NETHERLANDS TWIN REGISTER. Dorret Boomsma
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1 NETHERLANDS TWIN REGISTER Dorret Boomsma
2 I will discuss NTR: a longitudinal twin-family study Why twins Not only twins: Multigeneration An example: ACTION
3 Netherlands Twin Register Netherlands Twin Register Established around 1987 Recruits new-born twins -> Young NTR Recruits adolescent / adult twins -> ANTR Recruits twins, their parents and sibs/spouses/etc Surveys, projects, biobank, record linkage
4 grants
5 NTR history and recruitment First research project (1983): cardiovascular risk factors in Amsterdam twins and parents ~1989: approach all city councils in the Netherlands ~ 1987: Hello baby NTR website, press, Twinfo, via family members, etc.
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7 Nl Tijdschrift Geneeskunde 2013 Average maternal age at birth of children in Netherlands Number of twin pairs per thousand deliveries WW2
8 NTR participants: where do they live? Based on 4 digit postal code
9 Survey collection
10 Twin studies MZ (monozygotic) heritability = 2(rMZ rdz) Genetic Structural Equation modeling DZ (dizygotic) Monozygotic (MZ) pairs: (nearly) 100% genetically identical Dizygotic (DZ) pairs: share on average 50% of segregating genes Add siblings: Increased power Social interaction twin effects Add parents: Cultural inheritance Assortment GE correlation
11 Aggression scores in MZ (F) twin pairs: twin 1- vs twin 2 Family members resemble each other more than unrelated Ss MZ twins resemble each other more than DZ twins or sibs
12 Longitudinal Adult NTR Young NTR 1991 (L1) SR AD 1993 (L2) BDI 1995 (L3) SR AD 1997 (L4) SR AD BDI Plus CIDI interviews 2000 (L5) SR AD 2002 (L6) ASR AD 2004 (L7) 2009 (L8) ASR AD HADS Same survey 2011 (L9) ASR AD 3 yr parents CBCL AD 1 yr mother 5 yr parents DCB Anxiety 2 yr mother 7 yr parents CBCL AD teachers TRF AD Plus DISC interviews 9/10yr parents CBCL AD teachers TRF AD 12 yr parents CBCL AD teachers TRF AD YSR AD 14 yr YSR AD 16 yr YSR AD 18 yr YSR AD 2015 L11 and L yr (L8) ASR AD HADS 2014 L11 and L (L10) ASR AD CBCL: Child Behavior Checklist DCB: Devereux Child Behavior TRF: Teacher Rating Scale (similar items to CBCL) YSR: Youth Self Report (similar items to CBCL) ASR: Adult Self Report (similar items to CBCL) SR: Self Report (early version of YSR and ASR) BDI: Beck Depression Inventory (13 items) HADS: Hospital Anxiety and Depression Scale AD=anxious/depression scale DCB anxiety = anxiety problems CIDI =WHO Composite International Diagnostic Interview (in subsample) YNTR Age 3 12: both parents on twins Age 7 12: teachers on twins and sibs Age 12 16: for twins and sibs Age 18: for twins, sibs, parents ANTR 1991: twins 1993: twins, parents 1995: twins 1997: twins and sibs 2000: twins, sibs, spouses 2004/5: twins, sibs, spouses, parents 2009/10: twins, sibs, spouses, parents 2011: twins, sibs, spouses, parents 2013: twins, sibs, spouses, parents 2014: twins, sibs, spouses, parents 2015: twins, sibs, spouses, parents
13 European Commission Seventh Framework Programme The ACTION project: Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies A collaboration among Scandinavian, English, Australian and Dutch (twin) registers
14 NTR datasets on Aggression AGG CBCL/YSR/TRF/ASR/OASR Aggression ATT CBCL/YSR/TRF/ASR Attention problems RB CBCL/YSR/TRF/ASR Rule breaking
15 Young Netherlands Twin Register data Age 3: Age 7: Age 10: Age 12: Age 14: Age 16: Age 18: AGG M 3 F 3 M 7 F 7 T 7 M 10 F 10 T 10 M 12 F 12 T 12 S14 S16 S18 ATT M 3 F 3 M 7 F 7 T 7 M 10 F 10 T 10 M 12 F 12 T 12 S14 S16 S18 RB M 3 F 3 M 7 F 7 T 7 M 10 F 10 T 10 M 12 F 12 T 12 S14 S16 S18
16 Longitudinal Aggression data in Dutch twins (14 items ASEBA) Age Males MEANS AGG-14 items Females Argues Mean Demands Attention Destroys own things Destroys others Gets in fights Attacks people Screams a lot Stubborn, sullen Mood changes Teases a lot Temper Threatens others Loud
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18 Genetic or cultural transmission? r r F D E E D F s g 1 d e e d 1 g s Parental generation A a P F f F P M a f i 0 A Offspring Generation: 2 twins & 1 sibling A E P T1 A P T2 P Sib a a a e d e d d D E D D e A E 1 If this parameter is significant: evidence for cultural transmission (from Family environment to Phenotype in kids)
19 Netherlands Twin Register Total Survey Biobank ANS DSM Cognition EEG MRI Participants 200, ,041 9,991 4,204 2,554 3,766 1,532 1,230 ANTR surveys 41,800 41,800 9,056 3,446 1,938 2,655 1, YNTR surveys 119, , ,308 1,116 2, DNA (blood / buccal) 18,791 17,322 9,991 4,048 2,106 3,228 1,208 1,148 NTR Biobank 9,991 9,223 9,991 2, , GWA Genotyping 12,546 12,096 8,260 1,067 1,545 2, ,058 DNA methylation 3,025 2,956 3,025 1, DNA sequencing RNA expression 3,370 3,260 3,370 1, RNA sequencing 1,781 1,743 1, Metabolomics 5,615 5,482 5, Microbiome , ANS-function 4,204 3,871 2,365 4, , DSM-IV interview 2,554 2, , Cognition 3,766 3,613 1,491 2, ,766 1, EEG 1,532 1, ,530 1, Brain Imaging 1,230 1, Does not reflect longitudinal DNA, RNA, blood, urine, stool Autonomic Nervous System Psychiatric interviews IQ, not CITO / LvS Brain function & structure
20 Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies DNA: epigenetics phenotyping euproject.eu Urine: metabolomics 20
21 Current data uploads DANS (survey data TRF) dbgap The database of Genotypes and Phenotypes European Bioinformatics Institute (EMBL EBI) European Genome Phenome Archive (EGA) MetaboLights In the next 5 years: create a state of the art repository (NWO groot investment)
22 22
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