The gene expression profile of a normal-suffering monozygotic twin pair is investigated to explore biological mechanisms of spastic type cerebral palsy. Main works include following three aspects: First, a cDNA microarray test is carried out to get the differentially expressed genes of the patient with cerebral palsy compared to her monozygotic twin sister. Second, these differentially expressed genes are searched for their bioinformation within 4 biological databases: FatiGO, FatiGOPlus, KEGG, and SOURCE. Third, a set of special genes and gene families are screened out from the spastic type cerebral palsy patient. These biological analyses reveal that those genes for cell junction are mostly down-regulated, while those genes for metabolism are mostly up-regulated. The individual genes, gene family, and their associated biological functions can reflect the pathological and physiological characteristics of the cerebral palsy.

Sub-Saharan Africa has the highest natural twinning rate in the world. Unfortunately, due to lack of adequate care during pregnancy, labor and postnatally, twin mortality in Sub-Saharan Africa also remains very high. Thus, it has been estimated that one in five twins dies during the childhood years. In spite of this, surprisingly few twin studies have been conducted in the region, making additional epidemiological data much needed. In 2009, we established one of the first twin registries in Sub-Saharan Africa at the Bandim Health Project in Guinea-Bissau. The registry had two main objectives. First, we wanted to describe the twinning rate and mortality patterns among newborn twins, including mortality risk factors and hospitalization patterns. Such studies can help the local clinicians improve twin health by identifying the most vulnerable children. Second, and in light of the rapidly increasing diabetes rates in Africa, we wanted to use the registry to particularly focus on metabolic disorders. Twins are often born with low birth weight, which according to the ‘thrifty phenotype hypothesis’ could predispose them to metabolic disorders later in life. Yet, no such ‘fetal programming’ data have previously been available from African twins despite the fact that nutritional patterns and influences from other factors (e.g., infections) could be markedly different here compared to high-income settings. In this article, we summarize the findings and current status of the Guinea-Bissau twin registry.

We seek to identify factors that facilitate or inhibit transmission of drug abuse (DA) from high-risk parents to their children. In 44,250 offspring of these parents, ascertained from a Swedish national sample for having a mother and/or father with DA, we explored, using Cox models, how the prevalence of DA was predicted by potentially malleable risk factors in these high-risk parents, their spouses and the rearing environment they provided. Analyses of offspring of discordant high-risk siblings and offspring of discordant sibling-in-laws and step-parents aided causal inference. Risk for DA in the children was associated with high-risk and married-in parental externalizing psychopathology, a range of other features of these parents (e.g., low education and receipt of welfare), and aspects of the rearing environment (e.g., neighborhood deprivation and number of nearby drug dealers). Offspring of discordant high-risk siblings, siblings-in-laws and step-parents suggested that nearly all these associations were partly causal. A multivariate analysis utilizing offspring of discordant high-risk siblings identified the six most significant potentially malleable risk factors for offspring DA: (1) criminal behavior (CB) in married-in parent, (2) community peer deviance, (3) broken family, (4) DA in high-risk parent, (5) CB in high-risk parent and (6) number of family moves. Children in the lowest decile of risk had a 50% reduction in their DA prevalence, similar to that seen in the general population. We conclude that transmission of DA from high-risk parents to children partly results from a range of potentially malleable risk factors that could serve as foci for intervention.

Some, albeit not all studies on the relationship between intrauterine growth retardation (IUGR) and female pubertal development have found an earlier and rapidly progressing puberty as well as concomitant disorders of related functional systems such as polycystic ovary syndrome and short stature. These pubertal changes are part of a growing list of IUGR-related diseases, which includes non-insulin dependent diabetes mellitus and coronary heart disease. A pulsatile release of gonadotropin releasing hormone is thought to be a conditio-sinne-qua-non for the initiation of puberty. In the absence of prospective studies on gonadotropin releasing hormone pulse patterns in IUGR-children other markers of pubertal development such as age at menarche have been deployed. From these studies it is not clear, however, whether the findings of an earlier onset of puberty in IUGR-girls merely reflect a more rapid progression of puberty. Both the role for IUGR and the mechanisms behind the onset of puberty are still elusive. Assuming a connection between IUGR and pubertal development, parallels can be drawn between hypotheses on the longterm consequences of IUGR and hypotheses on the initiation of puberty. For example, the somatometer concept proposes a role for fat mass in the initiation of puberty, which is compatible with the hypothesis on non-skeletal catch-up growth after IUGR. The debate on the origins of puberty and the role of IUGR mainly focuses on nature and nurture. Judgmentally, studies in mono- and dizygotic twins discordant for birth weight may be of particular help.

The traditional frailty models used in genetic analysis of bivariate survival data assume that individual frailty (and longevity) is influenced by thousands of genes, and that the contribution of each separate gene is small. This assumption, however, does not have a solid biological basis. It may just happen that one or a small number of genes makes a major contribution to determining the human life span. To answer the questions about the nature of the genetic influence on life span using survival data, models are needed that specify the influence of major genes on individual frailty and longevity. The goal of this paper is to test the nature of genetic influences on individual frailty and longevity using survival data on Danish twins. We use a new bivariate survival model with one major gene influencing life span to analyse survival data on MZ (monozygotic) and DZ (dizygotic) twins. The analysis shows that two radically different classes of model provide an equally good fit to the data. However, the asymptotic behaviour of some conditional statistics is different in models from different classes. Because of the limited sample size of bivariate survival data we cannot draw reliable conclusions about the nature of genetic effects on life span. Additional information about tails of bivariate distribution or risk factors may help to solve this problem. Twin Research (2000) 3, 51–57.

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.

The genetic basis of cardiovascular disease (CVD) is complex and still largely elusive. Plasma lipid concentrations are well-established risk factors for cardiovascular disease (CVD), and have adult heritabilities ranging from 0.48 to 0.87. Estimates for adolescents are slightly higher (range 0.71 to 0.82). To identify loci affecting lipid concentrations across adolescence, we analyzed longitudinal lipid data in a sample of 134 monozygotic and 626 dizygotic twin pairs at ages twelve, fourteen and sixteen, and their siblings, from 760 Australian families. Univariate linkage analysis for each phenotype and time point was supplemented by multivariate analysis across the time points. A genome-wide association scan was also performed on a subset of the subjects (N = 441). The strongest linkage was seen for triglycerides on chromosome 6p24.3 (multivariate –log10p = 6.81; equivalent LOD = 6.13; p = 1.55 × 10–7). Significant linkage was also found for LDL cholesterol on chromosome 2q35 (multivariate –log10p = 5.59; equivalent LOD = 4.53; p = 2.57 × 10–6). In the association analysis, rs10503840 on 8p21.1 was significantly associated with total cholesterol levels at age fourteen (p = 8.24 × 10–7, estimated significance threshold 2.45 × 10–6). Association at p < 2.25 × 10–6 was also found between triglycerides at age 12 and rs10507266, in an intron of THRAP2 (MIM 608771) on 12q24.21; and between HDL-C at age 14 and rs10506325 in an intergenic region of 12q13.13. Suggestive evidence of association at ages twelve and fourteen was found between HDL-C and rs10492859 on 16q23 (p = 2.42 × 10–5 and 2.77 × 10–4, respectively). Further longitudinal genetic studies of cardiovascular risk factors, focused on critical periods of development or change, are needed.

Homeostasis model assessment (HOMA) provides indices of insulin secretion (β) and insulin resistance (R) derived from fasting plasma glucose (FPG) and fasting plasma insulin (FPI) levels. However, these indices could not account for a significant heritability of fasting plasma glucose (FPG) (h2 = 0.75, P < 0.01) in a group of 214 female twins. This result is consistent with a misclassification between effects due to insulin secretion and resistance in the HOMA indices. We report here evidence of such misclassification in the HOMA indices and describe a minor modification to the model which corrects it. Direct measures of insulin resistance (euglycaemic clamp) and secretion (i.v. glucose bolus) were obtained in 43 non-diabetic subjects. Heritability was estimated by statistical modelling of genetic and environmental influences in data from 214 non-diabetic female subjects. Modified HOMA (HOMA′) indices were obtained from β′ = (Ln(FPI)–c)/FPG and R′ = (Ln(FPI)–c)* FPG where c is a constant derived from regression analysis of Ln(FPI) vs FPG. Indices from both models correlated with the direct measures similarly (r = 0.63 (R), 0.49 (R′), 0.45 (β), 0.39 (β′), all P < 0.01). Directly measured insulin resistance and secretion were not significantly correlated (r = 0.13, P = 0.21). However, unmodified HOMA- and R were strongly related (r = 0.78, P < 0.0001 vs 0.13) demonstrating substantial misclassification. The relationship between β′ and R′ (r = 0.13) was not different from that between the two direct measures and significant heritability of β′ (h2 = 0.68, P < 0.01) and R′ (h2 = 0.59, P < 0.05) was evident in the twin data. The proposed modification to HOMA significantly reduces misclassification and reveals separate components of insulin resistance and insulin secretion in the heritability of FPG. Twin Research (2000) 3, 148–151.

Fetoscopic surgery is widely accepted as the preferred first-line treatment for twin–twin transfusion syndrome (TTTS). Nonetheless, the broad diffusion of this technique relies on a single multicentric-randomized trial. We hereby question this trial in a post-hoc Bayesian analysis, submitting its results to several scenarios comprising the alternative published non-randomized literature and pessimistic opinions regarding this surgery. Furthermore, we also discuss further refinements in indications, questioning potential alternatives in early stages of the disease.

The present article explores the social attraction that may evolve on the part of reared apart twins' spouses toward their brothers- and sisters-in-law, that is, their spouses' newly found co-twin. This topic was inspired by the fascinating story of monozygotic reared apart (MZA) twins who were reunited in Perth, Australia in 2008, at age 50. It is followed by brief reviews of twin research articles concerning divorce rates among mothers of multiples and X-chromosome inactivation in MZ female twin pairs. The final section presents informative human interest stories involving twins.

Several neuroimaging studies have reported associations between brain white matter microstructure and chronotype. However, it is unclear whether those phenotypic relationships are causal or underlined by genetic factors. In the present study, we use genetic data to examine the genetic overlap and infer causal relationships between chronotype and diffusion tensor imaging (DTI) measures. We identify 29 significant pairwise genetic correlations, of which 13 also show evidence for a causal association. Genetic correlations were identified between chronotype and brain-wide mean, axial and radial diffusivities. When exploring individual tracts, 10 genetic correlations were observed with mean diffusivity, 10 with axial diffusivity, 4 with radial diffusivity and 2 with mode of anisotropy. We found evidence for a possible causal association of eveningness with white matter microstructure measures in individual tracts including the posterior limb and the retrolenticular part of the internal capsule; the genu and splenium of the corpus callosum and the posterior, superior and anterior regions of the corona radiata. Our findings contribute to the understanding of how genes influence circadian preference and brain white matter and provide a new avenue for investigating the role of chronotype in health and disease.

The study is a critical analysis of the decisions to induce labour or schedule cesareans in the practice of a third level referral centre, with as outcome criterion the reduction of fetal death. 783 women pregnant with twins were included from 1.1.1993 to 31.12.1998, in three groups:originally booked, referred for care during pregnancy, or transferred from another institution. The results show that an important proportion of preterm deliveries result from a medical decision to induce labour or from a scheduled cesarean in the originally booked group with even higher proportions in groups of referred and transferred women. These results are discussed in relation to fetal death rates and causes. Deaths related to fetal growth restriction were not observed in women originally booked for care. The hospital bias has been discussed. The conclusion is that decisions to minimize fetal deaths in twin pregnancies increased preterm deliveries by medical decision.

Genetic linkage analysis for complex diseases offers a major challenge to geneticists. In these complex diseases multiple genetic loci are responsible for the disease and they may vary in the size of their contribution; the effect of any single one of them is likely to be small. In many situations, like in extensive twin registries, trait values have been recorded for a large number of individuals, and preliminary studies have revealed summary measures for those traits, like mean, variance and components of variance, including heritability. Given the small effect size, a random sample of twins will require a prohibitively large sample size. It is well known that selective sampling is far more efficient in terms of genotyping effort. In this paper we derive easy expressions for the information contributed by sib pairs for the detection of linkage to a quantitative trait locus (QTL). We consider random samples as well as samples of sib pairs selected on the basis of their trait values. These expressions can be rapidly computed and do not involve simulation. We extend our results for quantitative traits to dichotomous traits using the concept of a liability threshold model. We present tables with required sample sizes for height, insulin levels and migraine, three of the traits studied in the GenomEUtwin project.

The purpose of the present study was to do a psychometric evaluation of the somatic and psychological health report (SPHERE) among Chinese adolescents. Our participants were 116 twins (50 females). Psychometric evaluation indicated that the reliability and validity of this scale were good. The internal consistencies and split-half reliabilities of all subscales were above 0.80. Furthermore, the item-total correlations were acceptable for all the subscales (all the values were higher than 0.20). The present findings suggest that the SPHERE can be well used to measure Chinese adolescents’ somatic and psychological health.

Formation of identity and differentiation is crucial in the development process of adolescents and young people. Despite many studies on identity status and self-differentiation in adolescence and early adulthood stages, this issue has been less examined among twins. This study was conducted to compare self-differentiation and identity statuses in twins and nontwins. The sample of the study consisted of 128 identical twins, 176 nonidentical twins and 170 nontwins aged from 13 to 30 years and living in Mashhad in Iran, who completed the Objective Measure of Ego Identity Status and Self-Differentiation questionnaires. The results showed that the self-differentiation of identical and nonidentical twins was significantly higher than nontwins. The results also showed that level of Foreclosure identity, Moratorium identity and Achieved identity was similar among identical twins, nonidentical twins and nontwins, but significantly different in terms of Diffusion identity. Further, the results showed that twins younger than 18 years had scores higher than nontwins and twins over 18 years in terms of Diffusion identity. Findings revealed that females were significantly lower than males for Moratorium identity. The adolescence period and co-twins may be the reason for the high levels of Diffusion identity and self-differentiation. Also, it seems that identity development and differentiation are related to emotional and cognitive development.

The aim of this study was to compare the educational achievement of female twins (n = 577) and their matched singleton controls (n = 447), who were selected from participants of a national test of educational achievement in the years 1993 to 1998. To assure the representativeness of the selected groups we also compared the achievement scores of the twins and the controls to those of the total Dutch female population tested in the same period. We analyzed the results of the following educational achievement scales: Language, Mathematics and Information Processing. The results indicated that the singleton classmates performed significantly better than the twins on all three scales. However, the twins performed equally well as compared to the Dutch female population. We believe that our singleton control group was not as properly selected as we intended, a selection bias operative at the level of the schools may have confounded the comparison. We therefore conclude on the basis of a comparison with the performance of the total Dutch female population that there are no differences in educational achievement between female twins and singletons.

The Beijing Twin Study (BeTwiSt), which was established in 2006, is an ongoing study aiming to investigate the genetic and environmental etiology of adolescent psychopathology. Resting-state brain imaging datasets have been examined for same-sex twins, and other psychological traits and emotional and behavioral variables have been examined for all twins. Based on the registry, the main findings regarding the etiological mechanism underlying adolescent development, magnetic resonance imaging results, and genetic and environmental influences on other psychological traits have been published. This article summarizes the key findings in these three areas and discusses future plans for the BeTwiSt.

The relationship between pitch-naming ability and childhood onset of music training is well established and thought to reflect both genetic predisposition and music training during a critical period. However, the importance of the amount of practice during this period has not been investigated. In a population sample of twins (N = 1447, 39% male, 367 complete twin pairs) and a sample of 290 professional musicians (51% male), we investigated the role of genes, age of onset of playing music and accumulated childhood practice on pitch-naming ability. A significant correlation between pitch-naming scores for monozygotic (r = .27, p < .001) but not dizygotic twin pairs (r = −.04, p = .63) supported the role of genetic factors. In professional musicians, the amount of practice accumulated between ages 6 and 11 predicted pitch-naming accuracy (p = .025). In twins, age of onset was no longer a significant predictor once practice was considered. Combined, these findings are in line with the notion that pitch-naming ability is associated with both genetic factors and amount of early practice, rather than just age of onset per se. This may reflect a dose–response relation between practice and pitch-naming ability in genetically predisposed individuals. Alternatively, children who excel at pitch-naming may have an increased tendency to practice.