The National Twin Registry of Sri Lanka was established in 1997 as a volunteer register. To extend it to a population-based register, we examined the effectiveness of tracing older twins by inspecting birth records and recruiting them by postal invitation and in-person contact. Birth records at a divisional secretariat reported from 2 maternity hospitals between the years of 1954–1970 were scrutinised to identify a random sample of twins. These hospitals had the highest twin delivery rates for the whole country. We identified 620 twins and a questionnaire was mailed to them. Research assistants visited a cohort of non-respondents (71) in the postal survey. These 620 twins were identified after perusing 20,700 birth records. The twinning rate was estimated at 29.95 ([620/20700] × 1000) twins per 1000 registered births (CI 27.63–32.27). In the postal survey, 37 (12%) responded and 62 letters were returned (20%). Both twins were still alive in 20 pairs, one was still alive in 15 pairs, and both twins were dead in 2 pairs. During field visits, 42 (59.2%) addresses were located. Information was available on 16 twin pairs. Both twins were alive in 8 pairs, one each in 4 pairs, and both were dead in 4 pairs and at least one twin was traced in 10 pairs (14%). Both the postal and the field survey gave a low yield. This finding is different from tracing younger twins born between 1985–1997 by using the same methods. Migration, urbanization and development in the country might have affected tracing older twins from the birth record addresses, which were decades old.

The aim of the current study was to investigate the importance of genetic and environmental effects in the variation of body mass index, and to investigate linkage for obesity to previously reported candidate regions on chromosome 2 and 10. A sample of 1422 twin pairs from the population based Swedish Twin Registry was used in order to estimate the genetic and environmental effects in the variation of body mass index by means of structural equation modeling. A selection of those, 51 concordant and 155 discordant for obesity, was used for the linkage analysis by implementing the “combined” Haseman-Elston approach. Heritability of body mass index ranged from 59–70%, implying that genetic effects were of importance for the variation of obesity, and there were significant sex and age differences. Linkage could not be verified in candidate regions of chromosomes 2 and 10, indicating that these genetic variants have a significant effect in extreme obese populations rather than in moderately obese Caucasians. However, the results were sensitive to issues related to power, minor effects of the genes, ethnic differences and the complex mechanism underlying obesity.

Stroke is one of the leading causes of severe disability and death in the world. In the present article we outline possibilities and limitations for future stroke research within the GenomEUtwin. The combined sample of twins born before 1958 from Denmark, Finland, and Sweden, and available for follow-up into the second millennium for non-fatal and fatal stroke events through national inpatient and death registers exceeds 70,000 twin pairs. This sample size will enable the study of genetic influences on stroke and major stroke subtypes. Large samples of twins in GenomEUtwin have been followed up repeatedly through interviews and questionnaires concerning a variety of exposures and potential risk factors for stroke. We briefly outline how this information can be combined with the health register information for epidemiologic and genetic epidemiologic studies of stroke. We also present the number of twin pairs concordant and discordant for stroke in Denmark, Finland and Sweden, and time lags between events for twins concordant for stroke. This information illustrates that the number of affected sib pairs for linkage studies is relatively limited, but the sample sizes are promising for association studies.

Studies in singletons have found an association between birthweight and Type 2 diabetes in adult life. The aim of this study was to investigate whether this association could also be seen in twins. 59 monozygotic (MZ) and 69 dizygotic (DZ) same-sex twin pairs aged 19–50 years and 89 singleton controls matched for age, gestational age, gender, maternal age and parity were recruited from a local obstetric database. Associations between adult glucose, HbA1C and insulin levels and insulin resistance and birthweight were assessed by linear regression with adjustment for confounding variables. Twins were significantly lighter at birth than singleton controls, but there were no significant differences in adult weight, glucose, HbA1C and insulin levels or insulin resistance between twins and controls. The relationship between birthweight and fasting glucose and insulin levels, and insulin resistance was not significantly different from zero in either twins or controls, but birthweight was significantly negatively associated with HbA1C only in controls. There was no evidence of a difference between MZ and DZ twins in unpaired or within-pair analysis. These results provide little evidence that low birthweight in twins increases the risk of impaired glucose-insulin metabolism in young adults or that genetic factors can account for the association observed in singletons.

There has been much interest in evidence that people with lower birthweight have higher risk of adult cardiovascular disease, but the causal pathways underlying such observations are uncertain. Study of twins offers an opportunity to shed light on these pathways, in three different ways. First, in a twin pregnancy maternal nutritional resources and the “supply line” to the fetuses will be more “stretched”. We hypothesise that study of twin pregnancies is a more efficient way to identify modifiable maternal factors that influence later health than studies of singleton pregnancies. Second, twins have lower birthweight than singletons. Comparison of cardiovascular disease risk in twins versus that in singletons will provide insight into whether birthweight per se is in the underlying causal pathway of interest, and whether factors constraining fetal growth of twins (versus singletons) affect later outcome. Third, twin cohorts provide an opportunity to investigate the role of “shared” factors versus factors affecting each individual fetus, by comparing results of within-cohort versus within-pair analyses. Generalisability of findings in twins is debated. We suggest that findings in monochorionic twins (or in the absence of chorionicity data, those from monozygotic twins) need to be interpreted with caution.

Two families with twins — one in which adult DZ twins continue to face the risk of frontotemporal dementia, and the other in which a mother copes with brittle bones in a newborn infant MZ pair — are featured. The nature and progress of the disorders are reviewed and personal perspectives from the twins and other family members are variously provided. Next, four current twin studies are briefly summarized. Topics include sex differences in social support systems, new reproductive technologies, comparative twin-singleton frequencies of placenta previa, and the nature and complications of heterotopic pregnancies. This article concludes with a brief sampling of human interest stories involving twins: a different looking DZ pair, newborn sextuplets, conjoined twins and opposite-sex twin athletes.

Previous twin studies have indicated that approximately 25% of the variation in life span can be attributed to genetic factors and recent studies have also suggested a moderate clustering of extreme longevity within families. Here we discuss various definitions of extreme longevity and some analytical approaches with special attention to the challenges due to censored data. Lexis diagrams are provided for the Danish, Dutch, Finnish, Italian, Norwegian, and Swedish Twin registries hereby outlining possibilities for longevity studies within GenomEUtwin. We extend previous analyses of lifespan for the Danish 1870–1900 twin cohorts to include the new 1901–1910 cohorts, which are consistent with the previous findings. The size of the twin cohorts in GenomEUtwin and the existence of population-based, nationwide health and death registers make epidemiological studies of longevity very powerful. The combined GenomEUtwin sample will also allow detailed age-specific heritability analyses of lifespan. Finally, it will provide a resource for identifying unusual sibships (i.e., dizygotic twin pairs) where both survived to extreme ages, as a basis for discovering genetic variants of importance for extreme survival.

This paper reviews several aspects of discordant growth in multiple pregnancies. Discordant growth is not a chance event and therefore several patterns can be discerned. About 75% of twins exhibit < 15% discordance (concordant), 20% are 15–25% (mildly) discordant, and about 5% are more than 25% (severely) discordant. Higher frequencies and increased severity are seen among triplets. Five observations regarding discordance became generally accepted: (a) not all discordant pairs are similar; (b) the larger the discordance level the greater is the risk for an adverse outcome; (c) discordant growth does not necessarily represent growth restriction; (d) a discordance level may have a different clinical implication in different gestational ages; and (e) the smaller fetuses in severely discordant pairs are at disproportionate risk for neonatal mortality. Mild discordance may represent a normal variation between sibs whereas severely discordant pairs often exhibit patterns of growth restriction. Not infrequently, discordance may represent an adaptation to the limited intrauterine space in order to increase gestational age.

Significant familial aggregation was observed for plasma levels of lathosterol (an indicator of whole-body cholesterol synthesis) and plant sterols campesterol and β-sitosterol (indicators of cholesterol absorption) in 160 Dutch families consisting of adolescent mono- and dizygotic twin pairs and their parents. For lathosterol a moderate genetic heritability in parents and offspring (29%) was found. In addition, shared environment also contributed significantly (37%) to variation in plasma lathosterol concentrations in twin siblings. However, a model with different genetic heritabilities in the two generations (10% in parents and 68% in offspring) fitted the data almost as well. For plasma plant sterol concentrations high heritabilities were found. For campesterol heritability was 80% and for β-sitosterol it was 73%, without evidence for differences in heritability between sexes or generations. No influence of common environmental influences shared by family members was seen for either campesterol or β-sitosterol. Taken together, these results confirm and expand the hypothesis that individual differences in plasma levels of noncholesterol sterols are moderately (lathosterol) to highly (plant sterols) heritable.

Major reared apart twin studies and the principal investigators behind them are presented. Personal tributes to two early researchers are provided by their colleagues and associates. Next, current twin studies and discussions of posttraumatic stress, synaesthesia, vanishing twins and bioethical issues are summarized. Human interest stories include twins in literature, politics, photography and athletics.

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.

Previous studies have shown that a deficiency in DNA damage repair is associated with increased cancer risk, and exposure to UV radiation is a major risk factor for the development of malignant melanoma. High density of common nevi (moles) is a major risk factor for cutaneous melanoma. A nevus may result from a mutation in a single UV-exposed melanocyte which failed to repair DNA damage in one or more critical genes. XRCC3 and XRCC5 may have an effect on nevus count through their function as components of DNA repair processes that may be involved directly or indirectly in the repair of DNA damage due to UV radiation. This study aims to test the hypothesis that the frequency of flat or raised moles is associated with polymorphism at or near these DNA repair genes, and that certain alleles are associated with less efficient DNA repair, and greater nevus density. Twins were recruited from schools in south eastern Queensland and were examined close to their 12th birthday. Nurses examined each individual and counted all moles on the entire body surface. A 10cM genome scan of 274 families (642 individuals) was performed and microsatellite polymorphisms in XRCC3 and adjacent to XRCC5 were also typed. Linkage and association of nevus count to these loci were tested simultaneously using a structural-equation modeling approach implemented in MX. There is weak evidence for linkage of XRCC5 to a QTL influencing raised mole count, and also weak association. There is also weak evidence for association between flat mole count and XRCC3. No tests were significant after correction for testing multiple alleles, nor were any of the tests for total association significant. If variation in XRCC3 or XRCC5 influences UV sensitivity, and indirectly affects nevus density, then the effects are small.

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.

As the success rates of IVF clinics improve, one of the adverse consequences is the increased incidence of twins, due largely to the number of embryos transferred. Even if the number of embryos transferred is restricted to two, the twinning rate can exceed 40% of the pregnancies. An obvious way to reduce this high twin rate would be to transfer only one embryo. This would require that cryopreservation of the supernumerary embryos be efficacious enough so that the chance of achieving an ongoing pregnancy is not diminished by transferring a single embryo in the stimulated cycle. Previous studies utilising embryos on day 2 and 3 of development have shown that the pregnancy rates can be acceptable (about 40%) and that the cumulative rate can be up to 60%. Most of these studies, however, do not include a comparison with the cumulative pregnancy rate with two embryos transferred in the stimulated cycle. Therefore, the efficacy has not been proven. We present clinical data from the past few years to illustrate the increase in success rates and the concomitant increase in twinning rates. The increased success in the cryopreservation program has enabled us to trial a single embryo transfer program and compare the results to the transfer of two embryos. The results strongly suggest that the transfer of a single embryo is the better clinical option.

Plasma levels of lipoprotein(a) — Lp(a) — are associated with cardiovascular risk (Danesh et al., 2000) and were long believed to be influenced by the LPA locus on chromosome 6q27 only. However, a recent report of Broeckel et al. (2002) suggested the presence of a second quantitative trait locus on chromosome 1 influencing Lp(a) levels. Using a two-locus model, we found no evidence for an additional Lp(a) locus on chromosome 1 in a linkage study among 483 dizygotic twin pairs.

Gonadotrophin ovulation induction is currently used for a heterogeneous group of ovulation disorders and unexplained infertility. In the United States it is reported that multiple pregnancy rates of greater than 30% occur as a result of ovulation induction, most commonly after controlled ovarian hyperstimulation and intrauterine insemination. Treatment strategies to reduce the incidence of multiple pregnancies on ovulation induction programs can be targeted to reducing multiple follicular development and subsequent ovulation by a more aggressive cancellation policy, follicle reduction by fine needle aspiration or conversion to IVF; or dealing with the problem of multiple gestation after it has occurred (i.e., multifetal pregnancy reduction). The procedures and abilities exist to resolve this problem. What is needed are appropriate treatment guidelines and well constructed trials to demonstrate that higher order multiple pregnancies can be substantially reduced and/or eliminated without compromising a couple's chances to conceive.

The reports in this section demonstrate several ways in which longitudinal research with twins is informative for the study of development. All of these twins have been followed for long time periods. These results are the latest stage of study for each. By virtue of their long-term nature, together these studies provide information on patterns and changes in several developmental areas from infancy to adulthood. They also document when specific variables no longer exert any influence on development. The first report, by Alin Akerman and Suurvee (“The Cognitive and Identity Development of Twins at 16 Years of Age: A Follow-up Study of 32 Twin Pairs”) is a study of twins followed from birth to 16 years of age. The second report, by Ebeling, Porkka, Penninkilampi-Kerola, Berg, Jarvi, and Moilanen (“Inter-twin Relationships and Mental Health”), is a study of twins followed from pregnancy to 22–30 years of age. The third report, by Lange (“Coping Ability at Midlife in Relation to Genetic and Environmental Influences at Adolescence”), is a study of twins and singletons followed from 10 to 16 years of age to 35 years of age. The section attests to the perseverance of these authors as researchers, and to the strength of the personal relationships of these authors with the individuals in their projects.

This is a follow up study of twins within the Stockholm area, including 32 families and their twins attending grade nine. The twins have been followed from birth to 16 years of age. The main purpose of this study from its inception was to assess mental and cognitive development at different ages. Another aim was to see how the twins who were born prematurely are developing during the school ages. A third aim has been to gain a deeper insight into the relationship between co-twins and the development of their identities, which is the focus of this paper. Several ability tests have been used, as well as questionnaires about interests, attitudes toward school, and leisure activities. At the 16-year follow-up, a psychological method, the Wartegg drawing test, designed to examine identity, ego strength, dependency, ambition, anxiety, willpower, creativity, empathy and coping strategies has been used. The results indicate that it is difficult for twins to develop independence and a positive identity, as they have to emancipate themselves both from their parents and from their co-twins. Some differences in identity, anxiety and ambition were observed between female and male twins, MZ and DZ twins, preterm and fullterm twins. Prematurity, sex and zygosity no longer had any relation to cognitive development at 16 years of age.

Where you sit defines success in the world of multiple births. One person's success is a failure to others. Comments and observations come from years of working with parents of multiple clubs and presentations to and discussions with obstetricians and neonatologists.