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AbstractIn this article, we present the genomic DNA yield and the microsatellite and single nucleotide polymorphism (SNP) genotyping success rates of genomic DNA extracted from a large number of mouth swab samples. In total, the median yield and quality was determined in 714 individuals and the success rates in 378,480 genotypings of 915 individuals. The median yield of genomic DNA per mouth swab was 4.1 μg (range 0.1–42.2 μg) and was not reduced when mouth swabs were stored for at least 21 months prior to extraction. A maximum of 20 mouth swabs is collected per participant. Mouth swab samples showed in, respectively, 89% for 390 microsatellites and 99% for 24 SNPs a genotyping success rate higher than 75%. A very low success rate of genotyping (0%–10%) was obtained for 3.2% of the 915 mouth swab samples using microsatellite markers. Only 0.005% of the mouth swab samples showed a geno-typing success rate lower than 75% (range 58%–71%) using SNPs. Our results show that mouth swabs can be easily collected, stored by our conditions for months prior to DNA extraction and result in high yield and high-quality DNA appropriate for genotyping with high success rate including whole genome searches using microsatellites or SNPs.

The finding of a significant gene by environment interaction effect on depression of the serotonin transporter length polymorphism (5-HTTLPR) and the Number of experienced Life Events (NLE) was not replicated in two large meta-analyses (Munafo et al., 2009; Risch et al., 2009). These meta-analyses have been criticized on the grounds that large studies that get most weight in meta-analyses have the poorest measurement quality of life events and, as a consequence, do not find an effect. Another issue is the time frame across which the NLE are measured. Proximal life events appear to be better predictors of depression than more distal events. We present the results of analyses of the 5-HTTLPR × NLE effect on anxious depression and neuroticism scores in a sample of 1,155 twins and their parents and siblings from 438 families. The interaction effect was tested separately for NLE experienced across the life span and NLE experienced in the past year. There was a significant main effect of NLE on anxious depression and neuroticism, especially when these were experienced in the past year. No interaction with 5-HTTLPR was found for NLE either experienced across the life span or across the past year. Our results support the two recent meta-analyses. Given recent insights from genome wide association studies, it seems more useful to focus on the joint effect of several genes, that are, for example, part of the same biological pathway, in interaction with the environment, than on one candidate gene.

AbstractThrough its ability to induce the enhanced release and production of cytokines, amyloid-β is responsible for the chronic inflammatory response that contributes to Alzheimer's disease (AD). Determining whether the response of monocytes to amyloid-β stimulation is under genetic control may help understand the basis of why some people are more prone to develop neuronal degeneration than others. In the current study we investigated the heritability of the cytokine (IL-10, IL-6, IL-1β, IL-1ra, TNF-[.alpha]) production capacity upon ex vivo stimulation with amyloid-β in whole blood samples of 222 twins and 85 singleton siblings from 139 extended twin families. It was found that individual differences in amyloid-β-induced cytokine production capacity are to a large extent of genetic origin, with heritability estimates ranging from 55% (IL-1β) to 68% (IL-6). We conclude that genes influencing amyloid-β-induced cytokine response may provide clues to the progression of AD pathology.

Twin registers are wonderful research resources for research applications in medical and behavioral genetics, epidemiology, psychology, molecular genetics, and other areas of research. New registers continue to be launched all over the world as researchers from different disciplines recognize the potential to boost and widen their research agenda. In this article, we discuss multiple aspects that need to be taken into account when initiating a register, from its preliminary sketch to its actual development. This encompasses aspects related to the strategic planning and key elements of research designs, promotion and management of a twin register, including recruitment and retaining of twins and family members of twins, phenotyping, database organization, and collaborations between registers. We also present information on questions unique to twin registers and twin-biobanks, such as the assessment of zygosity by SNP arrays, the design of (biomarker) studies involving related participants, and the analyses of clustered data. Altogether, we provide a number of basic guidelines and recommendations for reflection when planning a twin register.

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.

AbstractHuman height is a highly heritable trait, with genetic factors explaining up to 90% of phenotypic variation. Vitamin D levels are known to influence several physiological processes, including skeletal growth. The vitamin D receptor (VDR) gene has been reported as contributing to variation in height. A meta-analysis of 13607 adult individuals found a small but significant association with the rs1544410 (BsmI) polymorphism. In contrast, the meta-analysis found no effect in a sample of 550 children. Two recent studies reported variants with large effect on height elsewhere in VDR (rs10735810 [FokI] and rs7139166 [-1521] polymorphisms). We genotyped large Caucasian samples from Australia (N= 3906) and the Netherlands (N= 1689) for polymorphisms in VDR. The Australian samples were twin families with height measures from 3 time points throughout adolescence. The Dutch samples were adult twins. We use the available family data to perform both within and between family tests of association. We found no significant associations for any of the genotyped variants after multiple testing correction. The (non-significant) effect of rs1544410 in the Australian adolescent cohort was in the same direction and of similar magnitude (additive effect 0.3cm) to the effect observed in the published adult meta-analysis. An effect of this size explains ~0.1% of the phenotypic variance in height — this implies that many, probably hundreds, of such variants are responsible for the observed genetic variation. Our results did not support any role for two other regions (rs10735810, rs7139166) of VDR in explaining variation in height.

AbstractMetabolites 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.

The European population is ageing rapidly: its median age is the highest in the world. The topic of ageing has received significant attention in recent years, as is evident in the multiple international reports on ageing published during the last five years and the existence of at least eight active working groups on ageing at the EU level. The SAPEA Working Group on Transforming the Future of Ageing aims to provide a scientific perspective to address the question of what policies at the EU level could support the member states in their response to the current and future opportunities and challenges posed by ageing. In this project, SAPEA assembled a large multi-disciplinary working group, with world-leading expertise in the biomedical, human, social and engineering sciences. The Federation of European Academies of Medicine network led the project. The resulting report reflects not only the outstanding knowledge of the experts, but also their exemplary commitment to the voluntary task of collaborating in an interdisciplinary way and bringing the best and latest scientific knowledge into evidence-based policymaking. The report aims to make a unique contribution from a broad public health standpoint to a complex topic in a way that complements other related resources, thereby providing evidence-based science advice for the highest policy level in Europe. In particular, the working group has made a conscious effort not to duplicate the same aspects of ageing covered in existing reports. Likewise, by adopting a multi-disciplinary approach in the present report, the working group has distinguished itself from other EU ageing-related initiatives. These include the European Innovative partnership for Active and Healthy Ageing, Horizon 2020 projects in response to identified societal challenges posed by ageing, and the EU health programme managed by DG Santé focusing on healthy ageing, as well as existing networks funded by the EU, such as Innovation, Futurage, Mopact, Nestpar, and SHARE . The choice of topics covered in this report, or excluded, is based upon the expressed interest of policymakers throughout the scoping process, e.g. health, social affairs, employment, and technology. SAPEA is an integral part of the European Commission's Scientific Advice Mechanism (SAM). This Evidence Review Report is presented to the European Group of Chief Scientific Advisors, informing their Scientific Opinion which will be published later in 2019. Both this report and the Scientific Opinion are delivered directly to the College of Commissioners, and will be used for planning and policymaking. By such means, the best available science, distilled and analysed by the leading experts in Europe, should have a direct and tangible impact on decisions taken by the European Commission which influences the lives of some 500 million people across our continent.

The European population is ageing rapidly: its median age is the highest in the world. The topic of ageing has received significant attention in recent years, as is evident in the multiple international reports on ageing published during the last five years and the existence of at least eight active working groups on ageing at the EU level. The SAPEA Working Group on Transforming the Future of Ageing aims to provide a scientific perspective to address the question of what policies at the EU level could support the member states in their response to the current and future opportunities and challenges posed by ageing. In this project, SAPEA assembled a large multi-disciplinary working group, with world-leading expertise in the biomedical, human, social and engineering sciences. The Federation of European Academies of Medicine network led the project. The resulting report reflects not only the outstanding knowledge of the experts, but also their exemplary commitment to the voluntary task of collaborating in an interdisciplinary way and bringing the best and latest scientific knowledge into evidence-based policymaking. The report aims to make a unique contribution from a broad public health standpoint to a complex topic in a way that complements other related resources, thereby providing evidence-based science advice for the highest policy level in Europe. In particular, the working group has made a conscious effort not to duplicate the same aspects of ageing covered in existing reports. Likewise, by adopting a multi-disciplinary approach in the present report, the working group has distinguished itself from other EU ageing-related initiatives. These include the European Innovative partnership for Active and Healthy Ageing, Horizon 2020 projects in response to identified societal challenges posed by ageing, and the EU health programme managed by DG Santé focusing on healthy ageing, as well as existing networks funded by the EU, such as Innovation, Futurage, Mopact, Nestpar, and SHARE . The choice of topics covered in this report, or excluded, is based upon the expressed interest of policymakers throughout the scoping process, e.g. health, social affairs, employment, and technology. SAPEA is an integral part of the European Commission's Scientific Advice Mechanism (SAM). This Evidence Review Report is presented to the European Group of Chief Scientific Advisors, informing their Scientific Opinion which will be published later in 2019. Both this report and the Scientific Opinion are delivered directly to the College of Commissioners, and will be used for planning and policymaking. By such means, the best available science, distilled and analysed by the leading experts in Europe, should have a direct and tangible impact on decisions taken by the European Commission which influences the lives of some 500 million people across our continent.

The European population is ageing rapidly: its median age is the highest in the world. The topic of ageing has received significant attention in recent years, as is evident in the multiple international reports on ageing published during the last five years and the existence of at least eight active working groups on ageing at the EU level. The SAPEA Working Group on Transforming the Future of Ageing aims to provide a scientific perspective to address the question of what policies at the EU level could support the member states in their response to the current and future opportunities and challenges posed by ageing. In this project, SAPEA assembled a large multi-disciplinary working group, with world-leading expertise in the biomedical, human, social and engineering sciences. The Federation of European Academies of Medicine network led the project. The resulting report reflects not only the outstanding knowledge of the experts, but also their exemplary commitment to the voluntary task of collaborating in an interdisciplinary way and bringing the best and latest scientific knowledge into evidence-based policymaking. The report aims to make a unique contribution from a broad public health standpoint to a complex topic in a way that complements other related resources, thereby providing evidence-based science advice for the highest policy level in Europe. In particular, the working group has made a conscious effort not to duplicate the same aspects of ageing covered in existing reports. Likewise, by adopting a multi-disciplinary approach in the present report, the working group has distinguished itself from other EU ageing-related initiatives. These include the European Innovative partnership for Active and Healthy Ageing, Horizon 2020 projects in response to identified societal challenges posed by ageing, and the EU health programme managed by DG Santé focusing on healthy ageing, as well as existing networks funded by the EU, such as Innovation, Futurage, Mopact, Nestpar, and SHARE . The choice of topics covered in this report, or excluded, is based upon the expressed interest of policymakers throughout the scoping process, e.g. health, social affairs, employment, and technology. SAPEA is an integral part of the European Commission's Scientific Advice Mechanism (SAM). This Evidence Review Report is presented to the European Group of Chief Scientific Advisors, informing their Scientific Opinion which will be published later in 2019. Both this report and the Scientific Opinion are delivered directly to the College of Commissioners, and will be used for planning and policymaking. By such means, the best available science, distilled and analysed by the leading experts in Europe, should have a direct and tangible impact on decisions taken by the European Commission which influences the lives of some 500 million people across our continent.