The Children of the Twins Early Development Study (CoTEDS) is a new prospective children-of-twins study in the UK, designed to investigate intergenerational associations across child developmental stages. CoTEDS will enable research on genetic and environmental factors that underpin parent–child associations, with a focus on mental health and cognitive-related traits. Through CoTEDS, we will have a new lens to examine the roles that parents play in influencing child development, as well as the genetic and environmental factors that shape parenting behavior and experiences. Recruitment is ongoing from the sample of approximately 20,000 contactable adult twins who have been enrolled in the Twins Early Development Study (TEDS) since infancy. TEDS twins are invited to register all offspring to CoTEDS at birth, with 554 children registered as of May 2019. By recruiting the second generation of TEDS participants, CoTEDS will include information on adult twins and their offspring from infancy. Parent questionnaire-based data collection is now underway for 1- and 2-year-old CoTEDS infants, with further waves of data collection planned. Current data collection includes the following primary constructs: child mental health, temperament, language and cognitive development; parent mental health and social relationships; parenting behaviors and feelings; and other socioecological factors. Measurement tools have been selected with reference to existing genetically informative cohort studies to ensure overlap in phenotypes measured at corresponding stages of development. This built-in study overlap is intended to enable replication and triangulation of future analyses across samples and research designs. Here, we summarize study protocols and measurement procedures and describe future plans.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.

A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.

For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.

There is considerable evidence for a unitary and dimensional view of the genetic vulnerability to symptoms of anxiety and depression. The GENESiS (Genetic Environmental–Nature of Emotional States in Siblings) Study aims to use a multivariate approach to detect genetic loci that contribute to individual differences in this vulnerability dimension. The study used the UK General Practice Research Framework to generate a community-based sample of siblings. Questionnaire measures of anxiety/depression included the short form of the neuroticism scale from the revised Eysenck Personality Questionnaire (EPQ-N), the General Health Questionnaire (GHQ-12), and the anxious arousal and high positive affect subscales from the Mood and Anxiety Symptoms Questionnaire (MASQ-AA and MASQ-HPA). Genetic model-fitting of 2658 unselected sibships provided evidence for a single common genetic (familial) factor that accounted for a substantial proportion of the genetic variances and covariances of these four measures. Using the parameter estimates of this model, we constructed a composite index of this common genetic factor. This index, which has a sib correlation of 0.22, will be used as a quantitative phenotype in the molecular genetic phase of GENESiS. Twin Research (2000) 3, 316–322.

The Twins' Early Development Study (TEDS) is a large-scale longitudinal study of twins from early childhood through adolescence. Since its conception, TEDS has had as its focus the study of problematic development within the context of normal variation, mainly in the development of language, cognitive and academic abilities and behavior problems from multivariate quantitative and molecular genetic perspectives. TEDS twins have been assessed at 2, 3, 4, 7, 9, 10 and (currently) 12 years of age, and DNA collected from more than 12,000 children. Identified from birth records of twins born in the United Kingdom between 1994 and 1996, more than 15,000 pairs of twins originally enrolled in TEDS, and well over 13,000 pairs — representative of the UK population — remain involved in the study to date. Similar to many other twin and adoption studies, TEDS data indicate that both genetic and environmental influences are important in nearly all areas of behavioral development. Multivariate genetic analyses allow researchers to go beyond this basic nature–nurture question, and TEDS results suggest that, especially in the area of learning abilities and disabilities, genes are generalists and environments are specialists. That is, genes largely contribute to similarity in performance within and between learning abilities and disabilities and across age, whereas the environment contributes to differences in performance. Quantitative genetic findings such as these chart the course for molecular genetic research. The TEDS dataset is proving valuable in genome-wide association research that tries to identify some of the many genes responsible for the ubiquitous heritability of behavior.

Quantitative and molecular genetic research requires large samples to provide adequate statistical power, but it is expensive to test large samples in person, especially when the participants are widely distributed geographically. Increasing access to inexpensive and fast Internet connections makes it possible to test large samples efficiently and economically online. Reliability and validity of Internet testing for cognitive ability have not been previously reported; these issues are especially pertinent for testing children. We developed Internet versions of reading, language, mathematics and general cognitive ability tests and investigated their reliability and validity for 10- and 12-year-old children. We tested online more than 2500 pairs of 10-year-old twins and compared their scores to similar internet-based measures administered online to a subsample of the children when they were 12 years old (> 759 pairs). Within 3 months of the online testing at 12 years, we administered standard paper and pencil versions of the reading and mathematics tests in person to 30 children (15 pairs of twins). Scores on Internet-based measures at 10 and 12 years correlated .63 on average across the two years, suggesting substantial stability and high reliability. Correlations of about .80 between Internet measures and in-person testing suggest excellent validity. In addition, the comparison of the internet-based measures to ratings from teachers based on criteria from the UK National Curriculum suggests good concurrent validity for these tests. We conclude that Internet testing can be reliable and valid for collecting cognitive test data on large samples even for children as young as 10 years.

There have been numerous exhortations for more ‘translational research’. A selective review of historical examples of research leading to health benefits is used to consider the various forms of successful interplay between basic science and clinical applications. This is followed by a consideration of key neuroscience findings that might be relevant for translation, and then by a discussion of the challenges and opportunities in relation to mental disorders. The time-frame for the pathway from science findings to health benefits is usually long, and generally requires an interactive interplay among different scientific strategies. There is a false dichotomy between so-called basic and applied research and translation needs to proceed from the bedside to the laboratory as well as in the opposite direction. There is a key need for bridging research of the hypothesis-testing experimental medicine variety. Health benefits may involve either public health considerations or the treatment of individual patients, or both. There are now some opportunities for direct translational research but there is a much greater need for hypothesis-based bridging studies that occupy a crucial mid-phase in the pathway from science findings to health benefits.

Background. The overall aim of the GENESiS project is to identify quantitative trait loci (QTLs) for anxiety/depression, and to examine the interaction between these loci and psychosocial adversity. Here we present life-events data with the aim of clarifying: (i) the aetiology of life events as inferred from sibling correlations; (ii) the relationship between life events and measures of anxiety and depression, as well as neuroticism; and (iii) the interaction between life events and neuroticism on anxiety/depression indices.

Methods. We assessed the occurrence of one network and three personal life-event categories and multiple indices of anxiety/depression including General Health Questionnaire, Anhedonic Depression, Anxious Arousal and Neuroticism in a large community-based sample of 2150 sib pairs, 410 trios and 81 quads. Liability threshold models and raw ordinal maximum likelihood were used to estimate within-individual and between-sibling correlations of life events. The relationship between life events and indices of emotional states and personality were assessed by multiple linear regression and canonical correlations.

Results. Life events showed sibling correlations of 0·37 for network events and between 0·10 and 0·19 for personal events. Adverse life events were related to anxiety and depression and, to a less extent, neuroticism. Trait-vulnerability (as indexed by co-sib's neuroticism, anxiety and depression) accounted for 11% and life events for 3% of the variance in emotional states. There were no interaction effects.

Conclusions. Life events show moderate familiality and are significantly related to symptoms of anxiety and depression in the community. Appropriate modelling of life events in linkage and association analyses should help to identify QTLs for depression and anxiety.

The Swedish Adoption/Twin Study of Aging (SATSA) is a longitudinal program of research in gerontological genetics which is currently in its fifth year. The base population is comprised of 351 pairs of twins reared apart and 407 matched control pairs of twins reared together who responded to a questionnaire (Q1) in 1984. Two additional stages of SATSA have recently been completed: a longitudinal follow-up questionnaire mailed out in 1987 (Q2) and extensive in-person testing (IPT1) which included a health examination and cognitive battery. A second wave of IPT was started in January 1989. A summary of some of the major findings from Q1 and a description of IPT1 are reported.

A sample of twins separated early in life has been identified in the Swedish Twin Registry. When the registry was compiled in 1961 (old cohort) and 1973 (young cohort), one or both members of 961 pairs indicated that they were separated by the age of 10. In May 1979, both members of 698 pairs were alive and were sent a questionnaire concerning the circumstances of separation. Items included reasons and timing of separation, biological relatedness of rearing parents, degree of contact after separation (including whether they lived in the same area, attended the same school, or lived together again), rough measures of selective placement, and current frequency of contact. An attempt was then made to categorize the pairs based on degree of separation. A total of 257 pairs met the criteria: rearing parents of one twin biologically unrelated to rearing parents of the cotwin, twins not living together again after separation, and contact after separation a few times a year or less. As much as 50% were separated by their first birthday, and 80% by the age of five. Various data from the twin registry are presented describing the entire sample of early separated twins as compared to a matched sample of twins reared together.