Conduct disorder (CD) symptoms and substance dependence commonly co-occur. Both phenotypes are highly heritable and a common genetic influence on the covariation has been suggested. The aim of this study was to determine the extent to which genes and environment contribute to the covariance between CD and drug dependence using twins from the Colorado Longitudinal Twin Sample and the Colorado Twin Registry. A total of 880 twin pairs (237 monozygotic [MZ] female, 195 MZ male, 116 dizygotic [DZ] female, 118 DZ male and 214 DZ opposite-sex) aged 13 to 18 (mean = 15.65) were included in the analysis. CD was assessed by lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) symptom count and a polysubstance dependence vulnerability index was developed from responses to the Composite International Diagnostic Interview — Substance Abuse Module. A bivariate Cholesky Decomposition model was used to partition the cause of variation and covariation of the two phenotypes. No sex-limitation was observed in our data, and male and female parameter estimates were constrained to be equal. Both CD symptoms and dependence vulnerability were significantly heritable, and genes, shared environment and nonshared environment all contributed to the covariation between them. Genes contributed 35% of the phenotypic covariance, shared environment contributed 46%, and nonshared environmental influences contributed the remaining 19% to the phenotypic covariance. Therefore, there appears to be pleiotropic genetic influence on CD symptoms and dependence vulnerability.

Two major challenges to conducting a community-based twin study of pathological gambling (PG) disorder are that: (a) it is relatively rare, and (b) individuals with the disorder in the community may be difficult to locate and recruit. We describe a new study of 4,764 individuals recruited from the Australian Twin Registry in which we attempt to effectively deal with the first challenge and examine the impact of the second challenge. The lifetime prevalence of DSM-IV PG in this Australian twin sample was 2.2%, which is 400–500% higher than has been obtained in prevalence surveys conducted in the United States. A number of predictors of non-participation were identified, including a lifetime PG disorder diagnosis, but these did not have a large net effect on the estimated number of individuals with PG or related characteristics in the twin sample. Results of biometric modeling suggested that the effect of genetic, shared family environmental, and nonshared environmental influences on the propensity to engage in 11 different specific forms of gambling (e.g., playing the lottery, betting on horse or dog races, playing electronic gaming machines) were generally moderate, low, and moderate, respectively, with mean parameter estimates obtained of 43%, 10%, and 46%. An intriguing comparison with results from a 1963 US adolescent twin study conducted by Loehlin and Nichols (1976) suggests that: (a) propensity genes for gambling involvement may be more likely to be expressed in the heavy-gambling Australian culture, or that (b) the family environment has a transient effect on the gambling behavior of young people.

Susceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n = 3261) completing the C-19 COVID-19 symptom tracker app allowed classical twin studies of COVID-19 symptoms, including predicted COVID-19, a symptom-based algorithm to predict true infection, derived from app users tested for SARS-CoV-2. We found heritability of 49% (32−64%) for delirium; 34% (20−47%) for diarrhea; 31% (8−52%) for fatigue; 19% (0−38%) for anosmia; 46% (31−60%) for skipped meals and 31% (11−48%) for predicted COVID-19. Heritability estimates were not affected by cohabiting or by social deprivation. The results suggest the importance of host genetics in the risk of clinical manifestations of COVID-19 and provide grounds for planning genome-wide association studies to establish specific genes involved in viral infectivity and the host immune response.

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.

Twin–twin transfusion syndrome (TTTS) is a severe complication of monochorionic (MC) twin pregnancies associated with high perinatal mortality and morbidity rates. Management in TTTS is a major challenge for obstetricians and neonatologists. Twins with TTTS are often born prematurely after an extremely distressing and highly hazardous fetal period. Follow-up studies report varying rates of cerebral palsy (CP) and long-term neurodevelopmental impairment (NDI). This review discusses the latest findings on the long-term outcome of TTTS survivors, possible risk factors for long-term impairment, and provides recommendations for future research.

Do women experience orgasm because this trait was shaped by natural selection to augment female fitness? Or are women merely the lucky recipients of developmental patterns favored by selection to produce orgasm in males? A recent and widely publicized book by Elisabeth Lloyd (2005a) contends that there is insufficient evidence to validate any of the adaptive explanations yet proposed for female orgasm. We agree. But our reading of the data differs from Lloyd's. In this essay, we outline why, unlike Caton (2006), whose review of Lloyd's book appeared previously in this journal, we are not persuaded by Lloyd's argument that female orgasm is a nonadaptive byproduct of orgasm in men. We hold this view because we disagree with the criteria Lloyd uses to evaluate evolutionary hypotheses, and because we believe Lloyd defines female orgasm too narrowly, ignoring critical information about its affective aspects.

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.

The population-based twin program of research at the Norwegian Institute of Public Health (NIPH) was begun in 1992. It consists of a number of questionnaire and clinical interview projects exploring a broad array of mental and physical health outcomes. This article provides a brief update summarizing our research activities, some research highlights, new developments and potentials for further developing the program of twin research. In the most recent years a large effort has concentrated on completing a mental health interview study of Axis I psychiatric and substance use disorders and Axis II personality disorders. Although still in the early planning phases, one of the most significant developments is that an agreement is now in place to centralize the Norwegian twin data into a national Norwegian Twin Registry. This new registry will include twin cohorts born from 1905 onwards. Other resources for building twin projects are described. Nationally, there is great potential for linking the NIPH twin data with other health registries and with information in a number of Norway's large population-based biobank studies. Internationally, platforms such as those developed within GenomEUtwin, for data standards and data sharing and access are greatly facilitating international collaborations in twin research.

Genetic and environmental sources of covariation among cognitive measures of verbal IQ, performance IQ (PIQ), academic achievement, 2-choice reaction time (CRT), inspection time (IT) and the 6 Openness facets of the NEO Personality Inventory-Revised (NEO PI-R) were examined. The number of twin and twin–sibling pairs ranged from 432 (182 MZ, 350 DZ/sibling) to 1023 (273 MZ, 750 DZ/sibling) for cognitive measures, and between 432 (90 MZ, 342 DZ/sibling) — 437 (91 MZ, 346 DZ/sibling) for Openness facets. Structural equation modeling best supported a model with a 3-factor additive genetic structure. A genetic general factor subsumed the 5 cognitive measures and 5 of the 6 Openness facets (Actions did not load significantly). A second additive genetic factor incorporated the 6 Openness facets, and a third additive genetic factor incorporated the 5 cognitive measures. Specific additive and dominance genetic effects were also evident, as were shared common and shared unique environmental influences, and specific unique environmental effects. The Openness facets of Ideas and Values evidenced the strongest phenotypic correlations with cognitive indices, particularly verbal measures. The genetic correlations among Openness facets and cognitive measures ranged from −.06 to .79. Results were interpreted as suggesting that Openness is related to general cognitive ability (g) through a genetic mechanism and that gengenders a minor but discernable disposition towards Openness for the majority of facets.

In twin studies of cardiovascular disease biomarkers the dizygotic correlations are often estimated to be less than half of monozygotic correlations indicating a potential influence of nonadditive genetic factors. Using a large and homogenous sample, we estimated the additive and dominance genetic influences on levels of high density lipoprotein, low density lipoprotein, apolipoprotein A-I, apolipoprotein B, total cholesterol, triglycerides, glucose, hemoglobin Alc and c-reactive protein, all of which are biomarkers associated with cardiovascular disease. The blood biomarkers were measured on 12,000 Swedish twins born between 1911 and 1958. The large sample allowed us to obtain heritability estimates with considerable precision and provided adequate statistical power for estimation of dominance genetic components. Our study showed complete absence of the shared environment component for the investigated traits. Dominant genetic component was shown to be significant for low density lipoprotein (0.18), glucose (0.31), Hemoglobin Alc (0.55), and c-reactive protein (0.27). To our knowledge, this is the first statistically significant evidence for dominance genetic variance found for low density lipoprotein, glucose, hemoglobin Alc, and c-reactive protein in a population based twin sample. The study highlights the importance of acknowledging nonadditive genes underlying the risk of developing cardiovascular diseases.

Etiological factors for stability and change in symptoms of anxiety and depression, including sex differences, are largely unexplored in young adults. Using biometric modeling and two-wave longitudinal data from 4393 Norwegian twins aged 18 to 31 we explored (i) heritabilities of symptoms of anxiety and depression, (ii) effects of genetic and environmental factors on the stability and change of such symptoms, and (iii) sex-specific effects. The phenotypic cross-time correlations for symptoms of anxiety and depression were estimated to .54 and .49 for males and females, respectively. The best fitting longitudinal model specified additive genetic and individual environmental influences and emerging effects from the shared environment for females only. For both males and females, long-term stability was mainly attributable to stable additive genetic factors, whereas change was essentially related to environmental influences. Minor time-specific genetic effects were indicated, and some stable variance was due to the individual environment. Additive genetic risk factors explained 87% and 68% of the phenotypic cross-time correlation for males and females, with the unique environment accounting for the remaining covariance. The results provide strong evidence for the temporal stability of genetic risk factors for symptoms of anxiety and depression in young adults, and substantial sex-specific influences on heritability, stability and change.

To our knowledge, no comprehensive, interdisciplinary initiatives have been taken to examine the role of genetic variants on patient-reported quality-of-life outcomes. The overall objective of this paper is to describe the establishment of an international and interdisciplinary consortium, the GENEQOL Consortium, which intends to investigate the genetic disposition of patient-reported quality-of-life outcomes. We have identified five primary patient-reported quality-of-life outcomes as initial targets: negative psychological affect, positive psychological affect, self-rated physical health, pain, and fatigue. The first tangible objective of the GENEQOL Consortium is to develop a list of potential biological pathways, genes and genetic variants involved in these quality-of-life outcomes, by reviewing current genetic knowledge. The second objective is to design a research agenda to investigate and validate those genes and genetic variants of patient-reported quality-of-life outcomes, by creating large datasets. During its first meeting, the Consortium has discussed draft summary documents addressing these questions for each patient-reported quality-of-life outcome. A summary of the primary pathways and robust findings of the genetic variants involved is presented here. The research agenda outlines possible research objectives and approaches to examine these and new quality-of-life domains. Intriguing questions arising from this endeavor are discussed. Insight into the genetic versus environmental components of patient-reported quality-of-life outcomes will ultimately allow us to explore new pathways for improving patient care. If we can identify patients who are susceptible to poor quality of life, we will be able to better target specific clinical interventions to enhance their quality of life and treatment outcomes.

Twin registries form an exceptionally rich source of information that is largely unexploited for phenotypic analyses. One obstacle to straightforward phenotypic statistical analysis is the inherent dependency, which is due to the clustering of cases within families. The present simulation study gauges the degree of the bias produced by the dependency of family data on the estimates of standard errors and chi-squared, when they are treated as independent observations in a phenotypic model, and assesses the efficiency of an estimator, which corrects for dependency. When family-clustered data are used for phenotypic analysis, in treating individuals as independent, and using standard maximum likelihood estimation, there is a tendency for the chi-square statistic to be overestimated, and the standard errors of the parameters to be underestimated. The bias increases with family resemblance, due to heritability or shared environment. The source of family resemblance — either heritability (h2) and/or shared environment (c2) — interacts with the composition of the sample. In the absence of c2, samples with twins, parents and spouses show the lowest bias, whereas in the presence of c2 samples with only twins show the lowest bias. In all conditions the bias remained below 15%. The use of the ‘complex option’ available in Mplus (clustering corrected robust maximum likelihood estimation) reduces the bias to the levels observed when only independent cases are considered. Thus with the use of robust estimates the bias due to family dependency becomes practically negligible in all conditions of dependency. In conclusion, the present study shows that the bias due to dependency in family data does not form a serious obstacle to phenotypic data analysis.

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.

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.

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.

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.

Traditionally, it is understood that dizygotic (DZ) twins always have a dichorionic placenta. However, with 8% blood chimerism in DZ twins, placental sharing is probably more common than previously has been recognized. In this article, we will review all available cases of monochorionic dizygotic (MCDZ) twins. A total of 31 twins have been described in literature. A monochorionic diamniotic placenta is reported in all cases. Assisted reproductive technology is responsible for the origin of the pregnancy in 82.1% of the cases. In 15.4% of the sex-discordant twins, a genital anomaly was reported in one of the twins. Chimerism is demonstrable in 90.3% of the twins, leading to various diagnostic difficulties. As this review shows that most MCDZ twins are discovered by accident, it can be argued that it is far more common than has been assumed until now. However, the prevalence is still unclear. Awareness of MCDZ twinning is important, with subsequently correct medical strategies. Similarly, the resulting (blood) chimerism is essential to consider in diagnostic procedures, pre- and postnatally. More research on the effect of placental transfusion between sex-discordant twins is required.

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.

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.