocrinology158, no. 1 (2017):31-40. https://academic.oup.com/endo/article/158/1/31/2751111. R835436 (Final)
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  • Journal Article Dou JF, Farooqui Z, Faulk CD, Barks AK, Jones T, Dolinoy DC, Bakulski KM. Perinatal Lead (Pb) Exposure and Cortical Neuron-Specific DNA Methylation in Male Mice. Genes 2019(4):274. R835436 (Final)
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  • Journal Article Jansen EC, Dolinoy DC, O’Brien LM, Peterson KE, Chervin RD, Banker M, Téllez-Rojo MM, Cantoral A, Mercado-Garcia A, Sanchez B, Goodrich JM. Sleep duration and fragmentation in relation to leukocyte DNA methylation in adolescents. Sleep 2019. R835436 (Final)
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  • Journal Article Perera BP, Faulk C, Svoboda LK, Goodrich JM, Dolinoy DC. The role of environmental exposures and the epigenome in health and disease. Environmental and molecular mutagenesis 2019. R835436 (Final)
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  • Progress and Final Reports:

    Original Abstract
  • 2013 Progress Report
  • 2015 Progress Report
  • 2016 Progress Report
  • 2017 Progress Report
  • Final Report