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1. Genome-wide characterization of circulating metabolic biomarkers

Author

Karjalainen, Minna K., Karthikeyan, Savita, Oliver-Williams, Clare, Sliz, Eeva, Allara, Elias, Fung, Wing Tung, Surendran, Praveen, Zhang, Weihua, Jousilahti, Pekka, Kristiansson, Kati, Salomaa, Veikko, Goodwin, Matt, Hughes, David A., Boehnke, Michael, Fernandes Silva, Lilian, Yin, Xianyong, Mahajan, Anubha, Neville, Matt J., van Zuydam, Natalie R., de Mutsert, Renée, Li-Gao, Ruifang, Mook-Kanamori, Dennis O., Demirkan, Ayse, Liu, Jun, Noordam, Raymond, Trompet, Stella, Chen, Zhengming, Kartsonaki, Christiana, Li, Liming, Lin, Kuang, Hagenbeek, Fiona A., Hottenga, Jouke Jan, Pool, René, Ikram, M. Arfan, van Meurs, Joyce, Haller, Toomas, Milaneschi, Yuri, Kähönen, Mika, Mishra, Pashupati P., Joshi, Peter K., Macdonald-Dunlop, Erin, Mangino, Massimo, Zierer, Jonas, Acar, Ilhan E., Hoyng, Carel B., Lechanteur, Yara T. E., Franke, Lude, Kurilshikov, Alexander, Zhernakova, Alexandra, Beekman, Marian, van den Akker, Erik B., Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Gieger, Christian, Waldenberger, Melanie, Asselbergs, Folkert W., Hayward, Caroline, Fu, Jingyuan, den Hollander, Anneke I., Menni, Cristina, Spector, Tim D., Wilson, James F., Lehtimäki, Terho, Raitakari, Olli T., Penninx, Brenda W. J. H., Esko, Tonu, Walters, Robin G., Jukema, J. Wouter, Sattar, Naveed, Ghanbari, Mohsen, Willems van Dijk, Ko, Karpe, Fredrik, McCarthy, Mark I., Laakso, Markku, Järvelin, Marjo-Riitta, Timpson, Nicholas J., Perola, Markus, Kooner, Jaspal S., Chambers, John C., van Duijn, Cornelia, Slagboom, P. Eline, Boomsma, Dorret I., Danesh, John, Ala-Korpela, Mika, Butterworth, Adam S., and Kettunen, Johannes

Published
2024
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2. Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms

Author

Jami, Eshim S, Hammerschlag, Anke R, Ip, Hill F, Allegrini, Andrea G, Benyamin, Beben, Border, Richard, Diemer, Elizabeth W, Jiang, Chang, Karhunen, Ville, Lu, Yi, Lu, Qing, Mallard, Travis T, Mishra, Pashupati P, Nolte, Ilja M, Palviainen, Teemu, Peterson, Roseann E, Sallis, Hannah M, Shabalin, Andrey A, Tate, Ashley E, Thiering, Elisabeth, Vilor-Tejedor, Natàlia, Wang, Carol, Zhou, Ang, Adkins, Daniel E, Alemany, Silvia, Ask, Helga, Chen, Qi, Corley, Robin P, Ehli, Erik A, Evans, Luke M, Havdahl, Alexandra, Hagenbeek, Fiona A, Hakulinen, Christian, Henders, Anjali K, Hottenga, Jouke Jan, Korhonen, Tellervo, Mamun, Abdullah, Marrington, Shelby, Neumann, Alexander, Rimfeld, Kaili, Rivadeneira, Fernando, Silberg, Judy L, van Beijsterveldt, Catharina E, Vuoksimaa, Eero, Whipp, Alyce M, Tong, Xiaoran, Andreassen, Ole A, Boomsma, Dorret I, Brown, Sandra A, Burt, S Alexandra, Copeland, William, Dick, Danielle M, Harden, K Paige, Harris, Kathleen Mullan, Hartman, Catharina A, Heinrich, Joachim, Hewitt, John K, Hopfer, Christian, Hypponen, Elina, Jarvelin, Marjo-Riitta, Kaprio, Jaakko, Keltikangas-Järvinen, Liisa, Klump, Kelly L, Krauter, Kenneth, Kuja-Halkola, Ralf, Larsson, Henrik, Lehtimäki, Terho, Lichtenstein, Paul, Lundström, Sebastian, Maes, Hermine H, Magnus, Per, Munafò, Marcus R, Najman, Jake M, Njølstad, Pål R, Oldehinkel, Albertine J, Pennell, Craig E, Plomin, Robert, Reichborn-Kjennerud, Ted, Reynolds, Chandra, Rose, Richard J, Smolen, Andrew, Snieder, Harold, Stallings, Michael, Standl, Marie, Sunyer, Jordi, Tiemeier, Henning, Wadsworth, Sally J, Wall, Tamara L, Whitehouse, Andrew JO, Williams, Gail M, Ystrøm, Eivind, Nivard, Michel G, Bartels, Meike, and Middeldorp, Christel M

Subjects
Biological Psychology, Psychology, Pediatric Research Initiative, Pediatric, Brain Disorders, Behavioral and Social Science, Human Genome, Mental Health, Biotechnology, Serious Mental Illness, Genetics, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Adolescent, Adult, Aggression, Anxiety, Attention Deficit Disorder with Hyperactivity, Autistic Disorder, Bipolar Disorder, Child, Child, Preschool, Depression, Genome-Wide Association Study, Humans, Loneliness, Polymorphism, Single Nucleotide, Schizophrenia, Sleep Initiation and Maintenance Disorders, depression, anxiety, repeated measures, genetic epidemiology, molecular genetics, Medical and Health Sciences, Psychology and Cognitive Sciences, Developmental & Child Psychology, Clinical sciences, Paediatrics, Applied and developmental psychology
Abstract

ObjectiveTo investigate the genetic architecture of internalizing symptoms in childhood and adolescence.MethodIn 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument.ResultsThe meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg| = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa.ConclusionGenetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

Published
2022

5. Genetic association study of childhood aggression across raters, instruments, and age.

Author

Ip, Hill, van der Laan, Camiel, Krapohl, Eva, Brikell, Isabell, Sánchez-Mora, Cristina, Nolte, Ilja, St Pourcain, Beate, Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Colodro-Conde, Lucía, Gordon, Scott, Zayats, Tetyana, Aliev, Fazil, Jiang, Chang, Wang, Carol, Saunders, Gretchen, Karhunen, Ville, Hammerschlag, Anke, Adkins, Daniel, Border, Richard, Peterson, Roseann, Prinz, Joseph, Thiering, Elisabeth, Seppälä, Ilkka, Vilor-Tejedor, Natàlia, Ahluwalia, Tarunveer, Day, Felix, Hottenga, Jouke-Jan, Allegrini, Andrea, Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Soler Artigas, María, Rovira, Paula, Bosch, Rosa, Español, Gemma, Ramos Quiroga, Josep, Neumann, Alexander, Ensink, Judith, Grasby, Katrina, Morosoli, José, Tong, Xiaoran, Marrington, Shelby, Middeldorp, Christel, Scott, James, Vinkhuyzen, Anna, Shabalin, Andrey, Corley, Robin, Evans, Luke, Sugden, Karen, Alemany, Silvia, Sass, Lærke, Vinding, Rebecca, Ruth, Kate, Tyrrell, Jess, Davies, Gareth, Ehli, Erik, Hagenbeek, Fiona, De Zeeuw, Eveline, Van Beijsterveldt, Toos, Larsson, Henrik, Snieder, Harold, Verhulst, Frank, Amin, Najaf, Whipp, Alyce, Korhonen, Tellervo, Vuoksimaa, Eero, Rose, Richard, Uitterlinden, André, Heath, Andrew, Madden, Pamela, Haavik, Jan, Harris, Jennifer, Helgeland, Øyvind, Johansson, Stefan, Knudsen, Gun, Njolstad, Pal, Lu, Qing, Rodriguez, Alina, Henders, Anjali, Mamun, Abdullah, Najman, Jackob, Brown, Sandy, Hopfer, Christian, Krauter, Kenneth, Reynolds, Chandra, Smolen, Andrew, Stallings, Michael, Wadsworth, Sally, Wall, Tamara, Silberg, Judy, Miller, Allison, Keltikangas-Järvinen, Liisa, Hakulinen, Christian, Pulkki-Råback, Laura, Havdahl, Alexandra, Magnus, Per, and Raitakari, Olli

Subjects
Adolescent, Aggression, Child, Child, Preschool, Female, Genetic Association Studies, Genome-Wide Association Study, Humans, Infant, Mental Disorders, Retrospective Studies
Abstract

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.

Published
2021

6. Integrative Multi-omics Analysis of Childhood Aggressive Behavior

Author

Hagenbeek, Fiona A., van Dongen, Jenny, Pool, René, Roetman, Peter J., Harms, Amy C., Hottenga, Jouke Jan, Kluft, Cornelis, Colins, Olivier F., van Beijsterveldt, Catharina E. M., Fanos, Vassilios, Ehli, Erik A., Hankemeier, Thomas, Vermeiren, Robert R. J. M., Bartels, Meike, Déjean, Sébastien, and Boomsma, Dorret I.

Published
2023
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8. Genome-wide association meta-analysis identifies 29 new acne susceptibility loci

Author

Mitchell, Brittany L., Saklatvala, Jake R., Dand, Nick, Hagenbeek, Fiona A., Li, Xin, Min, Josine L., Thomas, Laurent, Bartels, Meike, Jan Hottenga, Jouke, Lupton, Michelle K., Boomsma, Dorret I., Dong, Xianjun, Hveem, Kristian, Løset, Mari, Martin, Nicholas G., Barker, Jonathan N., Han, Jiali, Smith, Catherine H., Rentería, Miguel E., and Simpson, Michael A.

Published
2022
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9. DNA methylation in peripheral tissues and left-handedness

Author

Odintsova, Veronika V., Suderman, Matthew, Hagenbeek, Fiona A., Caramaschi, Doretta, Hottenga, Jouke-Jan, Pool, René, Dolan, Conor V., Ligthart, Lannie, van Beijsterveldt, Catharina E. M., Willemsen, Gonneke, de Geus, Eco J. C., Beck, Jeffrey J., Ehli, Erik A., Cuellar-Partida, Gabriel, Evans, David M., Medland, Sarah E., Relton, Caroline L., Boomsma, Dorret I., and van Dongen, Jenny

Published
2022
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10. Contributors

Author

Almqvist, Catarina, primary, Ando, Juko, additional, Bartels, Meike, additional, Bayartai, Munkh-Erdene, additional, Beam, Christopher R., additional, Beltz, Adriene M., additional, Berenbaum, Sheri A., additional, Boomsma, Dorret I., additional, Brikell, Isabell, additional, Bui, Minh, additional, Calais-Ferreira, Lucas, additional, Christensen, Kaare, additional, Corley, Robin P., additional, Cortessis, Victoria K., additional, Cozen, Wendy, additional, Craig, Jeffrey M., additional, DiLalla, Lisabeth Fisher, additional, DiLalla, David L., additional, Dolan, Conor V., additional, Dowty, James G., additional, Elman, Jeremy A., additional, Esser, Vivienne F.C., additional, Ferreira, Paulo H., additional, Finkel, Deborah, additional, Giardina, Irene, additional, Hagenbeek, Fiona A., additional, Haltrich, Irén, additional, Heikkinen, Aino, additional, Hopper, John L., additional, Hottenga, Jouke-Jan, additional, Hur, Yoon-Mi, additional, Jamnik, Matthew R., additional, Jayaweera, Kaushalya, additional, Kaprio, Jaakko, additional, Kim, Alice J., additional, Lam, Esther, additional, Larsson, Henrik, additional, Lee, Soo Ji, additional, Lengyel, Anna, additional, Li, Shuai, additional, Lichtenstein, Paul, additional, Littvay, Levente, additional, Loehlin, John C., additional, Loke, Yuk Jing, additional, Lundgren, Sara, additional, Mack, Thomas M., additional, Malta, Sue, additional, Marshall, Riley L., additional, Martin, Nicholas G., additional, McGue, Matt, additional, Medland, Sarah E., additional, Mitchell, Brittany L., additional, Mitrea, Elena Cristina, additional, Mohandas, Namitha, additional, Morosoli, José J., additional, Métneki, Julia, additional, Nguyen, Tuong L., additional, Niculae, Francisca J., additional, Odintsova, Veronika, additional, Ollikainen, Miina, additional, Ordoñana, Juan R., additional, Pali, Emily, additional, Panizzon, Matthew S., additional, Park, Hang A., additional, Pedersen, Nancy L., additional, Pham, Holly T., additional, Polderman, Tinca J.C., additional, Pool, René, additional, Pári, András, additional, Rankin, Monica, additional, Renzo, Gian Carlo Di, additional, Reynolds, Chandra A., additional, Salehi, Maryam, additional, Segal, Nancy L., additional, Silventoinen, Karri, additional, Slagboom, P. Eline, additional, Steinman, Gary, additional, Stephenson, Garth, additional, Sumathipala, Athula, additional, Sung, Joohon, additional, Tafforin, Carole, additional, Tarnoki, Adam D., additional, Tarnoki, David L., additional, Tosto, Valentina, additional, Tsibizova, Valentina, additional, Varjassy, Peter, additional, Vuoksimaa, Eero, additional, Willemsen, Gonneke, additional, Wong, Yen Ting, additional, de Geus, Eco, additional, de Vries, Lianne P., additional, van Dongen, Jenny, additional, and van de Weijer, Margot P., additional

Published
2022
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12. A multi-omics data analysis workflow packaged as a FAIR Digital Object

Author

Niehues, Anna, primary, de Visser, Casper, additional, Hagenbeek, Fiona A, additional, Kulkarni, Purva, additional, Pool, René, additional, Karu, Naama, additional, Kindt, Alida S D, additional, Singh, Gurnoor, additional, Vermeiren, Robert R J M, additional, Boomsma, Dorret I, additional, van Dongen, Jenny, additional, ’t Hoen, Peter A C, additional, and van Gool, Alain J, additional

Published
2024
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13. Identical twins carry a persistent epigenetic signature of early genome programming

Author

van Dongen, Jenny, Gordon, Scott D., McRae, Allan F., Odintsova, Veronika V., Mbarek, Hamdi, Breeze, Charles E., Sugden, Karen, Lundgren, Sara, Castillo-Fernandez, Juan E., Hannon, Eilis, Moffitt, Terrie E., Hagenbeek, Fiona A., van Beijsterveldt, Catharina E. M., Jan Hottenga, Jouke, Tsai, Pei-Chien, Min, Josine L., Hemani, Gibran, Ehli, Erik A., Paul, Franziska, Stern, Claudio D., Heijmans, Bastiaan T., Slagboom, P. Eline, Daxinger, Lucia, van der Maarel, Silvère M., de Geus, Eco J. C., Willemsen, Gonneke, Montgomery, Grant W., Reversade, Bruno, Ollikainen, Miina, Kaprio, Jaakko, Spector, Tim D., Bell, Jordana T., Mill, Jonathan, Caspi, Avshalom, Martin, Nicholas G., and Boomsma, Dorret I.

Published
2021
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14. Integrative multi‐omics analysis of genomic, epigenomic, and metabolomics data leads to new insights for Attention‐Deficit/Hyperactivity Disorder.

Author

Hubers, Nikki, Hagenbeek, Fiona A., Pool, René, Déjean, Sébastien, Harms, Amy C., Roetman, Peter J., van Beijsterveldt, Catharina E. M., Fanos, Vassilios, Ehli, Erik A., Vermeiren, Robert R. J. M., Bartels, Meike, Hottenga, Jouke Jan, Hankemeier, Thomas, van Dongen, Jenny, and Boomsma, Dorret I.

Published
2024
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15. Integrative multi‐omics analysis of genomic, epigenomic, and metabolomics data leads to new insights for Attention‐Deficit/Hyperactivity Disorder

Author

Hubers, Nikki, primary, Hagenbeek, Fiona A., additional, Pool, René, additional, Déjean, Sébastien, additional, Harms, Amy C., additional, Roetman, Peter J., additional, van Beijsterveldt, Catharina E. M., additional, Fanos, Vassilios, additional, Ehli, Erik A., additional, Vermeiren, Robert R. J. M., additional, Bartels, Meike, additional, Hottenga, Jouke Jan, additional, Hankemeier, Thomas, additional, van Dongen, Jenny, additional, and Boomsma, Dorret I., additional

Published
2023
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16. A Multi-omics Data Analysis Workflow Packaged as a FAIR Digital Object

Author

Niehues, Anna, primary, de Visser, Casper, additional, Hagenbeek, Fiona A., additional, Kulkarni, Purva, additional, Pool, Rene, additional, Karu, Naama, additional, Kindt, Alida S. D., additional, Singh, Gurnoor, additional, Vermeiren, Robert R. J. M., additional, Boomsma, Dorret I., additional, van Dongen, Jenny, additional, 't Hoen, Peter A. C., additional, and van Gool, Alain J., additional

Published
2023
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17. Childhood aggression and the co-occurrence of behavioural and emotional problems: results across ages 3–16 years from multiple raters in six cohorts in the EU-ACTION project

Author

Bartels, Meike, Hendriks, Anne, Mauri, Matteo, Krapohl, Eva, Whipp, Alyce, Bolhuis, Koen, Conde, Lucia Colodro, Luningham, Justin, Fung Ip, Hill, Hagenbeek, Fiona, Roetman, Peter, Gatej, Raluca, Lamers, Audri, Nivard, Michel, van Dongen, Jenny, Lu, Yi, Middeldorp, Christel, van Beijsterveldt, Toos, Vermeiren, Robert, Hankemeijer, Thomas, Kluft, Cees, Medland, Sarah, Lundström, Sebastian, Rose, Richard, Pulkkinen, Lea, Vuoksimaa, Eero, Korhonen, Tellervo, Martin, Nicholas G., Lubke, Gitta, Finkenauer, Catrin, Fanos, Vassilios, Tiemeier, Henning, Lichtenstein, Paul, Plomin, Robert, Kaprio, Jaakko, and Boomsma, Dorret I.

Published
2018
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20. Integrative Multi-omics Analysis of Childhood Aggressive Behavior

Author

Hagenbeek, Fiona A., primary, van Dongen, Jenny, additional, Pool, René, additional, Roetman, Peter J., additional, Harms, Amy C., additional, Hottenga, Jouke Jan, additional, Kluft, Cornelis, additional, Colins, Olivier F., additional, van Beijsterveldt, Catharina E. M., additional, Fanos, Vassilios, additional, Ehli, Erik A., additional, Hankemeier, Thomas, additional, Vermeiren, Robert R. J. M., additional, Bartels, Meike, additional, Déjean, Sébastien, additional, and Boomsma, Dorret I., additional

Published
2022
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21. INTEGRATIVE MULTI-OMICS APPROACHES TO CHILDHOOD AGGRESSION AND ATTENTION-DEFICIT/ HYPERACTIVITY DISORDER

Author

Hagenbeek, Fiona, primary, Hubers, Nikki, additional, van Dongen, Jenny, additional, Pool, Rene, additional, Roetman, Peter, additional, Harms, Amy, additional, Hottenga, Jouke-Jan, additional, Hankemeier, Thomas, additional, Veremeiren, Robert, additional, Bartels, Meike, additional, Déjean, Sébastien, additional, and Boomsma, Dorret, additional

Published
2022
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22. A Multi-omics Data Analysis Workflow Packaged as a FAIR Digital Object

Author

Niehues, Anna, de Visser, Casper, Hagenbeek, Fiona A., Karu, Naama, Kindt, Alida S.D., Kulkarni, Purva, Pool, René, Boomsma, Dorret I., van Dongen, Jenny, van Gool, Alain J., and 't Hoen, Peter A.C.

Subjects
Nextflow, RO-Crate, Singularity, metadata, General Medicine, ISA-API
Abstract

In current biomedical and complex trait research, increasing numbers of large molecular profiling (omics) data sets are being generated. At the same time, many studies fail to be reproduced (Baker 2016, Kim 2018). In order to improve study reproducibility and data reuse, including integration of data sets of different types and origins, it is imperative to work with omics data that is findable, accessible, interoperable, and reusable (FAIR, Wilkinson 2016) at the source. The data analysis, integration and stewardship pillar of the Netherlands X-omics Initiative aims to facilitate multi-omics research by providing tools to create, analyze and integrate FAIR omics data. We here report a joint activity of X-omics and the Netherlands Twin Register demonstrating the FAIRification of a multi-omics data set and the development of a FAIR multi-omics data analysis workflow. The implementation of FAIR principles (Wilkinson 2016) can improve scientific transparency and facilitate data reuse. However, Kim (2018) showed in a case study that the availability of data and code are required but not sufficient to reproduce data analyses. They highlighted the importance of interoperable and open formats, and structured metadata. In order to increase research reproducibility on the data analysis level, additional practices such as version-control, code licensing, and documentation have been proposed. These include recommendations for FAIR software by the Netherlands eScience Center and the Dutch Data Archiving and Networked Services (DANS), and FAIR principles for research software proposed by the Research Data Alliance (Chue Hong 2022). Data analysis in biomedical research usually comprises multiple steps often resulting in complex data analysis workflows and requiring additional practices, such as containerization, to ensure transparency and reproducibility (Goble 2020, Stoudt 2021). We apply these practices to a multi-omics data set that comprises genome-wide DNA methylation profiles, targeted metabolomics, and behavioral data of two cohorts that participated in the ACTION Biomarker Study (ACTION, Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies, see consortium members in Suppl. material 1) (Boomsma 2015, Bartels 2018, Hagenbeek 2020, van Dongen 2021, Hagenbeek 2022). The ACTION-NTR cohort consists of twins that are either longitudinally concordant or discordant for childhood aggression. The ACTION-Curium-LUMC cohort consists of children referred to the Dutch LUMC Curium academic center for child and youth psychiatry. With the joint analysis of multi-omics data and behavioral data, we aim to identify substructures in the ACTION-NTR cohort and link them to aggressive behavior. First, the individuals are clustered using Similarity Network Fusion (SNF, Wang 2014), and latent feature dimensions are uncovered using different unsupervised methods including Multi-Omics Factor Analysis (MOFA) (Argelaguet 2018) and Multiple Correspondence Analysis (MCA, Lê 2008, Husson 2017). In a second step, we determine correlations between -omics and phenotype dimensions, and use them to explain the subgroups of individuals from the ACTION-NTR cohort. In order to validate the results, we project data of the ACTION-Curium-LUMC cohort onto the latent dimensions and determine if correlations between omics and phenotype data can be reproduced. Integration of data across cohorts and across data types, requires interoperability. We applied different practices to make the data FAIR, including conversion of files to community-standard formats, and capturing experimental metadata using the ISA (Investigation, Study, Assay) metadata framework (Johnson 2021) and ontology-based annotations. All data analysis steps including pre-processing of different omics data types were implemented in either R or Python and combined in a modular Nextflow (Di Tommaso 2017) workflow, where the environment for each step is provided as a Singularity (Kurtzer 2017) container. The analysis workflow is packaged in a Research Object Crate (RO-Crate) (Soiland-Reyes 2022). The RO-Crate is a FAIR digital object that contains the Nextflow workflow including ontology-based annotations of each analysis step. Since omics data is considered to be potentially personally identifiable, the packaged workflow contains a minimal synthetic data set resembling the original data structure. Finally, the code is made available on GitHub and the workflow is registered at Workflowhub (Goble 2021). Since our Nextflow workflow is set up in a modular manner, the individual analysis steps can be reused in other workflows. We demonstrate this replicability by applying different sub-workflows to data from two different cohorts., {"references":["Argelaguet R, et al. (2018) Multi‐Omics Factor Analysis—a framework for unsupervised integration of multi‐omics data sets. Molecular Systems Biology 14: e8124. https://doi.org/10.15252/msb.20178124","Baker M (2016) 1,500 scientists lift the lid on reproducibility. Nature 533: 452‑454. https://doi.org/10.1038/533452a","Bartels M, et al. (2018) Childhood aggression and the co-occurrence of behavioural and emotional problems: results across ages 3–16 years from multiple raters in six cohorts in the EU-ACTION project. European Child & Adolescent Psychiatry 27: 1105‑1121. https://doi.org/10.1007/s00787-018-1169-1","Boomsma D (2015) Aggression in children: unravelling the interplay of genes and environment through (epi)genetics and metabolomics. Journal of Pediatric and Neonatal Individualized Medicine (JPNIM) 4 (2): e040251. https://doi.org/10.7363/040251","Chue Hong NP, et al. (2022) FAIR Principles for Research Software version 1.0. (FAIR4RS Principles v1.0). Research Data Alliance. https://doi.org/10.15497/RDA00068","Di Tommaso P, et al. (2017) Nextflow enables reproducible computational workflows. Nature Biotechnology 35: 316‑319. https://doi.org/10.1038/nbt.3820","Goble C, et al. (2020) FAIR Computational Workflows. Data Intelligence 2 (1-2): 108‑121. https://doi.org/10.1162/dint_a_00033","Goble C, et al. (2021) Implementing FAIR Digital Objects in the EOSC-Life Workflow Collaboratory. Zenodo https://doi.org/10.5281/zenodo.4605653","Hagenbeek F, et al. (2020) Urinary Amine and Organic Acid Metabolites Evaluated as Markers for Childhood Aggression: The ACTION Biomarker Study. Frontiers in Psychiatry 11: 165. https://doi.org/10.3389/fpsyt.2020.00165","Hagenbeek F, et al. (2022) Heritability of Urinary Amines, Organic Acids, and Steroid Hormones in Children. Metabolites 12 (6): 474. https://doi.org/10.3390/metabo12060474","Husson F, et al. (2017) Exploratory Multivariate Analysis by Example Using R. 2nd Edition. Chapman and Hall/CRC, New York, 262 pp. [ISBN 9780429225437] https://doi.org/10.1201/b21874","Johnson D, et al. (2021) ISA API: An open platform for interoperable life science experimental metadata. GigaScience 10 (9): giab060. https://doi.org/10.1093/gigascience/giab060","Kim Y, et al. (2018) Experimenting with reproducibility: a case study of robustness in bioinformatics. GigaScience 7 (7): giy077. https://doi.org/10.1093/gigascience/giy077","Kurtzer G, et al. (2017) Singularity: Scientific containers for mobility of compute. PLOS ONE 12 (5): e0177459. https://doi.org/10.1371/journal.pone.0177459","Lê S, et al. (2008) FactoMineR: An R Package for Multivariate Analysis. Journal of Statistical Software 25 (1): 1‑18. https://doi.org/10.18637/jss.v025.i01","Soiland-Reyes S, et al. (2022) Packaging research artefacts with RO-Crate. Data Science1‑42. https://doi.org/10.3233/ds-210053","Stoudt S, et al. (2021) Principles for data analysis workflows. PLOS Computational Biology 17 (3): e1008770. https://doi.org/10.1371/journal.pcbi.1008770","van Dongen J, et al. (2021) DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan. Molecular Psychiatry 26 (6): 2148‑2162. https://doi.org/10.1038/s41380-020-00987-x","Wang B, et al. (2014) Similarity network fusion for aggregating data types on a genomic scale. Nature Methods 11 (3): 333‑337. https://doi.org/10.1038/nmeth.2810","Wilkinson M, et al. (2016) The FAIR Guiding Principles for scientific data management and stewardship. Scientific Data 3 (1): 160018. https://doi.org/10.1038/sdata.2016.18"]}

Published
2022
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24. Supplementary material 1 from: Niehues A, de Visser C, Hagenbeek FA, Karu N, Kindt ASD, Kulkarni P, Pool R, Boomsma DI, van Dongen J, van Gool AJ, 't Hoen PAC (2022) A Multi-omics Data Analysis Workflow Packaged as a FAIR Digital Object. Research Ideas and Outcomes 8: e94042. https://doi.org/10.3897/rio.8.e94042

Author

Niehues, Anna, primary, de Visser, Casper, additional, Hagenbeek, Fiona, additional, Karu, Naama, additional, Kindt, Alida, additional, Kulkarni, Purva, additional, Pool, René, additional, Boomsma, Dorret, additional, van Dongen, Jenny, additional, van Gool, Alain, additional, and 't Hoen, Peter, additional

Published
2022
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25. A Multi-omics Data Analysis Workflow Packaged as a FAIR Digital Object

Author

Niehues, Anna, primary, de Visser, Casper, additional, Hagenbeek, Fiona, additional, Karu, Naama, additional, Kindt, Alida, additional, Kulkarni, Purva, additional, Pool, René, additional, Boomsma, Dorret, additional, van Dongen, Jenny, additional, van Gool, Alain, additional, and 't Hoen, Peter, additional

Published
2022
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26. Integrative multi-omics analysis of genomic, epigenomic, and metabolomics data leads to new insights for Attention-Deficit/Hyperactivity Disorder

Author

Hubers, Nikki, primary, Hagenbeek, Fiona A., additional, Pool, René, additional, Déjean, Sébastien, additional, Harms, Amy C., additional, Roetman, Peter J., additional, van Beijsterveldt, Catharina E. M., additional, Fanos, Vassilios, additional, Ehli, Erik A., additional, Vermeiren, Robert R. J. M., additional, Bartels, Meike, additional, Hottenga, Jouke Jan, additional, Hankemeier, Thomas, additional, van Dongen, Jenny, additional, and Boomsma, Dorret I., additional

Published
2022
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27. FAIR data and metadata – The X-omics FAIR Data Cube and its added value for multi-omics researchers

Author

Niehues, Anna, Liao, XiaoFeng, Brandt, Martin, Doorbos, Cenna, Ederveen, Tom, Hagenbeek, Fiona, Huang, Junda, Kulkarni, Purva, van der Velde, K. Joeri, de Visser, Casper, van Vliet, Michael, and 't Hoen, Peter A. C.

Abstract

The FAIR (Findable, Accessible, Interoperable and Reusable) (FAIR) principles were proposed [1] to guide researchers to describe and share their data to increase data reuse and research reproducibility. Creating FAIR data can be challenging for multi-omics researchers due to a lack of tooling and a diverse landscape of (meta)data standards differing across -omics types. Linked data structures and graph representations allow semantic queries and open up new possibilities of data analysis. However, large multi-omics data sets cannot easily be converted to such structures. In the Netherlands X-omics Initiative, we develop a FAIR Data Cube (FDCube) [2] – a set of tools and services that help researchers in different stages of the Research Data Life Cycle including creating and describing new data, and finding, understanding and reusing existing FAIR multi-omics data. To facilitate creation of FAIR multi-omics data and metadata, we collaborate with different initiatives such as the FAIR Genomes project [3]. We adopt and develop metadata schemas for different omics data types, and make use of the Investigation-Study-Assay (ISA) metadata framework [4] to capture experimental metadata. Example workflows to create such metadata are publicly shared [5]. Researchers can find and query multi-omics studies via a FAIR Data Point (FDP) instance [6], which links to public or access-protected data repositories. A set of accompanying tools allows the import of general study metadata to the FDP as well as performing semantic queries on additional metadata on samples, phenotypes, or molecular features represented in an RDF-based knowledge graph. In order to allow analysis of access-protected data, we further implement a vantage6-based architecture that allows bioinformaticians to send containerised computing requests to access-controlled omics data storage and receive aggregated results. A prototype FDCube implementation is being developed in collaboration with the Trusted World of Corona (TWOC) [7], in which we use public COVID-19 multi-omics data sources to demonstrate the strength and added value of the FDCube and its FAIR-based methodologies. We invite researchers to discuss with us about their own experiences, how the FDcube can facilitate their research, and how X-omics tools can further support them., {"references":["M. Wilkinson, M. Dumontier, I. Aalbersberg et al. \"The FAIR Guiding Principles for scientific data management and stewardship\". Sci Data 3:160018, 2016. https://doi.org/10.1038/sdata.2016.18","https://github.com/Xomics/FAIRDataCube","K.J. van der Velde, G. Singh, R. Kaliyaperumal. et al. \"FAIR Genomes metadata schema promoting Next Generation Sequencing data reuse in Dutch healthcare and research\". Sci Data 9:169, 2022. https://doi.org/10.1038/s41597-022-01265-x","S.A., Sansone, P. Rocca-Serra, D. Field et al. \"Toward interoperable bioscience data\". Nat Genet 44:121–126, 2012. https://doi.org/10.1038/ng.1054","https://github.com/Xomics/ISA-ACTION-Template","https://fdp.x-omics.nl, hosted by SURF","https://health-holland.com/project/2020/trusted-world-of-corona"]}

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2022
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28. Heritability of Urinary Amines, Organic Acids, and Steroid Hormones in Children

Author

Hagenbeek, Fiona A., primary, van Dongen, Jenny, additional, Pool, René, additional, Harms, Amy C., additional, Roetman, Peter J., additional, Fanos, Vassilios, additional, van Keulen, Britt J., additional, Walker, Brian R., additional, Karu, Naama, additional, Hulshoff Pol, Hilleke E., additional, Rotteveel, Joost, additional, Finken, Martijn J. J., additional, Vermeiren, Robert R. J. M., additional, Kluft, Cornelis, additional, Bartels, Meike, additional, Hankemeier, Thomas, additional, and Boomsma, Dorret I., additional

Published
2022
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29. Twins and omics: the role of twin studies in multi-omics

Author

Hagenbeek, Fiona A., van Dongen, Jenny, Pool, René, Boomsma, Dorret I., Tarnoki, Adam, Tarnoki, David, Harris, Jennifer, Segal, Nancy, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Personalized Medicine, Amsterdam Reproduction & Development, APH - Methodology, Tarnoki, Adam, Tarnoki, David, Harris, Jennifer, and Segal, Nancy

Subjects
Epigenome, Genome, Twin design, Metabolome, Twins, Omics, Transcriptome
Abstract

Genomics, transcriptomics, proteomics, and metabolomics are the four main omics domains, referring to high-throughput studies of the genome (DNA), transcriptome (RNA), proteome (proteins), and metabolome (metabolites). Together, these omics domains describe how proteins are formed by the transcription and translation of genetic information and how cells, tissues, and organisms’ function at the molecular level. Other omics layers reflect regulatory and modulatory processes or exposures to the environment. Twin designs offer powerful analytical tools to study variation in omics data and the influence of omics on phenotypes and phenotypic development. Here, we review and discuss the contribution of twin studies to omics and argue that twin research plays a valuable role in omics research.

Published
2022

30. Genetics and Not Shared Environment Explains Familial Resemblance in Adult Metabolomics Data

Author

Pool, Rene, Hagenbeek, Fiona A., Hendriks, Anne M., van Dongen, Jenny, Willemsen, Gonneke, de Geus, Eco, van Dijk, Ko Willems, Verhoeven, Aswin, Suchiman, H. Eka, Beekman, Marian, Slagboom, P. Eline, Harms, Amy C., Hankemeier, Thomas, Boomsma, Dorret, I, Beekman, M., Suchiman, H. E. D., Amin, N., Beulens, J. W., van der Bom, J. A., Bomer, N., Demirkan, A., van Hilten, J. A., Meessen, J. M. T. A., Pool, R., Moed, M. H., Fu, J., Onderwater, G. L. J., Rutters, F., So-Osman, C., van der Flier, W. M., van der Heijden, A. A. W. A., van der Spek, A., Asselbergs, F. W., Boersma, E., Elders, P. M., Geleijnse, J. M., Ikram, M. A., Kloppenburg, M., Meulenbelt, I, Mooijaart, S. P., Nelissen, R. G. H. H., Netea, M. G., Penninx, B. W. J. H., Stehouwer, C. D. A., Teunissen, C. E., Terwindt, G. M., 't Hart, L. M., van den Maagdenberg, A. M. J. M., van der Harst, P., van der Horst, I. C. C., van der Kallen, C. J. H., van Greevenbroek, M. M. J., van Spil, W. E., Wijmenga, C., Zwinderman, A. H., Zhernikova, A., Jukema, J. W., Wolf, J. J. H. Barkey, Cats, D., Mei, H., Slofstra, M., Swertz, M., van den Akker, E. B., Deelen, J., Reinders, M. J. T., Boomsma, D., I, van Duijn, C. M., Slagboom, P. E., Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), MUMC+: MA Endocrinologie (9), MUMC+: MA Maag Darm Lever (9), MUMC+: MA Hematologie (9), MUMC+: MA Medische Oncologie (9), MUMC+: MA Nefrologie (9), MUMC+: MA Reumatologie (9), RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Molecular Neuroscience and Ageing Research (MOLAR), Cardiovascular Centre (CVC), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Center for Liver, Digestive and Metabolic Diseases (CLDM), Medical Microbiology and Infection Prevention, Graduate School, Tytgat Institute for Liver and Intestinal Research, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Obstetrics and Gynaecology, Cardiology, Public and occupational health, Gastroenterology and Hepatology, Paediatric Endocrinology, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, Epidemiology and Data Science, Obstetrics and gynaecology, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, Anatomy and neurosciences, Anesthesiology, General practice, Internal medicine, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Laboratory Medicine, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Neuroinfection & -inflammation, Amsterdam Reproduction & Development (AR&D), AMS - Musculoskeletal Health, AMS - Tissue Function & Regeneration, Rheumatology, Gastroenterology and hepatology, APH - Aging & Later Life, and APH - Digital Health

Subjects
Male, Netherlands Twin Register (NTR), 0301 basic medicine, Shared environment, Metabolite, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Genome-wide association study, heritability, METABOLITES, Keywords: Classical twin design, chemistry.chemical_compound, 0302 clinical medicine, metabolite classes, Twins, Dizygotic, EPIDEMIOLOGY, Classical twin design, Genetics (clinical), Genetics, HERITABILITY, shared environment, Obstetrics and Gynecology, Phenotype, Quartile, Metabolome, Female, Adult, Dizygotic twin, POWER, TWIN, Environment, Biology, enrichment analysis, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Metabolomics, AGE, Diseases in Twins, Humans, Family, GENOME-WIDE ASSOCIATION, Classical twin design [Keywords], Twins, Monozygotic, PROFILES, Heritability, Diet, Metabolomics data, 030104 developmental biology, chemistry, Pediatrics, Perinatology and Child Health, Gene-Environment Interaction, 030217 neurology & neurosurgery
Abstract

Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term ‘metabolomics’ refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented.

Published
2020

31. DNA methylation in peripheral tissues and Left-handedness

Author

Odintsova, Veronika, primary, Sudermann, Matthew, additional, Hagenbeek, Fiona, additional, Caramaschi, Doretta, additional, Hottenga, Jouke-Jan, additional, Pool, Rene, additional, BIOS, Biobank-based Integrative Omics Study Consortium, additional, Dolan, Conor, additional, Ligthart, Lannie, additional, Beijsterveldt, Catharina van, additional, Willemsen, Gonneke, additional, de Geus, Eco, additional, Beck, Jeffrey, additional, Ehli, Erik, additional, Cuellar-Partida, Gabriel, additional, Evans, David, additional, Medland, Sarah, additional, Relton, Caroline, additional, Boomsma, Dorret, additional, and Dongen, Jenny van, additional

Published
2021
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32. Integrative multi-omics analysis of childhood aggressive behavior

Author

Hagenbeek, Fiona A., primary, van Dongen, Jenny, additional, Pool, René, additional, Roetman, Peter J., additional, Harms, Amy C., additional, Hottenga, Jouke Jan, additional, Kluft, Cornelis, additional, Colins, Olivier F., additional, van Beijsterveldt, Catharina E.M., additional, Fanos, Vassilios, additional, Ehli, Erik A., additional, Hankemeier, Thomas, additional, Vermeiren, Robert R. J. M., additional, Bartels, Meike, additional, Déjean, Sébastien, additional, and Boomsma, Dorret I., additional

Published
2021
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33. Predicting Complex Traits and Exposures From Polygenic Scores and Blood and Buccal DNA Methylation Profiles

Author

Odintsova, Veronika V., primary, Rebattu, Valerie, additional, Hagenbeek, Fiona A., additional, Pool, René, additional, Beck, Jeffrey J., additional, Ehli, Erik A., additional, van Beijsterveldt, Catharina E. M., additional, Ligthart, Lannie, additional, Willemsen, Gonneke, additional, de Geus, Eco J. C., additional, Hottenga, Jouke-Jan, additional, Boomsma, Dorret I., additional, and van Dongen, Jenny, additional

Published
2021
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34. 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

35. Epigenome-wide association study of left-handedness for different tissues and ages

Author

Odintsova, Veronika, primary, Sudermann, Matthew, additional, Hagenbeek, Fiona, additional, Caramaschi, Doretta, additional, Hottenga, Jouke-Jan, additional, Pool, René, additional, Dolan, Conor, additional, Ligthart, Lannie, additional, Beijsterveldt, Catharina van, additional, Willemsen, Gonneke, additional, de Geus, Eco, additional, Beck, Jeffrey, additional, Ehli, Erik, additional, Cuellar-Partida, Gabriel, additional, Evans, David, additional, Medland, Sarah, additional, Relton, Caroline, additional, Boomsma, Dorret, additional, and Dongen, Jenny van, additional

Published
2021
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36. Author Correction: Heritability estimates for 361 blood metabolites across 40 genome-wide association studies (Nature Communications, (2020), 11, 1, (39), 10.1038/s41467-019-13770-6)

Author

Hagenbeek, Fiona A., Pool, René, van Dongen, Jenny, Draisma, H. M., Jan Hottenga, Jouke, Willemsen, Gonneke, Abdellaoui, Abdel, Fedko, Iryna O., den Braber, Anouk, Visser, Pieter Jelle, de Geus, Eco J.C.N., Willems van Dijk, Ko, Verhoeven, Aswin, Suchiman, H. Eka, Beekman, Marian, Slagboom, P. Eline, van Duijn, Cornelia M., Barkey Wolf, J. J.H., Cats, D., Amin, N., Beulens, J. W., van der Bom, J. A., Bomer, N., Demirkan, A., van Hilten, J. A., Meessen, J. M.T.A., Moed, M. H., Fu, J., Onderwater, G. L.J., Rutters, F., So-Osman, C., van der Flier, W. M., van der Heijden, A. A.W.A., van der Spek, A., Asselbergs, F. W., Boersma, E., Elders, P. M., Geleijnse, J. M., Ikram, M. A., Kloppenburg, M., Meulenbelt, I., Mooijaart, S. P., Nelissen, R. G.H.H., Netea, M. G., Penninx, B. W.J.H., Stehouwer, C. D.A., Teunissen, C. E., Terwindt, G. M., ‘t Hart, L. M., van den Maagdenberg, A. M.J.M., van der Harst, P., van der Horst, I. C.C., van der Kallen, C. J.H., van Greevenbroek, M. M.J., van Spil, W. E., Wijmenga, C., Zwinderman, A. H., Zhernikova, A., Jukema, J. W., Mei, H., Slofstra, M., Swertz, M., van den Akker, E. B., Deelen, J., Reinders, M. J.T., Harms, Amy C., Hankemeier, Thomas, Bartels, Meike, Nivard, Michel G., Boomsma, Dorret I., Neurology, APH - Health Behaviors & Chronic Diseases, ACS - Heart failure & arrhythmias, Epidemiology and Data Science, General practice, APH - Methodology, APH - Mental Health, Psychiatry, Clinical chemistry, APH - Aging & Later Life, APH - Personalized Medicine, APH - Digital Health, and ACS - Diabetes & metabolism

Abstract

The original version of the Supplementary Information associated with this Article included an incorrect Supplementary Data 1 file, in which additional delimiters were included in the first column for a number of rows, resulting in column shifts for some of these rows. The HTML has been updated to include a corrected version of Supplementary Data 1; the original incorrect version of Supplementary Data 1 can be found as Supplementary Information associated with this Correction. In addition, the original version of this Article contained an error in the author affiliations. An affiliation of Abdel Abdellaoui with Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.

Published
2020

37. Epigenetics and handedness

Author

Odintsova, Veronika V., Suderman, Matthew, Hagenbeek, Fiona A., Caramaschi, Doretta, Hottenga, Jouke-Jan, Ligthart, Lannie R. S., van Beijsterveld, Catharina E. M., Willemsen, Gonneke, Ehli, Erik A., Davies, Gareth E., de Geus, Eco, Relton, Caroline, Boomsma, Dorret I., van Dongen, Jenny, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Personalized Medicine, APH - Methodology, and Amsterdam Reproduction & Development

Published
2020

38. Integrative multi-omics analysis of genomic, epigenomic, and metabolomic data for childhood aggressive behavior

Author

Hagenbeek, Fiona A., Dongen, Jenny, René Pool, Roetman, Peter J., Harms, Amy C., Hottenga, Jouke Jan, Kluft, Cornelis, Colins, Olivier F., Beijsterveldt, Catharina E. M., Vandenbosch, Marjolein M. L. J. Z., Zeeuw, Eveline L., Talens, Simone, Fanos, Vassilios, Ehli, Erik A., Davies, Gareth E., Vermeiren, Robert R. J. M., Hankemeier, Thomas, Bartels, Meike, Dejean, Sebastien, Boomsma, Dorret I., Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Personalized Medicine, Clinical Child and Family Studies, LEARN! - Child rearing, LEARN! - Educational neuroscience, learning and development, APH - Methodology, and Amsterdam Reproduction & Development

Published
2020

39. Genetic associations between childhood psychopathology and adult depression and associated traits in 42 998 individuals

Author

Akingbuwa, Wonuola A., Hammerschlag, Anke R., Jami, Eshim S., Allegrini, Andrea G., Karhunen, Ville, Sallis, Hannah, Ask, Helga, Askeland, Ragna B., Baselmans, Bart, Diemer, Elizabeth, Hagenbeek, Fiona A., Havdahl, Alexandra, Hottenga, Jouke-Jan, Mbarek, Hamdi, Rivadeneira, Fernando, Tesli, Martin, van Beijsterveldt, Catharina, Breen, Gerome, Lewis, Cathryn M., Thapar, Anita, Boomsma, Dorret I., Kuja-Halkola, Ralf, Reichborn-Kjennerud, Ted, Magnus, Per, Rimfeld, Kaili, Ystrom, Eivind, Jarvelin, Marjo-Riitta, Lichtenstein, Paul, Lundstrom, Sebastian, Munafò, Marcus R., Plomin, Robert, Tiemeier, Henning, Nivard, Michel G., Bartels, Meike, Middeldorp, Christel M., Holmans, Peter A., Richards, Alexander L., Escott-Price, Valentina, Forty, Liz, Fraser, Christine, Hamshere, Marian L., Craddock, Nicholas, Jones, Ian, Kirov, George, O'Donovan, Michael C., Owen, Michael J., Di Florio, Arianna, Tansey, Katherine E., and The Bipolar Disorder and Major Depressive Disorder Working Group

Abstract

Importance Adult mood disorders are often preceded by behavioral and emotional problems in childhood. It is yet unclear what explains the associations between childhood psychopathology and adult traits. Objective To investigate whether genetic risk for adult mood disorders and associated traits is associated with childhood disorders. Design, Setting, and Participants This meta-analysis examined data from 7 ongoing longitudinal birth and childhood cohorts from the UK, the Netherlands, Sweden, Norway, and Finland. Starting points of data collection ranged from July 1985 to April 2002. Participants were repeatedly assessed for childhood psychopathology from ages 6 to 17 years. Data analysis occurred from September 2017 to May 2019. Exposures Individual polygenic scores (PGS) were constructed in children based on genome-wide association studies of adult major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI). Main Outcomes and MeasuresRegression meta-analyses were used to test associations between PGS and attention-deficit/hyperactivity disorder (ADHD) symptoms and internalizing and social problems measured repeatedly across childhood and adolescence and whether these associations depended on childhood phenotype, age, and rater. Results The sample included 42 998 participants aged 6 to 17 years. Male participants varied from 43.0% (1040 of 2417 participants) to 53.1% (2434 of 4583 participants) by age and across all cohorts. The PGS of adult major depression, neuroticism, BMI, and insomnia were positively associated with childhood psychopathology (β estimate range, 0.023-0.042 [95% CI, 0.017–0.049]), while associations with PGS of subjective well-being and educational attainment were negative (β, −0.026 to −0.046 [95% CI, −0.020 to −0.057]). There was no moderation of age, type of childhood phenotype, or rater with the associations. The exceptions were stronger associations between educational attainment PGS and ADHD compared with internalizing problems (Δβ, 0.0561 [Δ95% CI, 0.0318-0.0804]; ΔSE, 0.0124) and social problems (Δβ, 0.0528 [Δ95% CI, 0.0282-0.0775]; ΔSE, 0.0126), and between BMI PGS and ADHD and social problems (Δβ, −0.0001 [Δ95% CI, −0.0102 to 0.0100]; ΔSE, 0.0052), compared with internalizing problems (Δβ, −0.0310 [Δ95% CI, −0.0456 to −0.0164]; ΔSE, 0.0074). Furthermore, the association between educational attainment PGS and ADHD increased with age (Δβ, −0.0032 [Δ 95% CI, −0.0048 to −0.0017]; ΔSE, 0.0008). Conclusions and Relevance Results from this study suggest the existence of a set of genetic factors influencing a range of traits across the life span with stable associations present throughout childhood. Knowledge of underlying mechanisms may affect treatment and long-term outcomes of individuals with psychopathology.

Published
2020

40. Twin studies of metabolomics traits and metabo-phenotype associations

Author

Boomsma, Dorret, René Pool, Hagenbeek, Fiona, Hankemeier, Thomas, Kluft, Cornelis, Fanos, Vassilios, Nivard, Michel, Bartels, Meike, Harms, Amy, Slagboom, Eline, Biological Psychology, APH - Mental Health, APH - Methodology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, and Amsterdam Reproduction & Development

Subjects
Netherlands Twin Register (NTR)
Published
2019

41. Genome-wide association meta-analysis of childhood and adolescent internalising symptoms

Author

Jami, Eshim S, primary, Hammerschlag, Anke R, additional, Ip, Hill F, additional, Allegrini, Andrea G, additional, Benyamin, Beben, additional, Border, Richard, additional, Diemer, Elizabeth W, additional, Jiang, Chang, additional, Karhunen, Ville, additional, Lu, Yi, additional, Lu, Qing, additional, Mallard, Travis T, additional, Mishra, Pashupati P, additional, Nolte, Ilja M, additional, Palviainen, Teemu, additional, Peterson, Roseann E, additional, Sallis, Hannah M, additional, Shabalin, Andrey A, additional, Tate, Ashley E, additional, Thiering, Elisabeth, additional, Vilor-Tejedor, Natàlia, additional, Wang, Carol, additional, Zhou, Ang, additional, Adkins, Daniel E, additional, Alemany, Silvia, additional, Ask, Helga, additional, Chen, Qi, additional, Corley, Robin P, additional, Ehli, Erik A, additional, Evans, Luke M, additional, Havdahl, Alexandra, additional, Hagenbeek, Fiona A, additional, Hakulinen, Christian, additional, Henders, Anjali K, additional, Hottenga, Jouke Jan, additional, Korhonen, Tellervo, additional, Mamun, Abdullah, additional, Marrington, Shelby, additional, Neumann, Alexander, additional, Rimfeld, Kaili, additional, Rivadeneira, Fernando, additional, Silberg, Judy L, additional, van Beijsterveldt, Catharina E, additional, Vuoksimaa, Eero, additional, Whipp, Alyce M, additional, Xiaoran, Tong, additional, Andreassen, Ole A, additional, Boomsma, Dorret, additional, Brown, Sandra A, additional, Burt, S Alexandra, additional, Copeland, William, additional, Costello, Elizabeth J, additional, Dick, Danielle M, additional, Eaves, Lindon J, additional, Harden, K Paige, additional, Harris, Kathleen Mullan, additional, Hartman, Catharina A, additional, Heinrich, Joachim, additional, Hewitt, John K, additional, Hopfer, Christian, additional, Hypponen, Elina, additional, Jarvelin, Marjo-Riitta, additional, Kaprio, Jaakko, additional, Keltikangas-Järvinen, Liisa, additional, Klump, Kelly L, additional, Krauter, Kenneth, additional, Kuja-Halkola, Ralf, additional, Larsson, Henrik, additional, Lehtimäki, Terho, additional, Lichtenstein, Paul, additional, Lundstrom, Sebastian, additional, Maes, Hermine H, additional, Magnus, Per, additional, Munafò, Marcus R, additional, Najman, Jake M, additional, Njølstad, Pål R, additional, Oldehinkel, Albertine J, additional, Pennell, Craig E, additional, Plomin, Robert, additional, Reichborn-Kjennerud, Ted, additional, Reynolds, Chandra, additional, Rose, Richard J, additional, Smolen, Andrew, additional, Snieder, Harold, additional, Stallings, Michael, additional, Standl, Marie, additional, Sunyer, Jordi, additional, Tiemeier, Henning, additional, Wadsworth, Sally, additional, Wall, Tamara L, additional, Whitehouse, Andrew J O, additional, Williams, Gail M, additional, Ystrom, Eivind, additional, Nivard, Michel G, additional, Bartels, Meike, additional, and Middeldorp, Christel M, additional

Published
2020
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42. Ketone body 3-hydroxybutyrate: a biomarker of aggression?

Author

whipp, alyce m, primary, vuoksimaa, eero, additional, korhonen, tellervo, additional, pool, rene, additional, ligthart, lannie, additional, hagenbeek, fiona, additional, bartels, meike, additional, bogl, leonie-helen, additional, pulkkinen, lea, additional, rose, richard j, additional, boomsma, dorret i, additional, and kaprio, jaakko a, additional

Published
2020
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43. Urinary Amine and Organic Acid Metabolites Evaluated as Markers for Childhood Aggression: The ACTION Biomarker Study

Author

Hagenbeek, Fiona A., primary, Roetman, Peter J., additional, Pool, René, additional, Kluft, Cornelis, additional, Harms, Amy C., additional, van Dongen, Jenny, additional, Colins, Olivier F., additional, Talens, Simone, additional, van Beijsterveldt, Catharina E. M., additional, Vandenbosch, Marjolein M. L. J. Z., additional, de Zeeuw, Eveline L., additional, Déjean, Sébastien, additional, Fanos, Vassilios, additional, Ehli, Erik A., additional, Davies, Gareth E., additional, Hottenga, Jouke Jan, additional, Hankemeier, Thomas, additional, Bartels, Meike, additional, Vermeiren, Robert R. J. M., additional, and Boomsma, Dorret I., additional

Published
2020
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44. Genetic Association Study of Childhood Aggression across raters, instruments and age

Author

Ip, Hill F., primary, van der Laan, Camiel M., additional, Krapohl, Eva M. L., additional, Brikell, Isabell, additional, Cristina, Sánchez-Mora, additional, Nolte, Ilja M., additional, St Pourcain, Beate, additional, Bolhuis, Koen, additional, Palviainen, Teemu, additional, Zafarmand, Hadi, additional, Colodro-Conde, Lucía, additional, Gordon, Scott, additional, Zayats, Tetyana, additional, Aliev, Fazil, additional, Jiang, Chang, additional, Wang, Carol A., additional, Saunders, Gretchen, additional, Karhunen, Ville, additional, Hammerschlag, Anke R., additional, Adkins, Daniel E., additional, Border, Richard, additional, Peterson, Roseann E., additional, Prinz, Joseph A., additional, Thiering, Elisabeth, additional, Seppälä, Ilkka, additional, Natàlia, Vilor-Tejedor, additional, Ahluwalia, Tarunveer S., additional, Day, Felix R., additional, Hottenga, Jouke-Jan, additional, Allegrini, Andrea G., additional, Rimfeld, Kaili, additional, Chen, Qi, additional, Lu, Yi, additional, Martin, Joanna, additional, Soler Artigas, María, additional, Rovira, Paula, additional, Bosch, Rosa, additional, Español, Gemma, additional, Ramos Quiroga, Josep Antoni, additional, Neumann, Alexander, additional, Ensink, Judith, additional, Grasby, Katrina, additional, Morosoli, José J., additional, Tong, Xiaoran, additional, Marrington, Shelby, additional, Middeldorp, Christel, additional, Scott, James G., additional, Vinkhuyzen, Anna, additional, Shabalin, Andrey A., additional, Corley, Robin, additional, Evans, Luke M., additional, Sugden, Karen, additional, Alemany, Silvia, additional, Sass, Lærke, additional, Vinding, Rebecca, additional, Ruth, Kate, additional, Tyrrell, Jess, additional, Davies, Gareth E., additional, Ehli, Erik A., additional, Hagenbeek, Fiona A., additional, De Zeeuw, Eveline, additional, Van Beijsterveldt, Toos C.E.M., additional, Larsson, Henrik, additional, Snieder, Harold, additional, Verhulst, Frank C., additional, Amin, Najaf, additional, Whipp, Alyce M., additional, Korhonen, Tellervo, additional, Vuoksimaa, Eero, additional, Rose, Richard J., additional, Uitterlinden, André G., additional, Heath, Andrew C., additional, Madden, Pamela, additional, Haavik, Jan, additional, Harris, Jennifer R., additional, Helgeland, Øyvind, additional, Johansson, Stefan, additional, Knudsen, Gun Peggy S., additional, Njolstad, Pal Rasmus, additional, Lu, Qing, additional, Rodriguez, Alina, additional, Henders, Anjali K., additional, Mamun, Abdullah, additional, Najman, Jackob M., additional, Brown, Sandy, additional, Hopfer, Christian, additional, Krauter, Kenneth, additional, Reynolds, Chandra, additional, Smolen, Andrew, additional, Stallings, Michael, additional, Wadsworth, Sally, additional, Wall, Tamara L., additional, Silberg, Judy L., additional, Miller, Allison, additional, Keltikangas-Järvinen, Liisa, additional, Hakulinen, Christian, additional, Pulkki-Råback, Laura, additional, Havdahl, Alexandra, additional, Magnus, Per, additional, Raitakari, Olli T., additional, Perry, John R.B., additional, Llop, Sabrina, additional, Lopez-Espinosa, Maria-Jose, additional, Bønnelykke, Klaus, additional, Bisgaard, Hans, additional, Sunyer, Jordi, additional, Lehtimäki, Terho, additional, Arseneault, Louise, additional, Standl, Marie, additional, Heinrich, Joachim, additional, Boden, Joseph, additional, Pearson, John, additional, Horwood, L John, additional, Kennedy, Martin, additional, Poulton, Richie, additional, Eaves, Lindon J., additional, Maes, Hermine H., additional, Hewitt, John, additional, Copeland, William E., additional, Costello, Elizabeth J., additional, Williams, Gail M., additional, Wray, Naomi, additional, Järvelin, Marjo-Riitta, additional, McGue, Matt, additional, Iacono, William, additional, Caspi, Avshalom, additional, Moffitt, Terrie E., additional, Whitehouse, Andrew, additional, Pennell, Craig E., additional, Klump, Kelly L., additional, Burt, S. Alexandra, additional, Dick, Danielle M., additional, Reichborn-Kjennerud, Ted, additional, Martin, Nicholas G., additional, Medland, Sarah E., additional, Vrijkotte, Tanja, additional, Kaprio, Jaakko, additional, Tiemeier, Henning, additional, Davey Smith, George, additional, Hartman, Catharina A., additional, Oldehinkel, Albertine J., additional, Casas, Miquel, additional, Ribasés, Marta, additional, Lichtenstein, Paul, additional, Lundström, Sebastian, additional, Plomin, Robert, additional, Bartels, Meike, additional, Nivard, Michel G., additional, and Boomsma, Dorret I., additional

Published
2019
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45. Integrative multi-omics analysis of epigenomic and metabolomic data for attention-deficit/ hyperactivity disorder

Author

Hubers, Nikki, Hagenbeek, Fiona A., Dongen, Jenny, Dejean, Sebastien, Roetman, Peter J., Harms, Amy C., Hottenga, Jouke Jan, Kluft, Cornelis, Colins, Olivier F., Beijsterveldt, Catharina E. M., Vandenbosch, Marjolein M. L. J. Z., Zeeuw, Eveline L., Talens, Simone, Fanos, Vassilios, Ehli, Erik A., Davies, Gareth E., Vermeiren, Robert R. J. M., Hankemeier, Thomas, Bartels, Meike, René Pool, Boomsma, Dorret I., Biological Psychology, Amsterdam Reproduction & Development, APH - Personalized Medicine, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, Clinical Child and Family Studies, LEARN! - Child rearing, LEARN! - Educational neuroscience, learning and development, and APH - Methodology

Published
2020

46. Genome-wide pleiotropy of adult aggression and blood metabolites

Author

Hagenbeek, Fiona, Nivard, Michel, René Pool, Dongen, Jenny, Hottenga, Jouke-Jan, Abdellaoui, Abdel, Willemsen, Gonneke, Vink, Jacqueline, Ligthart, Lannie, Harms, Amy, Hankemeier, Thomas, Bartels, Meike, Boomsma, Dorret, and Biological Psychology

Subjects
Netherlands Twin Register (NTR)
Published
2016

47. Genome-wide association study of plasma triglycerides, phospholipids and relation to cardio-metabolic risk factors

Author

Demirkan, Ayşe, primary, Pool, Rene, additional, Deelen, Joris, additional, Beekman, Marian, additional, Liu, Jun, additional, Harms, Amy C., additional, Vaarhorst, Anika, additional, Hagenbeek, Fiona A, additional, Willemsen, Gonneke, additional, Verhoeven, Aswin, additional, Amin, Najaf, additional, van Dijk, Ko Willems, additional, Hankemeier, Thomas, additional, Boomsma, Dorret I., additional, Slagboom, Eline, additional, and van Duijn, Cornelia M., additional

Published
2019
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48. Heritability estimates for 361 blood metabolites across 40 genome-wide association studies.

Author

Hagenbeek, Fiona A., Pool, René, van Dongen, Jenny, Draisma, Harmen H. M., Jan Hottenga, Jouke, Willemsen, Gonneke, Abdellaoui, Abdel, Fedko, Iryna O., den Braber, Anouk, Visser, Pieter Jelle, de Geus, Eco J. C. N., Willems van Dijk, Ko, Verhoeven, Aswin, Suchiman, H. Eka, Beekman, Marian, Slagboom, P. Eline, van Duijn, Cornelia M., BBMRI Metabolomics Consortium, Barkey Wolf, J. J. H., and Cats, D.

Subjects
HERITABILITY, SMALL molecules, ORGANIC acids, ESTIMATES, BLOOD, METABOLOMICS, METABOLITES
Abstract

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes. Blood metabolite levels are under the influence of environmental and genetic factors. Here, Hagenbeek et al. perform heritability estimations for metabolite measures and determine the contribution of known metabolite loci to metabolite levels using data from 40 genome-wide association studies. [ABSTRACT FROM AUTHOR]

Published
2020
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50. Discovery of biochemical biomarkers for aggression: A role for metabolomics in psychiatry

Author

Hagenbeek, Fiona A., primary, Kluft, Cornelis, additional, Hankemeier, Thomas, additional, Bartels, Meike, additional, Draisma, Harmen H. M., additional, Middeldorp, Christel M., additional, Berger, Ruud, additional, Noto, Antonio, additional, Lussu, Milena, additional, Pool, René, additional, Fanos, Vassilios, additional, and Boomsma, Dorret I., additional

Published
2016
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