The Australian Twin Registry.

The Australian Twin Registry (ATR), established in the late 1970s, is a volunteer registry of over 30,000 pairs of Australian twins of all zygosity types and ages unselected for their health or medical history. The ATR does not undertake research itself but acts as facilitator, providing an important national and international resource for medical and scientific researchers across a broad range of disciplines. Its core functions are the maintenance of an up-to-date database containing basic contact details and baseline information, and the management of access to the resource in ways that enhance research capacity within Australia while protecting the rights of twins. The ATR has facilitated more than 200 studies using a variety of designs, including classic biometrical twin and twin family studies, co-twin control studies, intervention studies, longitudinal studies, and studies of issues relevant specifically to twins. These have yielded more than 300 peer-reviewed publications to date. Areas of major research include studies of behavior, musculoskeletal conditions, teeth and face patterns, cardiovascular risk factors, substance abuse, and risk factors for melanoma and breast cancer. Extensive longitudinal data are available for around 10,000 pairs. DNA samples have been obtained from more than 6000 twins. Considerable efforts are devoted to maintaining the commitment of registry members and recruitment. The ATR hopes to secure funding to expand its activities, including the systematic collection of DNA samples, so that it can continue to play a major role in the development of twin research and contribute to the annotation of the human genome.     

Parent ratings of temperament in twins: explaining the 'too low' DZ correlations.

Twin studies of child temperament using objective measures consistently suggest moderate heritability for most dimensions. However, parent rating measures produce unusual patterns of results. Intraclass correlations for identical (MZ) twins are typically high, whereas fraternal (DZ) twin intraclass correlations are much lower than would be predicted from an additive genetic model. The 'too low' DZ correlations can be explained by parent-rating biases that either exaggerate the differences between DZ twins (contrast effects) or that inflate the similarity of MZ twins (assimilation effects), or by the presence of non-additive genetic variance. To evaluate the three possible explanations, we used model-fitting procedures applied to parent-rating data averaged across 14, 20, 24, and 36 months of age in a sample of 196 twin pairs participating in the MacArthur Longitudinal Twin Study. The data were best described by a model that included contrast effects. Implications for non-twin research are discussed.     

Classical twin studies and beyond

Twin studies have been a valuable source of information about the genetic basis of complex traits. To maximize the potential of twin studies, large, worldwide registers of data on twins and their relatives have been established. Here, we provide an overview of the current resources for twin research. These can be used to obtain insights into the genetic epidemiology of complex traits and diseases, to study the interaction of genotype with sex, age and lifestyle factors, and to study the causes of co-morbidity between traits and diseases. Because of their design, these registers offer unique opportunities for selected sampling for quantitative trait loci linkage and association studies.     

The continuing value of twin studies in the omics era

The classical twin study has been a powerful heuristic in biomedical, psychiatric and behavioural research for decades. Twin registries worldwide have collected biological material and longitudinal phenotypic data on tens of thousands of twins, providing a valuable resource for studying complex phenotypes and their underlying biology. In this Review, we consider the continuing value of twin studies in the current era of molecular genetic studies. We conclude that classical twin methods combined with novel technologies represent a powerful approach towards identifying and understanding the molecular pathways that underlie complex traits.     

Twins and friendship.

A growing body of literature asserts the importance of friendships for a child's emotional wellbeing, behavioural adjustment and developmental attainment. However, few studies have examined friendships in the twin situation. This paper examines the literature on friendships among children who are twins and asks two questions: (1) What are the implications of the twin situation for friendship formation? (2) How can the twin situation inform theoretical knowledge concerning friendship formation in the general population? The discussion examines the implications of the twin situation for the size and nature of twin children's friendship pool and questions whether children who are twins are more likely to be adaptive or maladaptive in their social behaviour. The paper argues for the need to study the process and mechanisms in friendship formation among twin children because the findings might inform not only studies of friendship but also behavioural genetic research.     

Asthma genetics and intermediate phenotypes: a review from twin studies.

It has been long recognised that asthma and related phenotypes have an important hereditary nature, in which inheritance does not follow the classical Mendelian patterns and the exact mode of inheritance is not known. Linkage, association studies and genome-wide screening suggest that many genes are involved in the pathogenesis of asthma. Twin studies have contributed significantly to our understanding on the genetics of asthma, especially the large-scale twin studies in different parts of the world which have showed comparable results. With the shortcomings of the twin method borne in mind, more twin studies are needed to investigate the heredity component of the intermediate phenotypes of asthma, that is, bronchial hyperresponsiveness, total immunoglobulin E, skin test reactivity, specific IgE against different aeroallergens, and the variability of lung function. Twin studies are very suitable to unravel the intricate network of genes and environment which plays a role in asthma. Monozygotic twins and the co-twin control design are suitable for this purpose, while longitudinal twin studies are needed to solve the problem of the age related expression of genes which probably are involved in the pathogenesis of asthma. In the near future twin studies will play an important role in the detection of new, as yet undiscovered genes, but may be even more important in answering the most challenging of all questions: how do the environment interact with the genetics of asthma? Exchange of information and collaboration between the different research groups involved in the genetics of asthma will contribute to a better understanding of this condition.     

Glucose and insulin metabolism in twins: influence of zygosity and birth weight.

Several epidemiological and metabolic studies have demonstrated an impact of the intrauterine environment on the development of disease in adult life, including Type 2 diabetes and glucose intolerance. Our finding of lower birth weights among monozygotic diabetic twins compared to their non-diabetic genetically identical co-twins confirms this association and, furthermore, eliminates the possibility that the association could be explained solely by common genes leading to both impaired intrauterine growth and increased risk of Type 2 diabetes. Due to an often shared placenta monozygotic twins may experience a more adverse intrauterine environment compared to dizygotic twins and may therefore be more prone to develop various metabolic abnormalities. Our findings of a higher glucose and insulin profile after oral glucose ingestion, and recently lower insulin-stimulated glucose uptake--indicating glucose intolerance and insulin resistance--among monozygotic compared to dizygotic twins may to some extent question the validity of classical twin studies in diabetes research where equal environmental influences in monozygotic and dizygotic twins is assumed. The potential role of an adverse intrauterine environment in causing Type 2 diabetes in humans, may to some degree alter our conception of the twin model in diabetes research including the interpretation of aetiological conclusions reached in previous classical twin studies of diabetes. However, our present knowledge is far too insufficient to discard the results from classical twin studies concerning the relative role of genes versus environment for the development of diabetes and its metabolic effects.     

Twins are more different than commonly believed,but made less different by compensating behaviors

Twin studies are popular, because twins are believed to be the same/similar in genes and environmental exposures. It is well documented, however, that the firstborns are healthier at birth. We use the entire U.S. record of twin births during 1995–2000 to show that the survival duration parameters differ between twins depending on the birth order. We also find that wiser (i.e., older or educated) or married (i.e., resource-richer) mothers take more care of the weaker, which is a “compensating” behavior reducing the twin difference, as opposed to “reinforcing (the twin difference)” behavior. The systematic survival pattern difference and the mother's intervention against nature send cautions to twin studies that regard twins homogeneous to interpret their findings accordingly. Since the survival duration in our data is 97% right-censored in one year, we devise a quantile-based ‘fixed-effect’ semiparametric estimator that can handle heavy censoring, which is our methodological contribution.     

The Italian Twin Project: from the personal identification number to a national twin registry.

The unique opportunity given by the "fiscal code", an alphanumeric identification with demographic information on any single person residing in Italy, introduced in 1976 by the Ministry of Finance, allowed a database of all potential Italian twins to be created. This database contains up to now name, surname, date and place of birth and home address of about 1,300,000 "possible twins". Even though we estimated an excess of 40% of pseudo-twins, this still is the world's largest twin population ever collected. The database of possible twins is currently used in population-based studies on multiple sclerosis, Alzheimer's disease, celiac disease, and type 1 diabetes. A system is currently being developed for linking the database with data from mortality and cancer registries. In 2001, the Italian Government, through the Ministry of Health, financed a broad national research program on twin studies, including the establishment of a national twin registry. Among all the possible twins, a sample of 500,000 individuals are going to be contacted and we expect to enrol around 120,000 real twin pairs in a formal Twin Registry. According to available financial resources, a sub sample of the enrolled population will be asked to donate DNA. A biological bank from twins will be then implemented, guaranteeing information on future etiological questions regarding genetic and modifiable factors for physical impairment and disability, cancers, cardiovascular diseases and other age related chronic illnesses.     

Twin-singleton differences in intelligence?

The twin method has been criticised for its alleged non-generalisability. When population parameters of intellectual abilities are estimated from a twin sample, critics point to the twin-singleton differences in intrauterine and family environments. These differences are suggested to lead to suboptimal cognitive development in twins. Although previous studies have reported twin-singleton differences in intelligence, these studies had two major drawbacks: they tested young twins, and twins were compared with (genetically) unrelated singletons. To test accurately whether twin-singleton differences in intelligence exist, a group of adult twins and their non-twin siblings were administered the Dutch WAIS-III. The group was large enough to detect twin-singleton differences of magnitudes reported in earlier investigations. The data were analysed using maximum likelihood model fitting. No evidence of differences between adult twins and their non-twin siblings on cognitive performance was found. It is concluded that twin studies provide reliable estimates of heritabilities of intellectual abilities which can be generalised to the singleton population.     

The foetal origins of adult disease: interpreting the evidence from twin studies.

Twin studies have a contribution to make to the debate concerning the foetal origins of adult disease. Twins are growth retarded compared to singletons and experience post-natal catch-up growth. However, there is no evidence that twins are at increased risk of cardiovascular disease. Studying whether discordance in size at birth within monozygotic twin pairs is predictive of discordance in later life disease should help resolve whether the association between size at birth and later disease is due to common genetic factors. Results from studies of blood pressure in childhood and adult life looking at these within twin effects are far from conclusive. There are, however, methodological problems in the interpretation of these results, not least of which is the relatively small numbers of twin pairs studied. Studies exploring the effect of zygosity and chorion type on later disease provide may provide a useful extension of the research agenda. In summary, twin studies to date have raised more questions about the foetal origins hypothesis than they have resolved.     

The heritability of insomnia: A meta-analysis of twin studies

Twin studies of insomnia exhibit heterogeneity in estimates of heritability. This heterogeneity is likely because of sex differences, age of the sample, the reporter and the definition of insomnia. The aim of the present study was to systematically search the literature for twin studies investigating insomnia disorder and insomnia symptoms and to meta-analyse the estimates of heritability derived from these studies to generate an overall estimate of heritability. We further examined whether heritability was moderated by sex, age, reporter and insomnia symptom. A systematic literature search of five online databases was completed on 24 January 2020. Two authors independently screened 5644 abstracts, and 160 complete papers for the inclusion criteria of twin studies from the general population reporting heritability statistics on insomnia or insomnia symptoms, written in English, reporting data from independent studies. We ultimately included 12 papers in the meta-analysis. The meta-analysis focussed on twin intra-class correlations for monozygotic and dizygotic twins. Based on these intra-class correlations, the meta-analytic estimate of heritability was estimated at 40%. Moderator analyses showed stronger heritability in females than males; and for parent-reported insomnia symptoms compared with self-reported insomnia symptoms. There were no other significant moderator effects, although this is likely because of the small number of studies that were comparable across levels of the moderators. Our meta-analysis provides a robust estimate of the heritability of insomnia, which can inform future research aiming to uncover molecular genetic factors involved in insomnia vulnerability.     

A Conversation with Bakhtin : On Inquiry and Dialogic Thinking

Two different traditions in psychology emphasize the study of twin-twin and mother-twin relationships. One line of research, the twin development approach, has compared parenting styles and sibling relationships in families with twin and singleton offspring. This research tradition is based on the assumption that twins, relative to singletons, may be at risk for developmental delays in motor, cognitive [1-3], linguistic [1,4,5], and social-emotional functioning [6,7] because of their increased rate of prematurity, lower birth weight [8-11], increased parenting demands that result in less interactive maternal speech [12-18], shared peer time [19], and other experiences that distinguish twins from singletons [7,8,19-21]. Although recent studies have not replicated the developmental concerns [22-26] or concerns about specific birth defects [27] that emerged from earlier studies comparing twins and singletons, there continues to be interest in the relational differences that may be present in twin and singleton families and in the need to address educational and social policies that promote twin development [28,29]. Within the framework of this approach, distinctions between twins and singletons have received more attention than distinctions between fraternal, dizygotic (DZ) and identical, monozygotic (MZ) twins.     

Twin studies in behavioral research: a skeptical view

We review in detail two major ongoing research projects that employ samples of twins reared apart (and in one case, twins reared together). The studies attempt, via model fitting, to estimate proportions of genetic and environmental variance for many human traits. We discuss problems concerning the representativeness of samples, the accuracy and reliability of the data, the extent of contact of nominally separated twins, the measurement of selective placement effects, and the particular model-fitting procedures. The two studies agree in their conclusions, but we do not find the conclusions to be convincing. We suggest that no scientific purpose is served by the flood of heritability estimates generated by these studies.     

The Norwegian Institute of Public Health Twin Panel: a description of the sample and program of research.

The Norwegian Institute of Public Health in Oslo has an ongoing program of twin research using population-based cohorts of twins. The current database includes information on twins identified through the Medical Birth Registry of Norway and born from 1967-1979, altogether 15,370 twins. This is a longitudinal study with a cohort sequential design whereby new cohorts are recruited into the study at 5-6 year intervals. Sub-samples of these twins have participated in questionnaire studies and clinical assessment sub-projects. These projects include national and international collaborations. Our primary areas of interest include mental health and psychological well-being, obesity, asthma and allergies, health behaviors and health perceptions, comorbidity, and perinatal influences on health outcomes. This paper provides a brief overview of the data, sample, and the various research projects associated with this twin program of research.     

Longitudinal studies of viral sequence, viral phenotype, and immunologic parameters of human immunodeficiency virus type 1 infection in perinatally infected twins with discordant disease courses.

Perinatal human immunodeficiency virus type 1 (HIV-1) infections cause a broad spectrum of clinical disease and are variable in both the age of the patient at onset of serious disease and the progression of the clinical course. Heterozygotic perinatally infected twins with a marked difference in their clinical courses were monitored during the first 2 years of life. Twin B, the second-born twin, developed AIDS by 6 months of age and died at 22 months of age, while twin A remained minimally symptomatic through the first 2 years. Sequential blood specimens were obtained from the twins in order to characterize the immunologic properties of the children and the phenotypes and genotypes of the HIV-1 isolates at various times. Twin A developed neutralizing antibodies and a high-level antibody-mediated cellular cytotoxicity (ADCC) response, while twin B had no neutralizing antibody and a much lower ADCC response. The virus isolates obtained from the two children at various time points proliferated equally well in peripheral blood mononuclear cells, were nonsyncytium inducing, and could not infect established T-cell lines. They differed in their ability to infect primary macrophages. In parallel to the biological studies, the HIV-1 tat and part of the env gene sequences of the longitudinal isolates at four time points were determined. Sequences of virus from both twins at different time points were highly conserved; the viruses evolved at a similar rate until the last analyzed time point, at which there was a dramatic increase in sequence diversity for the sicker child, especially in the tat gene. Our results show that the viruses isolated at different times do not have significant changes in growth properties. The absence or low levels of neutralizing antibodies may correlate with disease progression in the twins.     

Birth order,gestational age,and risk of delivery related perinatal death in twins: retrospective cohort study

ObjectiveTo determine whether twins born second are at increased risk of perinatal death because of complications during labour and delivery.DesignRetrospective cohort study.SettingScotland, 1992 and 1997.ParticipantsAll twin births at or after 24 weeks'' gestation, excluding twin pairs in which either twin died before labour or delivery or died during or after labour and delivery because of congenital abnormality, non-immune hydrops, or twin to twin transfusion syndrome.ResultsOverall, delivery related perinatal deaths were recorded for 23 first twins only and 23 second twins only of 1438 twin pairs born before 36 weeks (preterm) by means other than planned caesarean section (P>0.99). No deaths of first twins and nine deaths of second twins (P=0.004) were recorded among the 2436 twin pairs born at or after 36 weeks (term). Discordance between first and second twins differed significantly in preterm and term births (P=0.007). Seven of nine deaths of second twins at term were due to anoxia during the birth (2.9 (95% confidence interval 1.2 to 5.9) per 1000); five of these deaths were associated with mechanical problems with the second delivery following vaginal delivery of the first twin. No deaths were recorded among 454 second twins delivered at term by planned caesarean section.ConclusionsSecond twins born at term are at higher risk than first twins of death due to complications of delivery. Previous studies may not have shown an increased risk because of inadequate categorisation of deaths, lack of statistical power, inappropriate analyses, and pooling of data about preterm births and term births.

What is already known on this topic

It is difficult to assess the wellbeing of second twins during labourDeliveries of second twins are at increased risk of mechanical problems, such as cord prolapse and malpresentation, after vaginal delivery of first twinsIncreased risks of perinatal death in second twins have not been shown, but the methods of these studies were flawed

What this study adds

Second twins delivered at term are at increased risk of delivery related perinatal deathsIntrapartum anoxia caused 75% of these deaths in second twins, and most of these resulted from mechanical problems after vaginal delivery of first twinsPlanned caesarean section of twins at term may prevent perinatal deaths     

Establishing a twin register in Sri Lanka.

Nearly all twin registers are based in developed countries and there is no twin register in the developing world. Our objectives were to initiate the process of establishing a nationwide twin register in Sri Lanka by starting a volunteer register first and working towards a population-based register. Regular newspaper advertisements, feature articles, radio talks, and television programmes were used to publicise a competition for twins, their parents/relatives and friends requesting them to participate by sending in details of twins. The competition ran from 28 March 1997 for a period of 3 months. It offered prizes for three winners selected by drawing lots. Advertisements highlighted the objective of the competition as establishing a twin register for future research and emphasised that informed consent would be obtained for individual research projects. Those who registered comprise 4602 twin pairs (same sex: male--1564, female--1885; different sex--1153), 80 sets of triplets (same sex: male--17, female--31; different sex--42) and two sets of quadruplets (different sex). The oldest twins, triplets, quadruplets are 85, 46, and 5 years old, respectively; 88.0% of twins are less than 30 years old. Although others have previously used media publicity to enrol twins in twin registers, we believe this to be the first time that twins have been enrolled through competition. We have more young twins, and our gender and zygosity proportions after applying Weinburg's rule do not match the proportions expected from a volunteer twin sample. Establishing a twin register for research purposes has proved possible in a developing country.     

Mortality among twins after age 6: fetal origins hypothesis versus twin method.

OBJECTIVE--To test the validity of the fetal origins hypothesis and the classic twin method. DESIGN--Follow up study of pairs of same sex twins in which both twins survived to age 6. SETTING--Denmark. SUBJECTS--8495 twin individuals born 1870-1900, followed through to 31 December 1991. MAIN OUTCOME MEASURES--Mortality calculated on a cohort basis. RESULTS--Mortality among twins and the general population was not significantly different except among females aged 60-89, in whom mortality among twins was 1.14 times (SE 0.03) higher than in the general population. Mortality among female dizygotic twins was 1.77 times (0.18) higher than among monozygotic twins at age 30-59. Otherwise, mortality for monozygotic and dizygotic twins did not consistently differ after age 6. CONCLUSION--According to the fetal origins hypothesis the risk of adult morbidity and mortality is heightened by retardation in intrauterine growth. Twins, and in particular monozygotic twins, experience growth retardation in utero. The findings in the present study suggest that the fetal origins hypothesis is not true for the retardation in intrauterine growth experienced by twins. Furthermore, the data are inconsistent with the underlying assumption of a recent claim that the classic twin method is invalid for studies of adult diseases. The present study is, however, based on the one third of all pairs of twins in which both twins survived to age 6. The possible impact of this selection can be evaluated in future studies of cohorts of younger twins with lower perinatal and infant mortality.     

Twin research, and its multiple births and expressions: a short, personal voyage through its scope, history, and organization.

The notion of twins and twinning involves a multiplicity of meanings and contexts that altogether encompass an unexpectedly wide and significant part of human experience, culture, and endeavor. This cultural polysemy is, to some extent, also an attribute of twin research, which has structured itself around a multiplicity of scientific areas of enquiry, and across time, throughout a multiplicity of births and rebirths, periodically declining and resurging as a phoenix from its ashes. What is proposed is a short voyage through this polysemy and phoenixity of twinning and twin research, and through the structuring process that has accompanied its developments, international scope, and organization. No claim to completeness, but an attempt to dig into personal memory and experience, and share some recollections of the main steps of the process, and particularly the evolution of the journal, the society, the international meetings, and their role in supporting the area's persistence and continuous revivals and adaptations until today.