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1. Correlates of lifestyle patterns among children in Singapore aged 10 years: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study

Author

Tan, Sarah Yi Xuan, Chia, Airu, Tai, Bee Choo, Toh, Jia Ying, Colega, Marjorelee, Padmapriya, Natarajan, Setoh, Peipei, Kee, Michelle Zhi Ling, Yuan, Wen Lun, Lee, Yung Seng, Loo, Benny Kai Guo, Yap, Fabian Kok Peng, Tan, Kok Hian, Godfrey, Keith M., Chong, Yap Seng, Eriksson, Johan, Müller-Riemenschneider, Falk, and Chong, Mary Foong-Fong

Published
2024
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3. A machine-learning exploration of the exposome from preconception in early childhood atopic eczema, rhinitis and wheeze development

Author

Dong, Yizhi, Lau, Hui Xing, Suaini, Noor Hidayatul Aini, Kee, Michelle Zhi Ling, Ooi, Delicia Shu Qin, Shek, Lynette Pei-chi, Lee, Bee Wah, Godfrey, Keith M., Tham, Elizabeth Huiwen, Ong, Marcus Eng Hock, Liu, Nan, Wong, Limsoon, Tan, Kok Hian, Chan, Jerry Kok Yen, Yap, Fabian Kok Peng, Chong, Yap Seng, Eriksson, Johan Gunnar, Feng, Mengling, and Loo, Evelyn Xiu Ling

Published
2024
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5. Seemingly Unrelated Multi-State processes: a Bayesian semiparametric approach

Author

Cremaschi, Andrea, Argiento, Raffele, De Iorio, Maria, Shirong, Cai, Chong, Yap Seng, Meaney, Michael J., and Kee, Michelle Z. L.

Subjects
Statistics - Methodology
Abstract

Many applications in medical statistics as well as in other fields can be described by transitions between multiple states (e.g. from health to disease) experienced by individuals over time. In this context, multi-state models are a popular statistical technique, in particular when the exact transition times are not observed. The key quantities of interest are the transition rates, capturing the instantaneous risk of moving from one state to another. The main contribution of this work is to propose a joint semiparametric model for several possibly related multi-state processes (Seemingly Unrelated Multi-State, SUMS, processes), assuming a Markov structure for the transitions over time. The dependence between different processes is captured by specifying a joint random effect distribution on the transition rates of each process. We assume a flexible random effect distribution, which allows for clustering of the individuals, overdispersion and outliers. Moreover, we employ a graph structure to describe the dependence among processes, exploiting tools from the Gaussian Graphical model literature. It is also possible to include covariate effects. We use our approach to model disease progression in mental health. Posterior inference is performed through a specially devised MCMC algorithm.

Published
2021

6. The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells.

Author

McEwen, Lisa M, O'Donnell, Kieran J, McGill, Megan G, Edgar, Rachel D, Jones, Meaghan J, MacIsaac, Julia L, Lin, David Tse Shen, Ramadori, Katia, Morin, Alexander, Gladish, Nicole, Garg, Elika, Unternaehrer, Eva, Pokhvisneva, Irina, Karnani, Neerja, Kee, Michelle ZL, Klengel, Torsten, Adler, Nancy E, Barr, Ronald G, Letourneau, Nicole, Giesbrecht, Gerald F, Reynolds, James N, Czamara, Darina, Armstrong, Jeffrey M, Essex, Marilyn J, de Weerth, Carolina, Beijers, Roseriet, Tollenaar, Marieke S, Bradley, Bekh, Jovanovic, Tanja, Ressler, Kerry J, Steiner, Meir, Entringer, Sonja, Wadhwa, Pathik D, Buss, Claudia, Bush, Nicole R, Binder, Elisabeth B, Boyce, W Thomas, Meaney, Michael J, Horvath, Steve, and Kobor, Michael S

Subjects
Mouth Mucosa, Epithelial Cells, Humans, Cohort Studies, Longitudinal Studies, Epigenesis, Genetic, CpG Islands, Adolescent, Adult, Child, Child, Preschool, Infant, Female, Male, Young Adult, Epigenomics, DNA methylation, adolescence, age, development, epigenetic clock, Human Genome, Genetics, Pediatric, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Good Health and Well Being
Abstract

The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several age-related phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this gap, we aimed to develop a highly accurate, noninvasive, biological measure of age specific to pediatric samples using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032), with performance assessed in a separate test dataset (n = 689). DNAm at these 94 CpG sites was highly predictive of age in the test cohort (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease.

Published
2020

8. Perinatal Trajectories of Maternal Depressive Symptoms in Prospective, Community-Based Cohorts Across 3 Continents

Author

Kee, Michelle Z. L., primary, Cremaschi, Andrea, additional, De Iorio, Maria, additional, Chen, Helen, additional, Montreuil, Tina, additional, Nguyen, Tuong Vi, additional, Côté, Sylvana M., additional, O’Donnell, Kieran J., additional, Giesbrecht, Gerald F., additional, Letourneau, Nicole, additional, Chan, Shiao Yng, additional, and Meaney, Michael J., additional

Published
2023
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9. Safety, Tolerability, and Pharmacokinetics of β-Cryptoxanthin Supplementation in Healthy Women: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial

Author

Tan, Karen M. L., primary, Chee, Jolene, additional, Lim, Kezlyn L. M., additional, Ng, Maisie, additional, Gong, Min, additional, Xu, Jia, additional, Tin, Felicia, additional, Natarajan, Padmapriya, additional, Lee, Bee Lan, additional, Ong, Choon Nam, additional, Tint, Mya Thway, additional, Kee, Michelle Z. L., additional, Müller-Riemenschneider, Falk, additional, Gluckman, Peter D., additional, Meaney, Michael J., additional, Kumar, Mukkesh, additional, Karnani, Neerja, additional, Eriksson, Johan G., additional, Nandanan, Bindu, additional, Wyss, Adrian, additional, and Cameron-Smith, David, additional

Published
2023
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10. Seemingly Unrelated Multi-State Processes: A Bayesian Semiparametric Approach.

Author

Cremaschi, Andrea, Argiento, Raffaele, De Iorio, Maria, Shirong, Cai, Yap Seng Chong, Meaney, Michael, and Kee, Michelle

Subjects
MEDICAL statistics, BAYESIAN analysis, PARAMETRIC modeling, GAUSSIAN distribution, MARKOV chain Monte Carlo
Abstract

Many applications in medical statistics and other fields can be described by transitions between multiple states (e.g. from health to disease) experienced by individuals over time. In this context, multi-state models are a popular statistical technique, in particular when the exact transition times are not observed. The key quantities of interest are the transition rates, capturing the instantaneous risk of moving from one state to another. The main contribution of this work is to propose a joint semiparametric model for several possibly related multi-state processes (Seemingly Unrelated Multi-State, SUMS, processes), assuming a Markov structure for the transitions over time. The dependence between different processes is captured by specifying a joint prior distribution on the transition rates of each process. In this case, we assume a flexible distribution, which allows for clustering of the individuals, overdispersion and outliers. Moreover, we employ a graph structure to describe the dependence among processes, exploiting tools from the Gaussian Graphical model literature. It is also possible to include covariate effects. We use our approach to model disease progression in mental health. Posterior inference is performed through a specially devised MCMC algorithm. [ABSTRACT FROM AUTHOR]

Published
2023
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12. Associations Between Maternal Distress During Early Life Periods and Offspring Respiratory Infections and Allergic Outcomes

Author

Lau, Hui Xing, Kee, Michelle Zhi Ling, Yap, Qai Ven, Tham, Elizabeth Huiwen, Chan, Yiong Huak, Goh, Anne Eng Neo, Teoh, Oon Hoe, Eriksson, Johan G., Godfrey, Keith, Gluckman, Peter D., Chong, Yap-Seng, Chan, Jerry KY, van Bever, Hugo, Lee, Bee Wah, Shek, Lynette Pei-Chi, Meaney, Michael J., Loo, Evelyn Xiu-Ling, Clinicum, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, and University of Helsinki

Subjects
RISK, postnatal, preconception, maternal distress, allergic sensitization, rhinitis, PRENATAL STRESS, PREGNANCY, 3123 Gynaecology and paediatrics, wheeze, Pediatrics, Perinatology and Child Health, ATOPIC-DERMATITIS, ASTHMA, ANXIETY, CHILDHOOD ECZEMA, eczema, PITUITARY-ADRENAL AXIS, PSYCHOLOGICAL DISTRESS, MULTIDIMENSIONAL SCALE
Abstract

BackgroundIncreasing evidence suggests that maternal distress is a risk factor for development of respiratory infections and allergic diseases in the offspring. We aim to evaluate the link between maternal distress during critical periods in early life, namely the preconception, pregnancy and postnatal periods, and development of respiratory infections and allergic diseases in the offspring from the Singapore PREconception Study of long Term maternal and child Outcomes (S-PRESTO) cohort.MethodsMaternal perceived distress was evaluated using validated questionnaires including Beck Depression Inventory-II (BDI-II) administered during three time periods: preconception (three months apart at four timepoints), pregnancy (during each trimester) and postnatal (3 and 6 months post-delivery). Child eczema, rhinitis and wheeze outcomes were evaluated using a modified ISAAC questionnaire at ages 3, 6, 12, and 18 months. Child allergic sensitization was determined by skin prick testing at 18 months.ResultsAmong 332 mother-child pairs studied, higher maternal distress during preconception and pregnancy increased the risks of wheeze development in the first 18 months; for example, preconception and pregnancy BDI-II scores ≥20 were associated with increased risks of wheeze by 18 months [adjusted risk ratios 3.2 (95%CI 1.1–9.4) and 2.5 (1.0–5.9), respectively]. Emotional and practical support from family during preconception decreased the risks of offspring wheeze. No associations were observed between maternal distress and offspring eczema, rhinitis and allergic sensitization.ConclusionMaternal distress during critical early life periods was associated with offspring wheeze in the first 18 months of life. Supporting maternal mental health even before pregnancy could reduce the risk of offspring wheeze.

Published
2022

16. The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells

Author

McEwen, Lisa M., primary, O’Donnell, Kieran J., additional, McGill, Megan G., additional, Edgar, Rachel D., additional, Jones, Meaghan J., additional, MacIsaac, Julia L., additional, Lin, David Tse Shen, additional, Ramadori, Katia, additional, Morin, Alexander, additional, Gladish, Nicole, additional, Garg, Elika, additional, Unternaehrer, Eva, additional, Pokhvisneva, Irina, additional, Karnani, Neerja, additional, Kee, Michelle Z. L., additional, Klengel, Torsten, additional, Adler, Nancy E., additional, Barr, Ronald G., additional, Letourneau, Nicole, additional, Giesbrecht, Gerald F., additional, Reynolds, James N., additional, Czamara, Darina, additional, Armstrong, Jeffrey M., additional, Essex, Marilyn J., additional, de Weerth, Carolina, additional, Beijers, Roseriet, additional, Tollenaar, Marieke S., additional, Bradley, Bekh, additional, Jovanovic, Tanja, additional, Ressler, Kerry J., additional, Steiner, Meir, additional, Entringer, Sonja, additional, Wadhwa, Pathik D., additional, Buss, Claudia, additional, Bush, Nicole R., additional, Binder, Elisabeth B., additional, Boyce, W. Thomas, additional, Meaney, Michael J., additional, Horvath, Steve, additional, and Kobor, Michael S., additional

Published
2019
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17. Probing the function of neuronal populations : combining micromirror-based optogenetic photostimulation with voltage-sensitive dye imaging

Author

Tsuda, Sachiko, Kee, Michelle Z. L., Cunha, Catarina, Kim, Jinsook, Yan, Ping, Loew, Leslie M., Augustine, George J., Tsuda, Sachiko, Kee, Michelle Z. L., Cunha, Catarina, Kim, Jinsook, Yan, Ping, Loew, Leslie M., and Augustine, George J.

Abstract

Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Neuroscience Research 75 (2013): 76-81, doi:10.1016/j.neures.2012.11.006., Recent advances in our understanding of brain function have come from using light to either control or image neuronal activity. Here we describe an approach that combines both techniques: a micromirror array is used to photostimulate populations of presynaptic neurons expressing channelrhodopsin-2, while a red-shifted voltage-sensitive dye allows optical detection of resulting postsynaptic activity. Such technology allowed us to control the activity of cerebellar interneurons while simultaneously recording inhibitory responses in multiple Purkinje neurons, their postsynaptic targets. This approach should substantially accelerate our understanding of information processing by populations of neurons within brain circuits., This work was supported by a Grass Foundation fellowship, National Institutes of Health (NIH grant: R01 EB001963), Duke‐NUS Signature Research Program (SRP) block grant, CRP grant from the National Research Foundation (Singapore) and by the World Class Institute (WCI) Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology of Korea (MEST) (NRF Grant Number: WCI 2009-003).

Published
2013

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