45 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. 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
- Full Text
- View/download PDF
4. 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
5. 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
- Full Text
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6. 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.
- Abstract
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
7. 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
- Full Text
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8. 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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9. 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
10. 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., Mulder, Rosa H., 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.
- Abstract
The etiology of childhood appetitive traits is poorly understood. Early-life epigenetic processes may be involved in the developmental programming of appetite regulation in childhood. One such process is DNA methylation (DNAm), whereby a methyl group is added to a specific part of DNA, where a cytosine base is next to a guanine base, a CpG site. We meta-analyzed epigenome-wide association studies (EWASs) of cord blood DNAm and early-childhood appetitive traits. Data were from two independent cohorts: the Generation R Study (n = 1,086, Rotterdam, the Netherlands) and the Healthy Start study (n = 236, Colorado, USA). DNAm at autosomal methylation sites in cord blood was measured using the Illumina Infinium HumanMethylation450 BeadChip. Parents reported on their child's food responsiveness, emotional undereating, satiety responsiveness and food fussiness using the Children's Eating Behaviour Questionnaire at age 4–5 years. Multiple regression models were used to examine the association of DNAm (predictor) at the individual site- and regional-level (using DMRff) with each appetitive trait (outcome), adjusting for covariates. Bonferroni-correction was applied to adjust for multiple testing. There were no associations of DNAm and any appetitive trait when examining individual CpG-sites. However, when examining multiple CpGs jointly in so-called differentially methylated regions, we identified 45 associations of DNAm with food responsiveness, 7 associations of DNAm with emotional undereating, 13 associations of DNAm with satiety responsiveness, and 9 associations of DNAm with food fussiness. This study shows that DNAm in the newborn may partially explain variation in appetitive traits expressed in early childhood and provides preliminary support for early programming of child appetitive traits through DNAm. Investigating differential DNAm associated with appetitive traits could be an important first step in identifying biological pathways underlying the development of t
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- 2023
11. 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
12. 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.
- Abstract
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
13. 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
14. Epigenome-wide associations between observed maternal sensitivity and offspring DNA methylation: a population-based prospective study in children
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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
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15. 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
16. 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
17. Connecting the dots:social networks in the classroom and white matter connections in the brain
- Author
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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
18. 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.
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- 2022
19. Maternal Mediterranean diet in pregnancy and newborn DNA methylation: a meta-analysis in the PACE Consortium
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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
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- 2022
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20. Additional file 2 of 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.
- Abstract
Additional file2. Methods
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- 2022
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21. Additional file 1 of 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.
- 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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22. 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
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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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23. 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
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- 2021
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24. 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
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- 2021
25. DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan
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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
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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
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- 2021
26. 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, Lahti, Jari, 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
- Abstract
Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.
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- 2021
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27. DNA methylation signatures of aggression and closely related constructs:A meta-analysis of epigenome-wide studies across the lifespan
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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
28. Epigenome-wide change and variation in DNA methylation in childhood: trajectories from birth to late adolescence
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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.
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- 2021
29. Developmental Changes in Dynamic Functional Connectivity From Childhood Into Adolescence
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López-Vicente, Mónica, Agcaoglu, Oktay, Pérez-Crespo, Laura, Estévez-López, Fernando, Heredia-Genestar, José María, Mulder, Rosa H., Flournoy, John C., van Duijvenvoorde, Anna C.K., Güroğlu, Berna, White, Tonya, Calhoun, Vince, Tiemeier, Henning, Muetzel, Ryan L., López-Vicente, Mónica, Agcaoglu, Oktay, Pérez-Crespo, Laura, Estévez-López, Fernando, Heredia-Genestar, José María, Mulder, Rosa H., Flournoy, John C., van Duijvenvoorde, Anna C.K., Güroğlu, Berna, White, Tonya, Calhoun, Vince, Tiemeier, Henning, and Muetzel, Ryan L.
- Abstract
The longitudinal study of typical neurodevelopment is key for understanding deviations due to specific factors, such as psychopathology. However, research utilizing repeated measurements remains scarce. Resting-state functional magnetic resonance imaging (MRI) studies have traditionally examined connectivity as ‘static’ during the measurement period. In contrast, dynamic approaches offer a more comprehensive representation of functional connectivity by allowing for different connectivity configurations (time varying connectivity) throughout the scanning session. Our objective was to characterize the longitudinal developmental changes in dynamic functional connectivity in a population-based pediatric sample. Resting-state MRI data were acquired at the ages of 10 (range 8-to-12, n = 3,327) and 14 (range 13-to-15, n = 2,404) years old using a single, study-dedicated 3 Tesla scanner. A fully-automated spatially constrained group-independent component analysis (ICA) was applied to decompose multi-subject resting-state data into functionally homogeneous regions. Dynamic functional network connectivity (FNC) between all ICA time courses were computed using a tapered sliding window approach. We used a k-means algorithm to cluster the resulting dynamic FNC windows from each scan session into five dynamic states. We examined age and sex associations using linear mixed-effects models. First, independent from the dynamic states, we found a general increase in the temporal variability of the connections between intrinsic connectivity networks with increasing age. Second, when examining the clusters of dynamic FNC windows, we observed that the time spent in less modularized states, with low intra- and inter-network connectivity, decreased with age. Third, the number of transitions between states also decreased with age. Finally, compared to boys, girls showed a more mature pattern of dynamic brain connectivity, indicated by more time spent in a highly modularized state, less t
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- 2021
30. Neonatal DNA methylation and childhood low prosocial behavior:An epigenome-wide association meta-analysis
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Luo, Mannan, Meehan, Alan J., Walton, Esther, Röder, Stefan, Herberth, Gunda, Zenclussen, Ana C., Cosín-Tomás, Marta, Sunyer, Jordi, Mulder, Rosa H., Cortes Hidalgo, Andrea P., Bakermans-Kranenburg, Marian J., Felix, Janine F., Relton, Caroline, Suderman, Matthew, Pappa, Irene, Kok, Rianne, Tiemeier, Henning, van IJzendoorn, Marinus H., Barker, Edward D., Cecil, Charlotte A.M., Luo, Mannan, Meehan, Alan J., Walton, Esther, Röder, Stefan, Herberth, Gunda, Zenclussen, Ana C., Cosín-Tomás, Marta, Sunyer, Jordi, Mulder, Rosa H., Cortes Hidalgo, Andrea P., Bakermans-Kranenburg, Marian J., Felix, Janine F., Relton, Caroline, Suderman, Matthew, Pappa, Irene, Kok, Rianne, Tiemeier, Henning, van IJzendoorn, Marinus H., Barker, Edward D., and Cecil, Charlotte A.M.
- Abstract
Low prosocial behavior in childhood has been consistently linked to later psychopathology, with evidence supporting the influence of both genetic and environmental factors on its development. Although neonatal DNA methylation (DNAm) has been found to prospectively associate with a range of psychological traits in childhood, its potential role in prosocial development has yet to be investigated. This study investigated prospective associations between cord blood DNAm at birth and low prosocial behavior within and across four longitudinal birth cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium. We examined (a) developmental trajectories of “chronic-low” versus “typical” prosocial behavior across childhood in a case–control design (N = 2,095), and (b) continuous “low prosocial” scores at comparable cross-cohort time-points (N = 2,121). Meta-analyses were performed to examine differentially methylated positions and regions. At the cohort-specific level, three CpGs were found to associate with chronic low prosocial behavior; however, none of these associations was replicated in another cohort. Meta-analysis revealed no epigenome-wide significant CpGs or regions. Overall, we found no evidence for associations between DNAm patterns at birth and low prosocial behavior across childhood. Findings highlight the importance of employing multi-cohort approaches to replicate epigenetic associations and reduce the risk of false positive discoveries.
- Published
- 2021
31. MOESM1 of Epigenome-wide association study of seizures in childhood and adolescence
- Author
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Doretta Caramaschi, Hatcher, Charlie, Mulder, Rosa, Felix, Janine, Cecil, Charlotte, Relton, Caroline, and Walton, Esther
- Abstract
Additional file 1: Figure S1. Overlap of cases across time points. Figure S2. Overview of results. All models were adjusted for covariates as specified in the main text (including cell composition and surrogate variables). In MR analyses, epilepsy was chosen as a trait due to the availability of GWAS summary data as well as febrile and MMR-vaccine-related seizures. Figure S3. Plots displaying bivariate correlations between all variables included in the final models: (A) at birth, (B) during childhood and (C-D) adolescence (cross-sectional and lifetime seizure exposure, respectively). Figure S4. Miami plots displaying EWAS results: (A) at birth, (B) during childhood and (C-D) adolescence (cross-sectional and lifetime seizure exposure, respectively). The sign of the y-axis (-log(P-values) has been changed to indicate positive and negative changes in DNA methylation. Bonferroni cut-off line in red. Figure S5. Quantile-quantile plots displaying potential test statistic inflation in the final models (A) at birth, (B) during childhood and (C-D) adolescence (cross-sectional and lifetime seizure exposure, respectively). Lambda was calculated using the regression method. Figure S6. Differences in DNA methylation according to experienced seizures in ALSPAC and Generation R (top panel) in the BDNF gene. The bottom panel shows the location of the transcripts reverse strand. Figure S7. Cross-tissue correspondence of CpG sites, passing FDR correction in ALSPAC, based on data available at A-E) https://epigenetics.essex.ac.uk/bloodbrain and F-G) https://redgar598.shinyapps.io/BECon. PFC = prefrontal cortex; STG = superior temporal gyrus; EC = entorhinal cortex; CER = cerebellum. Figure S8. Tissue-specific expression of BDNF, MACROD2 and PRMT10, based on data available at www.gtexportal.org. Table S1. Sample descriptives of Generation R. Table S2. Association estimates for FDR
- Published
- 2020
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32. Epigenome-wide association study of seizures in childhood and adolescence
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Caramaschi, D, Hatcher, C, Mulder, Rosa, Felix, Janine, Cecil, Charlotte, Relton, CL, Walton, E, Caramaschi, D, Hatcher, C, Mulder, Rosa, Felix, Janine, Cecil, Charlotte, Relton, CL, and Walton, E
- Published
- 2020
33. Epigenomics of being bullied: changes in DNA methylation following bullying exposure
- Author
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Mulder, Rosa, Walton, E, Neumann, Alexander, Houtepen, LC, Felix, Janine, Bakermans-Kranenburg, MJ, Suderman, M, Tiemeier, Henning, IJzendoorn, Marinus, Relton, CL, Cecil, Charlotte, Mulder, Rosa, Walton, E, Neumann, Alexander, Houtepen, LC, Felix, Janine, Bakermans-Kranenburg, MJ, Suderman, M, Tiemeier, Henning, IJzendoorn, Marinus, Relton, CL, and Cecil, Charlotte
- Published
- 2020
34. Genome-wide DNA methylation patterns associated with sleep and mental health in children: a population-based study
- Author
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Koopman - Verhoeff, Elize, Mulder, Rosa, Saletin, JM, Reiss, Irwin, van der Horst, Bert, Felix, Janine, Carskadon, MA, Tiemeier, Henning, Cecil, Charlotte, Koopman - Verhoeff, Elize, Mulder, Rosa, Saletin, JM, Reiss, Irwin, van der Horst, Bert, Felix, Janine, Carskadon, MA, Tiemeier, Henning, and Cecil, Charlotte
- Published
- 2020
35. Epigenome-wide change and variation in DNA methylation in childhood: trajectories from birth to late adolescence
- Author
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Mulder, Rosa H, primary, Neumann, Alexander, additional, Cecil, Charlotte A M, additional, Walton, Esther, additional, Houtepen, Lotte C, additional, Simpkin, Andrew J, additional, Rijlaarsdam, Jolien, additional, Heijmans, Bastiaan T, additional, Gaunt, Tom R, additional, Felix, Janine F, additional, Jaddoe, Vincent W V, additional, Bakermans-Kranenburg, Marian J, additional, Tiemeier, Henning, additional, Relton, Caroline L, additional, van IJzendoorn, Marinus H, additional, and Suderman, Matthew, additional
- Published
- 2021
- Full Text
- View/download PDF
36. Epigenomics of being bullied: changes in DNA methylation following bullying exposure
- Author
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Mulder, Rosa H., primary, Walton, Esther, additional, Neumann, Alexander, additional, Houtepen, Lotte C., additional, Felix, Janine F., additional, Bakermans-Kranenburg, Marian J., additional, Suderman, Matthew, additional, Tiemeier, Henning, additional, van IJzendoorn, Marinus H., additional, Relton, Caroline L., additional, and Cecil, Charlotte A. M., additional
- Published
- 2020
- Full Text
- View/download PDF
37. Frequent Bullying Involvement and Brain Morphology in Children
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Muetzel, Ryan, Mulder, Rosa, Lamballais Tessensohn, Sander, Cortés Hidalgo, Andrea, Jansen, Pauline, Guroglu, B, Vernooij, Meike, Hillegers, Manon, White, Tonya, El Marroun, Hanan, Tiemeier, Henning, Muetzel, Ryan, Mulder, Rosa, Lamballais Tessensohn, Sander, Cortés Hidalgo, Andrea, Jansen, Pauline, Guroglu, B, Vernooij, Meike, Hillegers, Manon, White, Tonya, El Marroun, Hanan, and Tiemeier, Henning
- Published
- 2019
38. Frequent Bullying Involvement and Brain Morphology in Children
- Author
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Muetzel, Ryan L., primary, Mulder, Rosa H., additional, Lamballais, Sander, additional, Cortes Hidalgo, Andrea P., additional, Jansen, Pauline, additional, Güroğlu, Berna, additional, Vernooiji, Meike W., additional, Hillegers, Manon, additional, White, Tonya, additional, El Marroun, Hanan, additional, and Tiemeier, Henning, additional
- Published
- 2019
- Full Text
- View/download PDF
39. 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., Tiemeier, Henning, 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
- Abstract
Paediatric population neuroimaging is an emerging field that falls at the intersection between developmental neuroscience and epidemiology. A key feature of population neuroimaging studies involves large-scale recruitment that is representative of the general population. One successful approach for population neuroimaging is to embed neuroimaging studies within large epidemiological cohorts. The Generation R Study is a large, prospective population-based birth-cohort in which nearly 10,000 pregnant mothers were recruited between 2002 and 2006 with repeated measurements in the children and their parents over time. Magnetic resonance imaging was included in 2009 with the scanning of 1070 6-to-9-year-old children. The second neuroimaging wave was initiated in April 2013 with a total of 4245 visiting the MRI suite and 4087 9-to-11-year-old children being scanned. The sequences included high-resolution structural MRI, 35-direction diffusion weighted imaging, and a 6 min and 2 s resting-state functional MRI scan. The goal of this paper is to provide an overview of the imaging protocol and the overlap between the neuroimaging data and metadata. We conclude by providing a brief overview of results from our first wave of neuroimaging, which highlights a diverse array of questions that can be addressed by merging the fields of developmental neuroscience and epidemiology.
- Published
- 2018
40. Epigenome-wide association study meta-analysis of aggressive behavior
- Author
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Dongen, Jenny, Ismail, Khadeeja, Mulder, Rosa, Baselmans, Bart, Nivard, Michel, Jansen, Rick, Ligthart, Lannie, Miina Ollikainen, Vuoksimaa, Eero, Tiemeier, Henning, Kaprio, Jaakko, Bartels, Meike, Boomsma, Dorret, Biological Psychology, and EMGO+ - Mental Health
- Subjects
Netherlands Twin Register (NTR) - Published
- 2016
41. 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, White, Tonya J H, 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
- Published
- 2017
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42. Epigenome-wide association study meta-analysis of aggressive behavior
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van Dongen, Jenny, Ismail, Khadeeja, Mulder, Rosa, Baselmans, Bart, Nivard, Michel, Jansen, Rick, Ligthart, Lannie, Ollikainen, Miina, Vuoksimaa, Eero, Tiemeier, Henning, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Amsterdam Neuroscience - Complex Trait Genetics
- Published
- 2016
43. DNA methylation signatures of a broad spectrum of aggressive behavior: a meta-analysis of epigenome-wide studies across the lifespan
- Author
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Dongen, Jenny, Hagenbeek, Fiona A., Suderman, Matthew, Roetman, Peter, Sugden, Karen, Chiocchetti, Andreas G., Ismail, Khadeeja, Mulder, Rosa H., Hafferty, Jonathan, Adams, Mark J., Walker, Rosie M., Morris, Stewart W., Lahti, Jari, Kupers, Leanne K., Escaramis, Georgia, Alemany, Silvia, Bonder, Marc Jan, Meijer, Mandy, Ip, Hill F., Jansen, Rick, Baselmans, Bart M. L., Parmar, Priyanka, Lowry, Estelle, Streit, Fabian, Sirignano, Lea, Send, Tabea, Frank, Josef, Jylhava, Juulia, Wang, Yunzhang, Mishra, Pashupati Prasad, Colins, Olivier F., Corcoran, David, Poulton, Richie, Jonathan Mill, Hannon, Eilis J., Arseneault, Louise, Korhonen, Tellervo, Vuoksimaa, Eero, Felix, Janine, Bakermans-Kranenburg, Marian, Campbell, Archie, Czamara, Darina, Binder, Elisabeth, Corpeleijn, Eva, Ramon Gonzalez, Juan, Grazuleviciene, Regina, Gutzkow, Kristine B., Evandt, Jorunn, Vafeiadi, Marina, Klein, Marieke, Meer, Dennis, Ligthart, Lannie, Kluft, Cornelis, Davies, Gareth E., Hakulinen, Christian, Keltikangas-Jarvinen, Liisa, Franke, Barbara, Freitag, Christine M., Konrad, Kerstin, Hervas, Amaia, Fernandez-Rivas, Aranzazu, Vetro, Agnes, Raitakari, Olli, Lehtimaki, Terho, Vermeiren, Robert, Strandberg, Timo, Raikkonen, Katri, Snieder, Harold, Witt, Stephanie H., Deuschle, Michael, Pedersen, Nancy L., Hagg, Sara, Sunyer, Jordi, Franke, Lude, Kaprio, Jaakko, Ollikainen, Miina, Moffitt, Terrie E., Tiemeier, Henning, Ijzendoorn, Marinus H., Relton, Caroline, Vrijheid, Martine, Sebert, Sylvain, Jarvelin, Marjo-Riitta, Caspi, Avshalom, Evans, Kathryn L., Mcintosh, Andrew M., Bartels, Meike, Boomsma, Dorret, Biological Psychology, APH - Mental Health, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Methodology, and Amsterdam Reproduction & Development
44. Epigenome-wide association study meta-analysis of aggressive behavior
- Author
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Dongen, Jenny, Suderman, Matthew, Sugden, Karen, Ismail, Khadeeja, Mulder, Rosa H., Kupper, Leanne K., Bustamante, Mariona, Alemany, Silvia, Bonder, Marc Jan, Parmar, Priyanka, Lowry, Estelle, Jansen, Rick, Baselmans, Bart, Nivard, Michel, Corcoran, David, Poulton, Richie, Mill, Jon, Hannon, Eilis, Arseneault, Louise, Vuoksimaa, Eero, Ollikainen, Miina, Corpeleijn, Eva, Ligthart, Lannie, Relton, Caroline, Moffitt, Terrie, Caspi, Avshalom, Jaakko Kaprio, Tiemeier, Henning, Snieder, Harold, Sunyer, Jordi, Franke, Lude, Sebert, Sylvain, Marjo-riitta, Bartels, Meike, Boomsma, Dorret, Reproductive Origins of Adult Health and Disease (ROAHD), Lifestyle Medicine (LM), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Stem Cell Aging Leukemia and Lymphoma (SALL)
45. An epigenome-wide association study of child appetitive traits and DNA methylation.
- Author
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Harris HA, Friedman C, Starling AP, Dabelea D, Johnson SL, Fuemmeler BF, Jima D, Murphy SK, Hoyo C, Jansen PW, Felix JF, and Mulder R
- Abstract
Childhood appetitive traits are consistently associated with obesity risk, and yet their etiology is poorly understood. Appetitive traits are complex phenotypes which are hypothesized to be influenced by both genetic and environmental factors, as well as their interactions. Early-life epigenetic processes, such as DNA methylation (DNAm), may be involved in the developmental programming of appetite regulation in childhood. In the current study, we meta-analyzed epigenome-wide association studies (EWASs) of cord blood DNAm and early-childhood appetitive traits. Data were from two independent cohorts: the Generation R Study ( n =1,086, Rotterdam, the Netherlands) and the Healthy Start study ( n =236, Colorado, USA). DNAm at autosomal methylation sites in cord blood was measured using the Illumina Infinium HumanMethylation450 BeadChip. Parents reported on their child's food responsiveness, emotional undereating, satiety responsiveness and food fussiness using the Children's Eating Behaviour Questionnaire at age 4-5 years. Multiple regression models were used to examine the association of DNAm (predictor) at the individual site- and regional-level (using DMRff) with each appetitive trait (outcome), adjusting for covariates. Bonferroni-correction was applied to adjust for multiple testing. There were no associations of DNAm and any appetitive trait at the individual site-level. However, at the regional level, we identified 45 associations of DNAm with food responsiveness, 7 associations of DNAm with emotional undereating, 13 associations of DNAm with satiety responsiveness, and 9 associations of DNAm with food fussiness. This study shows that DNAm in the newborn may partially explain variation in appetitive traits expressed in early childhood and provides preliminary support for early programming of child appetitive traits through DNAm. Investigating differential DNAm associated with appetitive traits could be an important first step in identifying biological pathways underlying the development of these behaviors., Competing Interests: Declarations of interest: none
- Published
- 2023
- Full Text
- View/download PDF
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