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2. Fairness and bias correction in machine learning for depression prediction: results from four study populations

Author

Dang, Vien Ngoc, Cascarano, Anna, Mulder, Rosa H., Cecil, Charlotte, Zuluaga, Maria A., Hernández-González, Jerónimo, and Lekadir, Karim

Subjects
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

Published
2022

3. Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation

Author

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.

Published
2023
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8. Longitudinal associations of DNA methylation and sleep in children: a meta-analysis

Author

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.

Published
2022
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10. Epigenetic timing effects on child developmental outcomes: A longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium

Author

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

Published
2024
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12. Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation

Author

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

Published
2021
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13. Are some children genetically predisposed to poor sleep? A polygenic risk study in the general population.

Author

Kocevska, Desana, Trajanoska, Katerina, Mulder, Rosa H., Koopman‐Verhoeff, M. Elisabeth, Luik, Annemarie I., Tiemeier, Henning, and van Someren, Eus J.W.

Subjects
RISK assessment, CHILDREN'S health, GENOME-wide association studies, RESEARCH funding, INSOMNIA, MOTHERS, MEDICAL genetics, ACTIGRAPHY, AGE distribution, SLEEP duration, CHILD Behavior Checklist, CONFIDENCE intervals, DISEASE risk factors, ADOLESCENCE, CHILDREN
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. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation

Author

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.

Published
2024
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20. Mapping gene by early life stress interactions on child subcortical brain structures

Author

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

Subjects
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.

Published
2022

22. Additional file 2 of Longitudinal associations of DNA methylation and sleep in children: a meta-analysis

Author

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

Published
2022
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23. Additional file 1 of Longitudinal associations of DNA methylation and sleep in children: a meta-analysis

Author

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

Published
2022
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24. Fairness and bias correction in machine learning for depression prediction: results from four different study populations

Author

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

Published
2022
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25. Maternal Mediterranean diet in pregnancy and newborn DNA methylation: a meta-analysis in the PACE Consortium

Author

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
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26. Developmental Changes in Dynamic Functional Connectivity From Childhood Into Adolescence

Author

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
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27. Epigenome-wide associations between observed maternal sensitivity and offspring DNA methylation: a population-based prospective study in children.

Author

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
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28. DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

Author

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

29. Neonatal DNA methylation and childhood low prosocial behavior: An epigenome‐wide association meta‐analysis

Author

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
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30. Epigenome-wide change and variation in DNA methylation in childhood: trajectories from birth to late adolescence

Author

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
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31. Epigenome-wide associations between observed maternal sensitivity and offspring DNA methylation: a population-based prospective study in children

Author

Dall’ Aglio, Lorenza, primary, Rijlaarsdam, Jolien, additional, Mulder, Rosa H., additional, Neumann, Alexander, additional, Felix, Janine F., additional, Kok, Rianne, additional, Bakermans-Kranenburg, Marian J., additional, van Ijzendoorn, Marinus H., additional, Tiemeier, Henning, additional, and Cecil, Charlotte A.M., additional

Published
2020
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32. Epigenome-wide change and variation in DNA methylation from birth to late adolescence

Author

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
2020
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34. Epigenomics of being bullied: changes in DNA methylation following bullying exposure

Author

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
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35. Frequent Bullying Involvement and Brain Morphology in Children

Author

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
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37. EPIGENOME-WIDE ASSOCIATION STUDY META-ANALYSIS OF AGGRESSIVE BEHAVIOR

Author

van Dongen, Jenny, primary, Suderman, Matthew, additional, Sugden, Karen, additional, Chiocchetti, Andreas G., additional, Mulder, Rosa H., additional, Lahti, Jari, additional, Küpers, Leanne K., additional, Bustamante, Mariona, additional, Alemany, Silvia, additional, Bonder, Marc Jan, additional, Parmar, Priyanka, additional, Lowry, Estelle, additional, Jansen, Rick, additional, M. L. Baselmans, Bart, additional, and G. Nivard, Michel, additional

Published
2019
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39. Methylation matters: FK506 binding protein 51 (FKBP5) methylation moderates the associations of FKBP5 genotype and resistant attachment with stress regulation.

Author

Roisman, Glenn I., Cicchetti, Dante, Mulder, Rosa H., Rijlaarsdam, Jolien, Luijk, Maartje P. C. M., Verhulst, Frank C., Felix, Janine F., Tiemeier, Henning, Bakermans-Kranenburg, Marian J., and Van Ijzendoorn, Marinus H.

Subjects
TACROLIMUS, DNA methylation, CARRIER proteins, GENOTYPES, PSYCHOLOGICAL stress, EPIGENETICS, PARENT-child relationships
Abstract

The parent–child attachment relationship plays an important role in the development of the infant's stress regulation system. However, genetic and epigenetic factors such as FK506 binding protein 51 (FKBP5) genotype and DNA methylation have also been associated with hypothalamus–pituitary–adrenal axis functioning. In the current study, we examined how parent–child dyadic regulation works in concert with genetic and epigenetic aspects of stress regulation. We study the associations of attachment, extreme maternal insensitivity, FKBP5 single nucleotide polymorphism 1360780, and FKBP5 methylation, with cortisol reactivity to the Strange Situation Procedure in 298 14-month-old infants. The results indicate that FKBP5 methylation moderates the associations of FKBP5 genotype and resistant attachment with cortisol reactivity. We conclude that the inclusion of epigenetics in the field of developmental psychopathology may lead to a more precise picture of the interplay between genetic makeup and parenting in shaping stress reactivity. [ABSTRACT FROM PUBLISHER]

Published
2017
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40. DNA methylation signatures of a broad spectrum of aggressive behavior: a meta-analysis of epigenome-wide studies across the lifespan

Author

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

41. Epigenome-wide association study meta-analysis of aggressive behavior

Author

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)

42. Consortium Profile: The Methylation, Imaging and NeuroDevelopment (MIND) Consortium.

Author

Schuurmans IK, Mulder RH, Baltramonaityte V, Lahtinen A, Qiuyu F, Rothmann LM, Staginnus M, Tuulari J, Burt SA, Buss C, Craig JM, Donald KA, Felix JF, Freeman TP, Grassi-Oliveira R, Huels A, Hyde LW, Jones SA, Karlsson H, Karlsson L, Koen N, Lawn W, Mitchell C, Monk CS, Mooney MA, Muetzel R, Nigg JT, Belangero SIN, Notterman D, O'Connor T, O'Donnell KJ, Pan PM, Paunio T, Ryabinin P, Saffery R, Salum GA, Seal M, Silk TJ, Stein DJ, Zar H, Walton E, and Cecil CAM

Abstract

Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults. To bridge this gap, we established the Methylation, Imaging and NeuroDevelopment (MIND) Consortium, which aims to bring a developmental focus to the emerging field of Neuroimaging Epigenetics by (i) promoting collaborative, adequately powered developmental research via multi-cohort analyses; (ii) increasing scientific rigor through the establishment of shared pipelines and open science practices; and (iii) advancing our understanding of DNA methylation-brain dynamics at different developmental periods (from birth to emerging adulthood), by leveraging data from prospective, longitudinal pediatric studies. MIND currently integrates 15 cohorts worldwide, comprising (repeated) measures of DNA methylation in peripheral tissues (blood, buccal cells, and saliva) and neuroimaging by magnetic resonance imaging across up to five time points over a period of up to 21 years (N pooled DNAm = 11,299; N pooled neuroimaging = 10,133; N pooled combined = 4,914). By triangulating associations across multiple developmental time points and study types, we hope to generate new insights into the dynamic relationships between peripheral DNA methylation and the brain, and how these ultimately relate to neurodevelopmental and psychiatric phenotypes.

Published
2024
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43. What makes clocks tick? Characterizing developmental dynamics of adult epigenetic clock sites.

Author

Mulder RH, Neumann A, Felix JF, Suderman M, and Cecil CAM

Abstract

DNA methylation (DNAm) at specific sites can be used to calculate 'epigenetic clocks', which in adulthood are used as indicators of age( ing ). However, little is known about how these clock sites 'behave' during development and what factors influence their variability in early life. This knowledge could be used to optimize healthy aging well before the onset of age-related conditions. Here, we leveraged results from two longitudinal population-based cohorts ( N =5,019 samples from 2,348 individuals) to characterize trajectories of adult clock sites from birth to early adulthood. We find that clock sites (i) diverge widely in their developmental trajectories, often showing non-linear change over time; (ii) are substantially more likely than non-clock sites to vary between individuals already from birth, differences that are predictive of DNAm variation at later ages; and (iii) show enrichment for genetic and prenatal environmental exposures, supporting an early-origins perspective to epigenetic aging., Competing Interests: Competing interests The authors provide no competing interests.

Published
2024
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44. DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.

Author

van Dongen J, Hagenbeek FA, Suderman M, Roetman PJ, Sugden K, Chiocchetti AG, Ismail K, Mulder RH, Hafferty JD, Adams MJ, Walker RM, Morris SW, Lahti J, Küpers LK, Escaramis G, Alemany S, Jan Bonder M, Meijer M, Ip HF, Jansen R, Baselmans BML, Parmar P, Lowry E, Streit F, Sirignano L, Send TS, Frank J, Jylhävä J, Wang Y, Mishra PP, Colins OF, Corcoran DL, Poulton R, Mill J, Hannon E, Arseneault L, Korhonen T, Vuoksimaa E, Felix JF, Bakermans-Kranenburg MJ, Campbell A, Czamara D, Binder E, Corpeleijn E, Gonzalez JR, Grazuleviciene R, Gutzkow KB, Evandt J, Vafeiadi M, Klein M, van der Meer D, Ligthart L, Kluft C, Davies GE, Hakulinen C, Keltikangas-Järvinen L, Franke B, Freitag CM, Konrad K, Hervas A, Fernández-Rivas A, Vetro A, Raitakari O, Lehtimäki T, Vermeiren R, Strandberg T, Räikkönen K, Snieder H, Witt SH, Deuschle M, Pedersen NL, Hägg S, Sunyer J, Franke L, Kaprio J, Ollikainen M, Moffitt TE, Tiemeier H, van IJzendoorn MH, Relton C, Vrijheid M, Sebert S, Jarvelin MR, Caspi A, Evans KL, McIntosh AM, Bartels M, and Boomsma DI

Subjects
Adolescent, Adult, Aged, Aggression, Child, Child, Preschool, CpG Islands genetics, Epigenesis, Genetic genetics, Genome-Wide Association Study, Humans, Longevity, Middle Aged, Young Adult, DNA Methylation genetics, Epigenome
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., (© 2021. The Author(s).)

Published
2021
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45. Methylation matters: FK506 binding protein 51 (FKBP5) methylation moderates the associations of FKBP5 genotype and resistant attachment with stress regulation.

Author

Mulder RH, Rijlaarsdam J, Luijk MP, Verhulst FC, Felix JF, Tiemeier H, Bakermans-Kranenburg MJ, and Van Ijzendoorn MH

Subjects
Female, Genotype, Humans, Infant, Male, Polymorphism, Single Nucleotide, DNA Methylation physiology, Epigenesis, Genetic physiology, Hydrocortisone metabolism, Maternal Behavior physiology, Object Attachment, Stress, Psychological metabolism, Tacrolimus Binding Proteins metabolism
Abstract

The parent-child attachment relationship plays an important role in the development of the infant's stress regulation system. However, genetic and epigenetic factors such as FK506 binding protein 51 (FKBP5) genotype and DNA methylation have also been associated with hypothalamus-pituitary-adrenal axis functioning. In the current study, we examined how parent-child dyadic regulation works in concert with genetic and epigenetic aspects of stress regulation. We study the associations of attachment, extreme maternal insensitivity, FKBP5 single nucleotide polymorphism 1360780, and FKBP5 methylation, with cortisol reactivity to the Strange Situation Procedure in 298 14-month-old infants. The results indicate that FKBP5 methylation moderates the associations of FKBP5 genotype and resistant attachment with cortisol reactivity. We conclude that the inclusion of epigenetics in the field of developmental psychopathology may lead to a more precise picture of the interplay between genetic makeup and parenting in shaping stress reactivity.

Published
2017
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