What are the causes of individual differences between children in terms of aggressive behavior and associated behavioural problems?
| ISRCTN | ISRCTN14253704 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14253704 |
- Submission date
- 06/08/2019
- Registration date
- 01/10/2019
- Last edited
- 01/10/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Plain English summary of protocol
Background and study aims
Childhood aggression and its resulting social impairment inflict a huge personal and financial burden on affected children, their relatives, peers and society as a whole. The prevalence of clinical aggression in children ranges from 2-16%, and early-onset childhood aggression continues into adolescence and adulthood in a substantial proportion of children. There are large differences between children in aggression levels and this study asks “what are the causes of individual differences between in children for aggressive behaviour and associated behavioural problems?”. We look at genetic, epigenetic and metabolomics markers, in different cohorts that collected these data in birth cohorts and population-based registries. We combine information from cohorts in a series of meta-analyses.
Who can participate?
Children below age 18 years for whom information on aggression and attention problems is available and who have been genotyped on a genome-wide SNP (Single nucleotide polymorphism) arrays; participants of any age with information on aggressive and attention problems and genome-wide epigenetic data; children for whom information on aggressive and attention problems is available and for whom urine samples for metabolomics were collected.
What does the study involve?
Estimating the associations between the phenotypes (aggression and attention problems) and the biomarker data. Primary analyses are carried out by each cohort and results are combined in meta-analyses.
What are the possible benefits and risks of participating? This project generates information on associations of behaviour with biomarkers. There are no individual-level risks or benefits to participants.
Where is the study run from?
The cohort studies run in their own countries (USA, UK, Europe, Australia and New Zealand). The meta-analyses is carried out in the Netherlands.
When is the study starting and how long is it expected to run for?
The cohort studies run in their own countries and typically are longitudinal projects. The meta-analyses will be finished and submitted for publication in 2019.
Who is funding the study?
FP7-EU 602768
Who is the main contact?
DI. Boomsma
di.boomsma@vu.nl
Contact information
Scientific
Van der Boechorststraat 7
Amsterdam
1081 BT
Netherlands
 ORCID ID |
0000-0002-7099-7972 |
|---|---|
| Phone | +31 (0)205988787 |
| di.boomsma@vu.nl |
Study information
| Study design | Epidemiological meta-analysis |
|---|---|
| Primary study design | Observational |
| Secondary study design | Epidemiological study |
| Study setting(s) | Community |
| Study type | Other |
| Participant information sheet | http://www.action-euproject.eu/content/data-protocols |
| Scientific title | ACTION: Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies |
| Study acronym | ACTION |
| Study objectives | Improve the understanding of the genetic and non-genetic etiology of aggression in children to inform the development of novel prevention and treatment strategies by unraveling in large twin and genotyped cohorts the causes of variation in aggression, disentangling (epi)genetic and environmental effects and their interplay with a focus on critical developmental periods, gender, and comorbid disorders; by investigating metabolomic profiles of aggressive behavior to establish direction of causation for existing and new biomarkers and gain insight regarding the predictive power of pediatric aggression for adult outcome variables. |
| Ethics approval(s) | Meta-analysis of existing cohort studies does not require ethical approval (confirmed by Central Ethics Committee on Research Involving Human Subjects of the VU University Medical Centre; BS7 Kamer H-565l; +31 (0)20 44 45585; metc@vumc.nl), ref: 2014.252 |
| Health condition(s) or problem(s) studied | Childhood behavioral problems, with a focus on aggression and attention problems |
| Intervention | The researchers are doing a series of large meta-analyses, which either take cross-sectional or longitudinal data and test associations of trait outcomes (aggression and attention problems) with SNP data, epigenetics and metabolomics markers. in this work there is no follow-up (though the data mainly derive from ongoing population-based cohorts). Data were drawn from the following cohorts: Amsterdam Born Children and their Development Study Avon Longitudinal Study of Parents and Children Brain dEvelopment and Air polluTion ultrafine particles in scHool childrEn Child and Adolescent Twin Study in Sweden Christchurch Health and Development Study Collaborative Studies on the Genetics of Alcoholism Copenhagen Prospective Studies on Asthma in Childhood 2010 Dunedin Multidisciplinary Health and Development Study Environmental Risk Longitudinal Twin Study Finnish Twin Cohort Generation R Study German Infant study on the influence of Nutrition Intervention PLUS environmental and genetic influences on allergy development / The influence of Life-style factors on the development of the Immune System and Allergies in East and West Germany Great Smoky Mountains Study Institute for Behavioral Genetics Infancia y Medio Ambiente Impact of Neurodevelopmental disorders and School performance: genes and environment Minnesota Center for Twin and Family Research Norwegian Mother and Child Cohort Study Michigan State University Twin Register Mater University of Queensland Study of Pregnancy Northern Finland Birth Cohort 1986 Netherlands Twin Register Queensland Institute of Medical Research Western Australian Pregnancy Cohort (Raine) Study Swedisch Twin study of CHild and Adolescent Development Twin Early Development Study TRacking Adolescents' Individual Lives Survey Virginia Twin Study of Adolescent Behavioral Development Young Finns Study |
| Intervention type | Other |
| Primary outcome measure | Measures of association (from regression analyses) for biomarker-outcome analyses. For each set of biomarkers (metabolomics, SNP and epigenetic data) an appropriate level of statistical significance is specified. Outcome data on problem behaviors were collected by birth and child cohorts by standardized surveys. The most commonly employed instruments to assess childhood aggressive and attention problems came from the Achenbach System of Empirically based Assessment (ASEBA; Achenbach et al. 2017) and the Strengths and Difficulties Questionnaire (SDQ; Goodman 2001). These two instruments accounted for > 70% of the phenotype data. -Achenbach TM, Ivanova MY, Rescorla LA (2017) Empirically based assessment and taxonomy of psychopathology for ages 1½–90+ years: Developmental, multi-informant, and multicultural findings. Compr Psychiatry 79:4–18. doi: 10.1016/J.COMPPSYCH.2017.03.006 - Goodman R (2001) Psychometric Properties of the Strengths and Difficulties Questionnaire. J Am Acad Child Adolesc Psychiatry 40:1337–1345. doi: 10.1097/00004583-200111000-00015 |
| Secondary outcome measures | Based on primary analyses, gene-based and network tests were carried out. |
| Overall study start date | 01/06/2014 |
| Completion date | 01/06/2019 |
Eligibility
| Participant type(s) | Mixed |
|---|---|
| Age group | All |
| Sex | Both |
| Target number of participants | For metabolomics the target number of participants was 1600. For genetics and epigenetics meta-analyses the target was the largest possible number of participants. |
| Key inclusion criteria | Biomarker- outcome associations are tested in child (2-18 years) cohorts and for epigenetics also in adults. Inclusions into the original population-based cohort studies were voluntary. |
| Key exclusion criteria | For genetic studies, to avoid population stratification, ancestries that are different from EU are excluded |
| Date of first enrolment | 01/06/2014 |
| Date of final enrolment | 01/06/2019 |
Locations
Countries of recruitment
- Australia
- Denmark
- Finland
- Germany
- Netherlands
- New Zealand
- Norway
- Sweden
- Switzerland
- United Kingdom
- United States of America
Study participating centre
Amsterdam
1081 BT
Netherlands
Sponsor information
University/education
Van der Boechorststraat 7
Amsterdam
1081 BT
Netherlands
| Phone | +31 (0)205988787 |
|---|---|
| di.boomsma@vu.nl | |
| Website | www.vu.nl |
"ROR" |
https://ror.org/008xxew50 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- EC Seventh Framework Programm, European Commission Seventh Framework Programme, EU Seventh Framework Programme, European Union Seventh Framework Programme, EU 7th Framework Programme, European Union 7th Framework Programme, Siebten Rahmenprogramm, Séptimo Programa Marco, Septième programme-cadre, Settimo programma quadro, 7th Framework Programme, Seventh EU Framework Programme, FP7
Results and Publications
| Intention to publish date | 01/12/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Stored in repository |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | Over 30 cohorts are included in this effort, which each have their own repositories. The association results from all cohorts are uploaded to a central repository in the Netherlands. The full set of meta-analysis association results will be made available upon publication of the papers. |
Editorial Notes
07/08/2019: Trial's existence confirmed by Central Ethics Committee on Research Involving Human Subjects of the VU University Medical Centre
