The Netherlands Twin Register Biobank: A Resource for Genetic Epidemiological Studies

Willemsen, Gonneke; Geus, Eco J. C. de; Bartels, Meike; Beijsterveldt, Catharina E. M. van; Brooks, Andy; Burk, G. Frederique Estourgie-van; Fugman, Douglas A.; Hoekstra, Chantal; Hottenga, Jouke‐Jan; Kluft, Kees; Meijer, Piet; Montgomery, Grant W.; Rizzu, Patrizia; Sondervan, David; Smit, August B.; Spijker, Sabine; Suchiman, H. Eka D.; Tischfield, Jay A.; Lehner, Thomas; Slagboom, P. Eline; Boomsma, Dorret I.

doi:10.1375/twin.13.3.231

Cited by 147 publications

(169 citation statements)

References 33 publications

(29 reference statements)

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“…Participants are followed longitudinally; details about the cohort have been published previously. 34 A subsample of unselected twins and their family members has taken part in the NTR-Biobank, 35 in which biological samples, including DNA and RNA, were collected in a standardized manner after overnight fasting. Study protocols were approved by the medical ethics board of the VUMC Amsterdam, the Netherlands.…”

Section: Materials and Methods Populationsmentioning

confidence: 99%

Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

et al. 2013

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Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64-0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother-offspring (r ¼ 0.42; P-value ¼ 3.60 Â 10 À61 ) than father-offspring correlation (r ¼ 0.33; P-value ¼ 7.01 Â 10 À5 ), and a significant positive association with paternal age at offspring birth (b ¼ 0.005; P-value ¼ 7.01 Â 10 À5 ). Interestingly, a significant and quite substantial correlation in TL between spouses (r ¼ 0.25; P-value ¼ 2.82 Â 10 À30 ) was seen, which appeared stronger in older spouse pairs (mean age Z55 years; r ¼ 0.31; P-value ¼ 4.27 Â 10 À23 ) than in younger pairs (mean ageo55 years; r ¼ 0.20; P-value ¼ 3.24 Â 10 À10 ). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age. European Journal of Human Genetics (2013) 21, 1163-1168; doi:10.1038/ejhg.2012.303; published online 16 January 2013Keywords: telomere length; heritability; paternal age effect INTRODUCTIONTelomeres are specialized DNA structures located at the terminal ends of chromosomes. 1 Their primary function is to maintain genomic stability. Because of the inability of DNA polymerase to fully replicate the 3 0 end of the DNA strand, that is, the 'end-replication problem' , telomeres naturally shorten with each cell division and, therefore, with age. [2][3][4] In epidemiological studies, both of cross-sectional and prospective design, decreased telomere length (TL) in leukocytes was associated with increased mortality, 5-8 although this finding was not consistent. 9,10 Increased TL in leukocytes has been associated with longevity in a comparison of long-lived Ashkenazi Jews and their offspring with younger controls. 11 Genetic association studies have revealed associations between single-nucleotide polymorphisms (SNPs) in the TERC and TERT genes and TL. [11][12][13][14][15][16][17] Other studies reported associations between SNPs in TERC and POT1 with human longevity, 11,17,18 suggesting that genes regulating TL may influence human longevity.

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Section: Materials and Methods Populationsmentioning

confidence: 99%

Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

et al. 2013

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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%

“…Immediately after blood collection, tubes were inverted several times to prevent clotting and subjected to initial processing in a mobile laboratory. Within 3-6 h after the blood draw all samples were transported to the laboratory facility in Leiden, The Netherlands (for details see [30,31]). …”

Section: General Biobank Proceduresmentioning

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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“…To prevent clotting, all tubes were inverted gently 8-10 times immediately after collection (for details, see Willemsen et al, 2010).…”

Section: Subjectsmentioning

confidence: 99%

Genetic Architecture of the Pro-Inflammatory State in an Extended Twin-Family Design

et al. 2013

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In this study we examined the genetic architecture of variation in the pro-inflammatory state, using an extended twin-family design. Within the Netherlands Twin Register Biobank, fasting Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), C-Reactive Protein (CRP), and fibrinogen levels were available for 3,534 twins, 1,568 of their non-twin siblings, and 2,227 parents from 3,095 families. Heritability analyses took into account the effects of current and recent illness, anti-inflammatory medication, female sex hormone status, age, sex, body mass index, smoking status, month of data collection, and batch processing. Moderate broad-sense heritability was found for all inflammatory parameters (39%, 21%, 45%, and 46% for TNF-α, IL-6, CRP and fibrinogen, respectively). For all parameters, the remaining variance was explained by unique environmental influences and not by environment shared by family members. There was no resemblance between spouses for any of the inflammatory parameters, except for fibrinogen. Also, there was no evidence for twin-specific effects. A considerable part of genetic variation was explained by non-additive genetic effects for TNF-α, CRP, and fibrinogen. For IL-6, all genetic variance was additive. This study may have implications for future genome-wide association studies by setting a clear numerical target for genome-wide screens that aim to find genetic variants regulating the levels of these pro-inflammatory markers.

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The Netherlands Twin Register Biobank: A Resource for Genetic Epidemiological Studies

Cited by 147 publications

References 33 publications

Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

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

Genetic Architecture of the Pro-Inflammatory State in an Extended Twin-Family Design

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