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1. Maternal age is related to offspring DNA methylation: A meta‐analysis of results from the PACE consortium

Author

Yeung, Edwina, Biedrzycki, Richard J, Herrera, Laura C Gómez, Issarapu, Prachand, Dou, John, Marques, Irene Fontes, Mansuri, Sohail Rafik, Page, Christian Magnus, Harbs, Justin, Khodasevich, Dennis, Poisel, Eric, Niu, Zhongzheng, Allard, Catherine, Casey, Emma, Berstein, Fernanda Morales, Mancano, Giulia, Elliott, Hannah R, Richmond, Rebecca, He, Yiyan, Ronkainen, Justiina, Sebert, Sylvain, Bell, Erin M, Sharp, Gemma, Mumford, Sunni L, Schisterman, Enrique F, Chandak, Giriraj R, Fall, Caroline HD, Sahariah, Sirazul A, Silver, Matt J, Prentice, Andrew M, Bouchard, Luigi, Domellof, Magnus, West, Christina, Holland, Nina, Cardenas, Andres, Eskenazi, Brenda, Zillich, Lea, Witt, Stephanie H, Send, Tabea, Breton, Carrie, Bakulski, Kelly M, Fallin, M Daniele, Schmidt, Rebecca J, Stein, Dan J, Zar, Heather J, Jaddoe, Vincent WV, Wright, John, Grazuleviciene, Regina, Gutzkow, Kristine Bjerve, Sunyer, Jordi, Huels, Anke, Vrijheid, Martine, Harlid, Sophia, London, Stephanie, Hivert, Marie‐France, Felix, Janine, Bustamante, Mariona, and Guan, Weihua

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Prevention, Human Genome, Clinical Research, Women's Health, Aging, Pediatric, Good Health and Well Being, DNA Methylation, Humans, Female, Maternal Age, Infant, Newborn, Child, Adult, Male, Child, Preschool, CpG Islands, Pregnancy, aging, child, DNA methylation, melatonin, receptor, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR

Published
2024

2. Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence

Author

Choudhary, Priyanka, Monasso, Giulietta S, Karhunen, Ville, Ronkainen, Justiina, Mancano, Giulia, Howe, Caitlin G, Niu, Zhongzheng, Zeng, Xuehuo, Guan, Weihua, Dou, John, Feinberg, Jason I, Mordaunt, Charles, Pesce, Giancarlo, Baïz, Nour, Alfano, Rossella, Martens, Dries S, Wang, Congrong, Isaevska, Elena, Keikkala, Elina, Mustaniemi, Sanna, Thio, Chris HL, Fraszczyk, Eliza, Tobi, Elmar W, Starling, Anne P, Cosin-Tomas, Marta, Urquiza, Jose, Röder, Stefan, Hoang, Thanh T, Page, Christian, Jima, Dereje D, House, John S, Maguire, Rachel L, Ott, Raffael, Pawlow, Xenia, Sirignano, Lea, Zillich, Lea, Malmberg, Anni, Rauschert, Sebastian, Melton, Phillip, Gong, Tong, Karlsson, Robert, Fore, Ruby, Perng, Wei, Laubach, Zachary M, Czamara, Darina, Sharp, Gemma, Breton, Carrie V, Schisterman, Enrique, Yeung, Edwina, Mumford, Sunni L, Fallin, M Daniele, LaSalle, Janine M, Schmidt, Rebecca J, Bakulski, Kelly M, Annesi-Maesano, Isabella, Heude, Barbara, Nawrot, Tim S, Plusquin, Michelle, Ghantous, Akram, Herceg, Zdenko, Nisticò, Lorenza, Vafeiadi, Marina, Kogevinas, Manolis, Vääräsmäki, Marja, Kajantie, Eero, Snieder, Harold, Corpeleijn, Eva, Steegers-Theunissen, Regine PM, Yang, Ivana V, Dabelea, Dana, Fossati, Serena, Zenclussen, Ana C, Herberth, Gunda, Magnus, Maria, Håberg, Siri E, London, Stephanie J, Munthe-Kaas, Monica Cheng, Murphy, Susan K, Hoyo, Cathrine, Ziegler, Anette-G, Hummel, Sandra, Witt, Stephanie H, Streit, Fabian, Frank, Josef, Räikkönen, Katri, Lahti, Jari, Huang, Rae-chi, Almqvist, Catarina, Hivert, Marie-France, Jaddoe, Vincent WV, Järvelin, Marjo-Riitta, Kantomaa, Marko, Felix, Janine F, and Sebert, Sylvain

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Prevention, Nutrition, Women's Health, Maternal Health, Human Genome, Pediatric, Social Determinants of Health, Genetics, Pregnancy, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, 1.1 Normal biological development and functioning, Generic health relevance, Reproductive health and childbirth, Good Health and Well Being, Humans, DNA Methylation, Female, Adolescent, Epigenome, Child, Educational Status, Male, Genome-Wide Association Study, Epigenesis, Genetic, Prenatal Exposure Delayed Effects, Child, Preschool, Infant, Mothers, Infant, Newborn, Adult, Academic Success, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.

Published
2024

4. Sperm epigenetic clock associates with pregnancy outcomes in the general population.

Author

Pilsner, J Richard, Saddiki, Hachem, Whitcomb, Brian W, Suvorov, Alexander, Buck Louis, Germaine M, Mumford, Sunni L, Schisterman, Enrique F, Oluwayiose, Oladele A, and Balzer, Laura B

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Prevention, Aging, Clinical Research, Contraception/Reproduction, Reproductive health and childbirth, Child, Epigenesis, Genetic, Female, Humans, Male, Pregnancy, Pregnancy Outcome, Prospective Studies, Semen, Spermatozoa, Time-to-Pregnancy, sperm epigenetic clock, aging, methylation, infertility, pregnancy, machine learning, Medical and Health Sciences, Studies in Human Society, Obstetrics & Reproductive Medicine, Reproductive medicine
Abstract

Study questionIs sperm epigenetic aging (SEA) associated with probability of pregnancy among couples in the general population?Summary answerWe observed a 17% lower cumulative probability at 12 months for couples with male partners in the older compared to the younger SEA categories.What is known alreadyThe strong relation between chronological age and DNA methylation profiles has enabled the estimation of biological age as epigenetic 'clock' metrics in most somatic tissue. Such clocks in male germ cells are less developed and lack clinical relevance in terms of their utility to predict reproductive outcomes.Study design, size, durationThis was a population-based prospective cohort study of couples discontinuing contraception to become pregnant recruited from 16 US counties from 2005 to 2009 and followed for up to 12 months.Participants/materials, setting, methodsSperm DNA methylation from 379 semen samples was assessed via a beadchip array. A state-of-the-art ensemble machine learning algorithm was employed to predict age from the sperm DNA methylation data. SEA was estimated from clocks derived from individual CpGs (SEACpG) and differentially methylated regions (SEADMR). Probability of pregnancy within 1 year was compared by SEA, and discrete-time proportional hazards models were used to evaluate the relations with time-to-pregnancy (TTP) with adjustment for covariates.Main results and the role of chanceOur SEACpG clock had the highest predictive performance with correlation between chronological and predicted age (r = 0.91). In adjusted discrete Cox models, SEACpG was negatively associated with TTP (fecundability odds ratios (FORs)=0.83; 95% CI: 0.76, 0.90; P = 1.2×10-5), indicating a longer TTP with advanced SEACpG. For subsequent birth outcomes, advanced SEACpG was associated with shorter gestational age (n = 192; -2.13 days; 95% CI: -3.67, -0.59; P = 0.007). Current smokers also displayed advanced SEACpG (P

Published
2022

6. A Call for Quality: Substandard Research in Male Sexual and Reproductive Medicine During the COVID-19 Pandemic

Author

Pastuszak, Alexander W, Patel, Darshan P, Jenkins, Lawrence C, Hsieh, Tung-Chin, Yafi, Faysal A, Mumford, Sunni L, Mulhall, John P, and Hotaling, James M

Subjects
Biomedical and Clinical Sciences, Health Sciences, Psychology, Good Health and Well Being, COVID-19, Humans, Male, Pandemics, Reproductive Medicine, SARS-CoV-2, Sexual Behavior, Medical and Health Sciences, Psychology and Cognitive Sciences, Obstetrics & Reproductive Medicine, Biomedical and clinical sciences, Health sciences
Published
2022

7. Preconception Phthalate Exposure and Women's Reproductive Health: Pregnancy, Pregnancy Loss, and Underlying Mechanisms

Author

Nobles, Carrie J., Mendola, Pauline, Kim, Keewan, Pollack, Anna Z., Mumford, Sunni L., Perkins, Neil J., Silver, Robert M., and Schisterman, Enrique F.

Subjects
Phthalates -- Health aspects -- Statistics, Pregnancy, Complications of -- Risk factors -- Statistics -- Environmental aspects, Reproductive health -- Environmental aspects, Environmental issues, Health
Abstract

Background: Phthalates are endocrine-disrupting chemicals linked to adverse pregnancy outcomes. Despite the sensitivity of female reproductive processes to oxidation-reduction reaction stress and endocrine disruption, evidence for the impact of women's phthalate exposure on the ability to establish and maintain pregnancy has been inconclusive. Objectives: We aimed to determine the relationship of preconception phthalate metabolite exposure with a) fecundability and pregnancy loss and b) markers of potential biological mechanisms, including reproductive hormones, inflammation, and oxidative stress. Methods: Data were collected from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, a preconception study following 1,228 women who were attempting pregnancy, for up to six menstrual cycles and throughout pregnancy if they became pregnant. Twenty phthalate metabolites were measured in a consecutive 3-d pooled urine sample at enrollment. Pregnancy was determined through urinary human chorionic gonadotropin (hCG) at the expected date of menses during each cycle and pregnancy loss as an observed loss following positive hCG. Highly sensitive C-reactive protein (hsCRP) and isoprostanes were measured at enrollment, and reproductive hormones were measured during the follicular phase, ovulation, and luteal phase. Discrete-time Cox proportional hazards models evaluated the relationship of phthalate metabolites with fecundability and weighted Poisson models with robust variance evaluated the risk of pregnancy loss. Results: An interquartile range (IQR) higher mono-(2-ethylhexyl) phthalate [fecundability odds ratio (FOR) =0.88; 95% confidence interval (CI): 0.78, 1.00], mono-butyl phthalate (FOR = 0.82; 95% CI: 0.70, 0.96), and mono-benzyl phthalate (FOR = 0.85; 95% CI: 0.74, 0.98) was associated with lower fecundability. No consistent associations were observed with pregnancy loss. Preconception phthalates were consistently associated with higher hsCRP and isoprostanes, as well as lower estradiol and higher follicle-stimulating hormone across the menstrual cycle. Discussion: Women's preconception exposure to phthalates was associated with lower fecundability, changes in reproductive hormones, and increased inflammation and oxidative stress. The pre- and periconception periods may represent sensitive windows for intervening to limit the reproductive toxicity of phthalate exposure. https://doi.org/10.1289/EHP12287, Introduction Phthalates are esters of 1,2-benzene dicarboxylic acid commonly used as plasticizers in polyvinyl chloride and as stabilizers in many personal care products. Common sources of phthalate exposure include inhalation [...]

Published
2023
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12. The impact of zinc and folic acid supplementation on sperm DNA methylation: results from the folic acid and zinc supplementation randomized clinical trial (FAZST)

Author

Jenkins, Tim, Aston, Kenneth, Carrell, Douglas, DeVilbiss, Elizabeth, Sjaarda, Lindsey, Perkins, Neil, Mills, James L., Chen, Zhen, Sparks, Amy, Clemons, Traci, Chaney, Kayla, Peterson, C. Matthew, Emery, Benjamin, Hotaling, Jim, Johnstone, Erica, Schisterman, Enrique, and Mumford, Sunni L.

Published
2022
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18. Examination of newborn DNA methylation among women with polycystic ovary syndrome/hirsutism

Author

Polinski, Kristen J., primary, Robinson, Sonia L., additional, Putnick, Diane L., additional, Sundaram, Rajeshwari, additional, Bell, Erin, additional, Joseph, Paule V., additional, Segars, James, additional, Guan, Weihua, additional, Silver, Robert M., additional, Schisterman, Enrique F., additional, Mumford, Sunni L., additional, and Yeung, Edwina H., additional

Published
2023
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22. Bayesian inference on dependence in multivariate longitudinal data

Author

Yang, Hongxia, Li, Fan, Schisterman, Enrique F., Mumford, Sunni L., and Dunson, David

Subjects
Statistics - Applications
Abstract

In many applications, it is of interest to assess the dependence structure in multivariate longitudinal data. Discovering such dependence is challenging due to the dimensionality involved. By concatenating the random effects from component models for each response, dependence within and across longitudinal responses can be characterized through a large random effects covariance matrix. Motivated by the common problems in estimating this matrix, especially the off-diagonal elements, we propose a Bayesian approach that relies on shrinkage priors for parameters in a modified Cholesky decomposition. Without adjustment, such priors and previous related approaches are order-dependent and tend to shrink strongly toward an ARtype structure. We propose moment-matching (MM) priors to mitigate such problems. Efficient Gibbs samplers are developed for posterior computation. The methods are illustrated through simulated examples and are applied to a longitudinal epidemiologic study of hormones and oxidative stress., Comment: 31 pages, 6 figures

Published
2012

25. Tissue-specific DNA methylation variability and its potential clinical value

Author

Miller, Ryan H., primary, Pollard, Chad A., additional, Brogaard, Kristin R., additional, Olson, Andrew C., additional, Barney, Ryan C., additional, Lipshultz, Larry I., additional, Johnstone, Erica B., additional, Ibrahim, Yetunde O., additional, Hotaling, James M., additional, Schisterman, Enrique F., additional, Mumford, Sunni L., additional, Aston, Kenneth I., additional, and Jenkins, Tim G., additional

Published
2023
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26. Large-Scale Data Harmonization Across Prospective Studies

Author

Pan, Ke, primary, Bazzano, Lydia A, additional, Betha, Kalpana, additional, Charlton, Brittany M, additional, Chavarro, Jorge E, additional, Cordero, Christina, additional, Gunderson, Erica P, additional, Haggerty, Catherine L, additional, Hart, Jaime E, additional, Jukic, Anne Marie, additional, Ley, Sylvia H, additional, Mishra, Gita D, additional, Mumford, Sunni L, additional, Schisterman, Enrique F, additional, Schliep, Karen, additional, Shaffer, Jeffrey G, additional, Sotres-Alvarez, Daniela, additional, Stanford, Joseph B, additional, Wilcox, Allen J, additional, Wise, Lauren A, additional, Yeung, Edwina, additional, and Harville, Emily W, additional

Published
2023
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29. Pregnancy Complications and Long-Term Mortality in a Diverse Cohort

Author

Hinkle, Stefanie N., primary, Schisterman, Enrique F., additional, Liu, Danping, additional, Pollack, Anna Z., additional, Yeung, Edwina H., additional, Mumford, Sunni L., additional, Grantz, Katherine L., additional, Qiao, Yan, additional, Perkins, Neil J., additional, Mills, James L., additional, Mendola, Pauline, additional, and Zhang, Cuilin, additional

Published
2023
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31. Preconception sleep duration, sleep timing, and shift work in association with fecundability and live birth among women with a history of pregnancy loss

Author

Freeman, Joshua R., primary, Whitcomb, Brian W., additional, Bertone-Johnson, Elizabeth R., additional, Balzer, Laura B., additional, O’Brien, Louise M., additional, Dunietz, Galit L., additional, Purdue-Smithe, Alexandra C., additional, Kim, Keewan, additional, Silver, Robert M., additional, Schisterman, Enrique F., additional, and Mumford, Sunni L., additional

Published
2023
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32. Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence

Author

Choudhary, Priyanka, Monasso, Giulietta S., Karhunen, Ville, Ronkainen, Justiina, Mancano, Giulia, Howe, Caitlin G., Niu, Zhongzheng, Zeng, Xuehuo, Guan, Weihua, Dou, John, Feinberg, Jason I., Mordaunt, Charles, Pesce, Giancarlo, Baïz, Nour, Alfano, Rossella, Martens, Dries S., Wang, Congrong, Isaevska, Elena, Keikkala, Elina, Mustaniemi, Sanna, Thio, Chris H. L., Fraszczyk, Eliza, Tobi, Elmar W., Starling, Anne P., Cosin-Tomas, Marta, Urquiza, Jose, Röder, Stefan, Hoang, Thanh T., Page, Christian, Jima, Dereje D., House, John S., Maguire, Rachel L., Ott, Raffael, Pawlow, Xenia, Sirignano, Lea, Zillich, Lea, Malmberg, Anni, Rauschert, Sebastian, Melton, Phillip, Gong, Tong, Karlsson, Robert, Fore, Ruby, Perng, Wei, Laubach, Zachary M., Czamara, Darina, Sharp, Gemma, Breton, Carrie V., Schisterman, Enrique, Yeung, Edwina, Mumford, Sunni L., Fallin, M. Daniele, LaSalle, Janine M., Schmidt, Rebecca J., Bakulski, Kelly M., Annesi-Maesano, Isabella, Heude, Barbara, Nawrot, Tim S., Plusquin, Michelle, Ghantous, Akram, Herceg, Zdenko, Nisticò, Lorenza, Vafeiadi, Marina, Kogevinas, Manolis, Vääräsmäki, Marja, Kajantie, Eero, Snieder, Harold, Corpeleijn, Eva, Steegers-Theunissen, Regine P. M., Yang, Ivana V., Dabelea, Dana, Fossati, Serena, Zenclussen, Ana C., Herberth, Gunda, Magnus, Maria, Håberg, Siri E., London, Stephanie J., Munthe-Kaas, Monica C., Murphy, Susan K., Hoyo, Cathrine, Ziegler, Anette-G, Hummel, Sandra, Witt, Stephanie H., Streit, Fabian, Frank, Josef, Räikkönen, Katri, Lahti, Jari, Huang, Rae-chi, Almqvist, Catarina, Hivert, Marie-France, Jaddoe, Vincent W. V., Järvelin, Marjo-Riitta, Kantomaa, Marko, Felix, Janine F., Sebert, Sylvain, Choudhary, Priyanka, Monasso, Giulietta S., Karhunen, Ville, Ronkainen, Justiina, Mancano, Giulia, Howe, Caitlin G., Niu, Zhongzheng, Zeng, Xuehuo, Guan, Weihua, Dou, John, Feinberg, Jason I., Mordaunt, Charles, Pesce, Giancarlo, Baïz, Nour, Alfano, Rossella, Martens, Dries S., Wang, Congrong, Isaevska, Elena, Keikkala, Elina, Mustaniemi, Sanna, Thio, Chris H. L., Fraszczyk, Eliza, Tobi, Elmar W., Starling, Anne P., Cosin-Tomas, Marta, Urquiza, Jose, Röder, Stefan, Hoang, Thanh T., Page, Christian, Jima, Dereje D., House, John S., Maguire, Rachel L., Ott, Raffael, Pawlow, Xenia, Sirignano, Lea, Zillich, Lea, Malmberg, Anni, Rauschert, Sebastian, Melton, Phillip, Gong, Tong, Karlsson, Robert, Fore, Ruby, Perng, Wei, Laubach, Zachary M., Czamara, Darina, Sharp, Gemma, Breton, Carrie V., Schisterman, Enrique, Yeung, Edwina, Mumford, Sunni L., Fallin, M. Daniele, LaSalle, Janine M., Schmidt, Rebecca J., Bakulski, Kelly M., Annesi-Maesano, Isabella, Heude, Barbara, Nawrot, Tim S., Plusquin, Michelle, Ghantous, Akram, Herceg, Zdenko, Nisticò, Lorenza, Vafeiadi, Marina, Kogevinas, Manolis, Vääräsmäki, Marja, Kajantie, Eero, Snieder, Harold, Corpeleijn, Eva, Steegers-Theunissen, Regine P. M., Yang, Ivana V., Dabelea, Dana, Fossati, Serena, Zenclussen, Ana C., Herberth, Gunda, Magnus, Maria, Håberg, Siri E., London, Stephanie J., Munthe-Kaas, Monica C., Murphy, Susan K., Hoyo, Cathrine, Ziegler, Anette-G, Hummel, Sandra, Witt, Stephanie H., Streit, Fabian, Frank, Josef, Räikkönen, Katri, Lahti, Jari, Huang, Rae-chi, Almqvist, Catarina, Hivert, Marie-France, Jaddoe, Vincent W. V., Järvelin, Marjo-Riitta, Kantomaa, Marko, Felix, Janine F., and Sebert, Sylvain

Abstract

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.

Published
2023

49. Gender Influences on Editorial Decisions at Epidemiology

Author

Kiang, Chrystelle, Kaufman, Jay S., London, Stephanie J., Mumford, Sunni L., Swanson, Sonja A., Lash, Timothy L., Kiang, Chrystelle, Kaufman, Jay S., London, Stephanie J., Mumford, Sunni L., Swanson, Sonja A., and Lash, Timothy L.

Published
2022

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