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  • 1
    Online Resource
    Online Resource
    The Adult Netherlands Twin Register: Twenty-Five Years of Survey and Biological Data Collection
    Cambridge University Press (CUP) ; 2013
    In:  Twin Research and Human Genetics Vol. 16, No. 1 ( 2013-02), p. 271-281
    Details
    In: Twin Research and Human Genetics, Cambridge University Press (CUP), Vol. 16, No. 1 ( 2013-02), p. 271-281
    Abstract: Over the past 25 years, the Adult Netherlands Twin Register (ANTR) has collected a wealth of information on physical and mental health, lifestyle, and personality in adolescents and adults. This article provides an overview of the sources of information available, the main research findings, and an outlook for the future. Between 1991 and 2012, longitudinal surveys were completed by twins, their parents, siblings, spouses, and offspring. Data are available for 33,957 participants, with most individuals having completed two or more surveys. Smaller projects provided in-depth phenotyping, including measurements of the autonomic nervous system, neurocognitive function, and brain imaging. For 46% of the ANTR participants, DNA samples are available and whole genome scans have been obtained in more than 11,000 individuals. These data have resulted in numerous studies on heritability, gene x environment interactions, and causality, as well as gene finding studies. In the future, these studies will continue with collection of additional phenotypes, such as metabolomic and telomere length data, and detailed genetic information provided by DNA and RNA sequencing. Record linkage to national registers will allow the study of morbidity and mortality, thus providing insight into the development of health, lifestyle, and behavior across the lifespan.
    Type of Medium: Online Resource
    ISSN: 1832-4274 , 1839-2628
    URL: Article
    DOI: 10.1017/thg.2012.140
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2013
    detail.hit.zdb_id: 2184274-7
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  • 2
    Online Resource
    Online Resource
    Genetics and Not Shared Environment Explains Familial Resemblance in Adult Metabolomics Data
    Cambridge University Press (CUP) ; 2020
    In:  Twin Research and Human Genetics Vol. 23, No. 3 ( 2020-06), p. 145-155
    Details
    In: Twin Research and Human Genetics, Cambridge University Press (CUP), Vol. 23, No. 3 ( 2020-06), p. 145-155
    Abstract: Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term ‘metabolomics’ refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented.
    Type of Medium: Online Resource
    ISSN: 1832-4274 , 1839-2628
    URL: Article
    DOI: 10.1017/thg.2020.53
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2184274-7
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  • 3
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    Online Resource
    Familial Resemblance for Serum Metabolite Concentrations — Corrigendum
    Cambridge University Press (CUP) ; 2013
    In:  Twin Research and Human Genetics Vol. 16, No. 5 ( 2013-10), p. 1014-1014
    Details
    In: Twin Research and Human Genetics, Cambridge University Press (CUP), Vol. 16, No. 5 ( 2013-10), p. 1014-1014
    Abstract: The authors would like to apologize for omitting a number of contributors from the above publication who share rights to the authorship of this manuscript.
    Type of Medium: Online Resource
    ISSN: 1832-4274 , 1839-2628
    URL: Article
    DOI: 10.1017/thg.2013.70
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2013
    detail.hit.zdb_id: 2184274-7
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  • 4
    Online Resource
    Online Resource
    The Weighting is the Hardest Part: On the Behavior of the Likelihood Ratio Test and the Score Test Under a Data-Driven Weighting Scheme in Sequenced Samples
    Cambridge University Press (CUP) ; 2017
    In:  Twin Research and Human Genetics Vol. 20, No. 2 ( 2017-04), p. 108-118
    Details
    In: Twin Research and Human Genetics, Cambridge University Press (CUP), Vol. 20, No. 2 ( 2017-04), p. 108-118
    Abstract: Sequence-based association studies are at a critical inflexion point with the increasing availability of exome-sequencing data. A popular test of association is the sequence kernel association test (SKAT). Weights are embedded within SKAT to reflect the hypothesized contribution of the variants to the trait variance. Because the true weights are generally unknown, and so are subject to misspecification, we examined the efficiency of a data-driven weighting scheme. We propose the use of a set of theoretically defensible weighting schemes, of which, we assume, the one that gives the largest test statistic is likely to capture best the allele frequency–functional effect relationship. We show that the use of alternative weights obviates the need to impose arbitrary frequency thresholds. As both the score test and the likelihood ratio test (LRT) may be used in this context, and may differ in power, we characterize the behavior of both tests. The two tests have equal power, if the weights in the set included weights resembling the correct ones. However, if the weights are badly specified, the LRT shows superior power (due to its robustness to misspecification). With this data-driven weighting procedure the LRT detected significant signal in genes located in regions already confirmed as associated with schizophrenia — the PRRC2A ( p = 1.020e-06) and the VARS2 ( p = 2.383e-06) — in the Swedish schizophrenia case-control cohort of 11,040 individuals with exome-sequencing data. The score test is currently preferred for its computational efficiency and power. Indeed, assuming correct specification, in some circumstances, the score test is the most powerful test. However, LRT has the advantageous properties of being generally more robust and more powerful under weight misspecification. This is an important result given that, arguably, misspecified models are likely to be the rule rather than the exception in weighting-based approaches.
    Type of Medium: Online Resource
    ISSN: 1832-4274 , 1839-2628
    URL: Article
    DOI: 10.1017/thg.2017.7
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2017
    detail.hit.zdb_id: 2184274-7
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  • 5
    Online Resource
    Online Resource
    Familial Resemblance for Serum Metabolite Concentrations
    Cambridge University Press (CUP) ; 2013
    In:  Twin Research and Human Genetics Vol. 16, No. 5 ( 2013-10), p. 948-961
    Details
    In: Twin Research and Human Genetics, Cambridge University Press (CUP), Vol. 16, No. 5 ( 2013-10), p. 948-961
    Abstract: Metabolomics is the comprehensive study of metabolites, which are the substrates, intermediate, and end products of cellular metabolism. The heritability of the concentrations of circulating metabolites bears relevance for evaluating their suitability as biomarkers for disease. We report aspects of familial resemblance for the concentrations in human serum of more than 100 metabolites, measured using a targeted metabolomics platform. Age- and sex-corrected monozygotic twin correlations, midparent–offspring regression coefficients, and spouse correlations in subjects from two independent cohorts (Netherlands Twin Register and Leiden Longevity Study) were estimated for each metabolite. In the Netherlands Twin Register subjects, who were largely fasting, we found significant monozygotic twin correlations for 121 out of 123 metabolites. Heritability was confirmed by midparent–offspring regression. For most detected metabolites, the correlations between spouses were considerably lower than those between twins, indicating a contribution of genetic effects to familial resemblance. Remarkably high heritability was observed for free carnitine (monozygotic twin correlation 0.66), for the amino acids serine (monozygotic twin correlation 0.77) and threonine (monozygotic twin correlation 0.64), and for phosphatidylcholine acyl-alkyl C40:3 (monozygotic twin correlation 0.77). For octenoylcarnitine, a consistent point estimate of approximately 0.50 was found for the spouse correlations in the two cohorts as well as for the monozygotic twin correlation, suggesting that familiality for this metabolite is explained by shared environment. We conclude that for the majority of metabolites targeted by the used metabolomics platform, the familial resemblance of serum concentrations is largely genetic. Our results contribute to the knowledge of the heritability of fasting serum metabolite concentrations, which is relevant for biomarker research.
    Type of Medium: Online Resource
    ISSN: 1832-4274 , 1839-2628
    URL: Article
    DOI: 10.1017/thg.2013.59
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2013
    detail.hit.zdb_id: 2184274-7
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  • 6
    Online Resource
    Online Resource
    The Netherlands Twin Register: Longitudinal Research Based on Twin and Twin-Family Designs
    Cambridge University Press (CUP) ; 2019
    In:  Twin Research and Human Genetics Vol. 22, No. 6 ( 2019-12), p. 623-636
    Details
    In: Twin Research and Human Genetics, Cambridge University Press (CUP), Vol. 22, No. 6 ( 2019-12), p. 623-636
    Abstract: The Netherlands Twin Register (NTR) is a national register in which twins, multiples and their parents, siblings, spouses and other family members participate. Here we describe the NTR resources that were created from more than 30 years of data collections; the development and maintenance of the newly developed database systems, and the possibilities these resources create for future research. Since the early 1980s, the NTR has enrolled around 120,000 twins and a roughly equal number of their relatives. The majority of twin families have participated in survey studies, and subsamples took part in biomaterial collection (e.g., DNA) and dedicated projects, for example, for neuropsychological, biomarker and behavioral traits. The recruitment into the NTR is all inclusive without any restrictions on enrollment. These resources — the longitudinal phenotyping, the extended pedigree structures and the multigeneration genotyping — allow for future twin-family research that will contribute to gene discovery, causality modeling, and studies of genetic and cultural inheritance.
    Type of Medium: Online Resource
    ISSN: 1832-4274 , 1839-2628
    URL: Article
    DOI: 10.1017/thg.2019.93
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2184274-7
    SSG: 12
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