The Adult Netherlands Twin Register: Twenty-Five Years of Survey and Biological Data Collection

Willemsen, Gonneke; Vink, Jacqueline M.; Abdellaoui, Abdel; Braber, Anouk den; Beek, Jenny H. D. A. van; Draisma, Harmen H.M.; Dongen, Jenny van; Ent, Dennis van ‘t; Geels, Lot M.; Lien, René van; Ligthart, Lannie; Kattenberg, Mathijs; Mbarek, Hamdi; Moor, Marleen H. M. de; Neijts, Melanie; Pool, René; Stroo, N.; Kluft, C.; Suchiman, H. Eka D.; Slagboom, P. Eline; Geus, Eco J. C. de; Boomsma, Dorret I.

doi:10.1017/thg.2012.140

Cited by 186 publications

(217 citation statements)

References 65 publications

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“…Data for the present study came from participants in The Netherlands Twin Register Biobank pro jects, which took place between 2004 and 2008, and in 2011 [29][30][31]. After excluding outliers (i.e., absolute values exceeding mean ± 5 × standard deviation [SD]), NLR and PLR data were available for 9434 participants, clustered in 3411 families.…”

Section: Participantsmentioning

confidence: 99%

Causes of Variation in The Neutrophil–Lymphocyte and Platelet–Lymphocyte Ratios: a Twin-Family Study

et al. 2016

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Aim: Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are biomarkers for disease development, for whom little is known about causes of variation in the general population. Materials & methods: We estimated the heritability of PLR and NLR and examined their association with gender, demographic, lifestyle and environmental factors in a Dutch nonpatient twin family population (n = 8108). Results: Heritability was estimated at 64% for PLR and 36% for NLR. Men had on average higher NLR, but lower PLR levels than women. PLR and NLR increased significantly with age, decreased in colder months and showed small but significant sex-and age-specific associations with body composition and smoking. Conclusion: NLR and PLR levels are heritable and influenced by age, sex and environmental factors, such as seasonal conditions and lifestyle.

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Section: Participantsmentioning

confidence: 99%

Causes of Variation in The Neutrophil–Lymphocyte and Platelet–Lymphocyte Ratios: a Twin-Family Study

et al. 2016

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“…Venous blood samples were drawn in the morning after an overnight fast, and multiple ethylenediaminetetraacetic acid (EDTA) tubes were collected for isolation of DNA and RNA and assessment of hematological profiles. Phenotyping through longitudinal surveys and blood sampling procedures have been described in detail previously (Boomsma et al, 2006;van Beijsterveldt et al, 2013;Willemsen et al, 2010Willemsen et al, , 2013.…”

Section: Subjects and Samplesmentioning

confidence: 99%

Epigenome-Wide Association Study of Aggressive Behavior

et al. 2015

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Aggressive behavior is highly heritable, while environmental influences, particularly early in life, are also important. Epigenetic mechanisms, such as DNA methylation, regulate gene expression throughout development and adulthood, and may mediate genetic and environmental effects on complex traits. We performed an epigenome-wide association study (EWAS) to identify regions in the genome where DNA methylation level is associated with aggressive behavior. Subjects took part in longitudinal survey studies from the Netherlands Twin Register (NTR) and participated in the NTR biobank project between 2004 and 2011 (N = 2,029, mean age at blood sampling = 36.4 years, SD = 12.4, females = 69.2%). Aggressive behavior was rated with the ASEBA Adult Self-Report (ASR). DNA methylation was measured in whole blood by the Illumina HM450k array. The association between aggressive behavior and DNA methylation level at 411,169 autosomal sites was tested. Association analyses in the entire cohort showed top sites at cg01792876 (chr8; 116,684,801, nearest gene = TRPS1, p = 7.6 × 10 −7 , False discovery rate (FDR) = 0.18) and cg06092953 (chr18; 77,905,699, nearest gene = PARD6G-AS1, p = 9.0 ×10 −7 , FDR = 0.18). Next, we compared methylation levels in 20 pairs of monozygotic (MZ) twins highly discordant for aggression. Here the top sites were cg21557159 (chr 11; 107,795,699, nearest gene = RAB39, p = 5.7 × 10 −6 , FDR = 0.99), cg08648367 (chr 19; 51,925,472, nearest gene = SIGLEC10, p = 7.6 × 10 −6 , FDR = 0.99), and cg14212412 (chr 6; 105,918,992, nearest gene = PREP, p = 8.0 × 10 −6 , FDR = 0.99). The two top hits based on the entire cohort showed the same direction of effect in discordant MZ pairs (cg01792876, P discordant twins = 0.09 and cg06092953, P discordant twins = 0.24). The other way around, two of the three most significant sites in discordant MZ pairs showed the same direction of effect in the entire cohort (cg08648367, P entire EWAS = 0.59 and cg14212412, P entire EWAS = 3.1 × 10 −3 ). Gene ontology analysis highlighted significant enrichment of various central nervous system categories among higher-ranking methylation sites. Higher-ranking methylation sites also showed enrichment for DNase I hypersensitive sites and promoter regions, showing that DNA methylation in peripheral tissues is likely to be associated with aggressive behavior.

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“…The Netherlands Twin Register was established in 1987 and the NTR survey studies and the NTR BioBank project are described elsewhere (Boomsma et al, 2002(Boomsma et al, , 2006Willemsen et al, 2010Willemsen et al, , 2013. Genome-wide methylation in blood was profiled using the Infinium 450K platform (Van Dongen et al, 2015).…”

Section: Replication Sample 3: Netherlands Twin Register (Ntr)mentioning

confidence: 99%

DNA Methylation Changes in theIGF1RGene in Birth Weight Discordant Adult Monozygotic Twins

et al. 2015

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Low birth weight (LBW) can have an impact on health outcomes in later life, especially in relation to predisposition to metabolic disease. Several studies suggest that LBW resulting from restricted intrauterine growth leaves a footprint on DNA methylation in utero, and this influence likely persists into adulthood. To investigate this further, we performed epigenome-wide association analyses of blood DNA methylation using Infinium HumanMethylation450 BeadChip profiles in 71 adult monozygotic (MZ) twin pairs who were extremely discordant for birth weight. A signal mapping to the IGF1R gene (cg12562232, p = 2.62 × 10 −8 ), was significantly associated with birth weight discordance at a genome-wide false-discovery rate (FDR) of 0.05. We pursued replication in three additional independent datasets of birth weight discordant MZ pairs and observed the same direction of association, but the results were not significant. However, a meta-analysis across the four independent samples, in total 216 birth-weight discordant MZ twin pairs, showed a significant positive association between birth weight and DNA methylation differences at IGF1R (random-effects meta-analysis p = .04), and the effect was particularly pronounced in older twins (randomeffects meta-analysis p = .008, 98 older birth-weight discordant MZ twin pairs). The results suggest that severe intra-uterine growth differences (birth weight discordance >20%) are associated with methylation changes in the IGF1R gene in adulthood, independent of genetic effects.

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The Adult Netherlands Twin Register: Twenty-Five Years of Survey and Biological Data Collection

Cited by 186 publications

References 65 publications

Causes of Variation in The Neutrophil–Lymphocyte and Platelet–Lymphocyte Ratios: a Twin-Family Study

Causes of Variation in The Neutrophil–Lymphocyte and Platelet–Lymphocyte Ratios: a Twin-Family Study

Epigenome-Wide Association Study of Aggressive Behavior

DNA Methylation Changes in theIGF1RGene in Birth Weight Discordant Adult Monozygotic Twins

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