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2. Epigenetic associations with neonatal age in infants born very preterm, particularly among genes involved in neurodevelopment

Author

Hodge, Kenyaita M., Burt, Amber A., Camerota, Marie, Carter, Brian S., Check, Jennifer, Conneely, Karen N., Helderman, Jennifer, Hofheimer, Julie A., Hüls, Anke, McGowan, Elisabeth C., Neal, Charles R., Pastyrnak, Steven L., Smith, Lynne M., DellaGrotta, Sheri A., Dansereau, Lynne M., O’Shea, T. Michael, Marsit, Carmen J., Lester, Barry M., and Everson, Todd M.

Published
2024
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5. Neurodevelopmental and behavioral outcomes of very preterm infants: latent profile analysis in the Environmental influences on Child Health Outcomes (ECHO) Program

Author

Camerota, Marie, McGowan, Elisabeth C., Aschner, Judy, Stroustrup, Annemarie, O’Shea, T. Michael, Hofheimer, Julie A., Joseph, Robert M., Musci, Rashelle, Taylor, Genevieve, Carter, Brian S., Check, Jennifer, Dansereau, Lynne M., Gogcu, Semsa, Helderman, Jennifer B., Neal, Charles R., Pastyrnak, Steven L., Smith, Lynne M., Marsit, Carmen J., and Lester, Barry M.

Published
2024
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6. Exposure to melamine and its derivatives and aromatic amines among pregnant women in the United States: The ECHO Program

Author

Choi, Giehae, Kuiper, Jordan R, Bennett, Deborah H, Barrett, Emily S, Bastain, Theresa M, Breton, Carrie V, Chinthakindi, Sridhar, Dunlop, Anne L, Farzan, Shohreh F, Herbstman, Julie B, Karagas, Margaret R, Marsit, Carmen J, Meeker, John D, Morello-Frosch, Rachel, O'Connor, Thomas G, Pellizzari, Edo D, Romano, Megan E, Sathyanarayana, Sheela, Schantz, Susan, Schmidt, Rebecca J, Watkins, Deborah J, Zhu, Hongkai, Kannan, Kurunthachalam, Buckley, Jessie P, Woodruff, Tracey J, and Outcomes, program collaborators for Environmental influences on Child Health

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Chemical Sciences, Clinical Research, Amines, Aniline Compounds, Cotinine, Female, Humans, Nitrogen, Pregnancy, Pregnant Women, Toluidines, Triazines, United States, Biomonitoring, chemical exposure, pregnancy, aromatic amines, melamine, tobacco, program collaborators for Environmental influences on Child Health Outcomes, Aromatic amines, Melamine, Tobacco, Environmental Sciences, Meteorology & Atmospheric Sciences
Abstract

BackgroundMelamine, melamine derivatives, and aromatic amines are nitrogen-containing compounds with known toxicity and widespread commercial uses. Nevertheless, biomonitoring of these chemicals is lacking, particularly during pregnancy, a period of increased susceptibility to adverse health effects.ObjectivesWe aimed to measure melamine, melamine derivatives, and aromatic amine exposure in pregnant women across the United States (U.S.) and evaluate associations with participant and urine sample collection characteristics.MethodsWe measured 43 analytes, representing 45 chemicals (i.e., melamine, three melamine derivatives, and 41 aromatic amines), in urine from pregnant women in nine diverse ECHO cohorts during 2008-2020 (N = 171). To assess relations with participant and urine sample collection characteristics, we used generalized estimating equations to estimate prevalence ratios (PRs) for analytes dichotomized at the detection limit, % differences (%Δ) for continuous analytes, and 95% confidence intervals. Multivariable models included age, race/ethnicity, marital status, urinary cotinine, and year of sample collection.ResultsTwelve chemicals were detected in >60% of samples, with near ubiquitous detection of cyanuric acid, melamine, aniline, 4,4'-methylenedianiline, and a composite of o-toluidine and m-toluidine (99-100%). In multivariable adjusted models, most chemicals were associated with higher exposures among Hispanic and non-Hispanic Black participants. For example, concentrations of 3,4-dichloroaniline were higher among Hispanic (%Δ: +149, 95% CI: +17, +431) and non-Hispanic Black (%Δ: +136, 95% CI: +35, +311) women compared with non-Hispanic White women. We observed similar results for ammelide, o-/m-toluidine, 4,4'-methylenedianiline, and 4-chloroaniline. Most chemicals were positively associated with urinary cotinine, with strongest associations observed for o-/m-toluidine (%Δ: +23; 95% CI: +16, +31) and 3,4-dichloroaniline (%Δ: +25; 95% CI: +17, +33). Some chemicals exhibited annual trends (e.g., %Δ in melamine per year: -11; 95% CI: -19, -1) or time of day, seasonal, and geographic variability.DiscussionExposure to melamine, cyanuric acid, and some aromatic amines was ubiquitous in this first investigation of these analytes in pregnant women. Future research should expand biomonitoring, identify sources of exposure disparities by race/ethnicity, and evaluate potential adverse health effects.

Published
2022

7. Prenatal exposure to particulate matter and placental gene expression

Author

Enquobahrie, Daniel A, MacDonald, James, Hussey, Michael, Bammler, Theo K, Loftus, Christine T, Paquette, Alison G, Byington, Nora, Marsit, Carmen J, Szpiro, Adam, Kaufman, Joel D, LeWinn, Kaja Z, Bush, Nicole R, Tylavsky, Frances, Karr, Catherine J, and Sathyanarayana, Sheela

Subjects
Biological Sciences, Pollution and Contamination, Genetics, Epidemiology, Environmental Sciences, Health Sciences, Climate-Related Exposures and Conditions, Clinical Research, Human Genome, Prevention, Pediatric Research Initiative, Contraception/Reproduction, Pediatric, Aetiology, 2.2 Factors relating to the physical environment, Reproductive health and childbirth, Good Health and Well Being, Air Pollutants, Air Pollution, Child, Female, Gene Expression, Humans, Infant, Newborn, Male, Maternal Exposure, Particulate Matter, Placenta, Pregnancy, Prenatal Exposure Delayed Effects, Air pollution, Fine particulate matter, Gene expression, PM2, 5, PM(2.5)
Abstract

BackgroundWhile strong evidence supports adverse maternal and offspring consequences of air pollution, mechanisms that involve the placenta, a key part of the intrauterine environment, are largely unknown. Previous studies of air pollution and placental gene expression were small candidate gene studies that rarely considered prenatal windows of exposure or the potential role of offspring sex. We examined overall and sex-specific associations of prenatal exposure to fine particulate matter (PM2.5) with genome-wide placental gene expression.MethodsParticipants with placenta samples, collected at birth, and childhood health outcomes from CANDLE (Memphis, TN) (n = 776) and GAPPS (Seattle, WA) (n = 205) cohorts of the ECHO-PATHWAYS Consortium were included in this study. PM2.5 exposures during trimesters 1, 2, 3, and the first and last months of pregnancy, were estimated using a spatiotemporal model. Cohort-specific linear adjusted models were fit for each exposure window and expression of >11,000 protein coding genes from paired end RNA sequencing data. Models with interaction terms were used to examine PM2.5-offspring sex interactions. False discovery rate (FDR

Published
2022

8. Prenatal and perinatal factors associated with neonatal neurobehavioral profiles in the ECHO Program

Author

Camerota, Marie, McGowan, Elisabeth C., Aschner, Judy, Stroustrup, Annemarie, Karagas, Margaret R., Conradt, Elisabeth, Crowell, Sheila E., Brennan, Patricia A., Carter, Brian S., Check, Jennifer, Dansereau, Lynne M., DellaGrotta, Sheri A., Everson, Todd M., Helderman, Jennifer B., Hofheimer, Julie A., Kuiper, Jordan R., Loncar, Cynthia M., Marsit, Carmen J., Neal, Charles R., O’Shea, Thomas Michael, Pastyrnak, Steven L., Sheinkopf, Stephen J., Smith, Lynne M., Zhang, Xueying, and Lester, Barry M.

Published
2023
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12. Exposure to Contemporary and Emerging Chemicals in Commerce among Pregnant Women in the United States: The Environmental influences on Child Health Outcome (ECHO) Program

Author

Buckley, Jessie P, Kuiper, Jordan R, Bennett, Deborah H, Barrett, Emily S, Bastain, Tracy, Breton, Carrie V, Chinthakindi, Sridhar, Dunlop, Anne L, Farzan, Shohreh F, Herbstman, Julie B, Karagas, Margaret R, Marsit, Carmen J, Meeker, John D, Morello-Frosch, Rachel, O’Connor, Thomas G, Romano, Megan E, Schantz, Susan, Schmidt, Rebecca J, Watkins, Deborah J, Zhu, Hongkai, Pellizzari, Edo D, Kannan, Kurunthachalam, and Woodruff, Tracey J

Subjects
Environmental Sciences, Pollution and Contamination, Health Sciences, Pediatric, Behavioral and Social Science, Clinical Research, Basic Behavioral and Social Science, Conditions Affecting the Embryonic and Fetal Periods, Aetiology, 2.2 Factors relating to the physical environment, Good Health and Well Being, Child, Commerce, Environmental Exposure, Environmental Pollutants, Female, Humans, Outcome Assessment, Health Care, Phthalic Acids, Plasticizers, Pregnancy, Pregnant Women, United States, pregnancychild health, industrial chemical, pesticides, flame retardants, phthalates, bisphenols, parabens
Abstract

Prenatal chemical exposures can influence maternal and child health; however, few industrial chemicals are routinely biomonitored. We assessed an extensive panel of contemporary and emerging chemicals in 171 pregnant women across the United States (U.S.) and Puerto Rico in the Environmental influences on Child Health Outcomes (ECHO) Program. We simultaneously measured urinary concentrations of 89 analytes (103 total chemicals representing 73 parent compounds) in nine chemical groups: bactericides, benzophenones, bisphenols, fungicides and herbicides, insecticides, organophosphate esters (OPEs), parabens, phthalates/alternative plasticizers, and polycyclic aromatic hydrocarbons (PAHs). We estimated associations of creatinine-adjusted concentrations with sociodemographic and specimen characteristics. Among our diverse prenatal population (60% non-Hispanic Black or Hispanic), we detected 73 of 89 analytes in ≥1 participant and 36 in >50% of participants. Five analytes not currently included in the U.S. biomonitoring were detected in ≥90% of samples: benzophenone-1, thiamethoxam, mono-2-(propyl-6-carboxy-hexyl) phthalate, monocarboxy isooctyl phthalate, and monohydroxy-iso-decyl phthalate. Many analyte concentrations were higher among women of Hispanic ethnicity compared to those of non-Hispanic White women. Concentrations of certain chemicals decreased with the calendar year, whereas concentrations of their replacements increased. Our largest study to date identified widespread exposures to prevalent and understudied chemicals in a diverse sample of pregnant women in the U.S.

Published
2022

14. Evaluation of pediatric epigenetic clocks across multiple tissues

Author

Fang, Fang, Zhou, Linran, Perng, Wei, Marsit, Carmen J., Knight, Anna K., Cardenas, Andres, Aung, Max T., Hivert, Marie-France, Aris, Izzuddin M., Goodrich, Jaclyn M., Smith, Alicia K., Gaylord, Abigail, Fry, Rebecca C., Oken, Emily, O’Connor, George, Ruden, Douglas M., Trasande, Leonardo, Herbstman, Julie B., Camargo, Jr., Carlos A., Bush, Nicole R., Dunlop, Anne L., Dabelea, Dana M., Karagas, Margaret R., Breton, Carrie V., Ober, Carole, Everson, Todd M., Page, Grier P., and Ladd-Acosta, Christine

Published
2023
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18. A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health

Author

Fernandez-Jimenez, Nora, Fore, Ruby, Cilleros-Portet, Ariadna, Lepeule, Johanna, Perron, Patrice, Kvist, Tuomas, Tian, Fu-Ying, Lesseur, Corina, Binder, Alexandra M, Lozano, Manuel, Martorell-Marugán, Jordi, Loke, Yuk J, Bakulski, Kelly M, Zhu, Yihui, Forhan, Anne, Sammallahti, Sara, Everson, Todd M, Chen, Jia, Michels, Karin B, Belmonte, Thalia, Carmona-Sáez, Pedro, Halliday, Jane, Daniele Fallin, M, LaSalle, Janine M, Tost, Jorg, Czamara, Darina, Fernández, Mariana F, Gómez-Martín, Antonio, Craig, Jeffrey M, Gonzalez-Alzaga, Beatriz, Schmidt, Rebecca J, Dou, John F, Muggli, Evelyne, Lacasaña, Marina, Vrijheid, Martine, Marsit, Carmen J, Karagas, Margaret R, Räikkönen, Katri, Bouchard, Luigi, Heude, Barbara, Santa-Marina, Loreto, Bustamante, Mariona, Hivert, Marie-France, and Bilbao, Jose Ramon

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Genetics, Pediatric, Prevention, Obesity, Childhood Obesity, Clinical Research, Nutrition, Conditions Affecting the Embryonic and Fetal Periods, Perinatal Period - Conditions Originating in Perinatal Period, Human Genome, Pregnancy, Maternal Health, Women's Health, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Good Health and Well Being, Infant, Newborn, Child, Humans, Female, Body Mass Index, DNA Methylation, Placenta, Mothers, Child Health, Biological sciences, Biomedical and clinical sciences
Abstract

Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenome-wide placental DNA methylation (DNAm) in 10 studies from the PACE consortium, amounting to 2631 mother-child pairs. We identify 27 CpG sites at which we observe placental DNAm variations of up to 2.0% per 10 ppBMI-unit. The CpGs that are differentially methylated in placenta do not overlap with CpGs identified in previous studies in cord blood DNAm related to ppBMI. Many of the identified CpGs are located in open sea regions, are often close to obesity-related genes such as GPX1 and LGR4 and altogether, are enriched in cancer and oxidative stress pathways. Our findings suggest that placental DNAm could be one of the mechanisms by which maternal obesity is associated with metabolic health outcomes in newborns and children, although further studies will be needed in order to corroborate these findings.

Published
2022

19. Placental genomics mediates genetic associations with complex health traits and disease

Author

Bhattacharya, Arjun, Freedman, Anastasia N, Avula, Vennela, Harris, Rebeca, Liu, Weifang, Pan, Calvin, Lusis, Aldons J, Joseph, Robert M, Smeester, Lisa, Hartwell, Hadley J, Kuban, Karl CK, Marsit, Carmen J, Li, Yun, O’Shea, T Michael, Fry, Rebecca C, and Santos, Hudson P

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Perinatal Period - Conditions Originating in Perinatal Period, Human Genome, Prevention, Pediatric, Biotechnology, Pediatric Research Initiative, Aetiology, 2.1 Biological and endogenous factors, Reproductive health and childbirth, Adaptor Proteins, Signal Transducing, Animals, Disease, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Guanine Nucleotide Exchange Factors, Humans, Infant, Newborn, Mice, Multifactorial Inheritance, Placenta, Pregnancy, Quantitative Trait Loci, RNA-Seq, Transcriptome
Abstract

As the master regulator in utero, the placenta is core to the Developmental Origins of Health and Disease (DOHaD) hypothesis but is historically understudied. To identify placental gene-trait associations (GTAs) across the life course, we perform distal mediator-enriched transcriptome-wide association studies (TWAS) for 40 traits, integrating placental multi-omics from the Extremely Low Gestational Age Newborn Study. At [Formula: see text], we detect 248 GTAs, mostly for neonatal and metabolic traits, across 176 genes, enriched for cell growth and immunological pathways. In aggregate, genetic effects mediated by placental expression significantly explain 4 early-life traits but no later-in-life traits. 89 GTAs show significant mediation through distal genetic variants, identifying hypotheses for distal regulation of GTAs. Investigation of one hypothesis in human placenta-derived choriocarcinoma cells reveal that knockdown of mediator gene EPS15 upregulates predicted targets SPATA13 and FAM214A, both associated with waist-hip ratio in TWAS, and multiple genes involved in metabolic pathways. These results suggest profound health impacts of placental genomic regulation in developmental programming across the life course.

Published
2022

21. Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth.

Author

Everson, Todd M, Vives-Usano, Marta, Seyve, Emie, Cardenas, Andres, Lacasaña, Marina, Craig, Jeffrey M, Lesseur, Corina, Baker, Emily R, Fernandez-Jimenez, Nora, Heude, Barbara, Perron, Patrice, Gónzalez-Alzaga, Beatriz, Halliday, Jane, Deyssenroth, Maya A, Karagas, Margaret R, Íñiguez, Carmen, Bouchard, Luigi, Carmona-Sáez, Pedro, Loke, Yuk J, Hao, Ke, Belmonte, Thalia, Charles, Marie A, Martorell-Marugán, Jordi, Muggli, Evelyne, Chen, Jia, Fernández, Mariana F, Tost, Jorg, Gómez-Martín, Antonio, London, Stephanie J, Sunyer, Jordi, Marsit, Carmen J, Lepeule, Johanna, Hivert, Marie-France, and Bustamante, Mariona

Subjects
Placenta, Humans, Tobacco, Smoking, DNA Methylation, Epigenesis, Genetic, Fetal Development, Pregnancy, Genetic Heterogeneity, Female, Nucleotide Motifs
Abstract

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.

Published
2021

22. CpG methylation patterns in placenta and neonatal blood are differentially associated with neonatal inflammation

Author

Eaves, Lauren A., Enggasser, Adam E., Camerota, Marie, Gogcu, Semsa, Gower, William A., Hartwell, Hadley, Jackson, Wesley M., Jensen, Elizabeth, Joseph, Robert M., Marsit, Carmen J., Roell, Kyle, Santos Jr., Hudson P., Shenberger, Jeffrey S., Smeester, Lisa, Yanni, Diana, Kuban, Karl C. K., O’Shea, T. Michael, and Fry, Rebecca C.

Published
2023
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25. Incidence rates of childhood asthma with recurrent exacerbations in the US Environmental influences on Child Health Outcomes (ECHO) program

Author

Smith, P.B., Newby, K.L., Jacobson, L.P., Catellier, D.J., Gershon, R., Cella, D., Alshawabkeh, A., Aschner, J., Merhar, S., Ren, C., Reynolds, A., Keller, R., Pryhuber, G., Duncan, A., Lampland, A., Wadhawan, R., Wagner, C., Hudak, M., Mayock, D., Walshburn, L., Teitelbaum, S.L., Stroustrup, A., Trasande, L., Blair, C., Gatzke-Kopp, L., Swingler, M., Mansbach, J., Spergel, J., Puls, H., Stevenson, M., Bauer, C., Deoni, S., Duarte, C., Dunlop, A., Elliott, A., Croen, L., Bacharier, L., O’Connor, G., Kattan, M., Wood, R., Hershey, G., Ownby, D., Hertz-Picciotto, I., Hipwell, A., Karagas, M., Karr, C., Mason, A., Sathyanarayana, S., Lester, B., Carter, B., Neal, C., Smith, L., Helderman, J., Leve, L., Ganiban, J., Neiderhiser, J., Weiss, S., Zeiger, R., Tepper, R., Lyall, K., Landa, R., Ozonoff, S., Schmidt, R., Dager, S., Schultz, R., Piven, J., Volk, H., Vaidya, R., Obeid, R., Rollins, C., Bear, K., Pastyrnak, S., Lenski, M., Msall, M., Frazier, J., Washburn, L., Montgomery, A., Barone, C., McKane, P., Paneth, N., Elliott, M., Herbstman, J., Schantz, S., Porucznik, C., Silver, R., Conradt, E., Bosquet-Enlow, M., Huddleston, K., Bush, N., Nguyen, R., O'Connor, T., Samuels-Kalow, M., Miller, Rachel L., Schuh, Holly, Chandran, Aruna, Aris, Izzuddin M., Bendixsen, Casper, Blossom, Jeffrey, Breton, Carrie, Camargo, Carlos A., Jr., Canino, Glorisa, Carroll, Kecia N., Commodore, Sarah, Cordero, José F., Dabelea, Dana M., Ferrara, Assiamira, Fry, Rebecca C., Ganiban, Jody M., Gern, James E., Gilliland, Frank D., Gold, Diane R., Habre, Rima, Hare, Marion E., Harte, Robyn N., Hartert, Tina, Hasegawa, Kohei, Khurana Hershey, Gurjit K., Jackson, Daniel J., Joseph, Christine, Kerver, Jean M., Kim, Haejin, Litonjua, Augusto A., Marsit, Carmen J., McEvoy, Cindy, Mendonça, Eneida A., Moore, Paul E., Nkoy, Flory L., O’Connor, Thomas G., Oken, Emily, Ownby, Dennis, Perzanowski, Matthew, Rivera-Spoljaric, Katherine, Ryan, Patrick H., Singh, Anne Marie, Stanford, Joseph B., Wright, Rosalind J., Wright, Robert O., Zanobetti, Antonella, Zoratti, Edward, and Johnson, Christine C.

Published
2023
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26. Evidence for the placenta-brain axis: multi-omic kernel aggregation predicts intellectual and social impairment in children born extremely preterm

Author

Santos Jr, Hudson P, Bhattacharya, Arjun, Joseph, Robert M, Smeester, Lisa, Kuban, Karl CK, Marsit, Carmen J, O’Shea, T Michael, and Fry, Rebecca C

Subjects
Preterm, Low Birth Weight and Health of the Newborn, Genetics, Perinatal Period - Conditions Originating in Perinatal Period, Intellectual and Developmental Disabilities (IDD), Human Genome, Neurosciences, Mental Health, Biotechnology, Clinical Research, Brain Disorders, Infant Mortality, Pediatric, Autism, Behavioral and Social Science, Prevention, Aetiology, 2.1 Biological and endogenous factors, Reproductive health and childbirth, Mental health, Adult, Algorithms, Biomarkers, Brain, Case-Control Studies, Child, Cognition, CpG Islands, Female, Genome-Wide Association Study, Genomics, Humans, Infant, Extremely Premature, Infant, Newborn, Intellectual Disability, Intelligence Tests, Male, MicroRNAs, Multivariate Analysis, Placenta, Pregnancy, Premature Birth, RNA, Messenger, Social Behavior, Prenatal neurodevelopmental programming, Social and cognitive impairment, Placental gene regulation, Epigenome-wide association, Differential expression analysis, Multi-omic aggregation, Clinical Sciences
Abstract

BackgroundChildren born extremely preterm are at heightened risk for intellectual and social impairment, including Autism Spectrum Disorder (ASD). There is increasing evidence for a key role of the placenta in prenatal developmental programming, suggesting that the placenta may, in part, contribute to origins of neurodevelopmental outcomes.MethodsWe examined associations between placental transcriptomic and epigenomic profiles and assessed their ability to predict intellectual and social impairment at age 10 years in 379 children from the Extremely Low Gestational Age Newborn (ELGAN) cohort. Assessment of intellectual ability (IQ) and social function was completed with the Differential Ability Scales-II and Social Responsiveness Scale (SRS), respectively. Examining IQ and SRS allows for studying ASD risk beyond the diagnostic criteria, as IQ and SRS are continuous measures strongly correlated with ASD. Genome-wide mRNA, CpG methylation and miRNA were assayeds with the Illumina Hiseq 2500, HTG EdgeSeq miRNA Whole Transcriptome Assay, and Illumina EPIC/850 K array, respectively. We conducted genome-wide differential analyses of placental mRNA, miRNA, and CpG methylation data. These molecular features were then integrated for a predictive analysis of IQ and SRS outcomes using kernel aggregation regression. We lastly examined associations between ASD and the multi-omic-predicted component of IQ and SRS.ResultsGenes with important roles in neurodevelopment and placental tissue organization were associated with intellectual and social impairment. Kernel aggregations of placental multi-omics strongly predicted intellectual and social function, explaining approximately 8% and 12% of variance in SRS and IQ scores via cross-validation, respectively. Predicted in-sample SRS and IQ showed significant positive and negative associations with ASD case-control status.LimitationsThe ELGAN cohort comprises children born pre-term, and generalization may be affected by unmeasured confounders associated with low gestational age. We conducted external validation of predictive models, though the sample size (N = 49) and the scope of the available out-sample placental dataset are limited. Further validation of the models is merited.ConclusionsAggregating information from biomarkers within and among molecular data types improves prediction of complex traits like social and intellectual ability in children born extremely preterm, suggesting that traits within the placenta-brain axis may be omnigenic.

Published
2020

32. Trajectories of attention problems in preschoolers born very preterm

Author

Camerota, Marie, primary, Castellanos, Francisco Xavier, additional, Carter, Brian S., additional, Check, Jennifer, additional, Helderman, Jennifer B., additional, Hofheimer, Julie A, additional, McGowan, Elisabeth C., additional, Neal, Charles R., additional, Pastyrnak, Steven L., additional, Smith, Lynne M., additional, O’Shea, T. Michael, additional, Marsit, Carmen J., additional, and Lester, Barry M., additional

Published
2024
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34. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Author

Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, Morgen, Camilla S, van Kampen, Antoine HC, van Schaik, Barbera DC, Mentch, Frank D, Langenberg, Claudia, Luan, Jian’an, Scott, Robert A, Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M, Bennett, Amanda J, Gaulton, Kyle J, Fernandez-Tajes, Juan, van Zuydam, Natalie R, Medina-Gomez, Carolina, de Haan, Hugoline G, Rosendaal, Frits R, Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil VR, Fonvig, Cilius E, and Trier, Caecilie

Subjects
Biological Sciences, Genetics, Cardiovascular, Perinatal Period - Conditions Originating in Perinatal Period, Nutrition, Prevention, Preterm, Low Birth Weight and Health of the Newborn, Pediatric, Obesity, Conditions Affecting the Embryonic and Fetal Periods, Infant Mortality, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Good Health and Well Being, Adult, Birth Weight, Blood Pressure, Body Height, Diabetes Mellitus, Type 2, Female, Fetal Development, Genetic Predisposition to Disease, Genome-Wide Association Study, Heart Diseases, Humans, Infant, Newborn, Male, Maternal Inheritance, Maternal-Fetal Exchange, Metabolic Diseases, Models, Genetic, Polymorphism, Single Nucleotide, Pregnancy, Risk Factors, EGG Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

Published
2019

35. Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight.

Author

Küpers, Leanne K, Monnereau, Claire, Sharp, Gemma C, Yousefi, Paul, Salas, Lucas A, Ghantous, Akram, Page, Christian M, Reese, Sarah E, Wilcox, Allen J, Czamara, Darina, Starling, Anne P, Novoloaca, Alexei, Lent, Samantha, Roy, Ritu, Hoyo, Cathrine, Breton, Carrie V, Allard, Catherine, Just, Allan C, Bakulski, Kelly M, Holloway, John W, Everson, Todd M, Xu, Cheng-Jian, Huang, Rae-Chi, van der Plaat, Diana A, Wielscher, Matthias, Merid, Simon Kebede, Ullemar, Vilhelmina, Rezwan, Faisal I, Lahti, Jari, van Dongen, Jenny, Langie, Sabine AS, Richardson, Tom G, Magnus, Maria C, Nohr, Ellen A, Xu, Zongli, Duijts, Liesbeth, Zhao, Shanshan, Zhang, Weiming, Plusquin, Michelle, DeMeo, Dawn L, Solomon, Olivia, Heimovaara, Joosje H, Jima, Dereje D, Gao, Lu, Bustamante, Mariona, Perron, Patrice, Wright, Robert O, Hertz-Picciotto, Irva, Zhang, Hongmei, Karagas, Margaret R, Gehring, Ulrike, Marsit, Carmen J, Beilin, Lawrence J, Vonk, Judith M, Jarvelin, Marjo-Riitta, Bergström, Anna, Örtqvist, Anne K, Ewart, Susan, Villa, Pia M, Moore, Sophie E, Willemsen, Gonneke, Standaert, Arnout RL, Håberg, Siri E, Sørensen, Thorkild IA, Taylor, Jack A, Räikkönen, Katri, Yang, Ivana V, Kechris, Katerina, Nawrot, Tim S, Silver, Matt J, Gong, Yun Yun, Richiardi, Lorenzo, Kogevinas, Manolis, Litonjua, Augusto A, Eskenazi, Brenda, Huen, Karen, Mbarek, Hamdi, Maguire, Rachel L, Dwyer, Terence, Vrijheid, Martine, Bouchard, Luigi, Baccarelli, Andrea A, Croen, Lisa A, Karmaus, Wilfried, Anderson, Denise, de Vries, Maaike, Sebert, Sylvain, Kere, Juha, Karlsson, Robert, Arshad, Syed Hasan, Hämäläinen, Esa, Routledge, Michael N, Boomsma, Dorret I, Feinberg, Andrew P, Newschaffer, Craig J, Govarts, Eva, Moisse, Matthieu, Fallin, M Daniele, Melén, Erik, and Prentice, Andrew M

Subjects
Fetus, Humans, Prenatal Exposure Delayed Effects, Birth Weight, Folic Acid, DNA, Body Mass Index, Smoking, DNA Methylation, Epigenesis, Genetic, CpG Islands, Fetal Development, Pregnancy, Genome, Human, Adolescent, Adult, Child, Infant, Newborn, Female, Male, Genome-Wide Association Study, Epigenesis, Genetic, Genome, Human, Infant, Newborn
Abstract

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni

Published
2019

40. Pyrimidine Biosynthesis in Branching Morphogenesis Defects Induced by Prenatal Heavy Metal Exposure.

Author

Wongtrakool, Cherry, Ma, Jing, Jarrell, Zachery R., Liu, Ken H., Orr, Michael, Tran, ViLinh, Gauthier, Theresa W., Marsit, Carmen J., Jones, Dean P., Go, Young-Mi, and Hu, Xin

Subjects
INDUCTIVELY coupled plasma mass spectrometry, PYRIMIDINE nucleotides, LIQUID chromatography-mass spectrometry, STABLE isotope tracers, URIDINE diphosphate, URIDINE, GLUTAMINE
Abstract

This article discusses the impact of prenatal exposure to heavy metals, specifically cadmium (Cd) and arsenic (As), on the development of the respiratory system in mice. The study used a murine lung explant model and untargeted metabolomics to investigate the effects of Cd and As on airway formation and pyrimidine biosynthesis. The results showed that coexposure to Cd and As inhibited branching morphogenesis and reduced pyrimidine biosynthesis. The study highlights the potential long-term adverse effects of heavy metal exposure on lung development and suggests the need for further research in this area. [Extracted from the article]

Published
2024
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42. Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium

Author

Felix, Janine F, Joubert, Bonnie R, Baccarelli, Andrea A, Sharp, Gemma C, Almqvist, Catarina, Annesi-Maesano, Isabella, Arshad, Hasan, Baïz, Nour, Bakermans-Kranenburg, Marian J, Bakulski, Kelly M, Binder, Elisabeth B, Bouchard, Luigi, Breton, Carrie V, Brunekreef, Bert, Brunst, Kelly J, Burchard, Esteban G, Bustamante, Mariona, Chatzi, Leda, Munthe-Kaas, Monica Cheng, Corpeleijn, Eva, Czamara, Darina, Dabelea, Dana, Smith, George Davey, De Boever, Patrick, Duijts, Liesbeth, Dwyer, Terence, Eng, Celeste, Eskenazi, Brenda, Everson, Todd M, Falahi, Fahimeh, Fallin, M Daniele, Farchi, Sara, Fernandez, Mariana F, Gao, Lu, Gaunt, Tom R, Ghantous, Akram, Gillman, Matthew W, Gonseth, Semira, Grote, Veit, Gruzieva, Olena, Håberg, Siri E, Herceg, Zdenko, Hivert, Marie-France, Holland, Nina, Holloway, John W, Hoyo, Cathrine, Hu, Donglei, Huang, Rae-Chi, Huen, Karen, Järvelin, Marjo-Riitta, Jima, Dereje D, Just, Allan C, Karagas, Margaret R, Karlsson, Robert, Karmaus, Wilfried, Kechris, Katerina J, Kere, Juha, Kogevinas, Manolis, Koletzko, Berthold, Koppelman, Gerard H, Küpers, Leanne K, Ladd-Acosta, Christine, Lahti, Jari, Lambrechts, Nathalie, Langie, Sabine AS, Lie, Rolv T, Liu, Andrew H, Magnus, Maria C, Magnus, Per, Maguire, Rachel L, Marsit, Carmen J, McArdle, Wendy, Melén, Erik, Melton, Phillip, Murphy, Susan K, Nawrot, Tim S, Nisticò, Lorenza, Nohr, Ellen A, Nordlund, Björn, Nystad, Wenche, Oh, Sam S, Oken, Emily, Page, Christian M, Perron, Patrice, Pershagen, Göran, Pizzi, Costanza, Plusquin, Michelle, Raikkonen, Katri, Reese, Sarah E, Reischl, Eva, Richiardi, Lorenzo, Ring, Susan, Roy, Ritu P, Rzehak, Peter, Schoeters, Greet, Schwartz, David A, Sebert, Sylvain, Snieder, Harold, Sørensen, Thorkild IA, and Starling, Anne P

Subjects
Epidemiology, Public Health, Health Sciences, Statistics, Mathematical Sciences, Child Health, Cohort Studies, DNA Methylation, Environmental Pollution, Epigenesis, Genetic, Female, Folic Acid, Humans, Infant, Newborn, Maternal Exposure, Maternal Health, Pregnancy, Prenatal Exposure Delayed Effects, Public Health and Health Services, Public health
Published
2018

43. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium

Author

Sharp, Gemma C, Salas, Lucas A, Monnereau, Claire, Allard, Catherine, Yousefi, Paul, Everson, Todd M, Bohlin, Jon, Xu, Zongli, Huang, Rae-Chi, Reese, Sarah E, Xu, Cheng-Jian, Baïz, Nour, Hoyo, Cathrine, Agha, Golareh, Roy, Ritu, Holloway, John W, Ghantous, Akram, Merid, Simon K, Bakulski, Kelly M, Küpers, Leanne K, Zhang, Hongmei, Richmond, Rebecca C, Page, Christian M, Duijts, Liesbeth, Lie, Rolv T, Melton, Phillip E, Vonk, Judith M, Nohr, Ellen A, Williams-DeVane, ClarLynda, Huen, Karen, Rifas-Shiman, Sheryl L, Ruiz-Arenas, Carlos, Gonseth, Semira, Rezwan, Faisal I, Herceg, Zdenko, Ekström, Sandra, Croen, Lisa, Falahi, Fahimeh, Perron, Patrice, Karagas, Margaret R, Quraishi, Bilal M, Suderman, Matthew, Magnus, Maria C, Jaddoe, Vincent WV, Taylor, Jack A, Anderson, Denise, Zhao, Shanshan, Smit, Henriette A, Josey, Michele J, Bradman, Asa, Baccarelli, Andrea A, Bustamante, Mariona, Håberg, Siri E, Pershagen, Göran, Hertz-Picciotto, Irva, Newschaffer, Craig, Corpeleijn, Eva, Bouchard, Luigi, Lawlor, Debbie A, Maguire, Rachel L, Barcellos, Lisa F, Smith, George Davey, Eskenazi, Brenda, Karmaus, Wilfried, Marsit, Carmen J, Hivert, Marie-France, Snieder, Harold, Fallin, M Daniele, Melén, Erik, Munthe-Kaas, Monica C, Arshad, Hasan, Wiemels, Joseph L, Annesi-Maesano, Isabella, Vrijheid, Martine, Oken, Emily, Holland, Nina, Murphy, Susan K, Sørensen, Thorkild IA, Koppelman, Gerard H, Newnham, John P, Wilcox, Allen J, Nystad, Wenche, London, Stephanie J, Felix, Janine F, and Relton, Caroline L

Subjects
Biological Sciences, Genetics, Perinatal Period - Conditions Originating in Perinatal Period, Contraception/Reproduction, Pediatric, Human Genome, Obesity, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Adult, Body Mass Index, Cohort Studies, DNA Methylation, Epigenesis, Genetic, Epigenomics, Female, Humans, Infant, Newborn, Male, Maternal Inheritance, Mothers, Pregnancy, Pregnancy Outcome, Prenatal Exposure Delayed Effects, Medical and Health Sciences, Genetics & Heredity
Abstract

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (

Published
2017

45. Contributions of prenatal risk factors and neonatal epigenetics to cognitive outcome in children born very preterm.

Author

Camerota, Marie, primary, Lester, Barry M., additional, McGowan, Elisabeth C., additional, Carter, Brian S., additional, Check, Jennifer, additional, Dansereau, Lynne M., additional, DellaGrotta, Sheri A., additional, Helderman, Jennifer B., additional, Hofheimer, Julie A., additional, Loncar, Cynthia M., additional, Neal, Charles R., additional, O'Shea, T. Michael, additional, Pastyrnak, Steven L., additional, Smith, Lynne M., additional, Abrishamcar, Sarina, additional, Hüls, Anke, additional, Marsit, Carmen J., additional, and Everson, Todd M., additional

Published
2024
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46. Transdisciplinary approaches enhance the production of translational knowledge

Author

Ciesielski, Timothy H, Aldrich, Melinda C, Marsit, Carmen J, Hiatt, Robert A, and Williams, Scott M

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Clinical Sciences, Biological Sciences, Clinical Research, Generic health relevance, Animals, Decision Making, Epidemiologists, Humans, Interdisciplinary Communication, Models, Biological, Translational Research, Biomedical, Translational Medical Research, General Clinical Medicine, Biochemistry and cell biology, Clinical sciences
Abstract

The primary goal of translational research is to generate and apply knowledge that can improve human health. Although research conducted within the confines of a single discipline has helped us to achieve this goal in many settings, this unidisciplinary approach may not be optimal when disease causation is complex and health decisions are pressing. To address these issues, we suggest that transdisciplinary approaches can facilitate the progress of translational research, and we review publications that demonstrate what these approaches can look like. These examples serve to (1) demonstrate why transdisciplinary research is useful, and (2) stimulate a conversation about how it can be further promoted. While we note that open-minded communication is a prerequisite for germinating any transdisciplinary work and that epidemiologists can play a key role in promoting it, we do not propose a rigid protocol for conducting transdisciplinary research, as one really does not exist. These achievements were developed in settings where typical disciplinary and institutional barriers were surmountable, but they were not accomplished with a single predetermined plan. The benefits of cross-disciplinary communication are hard to predict a priori and a detailed research protocol or process may impede the realization of novel and important insights. Overall, these examples demonstrate that enhanced cross-disciplinary information exchange can serve as a starting point that helps researchers frame better questions, integrate more relevant evidence, and advance translational knowledge more effectively. Specifically, we discuss examples where transdisciplinary approaches are helping us to better explore, assess, and intervene to improve human health.

Published
2017

47. 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

Author

Breton, Carrie V, Marsit, Carmen J, Faustman, Elaine, Nadeau, Kari, Goodrich, Jaclyn M, Dolinoy, Dana C, Herbstman, Julie, Holland, Nina, LaSalle, Janine M, Schmidt, Rebecca, Yousefi, Paul, Perera, Frederica, Joubert, Bonnie R, Wiemels, Joseph, Taylor, Michele, Yang, Ivana V, Chen, Rui, Hew, Kinjal M, Freeland, Deborah M Hussey, Miller, Rachel, and Murphy, Susan K

Subjects
Public Health, Health Sciences, Genetics, Human Genome, Pediatric, Prevention, Aetiology, 2.2 Factors relating to the physical environment, Generic health relevance, Good Health and Well Being, Child, Child Health, Child Welfare, DNA Methylation, Environmental Exposure, Environmental Health, Epigenesis, Genetic, Epigenomics, Female, Group Processes, Humans, Longitudinal Studies, Pregnancy, Research, Environmental Sciences, Medical and Health Sciences, Toxicology, Biomedical and clinical sciences, Environmental sciences, Health sciences
Abstract

BackgroundCharacterization of the epigenome is a primary interest for children's environmental health researchers studying the environmental influences on human populations, particularly those studying the role of pregnancy and early-life exposures on later-in-life health outcomes.ObjectivesOur objective was to consider the state of the science in environmental epigenetics research and to focus on DNA methylation and the collective observations of many studies being conducted within the Children's Environmental Health and Disease Prevention Research Centers, as they relate to the Developmental Origins of Health and Disease (DOHaD) hypothesis.MethodsWe address the current laboratory and statistical tools available for epigenetic analyses, discuss methods for validation and interpretation of findings, particularly when magnitudes of effect are small, question the functional relevance of findings, and discuss the future for environmental epigenetics research.DiscussionA common finding in environmental epigenetic studies is the small-magnitude epigenetic effect sizes that result from such exposures. Although it is reasonable and necessary that we question the relevance of such small effects, we present examples in which small effects persist and have been replicated across populations and across time. We encourage a critical discourse on the interpretation of such small changes and further research on their functional relevance for children's health.ConclusionThe dynamic nature of the epigenome will require an emphasis on future longitudinal studies in which the epigenome is profiled over time, over changing environmental exposures, and over generations to better understand the multiple ways in which the epigenome may respond to environmental stimuli.

Published
2017

48. DNA Methylation-Derived Neutrophil-to-Lymphocyte Ratio: An Epigenetic Tool to Explore Cancer Inflammation and Outcomes

Author

Koestler, Devin C, Usset, Joseph, Christensen, Brock C, Marsit, Carmen J, Karagas, Margaret R, Kelsey, Karl T, and Wiencke, John K

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Prevention, Genetics, Clinical Research, Patient Safety, Human Genome, Cancer, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Breast Neoplasms, Case-Control Studies, DNA Methylation, Epigenesis, Genetic, Female, Head and Neck Neoplasms, Humans, Inflammation, Leukocytes, Lymphocyte Count, Male, Middle Aged, Neutrophils, Ovarian Neoplasms, Proportional Hazards Models, Urinary Bladder Neoplasms, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract

Background: The peripheral blood neutrophil-to-lymphocyte ratio (NLR) is a cytologic marker of both inflammation and poor outcomes in patients with cancer. DNA methylation is a key element of the epigenetic program defining different leukocyte subtypes and may provide an alternative to cytology in assessing leukocyte profiles. Our aim was to create a bioinformatic tool to estimate NLR using DNA methylation, and to assess its diagnostic and prognostic performance in human populations.Methods: We developed a DNA methylation-derived NLR (mdNLR) index based on normal isolated leukocyte methylation libraries and established cell-mixture deconvolution algorithms. The method was applied to cancer case-control studies of the bladder, head and neck, ovary, and breast, as well as publicly available data on cancer-free subjects.Results: Across cancer studies, mdNLR scores were either elevated in cases relative to controls, or associated with increased hazard of death. High mdNLR values (>5) were strong indicators of poor survival. In addition, mdNLR scores were elevated in males, in nonHispanic white versus Hispanic ethnicity, and increased with age. We also observed a significant interaction between cigarette smoking history and mdNLR on cancer survival.Conclusions: These results mean that our current understanding of mature leukocyte methylomes is sufficient to allow researchers and clinicians to apply epigenetically based analyses of NLR in clinical and epidemiologic studies of cancer risk and survival.Impact: As cytologic measurements of NLR are not always possible (i.e., archival blood), mdNLR, which is computed from DNA methylation signatures alone, has the potential to expand the scope of epigenome-wide association studies. Cancer Epidemiol Biomarkers Prev; 26(3); 328-38. ©2016 AACR.

Published
2017

49. Epigenome-wide analysis identifies genes and pathways linked to acoustic cry variation in preterm infants

Author

Aghagoli, Ghazal, Sheinkopf, Stephen J., Everson, Todd M., Marsit, Carmen J., Lee, Hannah, Burt, Amber A., Carter, Brian S., Helderman, Jennifer B., Hofheimer, Julie A., McGowan, Elisabeth C., Neal, Charles R., O’Shea, T. Michael, Pastyrnak, Steven L., Smith, Lynne M., Soliman, Antoine, Dansereau, Lynne M., DellaGrotta, Sheri A., Padbury, James F., and Lester, Barry M.

Published
2021
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