Depression scores (DSSI) were available for 1232 MZ and 751 DZ female twin pairs who completed a mailed questionnaire. Pairs were divided into those concordant for being in a marriage-like state, concordant for having no partners, and those discordant. The pattern of twin correlations differed according to marital status. Our results suggest that having a marriage-like relationship acts as a protective factor in reducing the impact of inherited liability to symptoms of depression in the general population.

We describe methods to fit structured latent growth curves to data from MZ and DZ twins. The well-known Gompertz, logistic and exponential curves may be written as a function of three components – asymptote, initial value, and rate of change. These components are allowed to vary and covary within individuals in a structured latent growth model. Such models are highly economical, requiring a small number of parameters to describe covariation across many occasions of measurement. We extend these methods to analyse longitudinal data from MZ and DZ twins and focus on the estimation of genetic and environmental variation and covariation in each of the asymptote, initial and rate of growth factors. For illustration, the models are fitted to longitudinal Bayley Infant Mental Development Scale data published by McArdle (1986). In these data, all three components of growth appear strongly familial with the majority of variance associated with the shared environment; differences between the models were not great. Occasion-specific residual factors not associated with the curve components account for approximately 40% of variance of which a significant proportion is additive genetic. Though the growth curve model fit less well than some others, they make restrictive, falsifiable predictions about the mean, variance and twin covariance of other (not yet measured) occasions of measurement. Twin Research (2000) 3, 165–177.

The present research examined the extent to which relations between social values and personality are due to shared genetic or environmental factors. Using the Rokeach (1973) Value Survey and a scoring key from Schwartz and Bilsky (1990), seven value scores (enjoyment, achievement, self-direction, maturity, prosocial, security, and restrictive conformity) were derived in a sample of twins. As expected, all of the value scales were found to have a significant genetic component, with values ranging from 36% for enjoyment to 63% for prosocial, and there were numerous significant phenotypic correlations found between the value scales and personality scores. Most important, bivariate genetic analyses revealed that some of these phenotypic correlations could be attributed to common genetic or environmental factors.

Cutaneous malignant melanoma (CMM) is a major health issue in Queensland, Australia, which has the world's highest incidence. Recent molecular and epidemiologic studies suggest that CMM arises through multiple etiological pathways involving gene–environment interactions. Understanding the potential mechanisms leading to CMM requires larger studies than those previously conducted. This article describes the design and baseline characteristics of Q-MEGA, the Queensland Study of Melanoma: Environmental and Genetic Associations, which followed up 4 population-based samples of CMM patients in Queensland, including children, adolescents, men aged over 50, and a large sample of adult cases and their families, including twins. Q-MEGA aims to investigate the roles of genetic and environmental factors, and their interaction, in the etiology of melanoma. Three thousand, four hundred and seventy-one participants took part in the follow-up study and were administered a computer-assisted telephone interview in 2002–2005. Updated data on environmental and phenotypic risk factors, and 2777 blood samples were collected from interviewed participants as well as a subset of relatives. This study provides a large and well-described population-based sample of CMM cases with follow-up data. Characteristics of the cases and repeatability of sun exposure and phenotype measures between the baseline and the follow-up surveys, from 6 to 17 years later, are also described.

Twin studies typically indicate shared environmental influence for cognitive abilities, especially in early childhood. However, across studies, DZ twin correlations tend to be greater than non-twin sibling correlations, suggesting that twin estimates of shared environment are to some extent specific to twins. We tested this hypothesis in a sample of more than 1800 MZ and 1800 same-sex DZ pairs from the Twins Early Development Study (TEDS), a study of twins born in England and Wales in 1994 and 1995. For this analysis, we obtained comparable data from more than 130 same-sex younger siblings of the twins. Twins and their younger siblings were assessed for language, cognitive abilities and behavior problems by their parents at 2 and 3 years of age. For language and cognitive measures at both 2 and 3 years, but not for behavior problems, estimates of shared environment were more than twice as large for twins as compared to non-twin siblings. We conclude that about half of twin study estimates of shared environment for cognitive abilities in early childhood are specific to twins. Although many possibilities exist for explaining the special shared environment effect for twins, we suggest that cognitive-relevant experiences that are not shared by siblings are shared by twins because they are exactly the same age.

Myasthenia gravis (MG) is an autoimmune disorder in which patients experience muscular fatigability due to the presence of anti-acetylcholine receptor (AChR) antibodies which inhibit signal transduction across the neuro-muscular junction. Like all complex disorders, disease is caused by an interaction between genetic and environmental factors. Although several genes have been identified which appear to be associated with MG, both classic twin studies and current multi-gene models are insufficient to explain either disease pathogenesis or inheritance. We examined the literature on MG to determine both mono- and dizygotic twin concordance rates, and used this data to (1) estimate the proportion of the population with underlying genetic predisposition to MG and the frequency of the environmental component and (2) derive the number of inherited genetic regions that are required to confer predisposition to MG. Using a MZ twin concordance rate of 35.5%, and a dizygotic rate of approximately 4–5% (based on family data), the probability of encountering environmental components necessary to develop MG in an individual with genetic predisposition is approximately 52.4%, making the frequency of predisposition (1:5240) roughly twice the rate of incidence. Furthermore, the number of genetic regions co-inherited between affected individuals is between two and four, which may be large haplotypes with interacting activity. Determining these haplotypes, by fully sequencing associated regions in cases and controls to identify mutations present, may therefore be a practically step toward the understanding of complex disease.

This review offers an update on research conducted with FinnTwin12 (FT12), the youngest of the three Finnish Twin Cohorts. FT12 was designed as a two-stage study. In the first stage, we conducted multiwave questionnaire research enrolling all eligible twins born in Finland during 1983–1987 along with their biological parents. In stage 2, we intensively studied a subset of these twins with in-school assessments at age 12 and semistructured poly-diagnostic interviews at age 14. At baseline, parents of intensively studied twins were administered the adult version of the interview. Laboratory studies with repeat interviews, neuropsychological tests, and collection of DNA were made of intensively studied twins during follow-up in early adulthood. The basic aim of the FT12 study design was to obtain information on individual, familial and school/neighborhood risks for substance use/abuse prior to the onset of regular tobacco and alcohol use and then track trajectories of use and abuse and their consequences into adulthood. But the longitudinal assessments were not narrowly limited to this basic aim, and with multiwave, multirater assessments from ages 11 to 12, the study has created a richly informative data set for analyses of gene–environment interactions of both candidate genes and genomewide measures with measured risk-relevant environments. Because 25 years have elapsed since the start of the study, we are planning a fifth-wave follow-up assessment.

The primary aim of the Michigan State University Twin Registry (MSUTR) is to examine developmental differences in genetic, environmental, neural, epigenetic, and neurobiological influences on psychopathology and resilience, particularly during childhood and adolescence. The MSUTR has two broad components: a large-scale, population-based registry of child, adolescent, and adult twins and their families (current N ~30,000) and a series of more focused and in-depth studies drawn from the registry (projected N ~7200). Participants in the population-based registry complete a family health and demographic questionnaire via mail. Families can then be recruited for one or more of the intensive, in-person studies from the population-based registry, using any one of several recruitment strategies (e.g., population-based, based on their answers to the registry questionnaire). These latter studies target a variety of biological, genetic, and environmental phenotypes, including multi-informant measures of psychiatric and behavioral phenotypes, functional and structural neuroimaging, comprehensive measures of the twin family environment (e.g., census and neighborhood informant reports of twin neighborhood characteristics, videotaped interactions of child twin families), buccal swab and salivary DNA samples, and/or assays of adolescent and adult steroid hormone levels. This article provides an overview of the MSUTR and describes current and future research directions.

Accurate determination of same-sex twin zygosity is important for medical, scientific and personal reasons. Determination may be based upon questionnaire data, blood group, enzyme isoforms and fetal membrane examination, but assignment of zygosity must ultimately be confirmed by genotypic data. Here methods are reviewed for calculating average probabilities of correctly concluding a twin pair is monozygotic, given they share the same genotypes across all loci for commonly utilized multiplex short tandem repeat (STR) kits. Numerous tools enabling convenient and accurate zygosity probability calculation may be accessed via the ZygProb homepage at http://genepi.qimr.edu.au/general/daleN/ZygProb/

Inherited disorders of mitochondrial oxidative phosphorylation are the most common group of inborn errors of metabolism and cause a wide range of clinical presentations. Mitochondrial DNA encodes 13 protein subunits required for oxidative phosphorylation plus 22 transfer RNAs and two ribosomal RNAs, and mutations in most of these genes cause human disease. Nuclear genes encode most of the protein subunits and all other proteins required for mitochondrial biogenesis and mitochondrial DNA replication and expression. Mutations in 64 nuclear genes and 34 mitochondrial genes are now known to cause mitochondrial disease and many novel mitochondrial disease genes await discovery. The genetic complexity of oxidative phosphorylation means that maternal, autosomal recessive, autosomal dominant and X-linked modes of inheritance can occur, along with de novo mutations. This complexity presents a challenge in planning efficient molecular genetic diagnosis of patients with suspected mitochondrial disease. In some situations, clinical phenotype can be strongly predictive of the underlying genotype. However, more often this is not the case and it is usually helpful, particularly with pediatric patients, to determine whether the activity of one or more of the individual oxidative phosphorylation enzymes is deficient before proceeding with mutation analysis. In this review we will summarize the genetic bases of mitochondrial disease and discuss some approaches to integrate information from clinical presentation, laboratory findings, family history, and imaging to guide molecular investigation.

The present study is the first behavioral genetic investigation of the Dark Triad traits of personality, consisting of Machiavellianism, narcissism, and psychopathy, and the variable of mental toughness, reflecting individual differences in the ability to cope when under pressure. The purpose of this investigation was to explore a potential explanation for the success of individuals exhibiting the Dark Triad traits in workplace and social settings. Participants were adult twins who completed the MACH-IV, the Narcissistic Personality Inventory, and the Self-Report Psychopathy Scale assessing Machiavellianism, narcissism, and psychopathy, respectively, as well as the MT48, measuring mental toughness. Correlational analyses of the data revealed significant positive phenotypic associations between mental toughness and narcissism. Psychopathy and Machiavellianism, however, both showed some significant negative phenotypic correlations with mental toughness. Bivariate behavioral genetic analyses of the data were conducted to assess the extent to which these significant phenotypic correlations were attributable to common genetic and/or common environmental factors. Results indicate that correlations between narcissism and mental toughness were attributable primarily to common non-shared environmental factors, correlations between Machiavellianism and mental toughness were influenced by both common genetic and common non-shared environmental factors, and the correlations between psychopathy and mental toughness were attributable entirely to correlated genetic factors. Implications of these findings in the context of etiology and organizational adaptation are discussed.

Rates of emotional and behavioral problems among children and adolescents in China are increasing and represent a major public health concern. To investigate the etiology of such problems, including the effects and interplay of genes and environment, the Beijing Twin Study (BeTwiSt) was established. A representative sample of adolescent twins in Beijing (N = 1,387 pairs of adolescent twins, mostly between the ages of 10 and 18 years) was recruited and assessed longitudinally. Data collection included the following: emotional and behavioral problems (e.g., depressive symptoms, anxiety, delinquency, drinking, and smoking); family, peer, and school environments; stress; social and academic competence; cognitive traits (e.g., emotion suppression, rumination, and effortful control); and saliva samples for DNA genotyping and sequencing. The combination of quantitative and molecular genetic approaches and the timeliness of the project, with the sample residing in a region with a rapidly changing economic and cultural climate, are particular strengths of this study. Findings from this study are expected to help understanding of the etiological mechanisms underlying child and adolescent normal and abnormal development in regions undergoing substantial social, cultural, and economic changes.

Previous studies of risk factors for sickness absence (SA) focus primarily on psychosocial and work environmental exposures. The aim of this study was to investigate the relative contribution of genetic influences on SA among women and men. The population-based study sample of Swedish twins (34,547) included 13,743 twin pairs of known zygosity, 3,495 monozygotic, 5,073 same-sexed dizygotic, and 5,175 opposite sexed. The point prevalence of long-term SA (≥15 days) in each zygosity and sex group was calculated. The risk of SA was estimated as an odds ratio (OR) with 95% confidence intervals (CI) where the odds for twins on SA to have a co-twin on SA was compared to the OR for SA in twins whose co-twin were not sickness absent. Intrapair correlations and probandwise concordance rates were calculated and standard biometrical genetic model-fitting methods were used to estimate the heritability of SA. The prevalence of SA was 8.8% (women 10.7%; men 6.5%). Intrapair similarity was higher among monozygotic than dizygotic twin pairs. The best-fitting model showed no sex differences in genetic effects or variance components contributing to SA. The heritability estimate was 36% (95% CI: 35–40%). Results suggest genetic contribution to the variation of SA and that environmental factors have an important role, for women and men. As SA seem to be influenced by genetic factors, future studies of associations between risk factors and SA should consider this potentially confounding effect.

It has been shown that lower birthweight is associated with lower IQ, but it remains unclear whether this association is causal or spurious. We examined the relationship between birthweight and IQ in two prospective longitudinal birth cohorts: a UK cohort of 1116 twin pairs (563 monozygotic [MZ] pairs), born in 1994–95, and a New Zealand cohort of 1037 singletons born in 1972–73. IQ was tested with the Wechsler Intelligence Scales for Children. Birthweight differences within MZ twin pairs predicted IQ differences within pairs, ruling out genetic and shared environmental explanations for the association. Birthweight predicted IQ similarly in the twin and nontwin cohorts after controlling for social disadvantage, attesting that the association generalized beyond twins. An increase of 1000 g in birthweight was associated with a 3 IQ point increase. Results from two cohorts add to evidence that low birthweight is a risk factor for compromised neurological health. Our finding that birthweight differences predict IQ differences within MZ twin pairs provides new evidence that the mechanism can be narrowed to an environmental effect during pregnancy, rather than any familial environmental influence shared by siblings, or genes. With the increasing numbers of low-birthweight infants, our results support the contention that birthweight could be a target for early preventive intervention to reduce the number of children with compromised IQ.

The intrauterine growth patterns for twins are characterized by normal development during the first two trimesters and reduced growth during the third trimester. According to the fetal origins hypothesis this growth pattern is associated with risk factors for cardiovascular morbidity and mortality. We studied cause-specific mortality of 19,986 Danish twin individuals from the birth cohorts 1870–1930 followed from 1952 through 1993. Despite the large sample size and follow-up period we were not able to detect any difference between twins and the general population with regard to all-cause mortality or cardiovascular mortality. Hence, the intrauterine growth retardation experienced by twins does not result in any “fetal programming” of cardiovascular diseases. There is still an important role for twins (and other sibs) to play in the testing of the fetal origins hypothesis, namely in studies of intra-pair differences, which can assess the role of genetic confounding in the association between fetal growth and later health outcome.

The main aim of this study was to develop and optimize a questionnaire-based zygosity determination method in Chinese adolescent twins. Participants were 471 pairs of same-sex twins (345 monozygotic, 126 dizygotic) with a mean age of 14.56 years (SD = 2.62). A second sample was recruited for cross-validation, including 382 pairs of same-sex twins (261 monozygotic, 121 dizygotic) with a mean age of 12.53 years (SD = 2.22). The questionnaire consisted of 12 questions dealing with co-twin similarity or frequency of confusion. Two means were put forward to improve the predictive accuracy of the questionnaire — adding parent-reports to the analysis, and using a 2-point rather than 3-point response format. DNA genotyping was performed on nine short tandem repeat loci, with an estimated zygosity classification accuracy very close to 100%. The validity of all questionnaires was assessed by being compared to the results of DNA analysis. Results of stepwise logistic regression analysis showed that the predictive accuracy of the 3-point self-reported questionnaire is 83.8%. Using parent-reports and 2-point scale led to 3.9% and 4.6% increase in predictive accuracy, respectively. When using the parent-reports and children's self-reports jointly, the predictive accuracy was enhanced to 90.6%. For the cross-validation, the equations and cut-offs derived from the first sample led to an acceptable accuracy (91.3%) in the second sample. In conclusion, the method we developed can be used in future studies among Chinese adolescent twins. Multiple-rater and 2-point response format were suggested for all twin studies for enhancing the predictive accuracy of questionnaires.

Previous studies have emphasized the importance of rater issues in studying the etiology of variation in internalizing and externalizing problems in children. Earlier results indicate only moderate agreement between parents, and assume that parents assess a specific aspect of their child's behavior. In comparable samples of younger children, additive genetic effects are the main factor explaining individual differences in both internalizing and externalizing behavior. It is unknown whether this pattern of rater influences and variance decomposition will be consistent in older children. Child Behavior Checklists (Achenbach, 1991), completed by both parents, were collected in a sample of 2956 Dutch 10-year-old twin pairs. The etiology of individual differences in internalizing and externalizing syndromes was examined using a model that corrected for possible rater bias, rater-specific effects and unreliability. The best fitting model suggested that disagreement between the parents is not merely the result of unreliability and/or rater bias, but each parent also provides specific information from his/her own perspective on the child's behavior. Significant influences of additive genetic, shared environmental and unique environmental factors were found for internalizing and externalizing syndromes.

The Southern California Twin Register was initiated in 1984 at the University of Southern California, and continues to grow. This article provides an update of the register since it was described in the 2002 special issue of this journal. The register has expanded considerably in the past 4 years, primarily as a result of recent access to Los Angeles County birth records and voter registration databases. Currently, this register contains nearly 5000 twin pairs, the majority of whom are school age. The potential for further expansion in adult twins using voter registration records is also described. Using the Los Angeles County voter registration database, we can identify a large group of individuals with a high probability of having a twin who also resides in Los Angeles County. In addition to describing the expansion of register, this article provides an overview of an ongoing investigation of 605 twin pairs who are participating in a longitudinal study of behavioral problems during childhood and adolescence. Characteristics of the twins and their families are presented, indicating baseline rates of conduct problems, depression and anxiety disorders, and attention-deficit/hyperactivity disorder diagnoses which are comparable to nontwins in this age range.

Genetic and environmental contributions to body size from birth to 5 years in a population-based twin cohort were studied. Sex differences in gene–environment etiology were also explored. Analyses used data from the Quebec Newborn Twin Study (QNTS), a population-based birth cohort of 672 twin pairs. The final sample consisted of 177 complete twin pairs. Heritability of weight was moderate at birth while common environmental factors accounted for almost half of the variance. Influence of family environment disappeared by 5 months and genetic effects were high (approximately 90%) for both sexes at 5 months and 5 years. Adjustment of weight for height yielded similar results as for weight alone. Slight but significant sex-limitation of genetic effects was observed at 5 months. Overall, genetic factors accounted for 40% of birthweight variance, with intrauterine environment influences explaining almost half. However, genetic factors accounted for most of the variance in weight. These results do not imply a lack of environmental effects on body weight, but rather a lack of: (1) environmental effects that are independent from genetic liability, and/or (2) a lack of significant environmental variation in the population (e.g., uniform nutritional habits) that leaves genetic differences between children to generate most of the variance in weight.

Objectives: The natural history of stage 1 Twin-to-twin transfusion syndrome (TTTS) remains unclear and its optimal management is yet to be established. The main aims of this meta-analysis were to quantify the incidence of progression in stage 1 TTTS and to ascertain survival in these pregnancies.

Methods: MEDLINE, EMBASE, and The Cochrane Library were searched. Reference lists within each article were hand-searched for additional reports. The outcomes included incidence of progression and survival in stage 1 TTTS. Randomized controlled trials, cohort and case-control studies were included. Case reports, studies including three or fewer cases of stage 1 TTTS, and editorials were excluded. Proportion meta-analysis was used for analysis (Registration number: CRD42016036190).

Results: The search yielded 3,085 citations; 18 studies were included in the review (172 pregnancies to assess progression and 433 pregnancies to assess the survival). The pooled incidence of progression in stage 1 TTTS was 27% [95% CI 16–39%]. The pooled overall survival, double survival and at least one survival in the pregnancies managed expectantly were 79% [95% CI 62–92%], 70% [95% CI 54–84%] and 87% [95% CI 69–98%], respectively. In those undergoing amnioreduction, the corresponding figures were 77% [95% CI 68–85%], 67% [95% CI 57–76%] and 86% [95% CI 76–94%], respectively. The survival rates were 68% [95% CI 54–81%], 54% [95% CI 36–72%], and 81% [95% CI 69–90%], when laser surgery was performed.

Conclusions: The optimal initial management of stage 1 TTTS remains in equipoise. The ongoing randomized trial comparing immediate laser surgery versus conservative management should provide a definitive answer.