DNA methylation (array)

Assessment of DNA methylation as obtained through DNA methylation arrays.

In NTR projects YC_ACTIONBB2 and YC_ACTIONBB3, genome-wide methylation data in buccal DNA samples was performed by the Human Genotyping facility (HugeF) of ErasmusMC (the Netherlands, http://www.glimdna.org/) on the Infinium MethylationEPIC BeadChip Kit (Illumina, San Diego, CA, USA). Recently, additional EPIC array data became available for NTR ACTION twins and siblings (generated by the Avera Institure of Human Genetics, Sioux Falls, South Dakota, USA). For information on the measurement of DNA methylation with the EPIC array, cleaning of DNA methtylation data, and estimation of proportion of cell counts see: https://doi.org/10.1038/s41380-020-00987-x.

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Keywords	biological sample buccal sample cell count dna epigenetics omics biomarker
Constructs	physiology
Waves	Young Netherlands Twin Register YC_ACTION - BB3   C S 6.0 - 13.0 years   From 2016-01-01 to 2017-01-01
Mode of collection	MeasurementsAndTests    Biological sample/measurement
Analysis unit	Individual
References	van Dongen, J., Hagenbeek, F. A., Suderman, M., Roetman, P. J., Sugden, K., Chiocchetti, A. G., Ismail, K., Mulder, R. H., Hafferty, J. D., Adams, M. J., Walker, R. M., Morris, S. W., Lahti, J., Küpers, L. K., Escaramis, G., Alemany, S., Jan Bonder, M., Meijer, M., … Ip, H. F. (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

Measure was collected within the following cohort study:

Netherlands Twin Register Cohort study

Purpose	The research carried out by the Netherlands Twin Register focuses on the role of heritability in mental and physical health. For instance, the NTR investigates why some people become more easily depressed than others, or why certain people get diabetes while others do not. Other research areas include lifestyle and habits that influence health and disease, such as smoking, drinking and exercise.
description
Alternate title	NTR
Data access information	Researchers with an approved data sharing request who abide by the rules of the European General Data Protection Regulation can receive temporary access to the NTR data for their own research projects. https://ntr-data-request.psy.vu.nl/
Publisher	Vrije Universiteit Amsterdam
Principal investigators	Boomsma, Dorret I. Vrije Universiteit Amsterdam
Cohort study international identifier
Language	NL
Funding information	Dutch Research Council Funder identifier Funder identifier type Funder identifier type URI Funder award title Funder award URI Dutch Research Council Funder identifier Funder identifier type Funder identifier type URI Funder award title Funder award URI Dutch Research Council Funder identifier Funder identifier type Funder identifier type URI Funder award title Funder award URI Dutch Research Council Funder identifier Funder identifier type Funder identifier type URI Funder award title Funder award URI
Contact information	NTR Data Management Vrije Universiteit Amsterdam ntr.datamanagement.fgb@vu.nl
References	Boomsma DI, de Geus EJ, Vink JM, Stubbe JH, Distel MA, Hottenga JJ, Posthuma D, van Beijsterveldt TC, Hudziak JJ, Bartels M, Willemsen G. Netherlands Twin Register: from twins to twin families. Twin Res Hum Genet. 2006 Dec;9(6):849-57. doi: 10.1375/183242706779462426. PMID: 17254420. Boomsma DI, Willemsen G, Vink JM, Bartels M, Groot P, Hottenga JJ, van Beijsterveldt CE, Stroet T, van Dijk R, Wertheim R, Visser M, van der Kleij F. Design and implementation of a twin-family database for behavior genetics and genomics studies. Twin Res Hum Genet. 2008 Jun;11(3):342-8. doi: 10.1375/twin.11.3.342. PMID: 18498212. van Beijsterveldt CE, Groen-Blokhuis M, Hottenga JJ, Franić S, Hudziak JJ, Lamb D, Huppertz C, de Zeeuw E, Nivard M, Schutte N, Swagerman S, Glasner T, van Fulpen M, Brouwer C, Stroet T, Nowotny D, Ehli EA, Davies GE, Scheet P, Orlebeke JF, Kan KJ, Smit D, Dolan CV, Middeldorp CM, de Geus EJ, Bartels M, Boomsma DI. The Young Netherlands Twin Register (YNTR): longitudinal twin and family studies in over 70,000 children. Twin Res Hum Genet. 2013 Feb;16(1):252-67. doi: 10.1017/thg.2012.118. Epub 2012 Nov 28. PMID: 23186620. Ligthart L, van Beijsterveldt CEM, Kevenaar ST, de Zeeuw E, van Bergen E, Bruins S, Pool R, Helmer Q, van Dongen J, Hottenga JJ, Van't Ent D, Dolan CV, Davies GE, Ehli EA, Bartels M, Willemsen G, de Geus EJC, Boomsma DI. The Netherlands Twin Register: Longitudinal Research Based on Twin and Twin-Family Designs. Twin Res Hum Genet. 2019 Dec;22(6):623-636. doi: 10.1017/thg.2019.93. Epub 2019 Oct 31. PMID: 31666148. Bartels M, van Beijsterveldt CE, Derks EM, Stroet TM, Polderman TJ, Hudziak JJ, Boomsma DI. Young Netherlands Twin Register (Y-NTR): a longitudinal multiple informant study of problem behavior. Twin Res Hum Genet. 2007 Feb;10(1):3-11. doi: 10.1375/twin.10.1.3.PMID: 17539360. Boomsma DI, Orlebeke JF, van Baal GC.Behav Genet. The Dutch Twin Register: growth data on weight and height. 1992 Mar;22(2):247-51. doi: 10.1007/BF01067004 Franić S, Dolan CV, van Beijsterveldt CE, Hulshoff Pol HE, Bartels M, Boomsma DI. Genetic and environmental stability of intelligence in childhood and adolescence. Twin Res Hum Genet. 2014 Jun;17(3):151-63. doi: 10.1017/thg.2014.
Additional info (URL)
Additional information
Contributors	YNTR administration Vrije Universiteit Amsterdam
Time method	Longitudinal
Universe	The recruitment into the NTR is fully inclusive without any restrictions on enrolment. In the CID data catalogue, only the NTR projects for children and adolescents (<18 years of age) have been included. This is refered to as the Young Netherlands Twin Register (YNTR).

Measure was collected within the following cohort(s):

NTR: Young Netherlands Twin Register Cohort

Alternate title	YNTR
Description	The Young Netherlands Twin Register (YNTR) consists of projects within the Netherlands Twin Register (NTR) that involve families with twins or other multiples under the age of 18.
Purpose	The purpose of the projects within the Young Netherlands Twin Register focus on the role of heritability in mental and physical health. For instance, the NTR investigates why some people become more easily depressed than others, or why certain people get diabetes while others do not. Other research areas include lifestyle and habits that influence health and disease, such as smoking, drinking and exercise.
Publisher	Vrije Universiteit Amsterdam
Creators	Boomsma, Dorret I. Vrije Universiteit Amsterdam
Language	NL
Cohort international identifier
Funding information	Dutch Research Council 480-15-001/674 Funder identifier https://ror.org/04jsz6e67 ROR Identifier type URI https://ror.org/ Funder award title Funder award URI Dutch Research Council 575-25-006 Funder identifier https://ror.org/04jsz6e67 ROR Identifier type URI https://ror.org/ Funder award title Funder award URI Dutch Research Council 480-04-004 Funder identifier https://ror.org/04jsz6e67 ROR Identifier type URI https://ror.org/ Funder award title Funder award URI Dutch Research Council 911-09-032 Funder identifier https://ror.org/04jsz6e67 ROR Identifier type URI https://ror.org/ Funder award title Funder award URI
Cohort reference papers
Classification
Contact information
Waves
Contributors	YNTR administration Vrije Universiteit Amsterdam
References	Boomsma DI, de Geus EJ, Vink JM, Stubbe JH, Distel MA, Hottenga JJ, Posthuma D, van Beijsterveldt TC, Hudziak JJ, Bartels M, Willemsen G. Netherlands Twin Register: from twins to twin families. Twin Res Hum Genet. 2006 Dec;9(6):849-57. doi: 10.1375/183242706779462426. PMID: 17254420. Boomsma DI, Willemsen G, Vink JM, Bartels M, Groot P, Hottenga JJ, van Beijsterveldt CE, Stroet T, van Dijk R, Wertheim R, Visser M, van der Kleij F. Design and implementation of a twin-family database for behavior genetics and genomics studies. Twin Res Hum Genet. 2008 Jun;11(3):342-8. doi: 10.1375/twin.11.3.342. PMID: 18498212. van Beijsterveldt CE, Groen-Blokhuis M, Hottenga JJ, Franić S, Hudziak JJ, Lamb D, Huppertz C, de Zeeuw E, Nivard M, Schutte N, Swagerman S, Glasner T, van Fulpen M, Brouwer C, Stroet T, Nowotny D, Ehli EA, Davies GE, Scheet P, Orlebeke JF, Kan KJ, Smit D, Dolan CV, Middeldorp CM, de Geus EJ, Bartels M, Boomsma DI. The Young Netherlands Twin Register (YNTR): longitudinal twin and family studies in over 70,000 children. Twin Res Hum Genet. 2013 Feb;16(1):252-67. doi: 10.1017/thg.2012.118. Epub 2012 Nov 28. PMID: 23186620. Ligthart L, van Beijsterveldt CEM, Kevenaar ST, de Zeeuw E, van Bergen E, Bruins S, Pool R, Helmer Q, van Dongen J, Hottenga JJ, Van't Ent D, Dolan CV, Davies GE, Ehli EA, Bartels M, Willemsen G, de Geus EJC, Boomsma DI. The Netherlands Twin Register: Longitudinal Research Based on Twin and Twin-Family Designs. Twin Res Hum Genet. 2019 Dec;22(6):623-636. doi: 10.1017/thg.2019.93. Epub 2019 Oct 31. PMID: 31666148.
Country code	NL
Geographic location
Lowest geographic reference	postal code
Highest geographic reference	country
Cohort universe description	Families with twins or other multiples under the age of 18.
Analysis unit
Additional info (URL)
Additional information
Time method	Longitudinal.CohortEventBased

Measure was collected within the following wave(s):

YC_ACTION - BB3 Wave

Wave alternate title	Main Study ACTION Biomarker Study YC_ACTION
Short description of the wave	The Main Study of the ACTION project (Aggression in Children: Unraveling gene-environment interplay to inform Treatment and interventION strategies Consortium; http://www.action-euproject.eu), after the technical pilots (YC_ACTION BB1_1 and BB1_2) and the Biochemical study (YC_ACTION BB2). Here, data collection of first-morning urine samples for metabolomics biomarker discovery and buccal-cell DNA samples for (epi)genetics was conducted in a large cohort of 6-13 year old twins born between 2004 and 2011 (mean age = 9.5 years, SD = 1.9 years). Family members living at the same address as the participating twin pairs were also asked to provide a buccal-cell DNA sample. The twins were selected to be part of a concordant low-scoring twin pair, a concordant high-scoring twin pair, or a discordant twin pair. Aggression had been assessed in the past by the age-appropriate version of the CBCL (Achenbach System of Empirically Based Assessment (ASEBA) Child Behavior Checklist). During the urine and buccal-cell collection, parents of the twins were asked to complete the ASEBA CBCL for school-aged children (6-18 years) to reflect the current child behaviors, and to provide information about health condition of the twins and conditions of urine collection. Biochemical measurement in urine included a dipstick, density (specific gravity), creatinine, neopterin, C-peptide, Substance P, and oxidized DNA/RNA. Metabolomics data of the Main Study together with the samples obtained in the Biochemical Study (ACTIONBB2) were were obtained from three metabolomics platforms: 1) a liquid chromatography mass spectrometry (LC-MS) platform targeting amines; 2) a LC-MS platform targeting steroid hormones; and 3) a gas chromatography (GC) MS platform targeting organic acids. Buccal-cell samples of the twins from the Main Study together with the samples obtained in the Biochemical Study (ACTIONBB2) were used for genome-wide methylation measurement on the Infinium MethylationEPIC BeadChip Kit (after conclussion of the ACTION project additional twin pairs and siblings were also measured on this platform). DNA samples from all family members were genotyped on the Affymetrix Axiom or Illumina GSA genotyping arrays.
Type of StudyUnit
Publisher	Vrije Universiteit Amsterdam
Creators	Vrije Universiteit Amsterdam Vrije Universiteit Amsterdam
Funding information	European Research Council 602768 Funder identifier ROR Identifier type URI https://ror.org/ Funder award title European Union Seventh Framework Program (FP7/2007–2013) Funder award URI
References	Bartels M, Hendriks A, Mauri M, Krapohl E, Whipp A, Bolhuis K, Conde LC, Luningham J, Fung Ip H, Hagenbeek F, Roetman P, Gatej R, Lamers A, Nivard M, van Dongen J, Lu Y, Middeldorp C, van Beijsterveldt T, Vermeiren R, Hankemeijer T, Kluft C, Medland S, Lundström S, Rose R, Pulkkinen L, Vuoksimaa E, Korhonen T, Martin NG, Lubke G, Finkenauer C, Fanos V, Tiemeier H, Lichtenstein P, Plomin R, Kaprio J, Boomsma DI. 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. Eur Child Adolesc Psychiatry. 2018 Sep;27(9):1105-1121. doi: 10.1007/s00787-018-1169-1. Epub 2018 May 29. PMID: 29845340; PMCID: PMC6133086. Hagenbeek FA, Roetman PJ, Pool R, Kluft C, Harms AC, van Dongen J, Colins OF, Talens S, van Beijsterveldt CEM, Vandenbosch MMLJZ, de Zeeuw EL, Déjean S, Fanos V, Ehli EA, Davies GE, Hottenga JJ, Hankemeier T, Bartels M, Vermeiren RRJM, Boomsma DI. Urinary Amine and Organic Acid Metabolites Evaluated as Markers for Childhood Aggression: The ACTION Biomarker Study. Front Psychiatry. 2020 Mar 31;11:165. doi: 10.3389/fpsyt.2020.00165. PMID: 32296350; PMCID: PMC7138132. Hagenbeek, F. A. (2022). Omics, Biomarkers, and Aggressive Behavior. https://research.vu.nl/en/publications/omics-biomarkers-and-aggressive-behavior. ISBN: 9789493270473. Boomsma DI. Aggression in children: unravelling the interplay of genes and environment through (epi)genetics and metabolomics. J Pediatr Neonat Individual Med. 2015;4(2):e040251. doi: 10.7363/040251
(sub) cohort	NTR: Young Netherlands Twin Register
Life stage
Coverage percentage of the measurement for this wave
Start date wave collection	2016-01-01
End date wave collection	2017-01-01
Wave universe description	6.0 - 13.0 years
Stage of measurement
Language	NL
Description of physical data product	Data collected through paper-and-pencil surveys have been scanned. All data digitally archived.
Additional info (URL)
Additional information
Contributors	Hagenbeek, Fiona A. Vrije Universiteit Amsterdam Vandenbosch, Marjolein M.L.J.Z. Vrije Universiteit Amsterdam