Background: Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. However, the reasons for this association are unclear. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Method: Data were drawn from the Australian Twin Registry, including 1,296 individual twins, their spouses, and offspring. We studied adult twins who were discordant for offspring ADHD. Using a discordant twin pairs design, we examined the extent to which genetic and environmental confounds, as well as measured parental and offspring characteristics, explain the ADHD–marital problems association. Results: Offspring ADHD predicted parental divorce and marital conflict. The associations were also robust when comparing differentially exposed identical twins to control for unmeasured genetic and environmental factors, when controlling for measured maternal and paternal psychopathology, when restricting the sample based on timing of parental divorce and ADHD onset, and when controlling for other forms of offspring psychopathology. Each of these controls rules out alternative explanations for the association. Conclusion: The results of the current study converge with those of prior research in suggesting that factors directly associated with offspring ADHD increase parental marital problems.

The primary aim of this study was to conduct a bivariate genetic analysis investigating the extent to which genetic and environmental factors contribute to stability and change in personality factors in the period from adolescence to young adulthood on a sample of Croatian twins. The sample used in this research was formed in 1992 based on a register of citizens of Zagreb and data was collected for 160 twin pairs (75 monozygotic and 85 dizygotic twin pairs). Twins were tested twice, 4 years apart with the Eysenck Personality Questionnaire (mean age at first time point was 17 years). Univariate analyses indicate that the best fitting model for extraversion, neuroticism, psychoticism and lie scale at both time points includes additive genetic (A) and nonshared environmental (E) influences, with heritability estimates in the .40 to .50 range. Longitudinal analyses using AE correlated factors model indicate that genetic factors contribute mainly to stability, while environmental factors contribute mainly to change in personality during that 4-year period of transition from adolescence to young adulthood.

Twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS) are complications unique to monochorionic twin pregnancies and their shared circulation. Both are the result of the transfusion imbalance in the intertwin circulation. TTTS is characterized by an amniotic fluid discordance, whereas in TAPS, there is a severe discordance in hemoglobin levels. The article gives an overview of the typical features of TTTS and TAPS placentas.

Monozygotic (MZ) twins are genetically identical at conception, making them informative subjects for studies on somatic mutations. Copy number variants (CNVs) are responsible for a substantial part of genetic variation, have relatively high mutation rates, and are likely to be involved in phenotypic variation. We conducted a genome-wide survey for post-twinning de novo CNVs in 1,097 MZ twin pairs. Comparisons between MZ twins were made by CNVs measured in DNA from blood or buccal epithelium with the Affymetrix 6.0 microarray and two calling algorithms. In addition, CNV concordance rates were compared between the different sources of DNA, and gene-enrichment association analyses were conducted for thought problems (TP) and attention problems (AP) using CNVs concordant within MZ pairs. We found a total of 153 putative post-twinning de novo CNVs >100 kb, of which the majority resided in 15q11.2. Based on the discordance of raw intensity signals a selection was made of 20 de novo CNVs for a qPCR validation experiments. Two out of 20 post-twinning de novo CNVs were validated with qPCR in the same twin pair. The 13-year-old MZ twin pair that showed two discordances in CN in 15q11.2 in their buccal DNA did not show large phenotypic differences. From the remaining 18 putative de novo CNVs, 17 were deletions or duplications that were concordant within MZ twin pairs. Concordance rates within twin pairs of CNV calls with CN ≠ 2 were ~80%. Buccal epithelium-derived DNA showed a slightly but significantly higher concordance rate, and blood-derived DNA showed significantly more concordant CNVs per twin pair. The gene-enrichment analyses on concordant CNVs showed no significant associations between CNVs overlapping with genes involved in neuronal processes and TP or AP after accounting for the source of DNA.

In an attempt to increase power to detect genetic associations with brain phenotypes derived from human neuroimaging data, we recently conducted a large-scale, genome-wide association meta-analysis of hippocampal, brain, and intracranial volume through the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium. Here, we present a freely available online interactive tool, EnigmaVis, which makes it easy to visualize the association results generated by the consortium alongside allele frequency, genes, and functional annotations. EnigmaVis runs natively within the web browser, and generates plots that show the level of association between brain phenotypes at user-specified genomic positions. Uniquely, EnigmaVis is dynamic; users can interact with elements on the plot in real time. This software will be useful when exploring the effect on brain structure of particular genetic variants influencing neuropsychiatric illness and cognitive function. Future projects of the consortium and updates to EnigmaVis will also be displayed on the site. EnigmaVis is freely available online at http://enigma.loni.ucla.edu/enigma-vis/

Using data from the Minnesota Twins Political Survey, this paper tests for the presence of unequal environments (EEA) by zygosity in political attitudes. Equal environment measures used include shared bedroom, friends, classes, and dressing alike. Results show an EEA violation at p < .05 in 5% of the models tested. The violations' impact on heritability estimates and their confidence levels appear random in magnitude and direction. No reasonable post hoc explanation emerged for understanding the presence of the violation in some items but not others. This article establishes reasonable priors for the absence of EEA violations in political phenotypes based on the tested environmental components. The findings place the burden on critics to present theoretical work on the specific mechanisms of EEA violations based on which additional empirical assessments could (and should) be conducted.

We examined whether externalizing problem behaviors (hyperactivity–impulsivity, aggressiveness, and inattention) predict illicit drug use independently, or whether their associations with drug use are mediated through cigarette smoking. We used a prospective longitudinal design within the FinnTwin12-17 study among Finnish adolescents with baseline at age 12 and follow-up surveys at ages 14 and 17. Path models were conducted with Mplus and included 1992 boys and 2123 girls. The outcome was self-reported ever use of cannabis or other illicit drugs at age 17. The predictors were: externalizing behaviors (hyperactivity–impulsivity, aggressiveness, and inattention) assessed by teachers and parents (age 12) and self-reported cigarette smoking (age 14). The findings differed across behavior studied. The association of hyperactivity–impulsivity with drug use was mostly mediated through earlier cigarette smoking. Concerning aggressiveness and inattention, the results were different among girls than boys. Among girls no significant mediation occurred, whereas among boys more consistent evidence on mediation was seen. Consistently in all models, the direct association of early cigarette smoking on drug use was strong and highly significant. We conclude that the associations of externalizing problem behaviors with illicit drug use are partially mediated through cigarette smoking. Although interventions targeting externalizing problem behaviors may protect adolescents from early onset smoking and subsequently experimenting with drugs, interventions to prevent cigarette smoking initiation are also important in reducing risk of later drug use.

The prevalence and frequency of comorbidity of possible bipolar disorder was examined with attention-deficit hyperactivity disorder (ADHD) in a nonreferred population of twins. Children and adolescents aged 7 to 18 years with a history of manic symptoms were identified from a population-based twin sample obtained from state birth records (n = 1610). The sample was enriched for ADHD; however, there was also a random control sample (n = 466), which allowed a look at the population prevalence of the disorder. Juveniles with threshold or below threshold manic episodes were further assessed for comorbidity with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) and population-defined ADHD subtypes (from latent class analysis) using Fisher's exact test. Nine juveniles who exhibited DSM-IV manic (n = 1), hypomanic (n = 2) or below threshold episodes (n = 6) were identified. The population prevalence of broadly defined mania in the random sample was 0.2%. The possible manic episodes showed significant comorbidity with population-defined severe combined and talkative ADHD subtypes. It can be concluded that there is a significant association of bipolar symptoms with two population-defined subtypes of ADHD. Episodes of possible bipolar disorders as defined by DSM-IV are uncommon in this nonreferred sample. Children and adolescents with ADHD appear to be only modestly at increased risk for bipolar disorders.

The prioritization of genes within a candidate genomic region is an important step in the identification of causal gene variants affecting complex traits. Surprisingly, there have been very few reports of bioinformatics tools to perform such prioritization. The purpose of this article is to investigate the performance of 3 positional candidate gene software tools available, PosMed, GeneSniffer and SUSPECTS. The comparison was made for 40, 20 and 10 Mb regions in the human genome centred around known susceptibility genes for the common diseases breast cancer, Crohn's disease, age-related macular degeneration and schizophrenia. The known susceptibility gene was not always ranked highly, or not ranked at all, by 1 or more of the software tools. There was a large variation between the 3 tools regarding which genes were prioritized, and their rank order. PosMed and GeneSniffer were most similar in their prioritization gene list, whereas SUSPECTS identified the same candidate genes only for the narrowest (10 Mb) regions. Combining 2 or all of the candidate gene finding tools was superior in terms of ranking positional candidates. It is possible to reduce the number of candidate genes from a starting set in a region of interest by combining a variety of candidate gene finding tools. Conversely, we recommend caution in relying solely on single positional candidate gene prioritization tools. Our results confirm the obvious, that is, that starting with a narrower positional region gives a higher likelihood that the true susceptibility gene is selected, and that it is ranked highly. A narrow confidence interval for the mapping of complex trait genes by linkage can be achieved by maximizing marker informativeness and by having large samples. Our results suggest that the best approach to classify a minimum set of candidate genes is to take those genes that are prioritized by multiple prioritization tools.

In Australian twins participating in three different studies (1979–1996), the contribution of genetic and environmental influences to variation in resting systolic (SBP) and diastolic blood pressure (DBP) was studied. The sample consisted of 368 monozygotic and 335 dizygotic twin pairs with measurements for both individuals. Blood pressure measurements in two studies were available for 115 complete twin pairs, and 49 twin pairs had measurements in three studies. This allowed assessment of blood pressure tracking over an average period of 12 years in the age range of 23 to 45 years. Multivariate analyses showed significant heritability (h2) of blood pressure in all studies (SBP h2 = 19%–56%, DBP h2 = 37%–52%). In addition, the analyses showed that the blood pressure tracking was explained by the same set of genetic factors. These results replicate an earlier finding in Dutch twins that also showed stability of the contribution of genetic factors to blood pressure tracking.

The present study is the first to assess phenotypic correlations between alexithymia and the Dark Triad traits of personality in a community sample, as well as the common genetic and environmental factors underlying these correlations. Participants were 232 North American adult twin pairs who completed the Narcissistic Personality Inventory, the Self-Report Psychopathy Scale, the MACH-IV, and the Toronto Alexithymia Scale. Results revealed that alexithymia correlates significantly and positively with psychopathy and Machiavellianism, and negatively with narcissism. Subsequent bivariate behavioral genetic analysis demonstrated that these phenotypic correlations were primarily attributable to common genetic and common non-shared environmental factors. The implication of these findings regarding the maladaptive functions of alexithymia within the antisocial realm of behavior and the need for replication are discussed.

Two observations suggest a genetic similarity among close friends: (1) the observed similarity among friends in certain traits and behaviors; (2) the evidence that many of these traits and behaviors have a genetic component. This hypothesis is tested using monozygotic (MZ) twins, dizygotic (DZ) twins, full biological siblings, and their best friends from the National Longitudinal Study of Adolescent Health (Add Health). Whether the resemblance between MZ twins' friends is larger than that between friends of DZ twins and full siblings is investigated with respect to 4 individual traits or behaviors: grade point average (GPA), AHPVT (the version Peabody Picture Vocabulary Test [PPVT] designed for Add Health), aggressive behavior, and depression. Our hypothesis is supported in analyses among same-sex friends (not among different-sex friends) for GPA, aggressive behavior, and AHPVT.

The Chinese National Twin Registry (CNTR), established in 2001, is the first and largest population-based twin registry in China. Based on the CNTR, a new twin cohort was recruited from 2011 to study the relationship between environmental risk factors and chronic diseases. So far, 33,874 twin pairs from nine provinces have been recruited, in which hundreds of disease-discordant twin pairs and even thousands of exposure-discordant twin pairs were found in this cohort. The updates of the CNTR will be introduced in detail in this article.

Aim: The present study aims to estimate the relative importance of genetic and environmental factors for health-related quality of life (HRQL) measured by the 12-item Short-Form Health Survey (SF-12). Methods: The study was based on two Danish twin cohorts (46,417 twin individuals) originating from the nationwide, population-based Danish Twin Registry. The twins were approached by a mailed-out questionnaire in 2002. The questionnaire included the SF-12, information on demographic factors, and questions on a variety of specific diseases. Heritability of the SF-12 includes the physical component summary (PCS) and the mental component summary (MCS); and etiologically important variance components were estimated using multivariate biometric models. The respondents were stratified into six groups, based on age and sex. Results: A total of 33,794 (73%) individual twins responded to the survey. The SF-12 was completed by 29,619 individuals, which included 9,120 complete twin pairs. Overall, the best-fitting model explaining the variance of HRQL was the ACE model. The estimated heritability of the SF-12 was between 11% and 35%, whereas between 65% and 89% could be explained by unique environmental or stochastic factors in the different sex and age groups. The highest heritability was seen among older twins. In addition, the genetic correlation between MCS and PCS scores was low (0.07 and 0.23 for males and females, respectively) among younger and high (0.26 and 0.45 for males and females, respectively) in the oldest age group. Both the largest genetic influence on HRQL and the largest genetic overlap between the scores were seen in the oldest age group, which consisted of twins older than 55. The unique environmental correlation between MCS and PCS were generally negative. Conclusion: The heritability of HRQL differs between different age groups. In general, most of the variance in the SF-12 summary components was determined by unique environmental factors.

The Tokyo Twin Cohort Project (ToTCoP) is a large-scale longitudinal study of 5 years based on 1619 pairs of infant twins reared together. The purpose of the study is to construct a population-based twin registry in Japan and to investigate human growth and development and twin themselves. It covers behavioral, neurological, physical and environmental variables measured by questionnaire, home visiting and brain imaging technology. The full registry contains over 47,000 multiple births collected from the Basic Resident Register, and the targeted population is 3070 probable twins of 0 to 2 years old. Preliminary analysis of the entry questionnaire data showed no serious sampling biases. Descriptive statistics of parental characteristics (parental age, gestation age, parity and placentation, maternal weight, parenting stress) and children's characteristics (body size at birth, 4 and 10 months of age, milk consumption, and sleeping and social behavior) and their correlations, genetic and environmental contributions and correlations are reported.

Results obtained from previous longitudinal studies of reading difficulties indicate that reading deficits are generally stable. However, little is known about the etiology of this stability. Thus, the primary objective of this first longitudinal twin study of reading difficulties is to provide an initial assessment of genetic and environmental influences on the stability of reading deficits. Data were analyzed from a sample of 56 twin pairs, 18 identical (monozygotic, MZ) and 38 fraternal (dizygotic, DZ), in which at least one member of each pair was classified as reading-disabled in the Colorado Learning Disabilities Research Center, and on whom follow-up data were available. The twins were tested at two time points (average age of 10.3 years at initial assessment and 16.1 years at follow-up). A composite measure of reading performance (PIAT Reading Recognition, Reading Comprehension and Spelling) was highly stable, with a stability correlation of .84. Data from the initial time point were first subjected to univariate DeFries-Fulker multiple regression analysis and the resulting estimate of the heritability of the group deficit (h2g) was .84 (± .26). When the initial and follow-up data were then fitted to a bivariate extension of the basic DF model, bivariate heritability was estimated at .65, indicating that common genetic influences account for approximately 75% of the stability between reading measures at the two time points.

The Australian Twin Registry (ATR) is a national volunteer resource of twin pairs and higher-order multiples willing to consider participating in health, medical, and scientific research. The vision of the ATR is ‘to realize the full potential of research involving twins to improve the health and well-being of all Australians’. The ATR has been funded continuously by the National Health and Medical Council for more than 30 years. Its core functions entail the recruitment and retention of twin members, the maintenance of an up-to-date database containing members’ contact details and baseline information, and the promotion and provision of open access to researchers from all institutes in Australia, and their collaborators, in a fair and equitable manner. The ATR is administered by The University of Melbourne, which acts as custodian. Since the late 1970s the ATR has enrolled more than 40,000 twin pairs of all zygosities and facilitated more than 500 studies that have produced at least 700 peer-reviewed publications from classical twin studies, co-twin control studies, within-pair comparisons, twin family studies, longitudinal twin studies, randomized controlled trials, and epigenetics studies, as well as studies of issues specific to twins. New initiatives include: a Health and Life Style Questionnaire; data collection, management, and archiving using a secure online software program (The Ark); and the International Network of Twin Registries. The ATR's expertise and 30 years of experience in providing services to national and international twin studies has made it an important resource for research across a broad range of disciplines.

The Southern California Twin Register is the result of an effort to recruit twins of all ages in the city of Los Angeles and surrounding areas. The register currently includes an ethnically diverse sample of more than 2600 twin pairs. The most recently recruited pairs have been drawn primarily from computerized records of enrollments in local public school districts, and are comparable in sex and ethnic distributions to the general public school population. An ongoing twin study of social and moral development in children, based on 600 pairs of 9-year-old twins from this register, is also described briefly in this paper.

Cause-specific mortality data on Danish monozygotic and dizygotic twins are used to analyze heritability estimates of susceptibility to coronary heart disease (CHD) after controlling for smoking and Body Mass Index (BMI). The sample includes 1209 like-sexed twin pairs born between 1890 and 1920, where both individuals were still alive in 1966. The participants completed a questionnaire in 1966 which included questions on smoking, height and weight. The analysis was conducted with both sexes pooled due to the relatively small number of twin pairs. Follow-up was conducted from January 1, 1966 to December 31, 1993. The correlated gammafrailty model with observed covariates was used for the genetic analysis of frailty to account for censoring and truncation in the lifetime data. During the follow-up, 1437 deaths occurred, including 435 deaths due to CHD. Proportions of variance of frailty attributable to genetic and environmental factors were analyzed using the structural equation model approach. Different standard biometric models are fitted to the data to evaluate the magnitude and nature of genetic and environmental factors on mortality. Using the best-fitting model without covariates, heritability of frailty to CHD was found to be 0.45 (0.11). This result changes only slightly to 0.55 (0.13) in a DE model after controlling for smoking and BMI. This analysis underlines the existence of a substantial genetic influence on individual frailty associated with mortality caused by CHD.

Teenage motherhood is associated with poor offspring outcomes but these associations may be influenced by offspring birth year because of substantial social changes in recent decades. Existing research also has not examined whether these associations are due to the specific effect of mother's age at childbirth or factors shared by siblings in a family. We used a population-based cohort study in Sweden comprising all children born from 1960 to 1989 (N = 3,162,239), and a subsample of siblings differentially exposed to maternal teenage childbearing (N = 485,259) to address these limitations. We examined the effect of teenage childbearing on offspring violent and non-violent criminal convictions, poor academic performance, and substance-related problems. Population-wide teenage childbearing was associated with offspring criminal convictions, poor academic performance, and substance-related problems. The magnitude of these associations increased over time. Comparisons of differentially exposed siblings indicated no within-family association between teenage childbearing and offspring violent and non-violent criminal convictions or poor academic performance, although offspring born to teenage mothers were more likely to experience substance-related problems than their later-born siblings. Being born to a teenage mother in Sweden has become increasingly associated with negative outcomes across time, but the nature of this association may differ by outcome. Teenage childbearing may be associated with offspring violent and non-violent criminal convictions and poor academic performance because of shared familial risk factors, but may be causally associated with offspring substance-related problems. The findings suggest that interventions to improve offspring outcomes should delay teenage childbearing and also target risk factors influencing all offspring of teenage mothers.