186 results on '"Mulder, Rosa"'
Search Results
2. Fairness and bias correction in machine learning for depression prediction: results from four study populations
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Dang, Vien Ngoc, Cascarano, Anna, Mulder, Rosa H., Cecil, Charlotte, Zuluaga, Maria A., Hernández-González, Jerónimo, and Lekadir, Karim
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Computer Science - Machine Learning ,Computer Science - Computers and Society - Abstract
A significant level of stigma and inequality exists in mental healthcare, especially in under-served populations. Inequalities are reflected in the data collected for scientific purposes. When not properly accounted for, machine learning (ML) models leart from data can reinforce these structural inequalities or biases. Here, we present a systematic study of bias in ML models designed to predict depression in four different case studies covering different countries and populations. We find that standard ML approaches show regularly biased behaviors. We also show that mitigation techniques, both standard and our own post-hoc method, can be effective in reducing the level of unfair bias. No single best ML model for depression prediction provides equality of outcomes. This emphasizes the importance of analyzing fairness during model selection and transparent reporting about the impact of debiasing interventions. Finally, we provide practical recommendations to develop bias-aware ML models for depression risk prediction., Comment: 11 pages, 2 figures
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- 2022
3. Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation
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Kotsakis Ruehlmann, Anna, Sammallahti, Sara, Cortés Hidalgo, Andrea P., Bakulski, Kelly M., Binder, Elisabeth B., Campbell, Megan Loraine, Caramaschi, Doretta, Cecil, Charlotte A. M., Colicino, Elena, Cruceanu, Cristiana, Czamara, Darina, Dieckmann, Linda, Dou, John, Felix, Janine F., Frank, Josef, Håberg, Siri E., Herberth, Gunda, Hoang, Thanh T., Houtepen, Lotte C., Hüls, Anke, Koen, Nastassja, London, Stephanie J., Magnus, Maria C., Mancano, Giulia, Mulder, Rosa H., Page, Christian M., Räikkönen, Katri, Röder, Stefan, Schmidt, Rebecca J., Send, Tabea S., Sharp, Gemma, Stein, Dan J., Streit, Fabian, Tuhkanen, Johanna, Witt, Stephanie H., Zar, Heather J., Zenclussen, Ana C., Zhang, Yining, Zillich, Lea, Wright, Rosalind, Lahti, Jari, and Brunst, Kelly J.
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- 2023
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4. Prenatal exposure to common infections and newborn DNA methylation: A prospective, population-based study
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Suleri, Anna, Salontaji, Kristina, Luo, Mannan, Neumann, Alexander, Mulder, Rosa H., Tiemeier, Henning, Felix, Janine F., Marioni, Riccardo E., Bergink, Veerle, and Cecil, Charlotte A.M.
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- 2024
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5. Early-life stress and the gut microbiome: A comprehensive population-based investigation
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Mulder, Rosa H., Kraaij, Robert, Schuurmans, Isabel K., Frances-Cuesta, Carlos, Sanz, Yolanda, Medina-Gomez, Carolina, Duijts, Liesbeth, Rivadeneira, Fernando, Tiemeier, Henning, Jaddoe, Vincent W.V., Felix, Janine F., and Cecil, Charlotte A.M.
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- 2024
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6. Facing ostracism: micro-coding facial expressions in the Cyberball social exclusion paradigm
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Mulder, Rosa H., Bakermans-Kranenburg, Marian J., Veenstra, Johan, Tiemeier, Henning, and van IJzendoorn, Marinus H.
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- 2023
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7. Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills
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Caramaschi, Doretta, Neumann, Alexander, Cardenas, Andres, Tindula, Gwen, Alemany, Silvia, Zillich, Lea, Pesce, Giancarlo, Lahti, Jari MT, Havdahl, Alexandra, Mulder, Rosa, Felix, Janine F, Tiemeier, Henning, Sirignano, Lea, Frank, Josef, Witt, Stephanie H, Rietschel, Marcella, Deuschle, Michael, Huen, Karen, Eskenazi, Brenda, Send, Tabea Sarah, Ferrer, Muriel, Gilles, Maria, de Agostini, Maria, Baïz, Nour, Rifas-Shiman, Sheryl L, Kvist, Tuomas, Czamara, Darina, Tuominen, Samuli T, Relton, Caroline L, Rai, Dheeraj, London, Stephanie J, Räikkönen, Katri, Holland, Nina, Annesi-Maesano, Isabella, Streit, Fabian, Hivert, Marie-France, Oken, Emily, Sunyer, Jordi, Cecil, Charlotte AM, and Sharp, Gemma
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Biological Psychology ,Reproductive Medicine ,Biomedical and Clinical Sciences ,Psychology ,Clinical Research ,Pediatric ,Human Genome ,Behavioral and Social Science ,Pediatric Research Initiative ,Mental Health ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,2.2 Factors relating to the physical environment ,Child ,Cognition ,CpG Islands ,DNA Methylation ,Epigenesis ,Genetic ,Epigenome ,Female ,Genome-Wide Association Study ,Humans ,Infant ,Newborn ,Pregnancy ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences ,Biological psychology ,Clinical and health psychology - Abstract
Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall (total N = 2196), verbal (total N = 2206) and non-verbal cognitive scores (total N = 3300). The associations at single CpG sites were weak for all of the cognitive domains investigated. One region near DUSP22 on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that variation in cord blood DNA methylation at single CpG sites is associated with cognitive skills and further studies are needed to confirm the association at DUSP22.
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- 2022
8. An epigenome-wide association study of child appetitive traits and DNA methylation
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Harris, Holly A., Friedman, Chloe, Starling, Anne P., Dabelea, Dana, Johnson, Susan L., Fuemmeler, Bernard F., Jima, Dereje, Murphy, Susan K., Hoyo, Cathrine, Jansen, Pauline W., Felix, Janine F., and Mulder, Rosa H.
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- 2023
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9. Longitudinal associations of DNA methylation and sleep in children: a meta-analysis
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Sammallahti, Sara, Koopman-Verhoeff, M. Elisabeth, Binter, Anne-Claire, Mulder, Rosa H., Cabré-Riera, Alba, Kvist, Tuomas, Malmberg, Anni L. K., Pesce, Giancarlo, Plancoulaine, Sabine, Heiss, Jonathan A., Rifas-Shiman, Sheryl L., Röder, Stefan W., Starling, Anne P., Wilson, Rory, Guerlich, Kathrin, Haftorn, Kristine L., Page, Christian M., Luik, Annemarie I., Tiemeier, Henning, Felix, Janine F., Raikkonen, Katri, Lahti, Jari, Relton, Caroline L., Sharp, Gemma C., Waldenberger, Melanie, Grote, Veit, Heude, Barbara, Annesi-Maesano, Isabella, Hivert, Marie-France, Zenclussen, Ana C., Herberth, Gunda, Dabelea, Dana, Grazuleviciene, Regina, Vafeiadi, Marina, Håberg, Siri E., London, Stephanie J., Guxens, Mònica, Richmond, Rebecca C., and Cecil, Charlotte A. M.
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- 2022
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10. What makes clocks tick? Characterizing developmental dynamics of adult epigenetic clock sites
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Mulder, Rosa H., primary, Neumann, Alexander, additional, Felix, Janine F., additional, Suderman, Matthew, additional, and Cecil, Charlotte A. M., additional
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- 2024
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11. Epigenetic timing effects on child developmental outcomes: A longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium
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Neumann, Alexander, primary, Sammallahti, Sara, additional, Cosin-Tomas, Marta, additional, Reese, Sarah E, additional, Suderman, Matthew, additional, Alemany, Silvia, additional, Almqvist, Catarina, additional, Andrusaityte, Sandra, additional, Arshad, Syed H, additional, Bakermans-Kranenburg, Marian J, additional, Beilin, Lawrence, additional, Breton, Carrie, additional, Bustamante, Mariona, additional, Czamara, Darina, additional, Dabelea, Dana, additional, Eng, Celeste, additional, Eskenazi, Brenda, additional, Fuemmeler, Bernard F, additional, Gilliland, Frank D, additional, Grazuleviciene, Regina, additional, Håberg, Siri E, additional, Herberth, Gunda, additional, Holland, Nina, additional, Hough, Amy, additional, Hu, Donglei, additional, Huen, Karen, additional, Hüls, Anke, additional, Jin, Jianping, additional, Julvez, Jordi, additional, Koletzko, Berthold V, additional, Koppelman, Gerard H, additional, Kull, Inger, additional, Lu, Xueling, additional, Maitre, Léa, additional, Mason, Dan, additional, Mélen, Erik, additional, Merid, Simon K, additional, Molloy, Peter L, additional, Mori, Trevor A, additional, Mulder, Rosa H, additional, Page, Christian M, additional, Richmond, Rebecca C, additional, Roder, Stefan, additional, Ross, Jason P, additional, Schellhas, Laura, additional, Sebert, Sylvain, additional, Sheppard, Dean, additional, Snieder, Harold, additional, Starling, Anne P, additional, Stein, Dan J, additional, Tindula, Gwen, additional, van IJzendoorn, Marinus H, additional, Vonk, Judith, additional, Walton, Esther, additional, Witonsky, Jonathan, additional, Xu, Cheng-Jian, additional, Yang, Ivana V, additional, Yousefi, Paul D, additional, Zar, Heather J, additional, Zenclussen, Ana C, additional, Zhang, Hongmei, additional, Tiemeier, Henning, additional, London, Stephanie J, additional, Felix, Janine F, additional, and Cecil, Charlotte, additional
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- 2024
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12. Genome-wide DNA methylation patterns associated with general psychopathology in children
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Rijlaarsdam, Jolien, Barker, Edward D., Caserini, Chiara, Koopman-Verhoeff, M. Elisabeth, Mulder, Rosa H., Felix, Janine F., and Cecil, Charlotte A.M.
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- 2021
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13. Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation
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Sammallahti, Sara, Cortes Hidalgo, Andrea P., Tuominen, Samuli, Malmberg, Anni, Mulder, Rosa H., Brunst, Kelly J., Alemany, Silvia, McBride, Nancy S., Yousefi, Paul, Heiss, Jonathan A., McRae, Nia, Page, Christian M., Jin, Jianping, Pesce, Giancarlo, Caramaschi, Doretta, Rifas-Shiman, Sheryl L., Koen, Nastassja, Adams, Charleen D., Magnus, Maria C., Baïz, Nour, Ratanatharathorn, Andrew, Czamara, Darina, Håberg, Siri E., Colicino, Elena, Baccarelli, Andrea A., Cardenas, Andres, DeMeo, Dawn L., Lawlor, Deborah A., Relton, Caroline L., Felix, Janine F., van IJzendoorn, Marinus H., Bakermans-Kranenburg, Marian J., Kajantie, Eero, Räikkönen, Katri, Sunyer, Jordi, Sharp, Gemma C., Houtepen, Lotte C., Nohr, Ellen A., Sørensen, Thorkild I. A., Téllez-Rojo, Martha M., Wright, Robert O., Annesi-Maesano, Isabella, Wright, John, Hivert, Marie-France, Wright, Rosalind J., Zar, Heather J., Stein, Dan J., London, Stephanie J., Cecil, Charlotte A. M., Tiemeier, Henning, and Lahti, Jari
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- 2021
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14. Are some children genetically predisposed to poor sleep? A polygenic risk study in the general population
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Kocevska, Desana, Trajanoska, Katerina, Mulder, Rosa H., Koopman-Verhoeff, M. Elisabeth, Luik, Annemarie I., Tiemeier, Henning, van Someren, Eus J.W., Kocevska, Desana, Trajanoska, Katerina, Mulder, Rosa H., Koopman-Verhoeff, M. Elisabeth, Luik, Annemarie I., Tiemeier, Henning, and van Someren, Eus J.W.
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Background: Twin studies show moderate heritability of sleep traits: 40% for insomnia symptoms and 46% for sleep duration. Genome-wide association studies (GWAS) have identified genetic variants involved in insomnia and sleep duration in adults, but it is unknown whether these variants affect sleep during early development. We assessed whether polygenic risk scores for insomnia (PRS-I) and sleep duration (PRS-SD) affect sleep throughout early childhood to adolescence. Methods: We included 2,458 children of European ancestry (51% girls). Insomnia-related items of the Child Behavior Checklist were reported by mothers at child's age 1.5, 3, and 6 years. At 10–15 years, the Sleep Disturbance Scale for Children and actigraphy were assessed in a subsample (N = 975). Standardized PRS-I and PRS-SD (higher scores indicate genetic susceptibility for insomnia and longer sleep duration, respectively) were computed at multiple p-value thresholds based on largest GWAS to date. Results: Children with higher PRS-I had more insomnia-related sleep problems between 1.5 and 15 years (BPRS-I < 0.001 =.09, 95% CI: 0.05; 0.14). PRS-SD was not associated with mother-reported sleep problems. A higher PRS-SD was in turn associated with longer actigraphically estimated sleep duration (BPRS-SD < 5e08 =.05, 95% CI: 0.001; 0.09) and more wake after sleep onset (BPRS-SD < 0.005 =.25, 95% CI: 0.04; 0.47) at 10–15 years, but these associations did not survive multiple testing correction. Conclusions: Children who are genetically predisposed to insomnia have more insomnia-like sleep problems, whereas those who are genetically predisposed to longer sleep have longer sleep duration, but are also more awake during the night in adolescence. This indicates that polygenic risk for sleep traits, based on GWAS in adults, affects sleep already in children.
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- 2024
15. Cord Blood Metabolite Profiles and Their Association with Autistic Traits in Childhood
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Kaupper, Christin S., primary, Blaauwendraad, Sophia M., additional, Cecil, Charlotte A. M., additional, Mulder, Rosa H., additional, Gaillard, Romy, additional, Goncalves, Romy, additional, Borggraefe, Ingo, additional, Koletzko, Berthold, additional, and Jaddoe, Vincent W. V., additional
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- 2023
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16. Are some children genetically predisposed to poor sleep? A polygenic risk study in the general population
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Kocevska, Desana, primary, Trajanoska, Katerina, additional, Mulder, Rosa H., additional, Koopman‐Verhoeff, M. Elisabeth, additional, Luik, Annemarie I., additional, Tiemeier, Henning, additional, and van Someren, Eus J.W., additional
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- 2023
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17. 11. GENOME-WIDE ASSOCIATION STUDIES OF CHILDHOOD FUSSY EATING AND AVOIDANT RESTRICTIVE FOOD INTAKE DISORDER (ARFID)
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Dinkler, Lisa, primary, Abdulkadir, Mohamed, additional, Herle, Moritz, additional, Mulder, Rosa, additional, Harris, Holly, additional, Jansen, Pauline, additional, Qi, Baiyu, additional, Munn-Chernoff, Melissa, additional, Thornton, Laura, additional, Pisetsky, Emily, additional, Johnson, Jessica, additional, Halvorsen, Matt, additional, Crowley, James, additional, Micali, Nadia, additional, and Bulik, Cynthia, additional
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- 2023
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18. Paediatric population neuroimaging and the Generation R Study: the second wave
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White, Tonya, Muetzel, Ryan L., Marroun, Hanan El, Blanken, Laura M. E., Jansen, Philip, Bolhuis, Koen, Kocevska, Desana, Mous, Sabine E., Mulder, Rosa, Jaddoe, Vincent W. V., van der Lugt, Aad, Verhulst, Frank C., and Tiemeier, Henning
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- 2018
19. DNA Methylation: A Mediator Between Parenting Stress and Adverse Child Development?
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Mulder, Rosa H., Rijlaarsdam, Jolien, Van IJzendoorn, Marinus H., Deater-Deckard, Kirby, editor, and Panneton, Robin, editor
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- 2017
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20. An epigenome-wide association study of child appetitive traits and DNA methylation
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Harris, Holly Ann, primary, Friedman, Chloe, additional, Starling, Ann, additional, Dabelea, Dana, additional, Johnson, Susan L., additional, Fuemmeler, Bernard F., additional, Jima, Dereje, additional, Murphy, Susan K, additional, Hoyo, Catherine, additional, Jansen, Pauline W., additional, Felix, Janine, additional, and Mulder, Rosa H, additional
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- 2023
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21. Epigenome-wide association study of seizures in childhood and adolescence
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Caramaschi, Doretta, Hatcher, Charlie, Mulder, Rosa H., Felix, Janine F., Cecil, Charlotte A. M., Relton, Caroline L., and Walton, Esther
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- 2020
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22. Mapping gene by early life stress interactions on child subcortical brain structures
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Bolhuis, Koen, Mulder, Rosa H., de Mol, Casper Louk, Defina, Serena, Warrier, Varun, White, Tonya, Tiemeier, Henning, Muetzel, Ryan L., Cecil, Charlotte A. M., Bolhuis, Koen [0000-0002-5410-1531], Mulder, Rosa H [0000-0002-2382-1704], Tiemeier, Henning [0000-0002-4395-1397], Cecil, Charlotte AM [0000-0002-2389-5922], Apollo - University of Cambridge Repository, Child and Adolescent Psychiatry / Psychology, Pediatrics, Erasmus MC other, and Epidemiology
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genome-wide association study ,SDG 3 - Good Health and Well-being ,early life stress ,General Earth and Planetary Sciences ,psychopathology ,General Environmental Science ,MRI ,gene-environment interaction - Abstract
BACKGROUND: Although it is well-established that both genetics and the environment influence brain development, they are typically examined separately. Here, we aimed to prospectively investigate the interactive effects of genetic variants-from a genome-wide approach-and early life stress (ELS) on child subcortical brain structures, and their association with subsequent mental health problems.METHOD: Primary analyses were conducted using data from the Generation R Study (N = 2257), including genotype and cumulative prenatal and postnatal ELS scores (encompassing life events, contextual risk, parental risk, interpersonal risk, direct victimisation). Neuroimaging data were collected at age 10 years, including intracranial and subcortical brain volumes (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus). Genome-wide association and genome-wide-by-environment interaction analyses (GWEIS, run separately for prenatal/postnatal ELS) were conducted for eight brain outcomes (i.e., 24 genome-wide analyses) in the Generation R Study (discovery). Polygenic scores (PGS) using the resulting weights were calculated in an independent (target) cohort (adolescent brain cognitive development Study; N = 10,751), to validate associations with corresponding subcortical volumes and examine links to later mother-reported internalising and externalising problems.RESULTS: One GWEIS-prenatal stress locus was associated with caudate volume (rs139505895, mapping onto PRSS12 and NDST3) and two GWEIS-postnatal stress loci with the accumbens (rs2397823 and rs3130008, mapping onto CUTA, SYNGAP1, and TABP). Functional annotation revealed that these genes play a role in neuronal plasticity and synaptic function, and have been implicated in neuro-developmental phenotypes, for example, intellectual disability, autism, and schizophrenia. None of these associations survived a more stringent correction for multiple testing across all analysis sets. In the validation sample, all PGSgenotype were associated with their respective brain volumes, but no PGSGxE associated with any subcortical volume. None of the PGS associated with internalising or externalising problems.CONCLUSIONS: This study lends novel suggestive insights into gene-environment interplay on the developing brain as well as pointing to promising candidate loci for future replication and mechanistic studies.
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- 2022
23. Cord Blood Metabolite Profiles and Their Association with Autistic Traits in Childhood
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Kaupper, Christin S., Blaauwendraad, Sophia M., Cecil, Charlotte A.M., Mulder, Rosa H., Gaillard, Romy, Goncalves, Romy, Borggraefe, Ingo, Koletzko, Berthold, Jaddoe, Vincent W.V., Kaupper, Christin S., Blaauwendraad, Sophia M., Cecil, Charlotte A.M., Mulder, Rosa H., Gaillard, Romy, Goncalves, Romy, Borggraefe, Ingo, Koletzko, Berthold, and Jaddoe, Vincent W.V.
- Abstract
Autism Spectrum Disorder (ASD) is a diverse neurodevelopmental condition. Gene–environmental interactions in early stages of life might alter metabolic pathways, possibly contributing to ASD pathophysiology. Metabolomics may serve as a tool to identify underlying metabolic mechanisms contributing to ASD phenotype and could help to unravel its complex etiology. In a population-based, prospective cohort study among 783 mother–child pairs, cord blood serum concentrations of amino acids, non-esterified fatty acids, phospholipids, and carnitines were obtained using liquid chromatography coupled with tandem mass spectrometry. Autistic traits were measured at the children’s ages of 6 (n = 716) and 13 (n = 648) years using the parent-reported Social Responsiveness Scale. Lower cord blood concentrations of SM.C.39.2 and NEFA16:1/16:0 were associated with higher autistic traits among 6-year-old children, adjusted for sex and age at outcome. After more stringent adjustment for confounders, no significant associations of cord blood metabolites and autistic traits at ages 6 and 13 were detected. Differences in lipid metabolism (SM and NEFA) might be involved in ASD-related pathways and are worth further investigation.
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- 2023
24. Facing ostracism:micro-coding facial expressions in the Cyberball social exclusion paradigm
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Mulder, Rosa H., Bakermans-Kranenburg, Marian J., Veenstra, Johan, Tiemeier, Henning, van IJzendoorn, Marinus H., Mulder, Rosa H., Bakermans-Kranenburg, Marian J., Veenstra, Johan, Tiemeier, Henning, and van IJzendoorn, Marinus H.
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Background: Social exclusion is often measured with the Cyberball paradigm, a computerized ball-tossing game. Most Cyberball studies, however, used self-report questionnaires, leaving the data vulnerable to reporter bias, and associations with individual characteristics have been inconsistent. Methods: In this large-scale observational study, we video-recorded 4,813 10-year-old children during Cyberball and developed a real-time micro-coding method measuring facial expressions of anger, sadness and contempt, in a multi-ethnic population-based sample. We estimated associations between facial expressions and self-reported negative feelings, explored associations of child characteristics such as sex and parental national origin with observed and self-reported feelings during social exclusion, and tested associations of observed and self-reported feelings during social exclusion with behavior problems at age 14. Results: Facial expressions of sadness and anger were associated with self-reported negative feelings during the game, but not with such feelings after the game. Further, girls reported to have had less negative feelings during the game than boys, but no such sex-differences were found in total observed emotions. Likewise, children with parents of Moroccan origin reported less negative feelings during the game than Dutch children, but their facial expressions did not indicate that they were differently affected. Last, observed emotions related negatively to later internalizing problems, whereas self-report on negative feelings during the game related positively to later internalizing and externalizing problems. Conclusions: We show that facial expressions are associated with self-reported negative feelings during social exclusion, discuss that reporter-bias might be minimized using facial expressions, and find divergent associations of observed facial expressions and self-reported negative feelings with later internalizing problems.
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- 2023
25. Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation
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Kotsakis Ruehlmann, Anna, Sammallahti, Sara, Cortés Hidalgo, Andrea P., Bakulski, Kelly M., Binder, Elisabeth B., Campbell, Megan Loraine, Caramaschi, Doretta, Cecil, Charlotte A. M., Colicino, Elena, Cruceanu, Cristiana, Czamara, Darina, Dieckmann, Linda, Dou, John, Felix, Janine F., Frank, Josef, Håberg, Siri E., Herberth, Gunda, Hoang, Thanh T., Houtepen, Lotte C., Hüls, Anke, Koen, Nastassja, London, Stephanie J., Magnus, Maria C., Mancano, Giulia, Mulder, Rosa H., Page, Christian M., Räikkönen, Katri, Röder, Stefan, Schmidt, Rebecca J., Send, Tabea S., Sharp, Gemma, Stein, Dan J., Streit, Fabian, Tuhkanen, Johanna, Witt, Stephanie H., Zar, Heather J., Zenclussen, Ana C., Zhang, Yining, Zillich, Lea, Wright, Rosalind, Lahti, Jari, and Brunst, Kelly J.
- Abstract
Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (N= 5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood. Children whose mothers reported higher levels of cumulative maternal stressful life events during pregnancy exhibited differential methylation of cg26579032 in ALKBH3. Stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative were also associated with differential methylation of CpGs in APTX, MyD88, and both UHRF1and SDCCAG8, respectively; these genes are implicated in neurodegeneration, immune and cellular functions, regulation of global methylation levels, metabolism, and schizophrenia risk. Thus, differences in DNA methylation at these loci may provide novel insights into potential mechanisms of neurodevelopment in offspring.
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- 2024
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26. Paediatric population neuroimaging and the Generation R Study: the second wave
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White, Tonya, Muetzel, Ryan L., El Marroun, Hanan, Blanken, Laura M. E., Jansen, Philip, Bolhuis, Koen, Kocevska, Desana, Mous, Sabine E., Mulder, Rosa, Jaddoe, Vincent W. V., van der Lugt, Aad, Verhulst, Frank C., and Tiemeier, Henning
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- 2017
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27. Peer interactions as moderators of the temperament-anxiety association, using data from the Generation R Study
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Harrewijn, Anita, Mulder, Rosa, van IJzendoorn, Marinus, Wieser, Matthias, and Jansen, Pauline
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Social Work ,Sports Studies ,Friendship ,Victimization ,Anxiety ,Social and Behavioral Sciences ,Peers ,Urban Studies and Planning ,FOS: Sociology ,Adolescence ,FOS: Psychology ,Clinical Psychology ,Developmental Psychology ,Psychology ,Child Psychology ,Temperament ,Social Exclusion - Abstract
Anxiety disorders are among the most prevalent psychiatric disorders in youth (Merikangas et al., 2010) and have many adverse consequences (Rapee, Schniering, & Hudson, 2009). Inhibited temperament, which is characterized by fear and avoidance of novelty in early childhood, is a strong predictor of anxiety disorders (Clauss & Blackford, 2012; Fox, Henderson, Marshall, Nichols, & Ghera, 2005; Sandstrom, Uher, & Pavlova, 2020), even three decades later (Tang et al., 2020). Of all children, 15-20% show an inhibited temperament in early childhood (Fox et al., 2005), but only about 40% of these children develop an anxiety disorder (Sandstrom et al., 2020). Identifying risk and protective factors for anxiety in children with an inhibited temperament could improve early detection and prevention of anxiety disorders. Anxiety disorders typically develop during early adolescence (Kessler, Berglund, Demler, Jin, & Walters, 2005), a developmental period during which peers become increasingly important (Blakemore, 2018; Blakemore & Mills, 2014). Therefore, we will focus on peer interactions as potential moderators of the relation between early childhood temperament and adolescent anxiety. Previous studies have shown that peer rejection strengthens the temperament-anxiety association (Degnan, Almas, & Fox, 2010), whereas adolescent social involvement weakens temperament-anxiety association (Frenkel et al., 2015). Here, we will focus on multi-modal assessment of peer interactions, combining mother-reported victimization, self-reported friendship quality, and self-reported feelings and facial expressions during social exclusion in a lab-based task. We will study this using existing data from the Generation R Study, a unique interdisciplinary prospective cohort following 1232 children since birth including in-depth behavioral assessments of temperament at 3 years (Kooijman et al., 2016).
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- 2022
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28. INTERACTION EFFECTS OF GENOTYPE AND PRENATAL STRESS ON EPIGENETIC VARIATION AT BIRTH
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Mulder, Rosa, primary, Baltromonaityte, Vilte, additional, Defina, Serena, additional, Walton, Esther, additional, Cecil, Charlotte, additional, and Felix, Janine, additional
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- 2022
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29. GENOME-WIDE ASSOCIATION STUDY OF CHILDHOOD FUSSY EATING
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Abdulkadir, Mohamed, primary, Herle, Moritz, additional, Mulder, Rosa, additional, Harris, Holly, additional, Jansen, Pauline, additional, and Micali, Nadi, additional
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- 2022
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30. MAPPING GENE BY EARLY LIFE STRESS INTERACTIONS ON CHILD SUBCORTICAL BRAIN STRUCTURES: A GENOME-WIDE PROSPECTIVE STUDY
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Bolhuis, Koen, primary, Mulder, Rosa, additional, de Moul, Louk, additional, Defina, Serena, additional, Warrier, Varun, additional, White, Tonya, additional, Tiemeier, Henning, additional, and Cecil, Charlotte, additional
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- 2022
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31. Epigenome-Wide Meta-Analysis of Prenatal Maternal Stressful Life Events and Newborn DNA Methylation
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Brunst, Kelly, primary, Ruehlmann, Anna K, additional, Sammallahti, Sara, additional, Hidalgo, Andrea P Cortes, additional, Bakulski, Kelly, additional, Binder, Elisabeth, additional, Campbell, Meghan, additional, Caramaschi, Doretta, additional, Cecil, Charlotte, additional, Colicino, Elena, additional, Cruceanu, Cristiana, additional, Czamara, Darina, additional, Dieckmann, Linda, additional, Dou, John, additional, Felix, Janine, additional, Frank, Josef, additional, Haberg, Siri, additional, Herberth, Gunda, additional, Hoang, Thanh, additional, Houtepan, Lotte, additional, Huels, Anke, additional, Koen, Nastassja, additional, London, Stephanie, additional, Magnus, Maria, additional, Mancano, Giulia, additional, Mulder, Rosa, additional, Page, Christian, additional, Räikkönen, Katri, additional, Roder, Stefan, additional, Schmidt, Rebecca J., additional, Send, Tabea, additional, Sharp, Gemma, additional, Stein, Dan, additional, Streit, Fabian, additional, Tuhkanen, Johanna, additional, Witt, Stephanie, additional, Zar, Heather, additional, Zenclussen, Ana, additional, Zhang, Yining, additional, Zillich, Lea, additional, Wright, Rosalind, additional, and Lahti, Jari, additional
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- 2022
- Full Text
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32. Connecting the dots: social networks in the classroom and white matter connections in the brain
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Mulder, Rosa H., primary, López‐Vicente, Mónica, additional, Cortes Hidalgo, Andrea P., additional, Steenkamp, Lisa R., additional, Güroğlu, Berna, additional, Tiemeier, Henning, additional, and Muetzel, Ryan L., additional
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- 2022
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33. Mapping gene by early life stress interactions on child subcortical brain structures:A genome-wide prospective study
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Bolhuis, Koen, Mulder, Rosa H, de Mol, Casper Louk, Defina, Serena, Warrier, Varun, White, Tonya, Tiemeier, Henning, Muetzel, Ryan L, Cecil, Charlotte A M, Bolhuis, Koen, Mulder, Rosa H, de Mol, Casper Louk, Defina, Serena, Warrier, Varun, White, Tonya, Tiemeier, Henning, Muetzel, Ryan L, and Cecil, Charlotte A M
- Abstract
BACKGROUND: Although it is well-established that both genetics and the environment influence brain development, they are typically examined separately. Here, we aimed to prospectively investigate the interactive effects of genetic variants-from a genome-wide approach-and early life stress (ELS) on child subcortical brain structures, and their association with subsequent mental health problems.METHOD: Primary analyses were conducted using data from the Generation R Study (N = 2257), including genotype and cumulative prenatal and postnatal ELS scores (encompassing life events, contextual risk, parental risk, interpersonal risk, direct victimisation). Neuroimaging data were collected at age 10 years, including intracranial and subcortical brain volumes (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus). Genome-wide association and genome-wide-by-environment interaction analyses (GWEIS, run separately for prenatal/postnatal ELS) were conducted for eight brain outcomes (i.e., 24 genome-wide analyses) in the Generation R Study (discovery). Polygenic scores (PGS) using the resulting weights were calculated in an independent (target) cohort (adolescent brain cognitive development Study; N = 10,751), to validate associations with corresponding subcortical volumes and examine links to later mother-reported internalising and externalising problems.RESULTS: One GWEIS-prenatal stress locus was associated with caudate volume (rs139505895, mapping onto PRSS12 and NDST3) and two GWEIS-postnatal stress loci with the accumbens (rs2397823 and rs3130008, mapping onto CUTA, SYNGAP1, and TABP). Functional annotation revealed that these genes play a role in neuronal plasticity and synaptic function, and have been implicated in neuro-developmental phenotypes, for example, intellectual disability, autism, and schizophrenia. None of these associations survived a more stringent correction for multiple testing across all analysis sets. In the validation s
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- 2022
34. Epigenome-wide associations between observed maternal sensitivity and offspring DNA methylation: a population-based prospective study in children
- Author
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Dall'Aglio, Lorenza, Rijlaarsdam, Jolien, Mulder, Rosa H., Neumann, Alexander, Felix, Janine F., Kok, Rianne, Bakermans-Kranenburg, Marian J., van Ijzendoorn, Marinus H., Tiemeier, Henning, Cecil, Charlotte A.M., Dall'Aglio, Lorenza, Rijlaarsdam, Jolien, Mulder, Rosa H., Neumann, Alexander, Felix, Janine F., Kok, Rianne, Bakermans-Kranenburg, Marian J., van Ijzendoorn, Marinus H., Tiemeier, Henning, and Cecil, Charlotte A.M.
- Abstract
Background. Experimental work in animals has shown that DNA methylation (DNAm), an epigenetic mechanism regulating gene expression, is influenced by typical variation in maternal care. While emerging research in humans supports a similar association, studies to date have been limited to candidate gene and cross-sectional approaches, with a focus on extreme deviations in the caregiving environment. Methods. Here, we explored the prospective association between typical variation in maternal sensitivity and offspring epigenome-wide DNAm, in a population-based cohort of children (N = 235). Maternal sensitivity was observed when children were 3- and 4-years-old. DNAm, quantified with the Infinium 450 K array, was extracted at age 6 (whole blood). The influence of methylation quantitative trait loci (mQTLs), DNAm at birth (cord blood), and confounders (socioeconomic status, maternal psychopathology) was considered in follow-up analyses. Results. Genome-wide significant associations between maternal sensitivity and offspring DNAm were observed at 13 regions (p < 1.06 × 10-07), but not at single sites. Follow-up analyses indicated that associations at these regions were in part related to genetic factors, confounders, and baseline DNAm levels at birth, as evidenced by the presence of mQTLs at five regions and estimate attenuations. Robust associations with maternal sensitivity were found at four regions, annotated to ZBTB22, TAPBP, ZBTB12, and DOCK4. Conclusions. These findings provide novel leads into the relationship between typical variation in maternal caregiving and offspring DNAm in humans, highlighting robust regions of associations, previously implicated in psychological and developmental problems, immune functioning, and stress responses.
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- 2022
- Full Text
- View/download PDF
35. Longitudinal associations of DNA methylation and sleep in children:a meta-analysis
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Sammallahti, Sara, Koopman-Verhoeff, M. Elisabeth, Binter, Anne Claire, Mulder, Rosa H., Cabré-Riera, Alba, Kvist, Tuomas, Malmberg, Anni L.K., Pesce, Giancarlo, Plancoulaine, Sabine, Heiss, Jonathan A., Rifas-Shiman, Sheryl L., Röder, Stefan W., Starling, Anne P., Wilson, Rory, Guerlich, Kathrin, Haftorn, Kristine L., Page, Christian M., Luik, Annemarie I., Tiemeier, Henning, Felix, Janine F., Raikkonen, Katri, Lahti, Jari, Relton, Caroline L., Sharp, Gemma C., Waldenberger, Melanie, Grote, Veit, Heude, Barbara, Annesi-Maesano, Isabella, Hivert, Marie France, Zenclussen, Ana C., Herberth, Gunda, Dabelea, Dana, Grazuleviciene, Regina, Vafeiadi, Marina, Håberg, Siri E., London, Stephanie J., Guxens, Mònica, Richmond, Rebecca C., Cecil, Charlotte A.M., Sammallahti, Sara, Koopman-Verhoeff, M. Elisabeth, Binter, Anne Claire, Mulder, Rosa H., Cabré-Riera, Alba, Kvist, Tuomas, Malmberg, Anni L.K., Pesce, Giancarlo, Plancoulaine, Sabine, Heiss, Jonathan A., Rifas-Shiman, Sheryl L., Röder, Stefan W., Starling, Anne P., Wilson, Rory, Guerlich, Kathrin, Haftorn, Kristine L., Page, Christian M., Luik, Annemarie I., Tiemeier, Henning, Felix, Janine F., Raikkonen, Katri, Lahti, Jari, Relton, Caroline L., Sharp, Gemma C., Waldenberger, Melanie, Grote, Veit, Heude, Barbara, Annesi-Maesano, Isabella, Hivert, Marie France, Zenclussen, Ana C., Herberth, Gunda, Dabelea, Dana, Grazuleviciene, Regina, Vafeiadi, Marina, Håberg, Siri E., London, Stephanie J., Guxens, Mònica, Richmond, Rebecca C., and Cecil, Charlotte A.M.
- Abstract
Background: Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have been proposed to underlie variation in sleep or may be an early-life marker of sleep disturbances. We examined if DNA methylation at birth or in school age is associated with parent-reported and actigraphy-estimated sleep outcomes in children. Methods: We meta-analysed epigenome-wide association study results. DNA methylation was measured from cord blood at birth in 11 cohorts and from peripheral blood in children (4–13 years) in 8 cohorts. Outcomes included parent-reported sleep duration, sleep initiation and fragmentation problems, and actigraphy-estimated sleep duration, sleep onset latency and wake-after-sleep-onset duration. Results: We found no associations between DNA methylation at birth and parent-reported sleep duration (n = 3658), initiation problems (n = 2504), or fragmentation (n = 1681) (p values above cut-off 4.0 × 10–8). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 × 10–8, n = 577) and sleep onset latency (p = 8.8 × 10–9, n = 580), respectively. DNA methylation in childhood was not cross-sectionally associated with any sleep outcomes (n = 716–2539). Conclusion: DNA methylation, at birth or in childhood, was not associated with parent-reported sleep. Associations observed with objectively measured sleep outcomes could be studied further if additional data sets become available.
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- 2022
36. Maternal Mediterranean diet in pregnancy and newborn DNA methylation:a meta-analysis in the PACE Consortium
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Küpers, Leanne K., Fernández-Barrés, Sílvia, Nounu, Aayah, Friedman, Chloe, Fore, Ruby, Mancano, Giulia, Dabelea, Dana, Rifas-Shiman, Sheryl L., Mulder, Rosa H., Oken, Emily, Johnson, Laura, Bustamante, Mariona, Jaddoe, Vincent W.V., Hivert, Marie France, Starling, Anne P., de Vries, Jeanne H.M., Sharp, Gemma C., Vrijheid, Martine, Felix, Janine F., Küpers, Leanne K., Fernández-Barrés, Sílvia, Nounu, Aayah, Friedman, Chloe, Fore, Ruby, Mancano, Giulia, Dabelea, Dana, Rifas-Shiman, Sheryl L., Mulder, Rosa H., Oken, Emily, Johnson, Laura, Bustamante, Mariona, Jaddoe, Vincent W.V., Hivert, Marie France, Starling, Anne P., de Vries, Jeanne H.M., Sharp, Gemma C., Vrijheid, Martine, and Felix, Janine F.
- Abstract
Higher adherence to the Mediterranean diet during pregnancy is related to a lower risk of preterm birth and to better offspring cardiometabolic health. DNA methylation may be an underlying biological mechanism. We evaluated whether maternal adherence to the Mediterranean diet was associated with offspring cord blood DNA methylation. We meta-analysed epigenome-wide association studies (EWAS) of maternal adherence to the Mediterranean diet during pregnancy and offspring cord blood DNA methylation in 2802 mother–child pairs from five cohorts. We calculated the relative Mediterranean diet (rMED) score with range 0–18 and an adjusted rMED excluding alcohol (rMEDp, range 0–16). DNA methylation was measured using Illumina 450K arrays. We used robust linear regression modelling adjusted for child sex, maternal education, age, smoking, body mass index, energy intake, batch, and cell types. We performed several functional analyses and examined the persistence of differential DNA methylation into childhood (4.5–7.8 y). rMEDp was associated with cord blood DNA methylation at cg23757341 (0.064% increase in DNA methylation per 1-point increase in the rMEDp score, SE = 0.011, P = 2.41 × 10−8). This cytosine–phosphate–guanine (CpG) site maps to WNT5B, associated with adipogenesis and glycaemic phenotypes. We did not identify associations with childhood gene expression, nor did we find enriched biological pathways. The association did not persist into childhood. In this meta-analysis, maternal adherence to the Mediterranean diet (excluding alcohol) during pregnancy was associated with cord blood DNA methylation level at cg23757341. Potential mediation of DNA methylation in associations with offspring health requires further study.
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- 2022
37. Connecting the dots:social networks in the classroom and white matter connections in the brain
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Mulder, Rosa H., López-Vicente, Mónica, Cortes Hidalgo, Andrea P., Steenkamp, Lisa R., Güroğlu, Berna, Tiemeier, Henning, Muetzel, Ryan L., Mulder, Rosa H., López-Vicente, Mónica, Cortes Hidalgo, Andrea P., Steenkamp, Lisa R., Güroğlu, Berna, Tiemeier, Henning, and Muetzel, Ryan L.
- Abstract
Background: Peer connections in school classrooms play an important role in social–emotional development and mental health. However, research on the association between children's peer relationships and white matter connections in the brain is scarce. We studied associations between peer relationships in the classroom and white matter structural connectivity in a pediatric population-based sample. Methods: Bullying and victimization, as well as rejection and acceptance, were assessed in classrooms in 634 children at age 7. White matter microstructure (fractional anisotropy (FA), mean diffusivity (MD)) was measured with diffusion tensor imaging at age 10. We examined global metrics of white matter microstructure and used Tract-Based Spatial Statistics (TBSS) for voxel-wise associations. Results: Peer victimization was associated with higher global FA and lower global MD and peer rejection was associated with lower global MD; however, these associations did not remain after multiple testing correction. Voxel-wise TBSS results for peer victimization and rejection were in line with global metrics both in terms of direction and spatial extent of the associations, with associated voxels (pFWE <.05) observed throughout the brain (including corpus callosum, corona radiata, sagittal stratum and superior longitudinal fasciculi). Conclusions: Although based only on cross-sectional data, the findings could indicate accelerated white matter microstructure maturation in certain brain areas of children who are victimized or rejected more often. However, repeated measurements are essential to unravel this complex interplay of peer connections, maturation and brain development over time.
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- 2022
38. Maternal Mediterranean diet in pregnancy and newborn DNA methylation : a meta-analysis in the PACE Consortium
- Author
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Küpers, Leanne K., Fernández-Barrés, Sílvia, Nounu, Aayah, Friedman, Chloe, Fore, Ruby, Mancano, Giulia, Dabelea, Dana, Rifas-Shiman, Sheryl L., Mulder, Rosa H., Oken, Emily, Johnson, Laura, Bustamante, Mariona, Jaddoe, Vincent W.V., Hivert, Marie France, Starling, Anne P., de Vries, Jeanne H.M., Sharp, Gemma C., Vrijheid, Martine, Felix, Janine F., Küpers, Leanne K., Fernández-Barrés, Sílvia, Nounu, Aayah, Friedman, Chloe, Fore, Ruby, Mancano, Giulia, Dabelea, Dana, Rifas-Shiman, Sheryl L., Mulder, Rosa H., Oken, Emily, Johnson, Laura, Bustamante, Mariona, Jaddoe, Vincent W.V., Hivert, Marie France, Starling, Anne P., de Vries, Jeanne H.M., Sharp, Gemma C., Vrijheid, Martine, and Felix, Janine F.
- Abstract
Higher adherence to the Mediterranean diet during pregnancy is related to a lower risk of preterm birth and to better offspring cardiometabolic health. DNA methylation may be an underlying biological mechanism. We evaluated whether maternal adherence to the Mediterranean diet was associated with offspring cord blood DNA methylation. We meta-analysed epigenome-wide association studies (EWAS) of maternal adherence to the Mediterranean diet during pregnancy and offspring cord blood DNA methylation in 2802 mother–child pairs from five cohorts. We calculated the relative Mediterranean diet (rMED) score with range 0–18 and an adjusted rMED excluding alcohol (rMEDp, range 0–16). DNA methylation was measured using Illumina 450K arrays. We used robust linear regression modelling adjusted for child sex, maternal education, age, smoking, body mass index, energy intake, batch, and cell types. We performed several functional analyses and examined the persistence of differential DNA methylation into childhood (4.5–7.8 y). rMEDp was associated with cord blood DNA methylation at cg23757341 (0.064% increase in DNA methylation per 1-point increase in the rMEDp score, SE = 0.011, P = 2.41 × 10−8). This cytosine–phosphate–guanine (CpG) site maps to WNT5B, associated with adipogenesis and glycaemic phenotypes. We did not identify associations with childhood gene expression, nor did we find enriched biological pathways. The association did not persist into childhood. In this meta-analysis, maternal adherence to the Mediterranean diet (excluding alcohol) during pregnancy was associated with cord blood DNA methylation level at cg23757341. Potential mediation of DNA methylation in associations with offspring health requires further study.
- Published
- 2022
39. Incidental Findings on Brain Imaging in the General Pediatric Population
- Author
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Jansen, Philip R., Dremmen, Marjolein, van den Berg, Aaike, Dekkers, Ilona A., Blanken, Laura M.E., Muetzel, Ryan L., Bolhuis, Koen, Mulder, Rosa M., Kocevska, Desana, Jansen, Toyah A., de Wit, Marie-Claire Y., Neuteboom, Rinze F., Polderman, Tinca J.C., Posthuma, Danielle, Jaddoe, Vincent W.V., Verhulst, Frank C., Tiemeier, Henning, van der Lugt, Aad, and White, Tonya J.H.
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- 2017
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40. Maternal Mediterranean diet in pregnancy and newborn DNA methylation: a meta-analysis in the PACE Consortium
- Author
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Küpers, Leanne K., primary, Fernández-Barrés, Sílvia, additional, Nounu, Aayah, additional, Friedman, Chloe, additional, Fore, Ruby, additional, Mancano, Giulia, additional, Dabelea, Dana, additional, Rifas-Shiman, Sheryl L., additional, Mulder, Rosa H., additional, Oken, Emily, additional, Johnson, Laura, additional, Bustamante, Mariona, additional, Jaddoe, Vincent W.V., additional, Hivert, Marie-France, additional, Starling, Anne P., additional, de Vries, Jeanne H.M., additional, Sharp, Gemma C., additional, Vrijheid, Martine, additional, and Felix, Janine F., additional
- Published
- 2022
- Full Text
- View/download PDF
41. Additional file 2 of Longitudinal associations of DNA methylation and sleep in children: a meta-analysis
- Author
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Sammallahti, Sara, Koopman-Verhoeff, M. Elisabeth, Binter, Anne-Claire, Mulder, Rosa H., Cabré-Riera, Alba, Kvist, Tuomas, Malmberg, Anni L. K., Pesce, Giancarlo, Plancoulaine, Sabine, Heiss, Jonathan A., Rifas-Shiman, Sheryl L., Röder, Stefan W., Starling, Anne P., Wilson, Rory, Guerlich, Kathrin, Haftorn, Kristine L., Page, Christian M., Luik, Annemarie I., Tiemeier, Henning, Felix, Janine F., Raikkonen, Katri, Lahti, Jari, Relton, Caroline L., Sharp, Gemma C., Waldenberger, Melanie, Grote, Veit, Heude, Barbara, Annesi-Maesano, Isabella, Hivert, Marie-France, Zenclussen, Ana C., Herberth, Gunda, Dabelea, Dana, Grazuleviciene, Regina, Vafeiadi, Marina, Håberg, Siri E., London, Stephanie J., Guxens, Mònica, Richmond, Rebecca C., and Cecil, Charlotte A. M.
- Abstract
Additional file2. Methods
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- 2022
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42. Additional file 1 of Longitudinal associations of DNA methylation and sleep in children: a meta-analysis
- Author
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Sammallahti, Sara, Koopman-Verhoeff, M. Elisabeth, Binter, Anne-Claire, Mulder, Rosa H., Cabré-Riera, Alba, Kvist, Tuomas, Malmberg, Anni L. K., Pesce, Giancarlo, Plancoulaine, Sabine, Heiss, Jonathan A., Rifas-Shiman, Sheryl L., Röder, Stefan W., Starling, Anne P., Wilson, Rory, Guerlich, Kathrin, Haftorn, Kristine L., Page, Christian M., Luik, Annemarie I., Tiemeier, Henning, Felix, Janine F., Raikkonen, Katri, Lahti, Jari, Relton, Caroline L., Sharp, Gemma C., Waldenberger, Melanie, Grote, Veit, Heude, Barbara, Annesi-Maesano, Isabella, Hivert, Marie-France, Zenclussen, Ana C., Herberth, Gunda, Dabelea, Dana, Grazuleviciene, Regina, Vafeiadi, Marina, Håberg, Siri E., London, Stephanie J., Guxens, Mònica, Richmond, Rebecca C., and Cecil, Charlotte A. M.
- Abstract
Additional file1: Table S1. Characteristics of the participating cohorts in analyses of DNAm in childhood and child sleep outcomes. Table S2. Overlap between cord blood and peripheral blood in childhood DNA methylation analyses. Table S3. Site-specific results for the 25 CpGs that came closest to statistical significance (p
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- 2022
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43. Fairness and bias correction in machine learning for depression prediction: results from four different study populations
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Dang, Vien Ngoc, Cascarano, Anna, Mulder, Rosa H., Cecil, Charlotte, Zuluaga, Maria A., Hernández-González, Jerónimo, and Lekadir, Karim
- Subjects
FOS: Computer and information sciences ,Computer Science - Machine Learning ,Computer Science - Computers and Society ,Computers and Society (cs.CY) ,Machine Learning (cs.LG) - Abstract
A significant level of stigma and inequality exists in mental healthcare, especially in under-served populations, which spreads through collected data. When not properly accounted for, machine learning (ML) models learned from data can reinforce the structural biases already present in society. Here, we present a systematic study of bias in ML models designed to predict depression in four different case studies covering different countries and populations. We find that standard ML approaches show regularly biased behaviors. However, we show that standard mitigation techniques, and our own post-hoc method, can be effective in reducing the level of unfair bias. We provide practical recommendations to develop ML models for depression risk prediction with increased fairness and trust in the real world. No single best ML model for depression prediction provides equality of outcomes. This emphasizes the importance of analyzing fairness during model selection and transparent reporting about the impact of debiasing interventions., Comment: 25 pages, 4 figures
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- 2022
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44. Developmental Changes in Dynamic Functional Connectivity From Childhood Into Adolescence
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López-Vicente, Mónica, primary, Agcaoglu, Oktay, additional, Pérez-Crespo, Laura, additional, Estévez-López, Fernando, additional, Heredia-Genestar, José María, additional, Mulder, Rosa H., additional, Flournoy, John C., additional, van Duijvenvoorde, Anna C. K., additional, Güroğlu, Berna, additional, White, Tonya, additional, Calhoun, Vince, additional, Tiemeier, Henning, additional, and Muetzel, Ryan L., additional
- Published
- 2021
- Full Text
- View/download PDF
45. Epigenome-wide associations between observed maternal sensitivity and offspring DNA methylation: a population-based prospective study in children.
- Author
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Dall' Aglio, Lorenza, Rijlaarsdam, Jolien, Mulder, Rosa H., Neumann, Alexander, Felix, Janine F., Kok, Rianne, Bakermans-Kranenburg, Marian J., van Ijzendoorn, Marinus H., Tiemeier, Henning, and Cecil, Charlotte A.M.
- Subjects
CHILD development ,MOTHERHOOD ,PARENTING ,DNA methylation ,SOCIOECONOMIC factors ,GENE expression ,SOCIAL classes ,PATHOLOGICAL psychology ,DESCRIPTIVE statistics ,EPIGENOMICS ,MOTHER-child relationship ,LONGITUDINAL method - Abstract
Background: Experimental work in animals has shown that DNA methylation (DNAm), an epigenetic mechanism regulating gene expression, is influenced by typical variation in maternal care. While emerging research in humans supports a similar association, studies to date have been limited to candidate gene and cross-sectional approaches, with a focus on extreme deviations in the caregiving environment. Methods: Here, we explored the prospective association between typical variation in maternal sensitivity and offspring epigenome-wide DNAm, in a population-based cohort of children (N = 235). Maternal sensitivity was observed when children were 3- and 4-years-old. DNAm, quantified with the Infinium 450 K array, was extracted at age 6 (whole blood). The influence of methylation quantitative trait loci (mQTLs), DNAm at birth (cord blood), and confounders (socioeconomic status, maternal psychopathology) was considered in follow-up analyses. Results: Genome-wide significant associations between maternal sensitivity and offspring DNAm were observed at 13 regions (p < 1.06 × 10
−07 ), but not at single sites. Follow-up analyses indicated that associations at these regions were in part related to genetic factors, confounders, and baseline DNAm levels at birth, as evidenced by the presence of mQTLs at five regions and estimate attenuations. Robust associations with maternal sensitivity were found at four regions, annotated to ZBTB22 , TAPBP , ZBTB12 , and DOCK4. Conclusions: These findings provide novel leads into the relationship between typical variation in maternal caregiving and offspring DNAm in humans, highlighting robust regions of associations, previously implicated in psychological and developmental problems, immune functioning, and stress responses. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
46. Neonatal DNA methylation and childhood low prosocial behavior: An epigenome‐wide association meta‐analysis
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Luo, Mannan, primary, Meehan, Alan J., additional, Walton, Esther, additional, Röder, Stefan, additional, Herberth, Gunda, additional, Zenclussen, Ana C., additional, Cosín‐Tomás, Marta, additional, Sunyer, Jordi, additional, Mulder, Rosa H., additional, Cortes Hidalgo, Andrea P., additional, Bakermans‐Kranenburg, Marian J., additional, Felix, Janine F., additional, Relton, Caroline, additional, Suderman, Matthew, additional, Pappa, Irene, additional, Kok, Rianne, additional, Tiemeier, Henning, additional, van IJzendoorn, Marinus H., additional, Barker, Edward D., additional, and Cecil, Charlotte A. M., additional
- Published
- 2021
- Full Text
- View/download PDF
47. DNA methylation and stress in child development: A population-based approach
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Mulder, Rosa, van IJzendoorn, Marinus, Tiemeier, Henning, Bakermans-Kranenburg, MJ, and Erasmus MC other
- Published
- 2021
48. DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan
- Author
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van Dongen, Jenny, Hagenbeek, Fiona A., Suderman, Matthew, Roetman, Peter J., Sugden, Karen, Chiocchetti, Andreas G., Ismail, Khadeeja, Mulder, Rosa H., Hafferty, Jonathan D., Adams, Mark J., Walker, Rosie M., Morris, Stewart W., Lahti, Jari, Küpers, Leanne K., Escaramis, Georgia, Alemany, Silvia, Jan Bonder, Marc, Meijer, Mandy, Ip, Hill F., Jansen, Rick, Baselmans, Bart M. L., Parmar, Priyanka, Lowry, Estelle, Streit, Fabian, Sirignano, Lea, Send, Tabea S., Frank, Josef, Jylhävä, Juulia, Wang, Yunzhang, Mishra, Pashupati Prasad, Colins, Olivier F., Corcoran, David L., Poulton, Richie, Mill, Jonathan, Hannon, Eilis, Arseneault, Louise, Korhonen, Tellervo, Vuoksimaa, Eero, Felix, Janine F., Bakermans-Kranenburg, Marian J., Campbell, Archie, Czamara, Darina, Binder, Elisabeth, Corpeleijn, Eva, Gonzalez, Juan R., Grazuleviciene, Regina, Gutzkow, Kristine B., Evandt, Jorunn, Vafeiadi, Marina, Klein, Marieke, van der Meer, Dennis, Ligthart, Lannie, Heijmans, Bastiaan T., ’t Hoen, Peter A. C., van Meurs, Joyce, Franke, Lude, Boomsma, Dorret I., Pool, René, Hottenga, Jouke J., van Greevenbroek, Marleen M. J., Stehouwer, Coen D. A., van der Kallen, Carla J. H., Schalkwijk, Casper G., Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje F., Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, Veldink, Jan H., van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Isaacs, Aaron, Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., van ’t Hof, Peter, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik. W., ’t Hoen, Peter-Bram, Kluft, Cornelis, Davies, Gareth E., Hakulinen, Christian, Keltikangas-Järvinen, Liisa, Franke, Barbara, Freitag, Christine M., Konrad, Kerstin, Hervas, Amaia, Fernández-Rivas, Aranzazu, Vetro, Agnes, Raitakari, Olli, Lehtimäki, Terho, Vermeiren, Robert, Strandberg, Timo, Räikkönen, Katri, Snieder, Harold, Witt, Stephanie H., Deuschle, Michael, Pedersen, Nancy L., Hägg, Sara, Sunyer, Jordi, Kaprio, Jaakko, Ollikainen, Miina, Moffitt, Terrie E., Tiemeier, Henning, van IJzendoorn, Marinus H., Relton, Caroline, Vrijheid, Martine, Sebert, Sylvain, Jarvelin, Marjo-Riitta, Caspi, Avshalom, Evans, Kathryn L., McIntosh, Andrew M., Bartels, Meike, Child and Adolescent Psychiatry / Psychology, Pediatrics, Internal Medicine, Urology, Epidemiology, Orthopedics and Sports Medicine, Clinical Child and Family Studies, van der Kallen, Carla J. H., Schalkwijk, Casper G., Wijmenga, Cisca, Franke, Lude, Zhernakova, Sasha, Tigchelaar, Ettje F., Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, Veldink, Jan H., van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Isaacs, Aaron, Uitterlinden, André G., van Meurs, Joyce, Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., Jansen, Rick, van 't Hof, Peter, Deelen, Patrick, Nooren, Irene, 't Hoen, Peter A. C., Heijmans, Bastiaan T., Moed, Matthijs, Vermaat, Martijn, Luijk, René, Jan Bonder, Marc, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik W., 't Hoen, Peter-Bram, Boomsma, Dorret I., Pool, René, van Dongen, Jenny, Hottenga, Jouke J., van Greevenbroek, Marleen M. J., Stehouwer, Coen D. A., Institute for Molecular Medicine Finland, University of Helsinki, Doctoral Programme in Cognition, Learning, Instruction and Communication, Department of Psychology and Logopedics, Faculty of Medicine, Tellervo Korhonen / Principal Investigator, Genetic Epidemiology, Faculty Common Matters (Faculty of Medicine), Cognitive and Brain Aging, Helsinki Inequality Initiative (INEQ), Psychosocial factors and health, Faculty Common Matters (Faculty of Education), Medicum, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, Geriatrian yksikkö, Reproductive Origins of Adult Health and Disease (ROAHD), Life Course Epidemiology (LCE), Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Pediatric surgery, APH - Mental Health, Amsterdam Reproduction & Development (AR&D), APH - Personalized Medicine, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Methodology, Tampere University, Health Sciences, Department of Clinical Chemistry, Clinical Medicine, RS: MHeNs - R2 - Mental Health, and Psychiatrie & Neuropsychologie
- Subjects
0301 basic medicine ,Molecular biology ,ADN ,Physiology ,CHILDREN ,3124 Neurology and psychiatry ,Epigenesis, Genetic ,Epigenome ,0302 clinical medicine ,Child ,RISK ,ASSOCIATION ,Middle Aged ,Justice and Strong Institutions ,Aggression ,Psychiatry and Mental health ,Schizophrenia ,TWINS ,Meta-analysis ,Cord blood ,Child, Preschool ,DNA methylation ,HEALTH ,medicine.symptom ,SMOKING ,Adult ,SDG 16 - Peace ,Adolescent ,515 Psychology ,Longevity ,Biology ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Young Adult ,SDG 3 - Good Health and Well-being ,Genetic variation ,medicine ,Genetics ,Humans ,ddc:610 ,EXPOSURE ,ABUSE ,Genetic association ,Aged ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,SDG 16 - Peace, Justice and Strong Institutions ,3112 Neurosciences ,GENOME-WIDE ,DNA Methylation ,Epigenètica ,medicine.disease ,3141 Health care science ,030104 developmental biology ,COHORT PROFILE ,1182 Biochemistry, cell and molecular biology ,CpG Islands ,3111 Biomedicine ,Metaanàlisi ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Molecular psychiatry 26(6), 2148-2162 (2021). doi:10.1038/s41380-020-00987-x, Published by Macmillan, London
- Published
- 2021
49. DNA methylation signatures of aggression and closely related constructs:A meta-analysis of epigenome-wide studies across the lifespan
- Author
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Hagenbeek, Fiona A., Suderman, Matthew, van Dongen, Jenny, Roetman, Peter J., Sugden, Karen, Chiocchetti, Andreas G., Ismail, Khadeeja, Mulder, Rosa H., Hafferty, Jonathan D., Adams, Mark J., Walker, Rosie M., Morris, Stewart W., Lahti, Jari, Küpers, Leanne K., Escaramis, Georgia, Alemany, Silvia, Jan Bonder, Marc, Meijer, Mandy, Ip, Hill F., Jansen, Rick, Baselmans, Bart M.L., Parmar, Priyanka, Lowry, Estelle, Streit, Fabian, Sirignano, Lea, Send, Tabea S., Frank, Josef, Jylhävä, Juulia, Wang, Yunzhang, Mishra, Pashupati Prasad, Colins, Olivier F., Felix, Janine F., Ligthart, Lannie, van Meurs, Joyce, Hottenga, Jouke J., van Duijn, Cornelia M., Hofman, Bert A., Isaacs, Aaron, Uitterlinden, André G., Verbiest, Michael, Verkerk, Marijn, van Rooij, Jeroen, van Dijk, Freerk, Tiemeier, Henning, van IJzendoorn, Marinus H., Bartels, Meike, Hagenbeek, Fiona A., Suderman, Matthew, van Dongen, Jenny, Roetman, Peter J., Sugden, Karen, Chiocchetti, Andreas G., Ismail, Khadeeja, Mulder, Rosa H., Hafferty, Jonathan D., Adams, Mark J., Walker, Rosie M., Morris, Stewart W., Lahti, Jari, Küpers, Leanne K., Escaramis, Georgia, Alemany, Silvia, Jan Bonder, Marc, Meijer, Mandy, Ip, Hill F., Jansen, Rick, Baselmans, Bart M.L., Parmar, Priyanka, Lowry, Estelle, Streit, Fabian, Sirignano, Lea, Send, Tabea S., Frank, Josef, Jylhävä, Juulia, Wang, Yunzhang, Mishra, Pashupati Prasad, Colins, Olivier F., Felix, Janine F., Ligthart, Lannie, van Meurs, Joyce, Hottenga, Jouke J., van Duijn, Cornelia M., Hofman, Bert A., Isaacs, Aaron, Uitterlinden, André G., Verbiest, Michael, Verkerk, Marijn, van Rooij, Jeroen, van Dijk, Freerk, Tiemeier, Henning, van IJzendoorn, Marinus H., and Bartels, Meike
- Abstract
DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
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- 2021
50. Epigenome-wide change and variation in DNA methylation in childhood: trajectories from birth to late adolescence
- Author
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Mulder, Rosa, Neumann, Alexander, Cecil, Charlotte, Walton, Esther, Houtepen, Lotte C., Simpkin, AJ, Rijlaarsdam, Jolien, Heijmans, Bastiaan T., Gaunt, T. R., Felix, Janine, Jaddoe, Vincent, Bakermans-Kranenburg, Marian J., Tiemeier, Henning, Relton, Caroline, van IJzendoorn, Marinus, Suderman, Matthew, Mulder, Rosa, Neumann, Alexander, Cecil, Charlotte, Walton, Esther, Houtepen, Lotte C., Simpkin, AJ, Rijlaarsdam, Jolien, Heijmans, Bastiaan T., Gaunt, T. R., Felix, Janine, Jaddoe, Vincent, Bakermans-Kranenburg, Marian J., Tiemeier, Henning, Relton, Caroline, van IJzendoorn, Marinus, and Suderman, Matthew
- Abstract
DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5019 blood samples collected at multiple time-points from birth to late adolescence from 2348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases, DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for non-linear change and inter-individual variation in non-linear trajectories was somewhat less common (11 and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. In contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often non-linear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu.ac.uk.
- Published
- 2021
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