The post-genomic era is witnessing a proliferation of large-scale and population based genetic and genomic research projects. Many countries have or are establishing research biobanks and, as with GenomEUtwin, there is great interest in building multinational projects that link genotypic and phenotypic information from different centers. Clearly, the conduct of these projects raises multiple ethical issues, and the knowledge generated will continually recast the ethical, legal and social implications (ELSI) of such research. Maximising the scientific profit from this work while minimizing the risks to the participants requires full integration of ethics components into the structure and functioning of these projects. GenomEUtwin is organized around five intellectual cores, including an Ethics Core which operates across the entire project. This paper describes the role of the Ethics Core and presents an overview of the guidelines on which the principles followed in GenomEUtwin are based. We outline the major ethical concerns of our project and highlight complexities arising from diverse national legislations. Finally, the role of empirically based ethics research is discussed for understanding the ethical, legal, social and economic implications of human genetics and genomics research.

The aim of this study was to determine the effects of intrauterine environment on the magnitude of intrapair differences in six somatic traits of monozygotic (MZ) and dizygotic (DZ) twins (1,263 pairs; 424 MZ twins and 839 DZ twins). Differences in intrauterine environments of MZ twins enforced division of the research material into four groups: (1) MZ-MC-TTTS — MZ twins from monochorionic (MC) pregnancies with twin-to-twin transfusion syndrome (TTTS), (2) MZ-MC (without TTTS)—MZ twins from MC pregnancies without TTTS, (3) MZ-DC—MZ twins from dichorionic (DC) pregnancies, and (4) DZ—DZ twins. The intrapair differences in all analyzed somatic traits, especially body weight and circumference of the chest, were the largest in the case of MZ twins from MC pregnancies with TTTS. DZ twins were the group presenting with the second largest intrapair differences in the analyzed traits. At the end of pregnancy, that is, in lunar months 9 and 10, the magnitude of intrapair differences in all traits of twins from this group was significantly greater than in MZ twins from both MC and DC pregnancies. Irrespective of the analyzed period, the least evident, statistically insignificant intrapair differences in the studied traits were documented in the case of MZ twins from MC pregnancies without TTTS and twins from DC pregnancies. These findings imply that the differentiating effect of intrauterine environment is associated with the occurrence of TTTS, rather than with chorionicity, as postulated previously.

We report a case of a monochorionic diamniotic twin with an uncomplicated pregnancy, but with an unexpected large intertwin hemoglobin (Hb) difference at birth. Twin 1 was delivered vaginally and had an uneventful neonatal course. The umbilical cord of Twin 1 was clamped approximately 5 min after birth. After the birth of Twin 1, Twin 2 developed severe bradycardia and showed limited cardiac output on ultrasound, for which an emergency cesarean section was performed. A full blood count revealed an Hb of 20.1 g/dL for Twin 1 and 10.2 g/dL for Twin 2 (intertwin difference 9.9 g/dL). Reticulocyte counts were similar, 40‰ and 38‰, respectively. Placental examination revealed 10 vascular anastomoses, including one arterio-arterial anastomosis with a diameter of 1.4 mm. Additionally, a large chorangioma was present on the placental surface of Twin 2. There was no color difference on the maternal side of the placenta. Based on the reticulocyte count ratio and the placental characteristics, twin anemia polycythemia sequence was ruled out as the cause of the large intertwin Hb difference. In this report, we discuss the various potential causes that could explain the large intertwin Hb difference including the role of delayed cord clamping in Twin 1, and the role of a large chorangioma, which may have attracted blood from the fetal circulation of Twin 2.

Multiple pregnancy represents a challenge for obstetrics and also poses significant psychological, social and economic problems. The chances of a successful outcome may be improved by appropriate preventive, diagnostic and management strategies, by the availability of specific skills and experience and by a multidisciplinary approach. In this paper are indicated and discussed, on the basis of current evidences, what can be considered the ten “commandments” in terms of providing optimal care in multiple pregnancies. In particular in this review we focus on the following topics: psychological support and clinical counseling; diagnosis and characterization of chorionicity; management at referral centers; individualization of care; avoidance of most frequent complications; consideration of specific pathologies; evaluation of fetal anatomy; monitoring of fetuses; planning of time and mode of delivery; monitoring of the mother during postpartum.

The hippocampus is a complex brain structure with key roles in cognitive and emotional processing and with subregion abnormalities associated with a range of disorders and psychopathologies. Here we combine data from two large independent young adult twin/sibling cohorts to obtain the most accurate estimates to date of genetic covariation between hippocampal subfield volumes and the hippocampus as a single volume. The combined sample included 2148 individuals, comprising 1073 individuals from 627 families (mean age = 22.3 years) from the Queensland Twin IMaging (QTIM) Study, and 1075 individuals from 454 families (mean age = 28.8 years) from the Human Connectome Project (HCP). Hippocampal subfields were segmented using FreeSurfer version 6.0 (CA4 and dentate gyrus were phenotypically and genetically indistinguishable and were summed to a single volume). Multivariate twin modeling was conducted in OpenMx to decompose variance into genetic and environmental sources. Bivariate analyses of hippocampal formation and each subfield volume showed that 10%–72% of subfield genetic variance was independent of the hippocampal formation, with greatest specificity found for the smaller volumes; for example, CA2/3 with 42% of genetic variance being independent of the hippocampus; fissure (63%); fimbria (72%); hippocampus-amygdala transition area (41%); parasubiculum (62%). In terms of genetic influence, whole hippocampal volume is a good proxy for the largest hippocampal subfields, but a poor substitute for the smaller subfields. Additive genetic sources accounted for 49%–77% of total variance for each of the subfields in the combined sample multivariate analysis. In addition, the multivariate analyses were sufficiently powered to identify common environmental influences (replicated in QTIM and HCP for the molecular layer and CA4/dentate gyrus, and accounting for 7%–16% of total variance for 8 of 10 subfields in the combined sample). This provides the clearest indication yet from a twin study that factors such as home environment may influence hippocampal volumes (albeit, with caveats).

The aim of the present article was to study the prevalence and the heritability of the initiation of breastfeeding in the Netherlands. The study was carried out in 5,581 participants from the Netherlands Twin Register, and included female twins, their sisters and mothers. All of the participants were born between 1911 and 1991. Breastfeeding was self-reported by the participants, and its prevalence was estimated conditional on birth cohort (born before 1955, 1955–1964, 1965–1974, 1975, or later). To estimate the heritability, we conducted extended twin-family modeling using the SEM package OpenMx in R. Mothers of twins had lower prevalence to initiate breastfeeding and the prevalence of initiation of breastfeeding increased with birth cohort: among mothers of twins 66% in the oldest (pre-1955) to 74% in the youngest (post-1974) and among mothers, who were twins themselves or sisters of twins, 79% in the oldest (pre-1955) to 85% in the youngest (post-1974). When accounting for prevalence differences between mothers of twins and other women, heritability of initiation of breastfeeding was 70%. However, the familial resemblance for sister and mother-daughter pairs was clearly lower than for DZ twin pairs, but as the number of non-twin sisters was relatively low, this observation did not lead to a significant contribution of a special shared twin environment.

In this ongoing longitudinal study of adolescent twins/sibling pairs and their parents in Taipei, we aimed to investigate the genetic and environmental influences on adolescent behavioral development, metabolic risk factors, and the associations between the two. Special focus is on anxious depression, metabolic profile, and hormonal factors such as cortisol and leptin. The first wave of assessment was completed during the period of 2002 to 2005 and included 192 twin pairs, 6 triplets, 56 sibling pairs and their first-degree relatives (484 parents and 142 siblings). We are currently in the process of a second wave assessment as follow-up. Dimensional psychological assessments using self-report questionnaires, as well as categorical assessments based on semistructured clinical interviews, were performed. All subjects received a 2-hour oral glucose tolerance test at the examination site. The metabolic phenotypes including body mass index, blood pressure, levels of glucose, insulin, and lipid profile as well as related hormonal levels were measured. Zygosity was determined using DNA, except for a few twins whose DNA was not available. Such a combination of detailed psychological assessments and metabolic function tests is expected to help shed light on the interrelation of psychological well-being and metabolic functioning.

The Wisconsin Twin Panel was initiated in 1994 to serve a study of the development of childhood mood and behavioral disorders. Families who give birth to twins within the state of Wisconsin are recruited within 6 months of the birth. The panel currently supports three ongoing, longitudinal research projects. Research foci include studying epigenetic contributions to emotional, physical, cognitive, and motoric development of infant and toddler twins; physiological concomitants of childhood temperament; and early risk and resiliency factors related to child psychopathology. All three studies include videotaped observational assessments and biological measures.

Introduction: Neuroticism is an important marker of vulnerability for both mental and physical disorders. Its link with multiple etiological pathways has been studied before. Inflammatory markers have been demonstrated to predict similar mental and physical disorders as neuroticism. However, currently no study has focused on the shared genetic background of neuroticism and inflammatory markers. In the present study we will focus on the phenotypic and genetic relationship between neuroticism and three commonly used inflammatory markers: C-reactive protein (CRP), fibrinogen and Immunoglobulin-G (IgG). Material and Methods: The study was conducted in 125 Dutch female twin pairs. For each participant, four different neuroticism scores were available to calculate a neuroticism composite score that was used in the statistical analyses. Blood samples for inflammatory marker determination were taken after an overnight fast. Heritabilities, phenotypic and genetic correlations were estimated using bivariate structural equation modeling. Results: Heritabilities are fair for neuroticism (0.55), CRP (0.52) and fibrinogen (0.67) and moderate for IgG (0.43). No significant phenotypic or genetic correlations were found between neuroticism and the inflammatory markers. Interaction models yielded no moderation of the genetic and environmental pathways in the regulation of inflammatory markers by neuroticism. Conclusion: Substantial heritabilities were observed for all variables. No evidence was found for significant shared (or moderation of) genetic or environmental pathways underlying neuroticism and inflammatory status.

In this study, we analyzed the estimated frequency of monozygotic (MZ) and dizygotic (DZ) spontaneous twins in Lombardy during the period 2007−2017. This is a population-based study using the regional healthcare utilization databases of the Lombardy Region. The total number of spontaneous twin deliveries, in separate strata of like and unlike sex, was obtained. Moreover, estimates of DZ and MZ twin births were calculated using Weinberg’s method. The standardized rates (SRs), adjusted for maternal age, of DZ and MZ twin births were computed according to calendar period. The twinning rates were calculated among strata of parity and maternal age. Finally, DZ:MZ ratio was calculated. Among the 734,278 spontaneous deliveries, 9176 (12.5 out of 1000 births) couples of twins were identified. In the three periods considered (i.e. 2007−2010, 2011−2014 and 2015−2017), no trend in the SRs of MZ twins was observed, respectively 0.41 (95% CI [0.40, 0.43]), 0.43 (95% CI [0.42, 0.45]) and 0.43 (95% CI[0.42, 0.45]). Differently, a slightly decreasing trend was observed in DZ twins SRs, respectively 0.87 (95% CI [0.84, 0.89]), 0.81 (95% CI [0.79, 0.83]), and 0.78 (95% CI [0.76, 0.80]). As concerns parity and maternal age, the rate of DZ twin births was consistently higher in nulliparae women aged 35 years or more. In our cohort, despite the increase of maternal age, a decline of spontaneous twin births emerged, especially due to the downward trend of DZ twins.

Monozygotic twins (MZT) are 2.5 times more frequent in ART than in natural conceptions. A number of ART-related mechanisms have been probably linked with MZT. Studies that retrospectively analyze the time-lapse (TL) records resulting in MZT suggest that some morphokinetic traits of the inner cell mass and the trophectoderm could be predictors of MZT, but results are controversial. We present the complete TL record of one case of MZT that split itself at the very moment of the division into two cells, with one of the cells coming out through a hole in the zona pellucida (ZP). Both resulting embryos developed normally, and were vitrified. It is suggested that the hole in the ZP may facilitate the extrusion of some cells of the <day 4 embryo and that this cell development is not constrained by being inside the ZP. Despite the lack of the inhibition of the ZP itself or the influence of the other embryo cells, the totipotent cell was then able to develop correctly from the start. Moreover, the embryo inside the ZP compensated for the loss of this cell apparently without problems. Our findings are discussed in the context of previous literature and ethical problems are addressed.

Ten classic works in twin research are described. These volumes are rich in data, interpretation, and impact, and contain life history material that adds depth and dimension to the quantitative findings. Next, research on social relationships in older twins, superfecundated twinning in chimpanzees; effects of embryo transfer on conjoined twinning and the reduced frequency of in vitro multiples is reviewed. Finally, there has been considerable public interest surrounding the first identical twin renal transplant, an identical triplet wedding; identical twin boxers, a twin living in space, and a politically active twin pair.

The objective of this study was to examine the heritability of an endophenotype relevant to nicotine dependence, namely tension reduction after smoking. This study also examined whether common genetic, shared environmental, and nonshared environmental factors influence this endophenotype measured repeatedly during an experimental paradigm. Twin and sibling pairs, all of whom were regular smokers, completed a laboratory paradigm in which they reported on levels of tension at baseline and after smoking each of 3 cigarettes. Univariate twin analyses suggested a sizeable role of additive genetic effects on tension reduction, with heritability estimates ranging between 47 and 68%. Result of multivariate Cholesky analyses indicated that there were additive genetic influences common to tension reduction assessed after cigarettes 1, 2, and 3. Multivariate models including genetic and nonshared environmental effects provided the best fit to the data. To the best of our knowledge, this is the first study to examine the genetic basis of a laboratory smoking endophenotype, in this case tension reduction after smoking. Implications for genetic association studies are discussed.

The aim of the study was to examine the Family and School Psychosocial Environment (FSPE) questionnaire in relation to a possible genotype–environment correlation and genetic mediation between the FSPE variables and personality variables, assessed by the Junior Eysenck Personality Questionnaire. A sample of 506 Swedish children aged 10–20 years from 253 families were recruited via the Swedish state population and address register and SchoolList.Eu. The children were divided into 253 pairs: 46 monozygotic twin pairs, 42 dizygotic twin pairs, 140 pairs of full siblings and 25 pairs of half-siblings. The behavioral genetic analysis showed that both FSPE factors, Warmth and Conflicts, may be partly influenced by genetic factors (suggesting genotype–environment correlation) and that nonadditive genetic factors may mediate the relationship between FSPE factors and psychoticism/antisocial personality (P). An indication of a special shared monozygotic twin environment was found for P and Lie/social desirability, but based on prior research findings this factor may have a minor influence on P and L. P and L were negatively correlated, and the relationship seems to be partly mediated by nonadditive genetic factors. Nonshared environment and measurement errors seem to be the most influential mediating factors, but none of the cross-twin cross-dimension correlations suggest a common shared environmental mediating factor.

Since saliva collection is noninvasive, painless and inexpensive, it may become an alternative to obtain genomic DNA, which is critical to evaluate zygosity and the role of genetic factors in twin research. This study provided a rough description of salivary DNA in Chinese twin children, and presented the DNA yield and quality extracted from saliva in a large-scale children sample, which supplied an example for saliva sample using in genetic epidemiology. Three milliliters of saliva was collected from 356 twin children aged 6 to 15, and DNA was extracted by a com mercial DNA isolation kit. The DNA yield and purity was determined by spectrophotometry at 260nm and 280nm. The zygosity determination of the same-sex twins and the assay of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism indicated the quality of salivary DNA. The amount of extracted DNA from three milliliters of saliva was about 34.91μg (2.20 ~ 122.04μg), average OD260/280 values was 1.84. Saliva DNA is a reliable sample for the determination of twins' zygosity. We conclude that saliva may be a feasible and reliable source of DNA for genetic epidemiology studies, especially for twin research.

Psychological distress (PSYCH), somatic distress (SOMA), affective disorders (AD), and substance use (SU) frequently co-occur. The genetic relationship between PSYCH and SOMA, however, remains understudied. We examined the genetic and environmental influences on these two disorders and their comorbid AD and SU using structural equation modeling. Self-reported PSYCH and SOMA were measured in 1,548 twins using the two subscales of a 12-item questionnaire, the Somatic and Psychological Health Report. Its reliability and psychometric properties were examined. Six ADs, involvement of licit and illicit substance, and two SU disorders were obtained from 1,663–2,132 twins using the World Mental Health Composite International Diagnostic Interview and/or from an online adaption of the same. SU phenotypes (heritability: 49–79%) were found to be more heritable than the affective disorder phenotypes (heritability: 32–42%), SOMA (heritability: 25%), and PSYCH (heritability: 23%). We fit separate non-parametric item response theory models for PSYCH, SOMA, AD, and SU. The IRT scores were used as the refined phenotypes for fitting multivariate genetic models. The best-fitting model showed the similar amount of genetic overlap between PSYCH–AD (genetic correlation rG = 0.49) and SOMA–AD (rG =0.53), as well as between PSYCH–SU (rG = 0.23) and SOMA–SU (rG = 0.25). Unique environmental factors explained 53% to 76% of the variance in each of these four phenotypes, whereas additive genetic factors explained 17% to 46% of the variance. The covariance between the four phenotypes was largely explained by unique environmental factors. Common genetic factor had a significant influence on all the four phenotypes, but they explained a moderate portion of the covariance.

Non-syndromic agenesis of permanent teeth is one of the most common anomalies in human development, a multifactorial characteristic caused by genetic and environmental factors. We describe a pair of monozygotic twins who showed second premolar and third molar agenesis, albeit with different expressions. We studied the DNA of two genes, paired domain box gene 9 (PAX9) and muscle segment homeodomain-homeobox1 (MSX1), encoding transcription factors that earlier studies found were involved in the manifestation of this condition. No specific causative mutation was found. However, we detected a C→T change in MSX1 exon 2 in both twins, suggesting that this polymorphism might be involved in the trait's expression.

The Mid-Atlantic Twin Registry (MATR) is a population-based registry of more than 60,000 twins primarily born or living in Virginia, North Carolina and South Carolina. Researchers may utilize the MATR for administration of research services, including study recruitment, data or sample (e.g., DNA) collection, archival dataset creation, as well as data collection through mailed, phone or online surveys. In addition, the MATR houses the MATR Repository, with over 1700 DNA samples primarily from whole blood available for researchers interested in DNA genotyping. For over 40 years MATR twins have participated in research studies with investigators from a range of scientific disciplines and institutions. These studies, which have resulted in numerous publications, explored diverse topics, including substance use, smoking behaviors, developmental psychopathology, bullying, children’s health, cardiovascular disease, cancer, the human microbiome, epigenetics of aging, children of twins and sleep homeostasis. Researchers interested in utilizing twins are encouraged to contact the MATR to discuss potential research opportunities.

Loss of a twin has been largely overlooked by bereavement counselors and clinicians. This particular type of loss is also poorly understood among the public. Consequently, some bereaved twins have established a unique organization, Twinless Twins Support Group International, for the purpose of sharing this traumatic life experience with one another. The present article reviews events from the annual convention of Twinless Twins, held in July 2009, in Denver, Colorado. Selected findings from research on twin loss are also presented. Next, twin research concerned with the origins and implications of empathy, hormone replacement therapy and multiple birth conception will be reviewed. This article concludes with summaries of real life stories of twins' kidney disease, literary talent and retirement festivities.