The aim of this study was to investigate the role of genes and environment in susceptibility to breast cancer and to give an estimate of heritability in the propensity to develop the disease. To do this we applied an interdisciplinary approach, merging models developed in the field of demography and survival analysis — so-called frailty models — and models coming from quantitative genetics and epidemiology, namely genetic models. In our study, the inferential problem was solved in a Bayesian framework and the numerical work was carried out using MCMC methods. We used the special information coming from twin data, particularly breast cancer data, from the Swedish Twin Register. The application of a correlated log-normal frailty model leads to a very large estimate of the population heterogeneity (σ = 6.7), and relatively small correlations between co-twins' frailties — around 0.3 for monozygotic and 0.1 for dizygotic twins. Comparing three different genetic models (an ACE, an AE and an ADE model), we furthermore concluded that genetic effects would explain globally almost 30% of the total variability of propensity to breast cancer. Environmental effects would be predominant in determining breast cancer susceptibility and these effects would be primarily individual-specific, that is, non-shared effects. Finally, a model which includes dominance genetic effects (ADE model) is preferred for genetic and statistical reasons.

The aim of this tertiary hospital–based cohort study was to determine and compare perinatal outcome and neonatal morbidities of pregnancies with twin–twin transfusion syndrome (TTTS) before and after the introduction of a treatment program with laser ablation of placental communicating vessels. Twenty-seven pregnancies with Stage II–IV TTTS treated with amnioreduction were identified (amnioreduction group). The data were compared with that obtained from the first 31 pregnancies with Stage II–IV TTTS managed with laser ablation of placental communicating vessels (laser group). Comparisons were made for perinatal survival and neonatal morbidities including abnormalities on brain imaging. The median gestation at therapy was similar between the two groups (20 vs. 21 weeks, p = .24), while the median gestation at delivery was significantly greater in the laser treated group (34 vs. 28 weeks, p = .002). The perinatal survival rate was higher in the laser group (77.4% vs. 59.3%, p = .03). Neonatal morbidities including acute respiratory distress, chronic lung disease, requirement for ventilatory assistance, patent ductus arteriosus, hypotension, and oliguric renal failure had a lower incidence in the laser group. On brain imaging, ischemic brain injury was seen in 12% of the amnioreduction group and none of the laser group of infants (p = .01). In conclusion, these findings indicate that perinatal outcomes are improved with less neonatal morbidity for monochorionic pregnancies with severe TTTS treated by laser ablation of communicating placental vessels when compared to treatment by amnioreduction.

Absolute pitch is a rare pitch-naming ability with unknown etiology. Some scientists maintain that its manifestation depends solely on environmental factors, while others suggest that genetic factors contribute to it. We sought to further investigate the hypothesis that genetic factors support the acquisition of absolute pitch and to better elucidate the inheritance pattern of this trait. To this end, we conducted a twin study and a segregation analysis using data collected from a large population of absolute pitch possessors. The casewise concordance rate of 14 monozygotic twin pairs, 78.6%, was significantly different from that of 31 dizygotic twin pairs, 45.2%, assuming single ascertainment (x2 = 5.57, 1 df, p = .018), supporting a role for genetics in the development of absolute pitch. Segregation analysis of 1463 families, assuming single ascertainment, produced a segregation ratio pD = .089 with SEpD = 0.006. Unlike an earlier segregation analysis on a small number of absolute pitch probands from musically educated families, our study indicates that absolute pitch is not inherited in a simple Mendelian fashion. Based on these data, absolute pitch is likely genetically heterogeneous, with environmental, epigenetic, and stochastic factors also perhaps contributing to its genesis. These findings are in agreement with the results of our recent linkage analysis.

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.

Interest in politics is important for a host of political behaviors and beliefs. Yet little is known about where political interest comes from. Most studies exploring the source of political interest focus on parental influences, economic status, and opportunity. Here, we investigate an alternative source: genetic transmission. Using two twin samples, one drawn from Denmark and the other from USA, we find that there is a high degree of heritability in political interest. Furthermore, we show that interest in politics and political efficacy share the same underlying, latent genetic factor. These findings add to the growing body of literature that documents political behaviors and attitudes as not simply the result of socialization, but also as part of an individual's genetically informed disposition.

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.

Twin gestation is known to be a risk factor for hypertensive disorders of pregnancy. However, the relationship between hypertensive disorders (pre-eclampsia (PE) and gestational hypertension (GH)) and chorionicity of twin pregnancy is unclear, and published data is conflicting. We decided to analyze the relationship between placentation and prevalence of hypertensive disorders. It was a retrospective cohort study. 312 twin pregnancies delivered between 2009 and 2014 were analyzed, 79 of which were monochorionic and 233 dichorionic. The occurrence of PE and GH was established according to American College of Obstetricians and Gynecologists’ (ACOG) guidelines. Hypertensive disorders were diagnosed significantly more often in dichorionic than in monochorionic twin pregnancies (19.7% vs. 8.9%; OR = 2.53 95% CI 1.04–6.45; p = .03). PE occurred more frequently in DCP (13.3% vs. 3.8%; OR = 3.88 95% CI 1.09–16.46; p = .02). There were no differences between those two groups in the prevalence of GH (6.4% vs. 5.1%; p = .79). The logistic regression model for the occurrence of PE included chorionicity, mother's age lower than 18 or higher than 40, pre-gestational obesity, in vitro fertilization, primiparity, gestational age at delivery, gestational diabetes, and active smoking. It showed that dichorionicity remained an independent risk factor for PE (adjusted OR = 4.97.0 95% CI 1.06–23.38; p = .04). Dichorionicity seems to be a risk factor for PE but not for GH development.

Sex differences in the heritability of self-reported body-height in two Finnish twin cohorts were studied by using sex-limitation models. The first cohort was born in 1938–1949 (N = 4873 twin pairs) and the second in 1975–1979 (N = 2374 twin pairs). Body-height was greater in the younger cohort (difference of 3.1 cm for men and 2.9 cm for women). The heritability estimates were higher among men (h2 = 0.87 in the older cohort and h2 = 0.82 in the younger cohort) than women (h2 = 0.78 and h2 = 0.67, respectively). Sex-specific genetic factors were not statistically significant in either cohort, suggesting that the same genes contribute to variation in body height for both men and women. The stronger contribution of environmental factors to body-height among women questions the hypothesis that women are better buffered against environmental stress, at least for this phenotype.

We studied the influence of mental stress on the contributions of genes and environment to individual variation in systolic (SBP) and diastolic (DBP) blood pressure by structural equation modelling in 320 adolescent male and female twins. Blood pressure data were collected during rest and during a reaction time and a mental arithmetic task. Univariate analyses of SBP and DBP showed familial aggregation for blood pressure. A genetic explanation for this resemblance was most likely, although during rest conditions a model that attributed familial resemblance to shared environmental factors, also fitted the data. There was no evidence for sex differences in heritabilities. Multivariate analyses showed significant heterogeneity between sexes for the intercorrelations of the blood pressure data measured under different rest and task conditions. Multivariate genetic analyses were therefore carried out separately in males and females. For SBP and DBP in females and for SBP in males an increase in heritabilities was seen for blood pressure measured during stress, as compared to rest measurements. The influence of shared environ-mental factors decreased during stress. For DBP in males no significant contributions of shared environment were found. The multivariate analyses indicated that the same genetic and environmental influences are expressed during rest and stress conditions.

Little is known regarding the underlying relationship between smoking initiation and current quantity smoked during adolescence into young adulthood. It is possible that the influences of genetic and environmental factors on this relationship vary across sex and age. To investigate this further, the current study applied a common causal contingency model to data from a Virginia-based twin study to determine: (1) if the same genetic and environmental factors are contributing to smoking initiation and current quantity smoked; (2) whether the magnitude of genetic and environmental factor contributions are the same across adolescence and young adulthood; and (3) if qualitative and quantitative differences in the sources of variance between males and females exist. Study results found no qualitative or quantitative sex differences in the relationship between smoking initiation and current quantity smoked, though relative contributions of genetic and environmental factors changed across adolescence and young adulthood. More specifically, smoking initiation and current quantity smoked remain separate constructs until young adulthood, when liabilities are correlated. Smoking initiation is explained by genetic, shared, and unique environmental factors in early adolescence and by genetic and unique environmental factors in young adulthood; while current quantity smoked is explained by shared environmental and unique environmental factors until young adulthood, when genetic and unique environmental factors play a larger role.

Genome-wide association studies (GWAS) have revolutionized the field of gene mapping. As the GWAS field matures, it is becoming clear that for many complex traits, a proportion of the missing heritability is attributable to common variants of individually small effect. Detecting these small effects individually can be difficult, and statistical power would be increased if relevant variants could be grouped together for testing. Here, we propose a VEGAS2Pathway approach that aggregates association strength of individual markers into pre-specified biological pathways. It accounts for gene size and linkage disequilibrium between markers using simulations from the multivariate normal distribution. Pathway size is taken into account via a resampling approach. Importantly, since the approach only requires summary data, the method can easily be applied in all GWASs, including meta-analysis, singleton-based, family-based, and DNA-pooling-based designs. This approach is implemented in a user-friendly web page https://vegas2.qimrberghofer.edu.au and a command line tool. The web implementation uses gene-sets from the gene ontology (GO), curated gene-sets from MSigDB (containing canonical pathways and gene-sets from BIOCARTA, REACTOME, KEGG databases), PANTHER, and pathway commons databases, enabling analysis of a wide range of complex traits. We applied this method on a colorectal cancer GWAS meta-analysis data set (10,934 cases, 12,328 controls) from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). We report statistically significant enrichment of association signal for the ‘BMP signaling’ and ‘muscle cell differentiation’ pathways, suggesting a possible role for these pathways onto the risk of colorectal cancer.

Birthweight has implications for physical and mental health in later life. Using data from Caucasian twins collected in Australia, the Netherlands and the United States, and from East Asian twins collected in Japan and South Korea, we compared the total phenotypic, genetic and environmental variances of birthweight between Caucasians and East Asians. Model-fitting analyses yielded four major findings. First, for both males and females, the total phenotypic variances of birthweight were about 45% larger in Caucasians than in East Asians. The larger phenotypic variances were mainly attributable to a greater shared environmental variance of birth- weight in Caucasians (ranging from 62% to 67% of variance) than Asians (48% to 53%). Second, the genetic variance of birthweight was equal in Caucasians and East Asians for both males and females, explaining a maximum of 17% of variance. Third, small variations in total phenotypic variances of birthweight within Caucasians and within East Asians were mainly due to differences in nonshared environmental variances. We speculate that maternal effects (both genetic and environmental) explain the large shared environmental variance in birthweight and may account for the differences in phenotypic variance in birthweight between Caucasians and East Asians. Recent molecular findings and specific environmental factors that are subsumed by maternal effects are discussed.

Twin studies of complex traits, such as behavior or psychiatric diagnoses, frequently involve univariate analysis of a sum score derived from multiple items. In this article, we show that absence of measurement invariance across zygosity can bias estimates of genetic and environmental components of variance. Specifically, if the item responses are considered as multiple indicators of a latent factor, and the aim is to partition the variance in the latent factor, then the factor loadings relating the items to the factor should be equal for monozygotic (MZ) and dizygotic (DZ) twins. While it seems unlikely, a priori, that these loadings should differ as a function of zygosity, certain special measurement situations are cause for concern. Ratings by parents, or self-ratings of pheno- types which are more easily observed in others than via introspection, may be tainted by the co-twin's phenotype to a greater extent in MZ than DZ pairs. We also show that the analysis of sum scores typically biases both MZ and DZ correlations compared to the true latent trait correlation. These two sources of bias are quantified for a range of values and are shown to be especially acute for sum scores based on binary items. Solutions to these problems include formal tests for measurement invariance across zygosity prior to analysis of the sum or scale scores, and multivariate genetic analysis at the individual item or symptom level.

The South Korean Twin Registry (SKTR), previously called the Seoul Twin Family Study, is a nationwide volunteer registry of South Korean twins and their families. Since 2002, the SKTR has been updated in 4 important ways. First, continued sampling led to an increase in the number of twins. Second, the target area, Seoul, was enlarged to include other cities and rural areas in the country. Third, the target population was extended from school-aged twins to preschool and adult twins. Fourth, the research focus was expanded to include psychiatric and physical disease phenotypes. The present article describes a brief history of the SKTR, goals and current research highlights, recent major accomplishments, and future directions.

The Minnesota Center for Twin and Family Research (MCTFR) comprises multiple longitudinal, community-representative investigations of twin and adoptive families that focus on psychological adjustment, personality, cognitive ability and brain function, with a special emphasis on substance use and related psychopathology. The MCTFR includes the Minnesota Twin Registry (MTR), a cohort of twins who have completed assessments in middle and older adulthood; the Minnesota Twin Family Study (MTFS) of twins assessed from childhood and adolescence into middle adulthood; the Enrichment Study (ES) of twins oversampled for high risk for substance-use disorders assessed from childhood into young adulthood; the Adolescent Brain (AdBrain) study, a neuroimaging study of adolescent twins; and the Siblings Interaction and Behavior Study (SIBS), a study of adoptive and nonadoptive families assessed from adolescence into young adulthood. Here we provide a brief overview of key features of these established studies and describe new MCTFR investigations that follow up and expand upon existing studies or recruit and assess new samples, including the MTR Study of Relationships, Personality, and Health (MTR-RPH); the Colorado-Minnesota (COMN) Marijuana Study; the Adolescent Brain Cognitive Development (ABCD) study; the Colorado Online Twins (CoTwins) study and the Children of Twins (CoT) study.

The purpose of this prospective cohort study of twins and triplets was to evaluate perinatal and early childhood outcomes through 18 months of age. The study population included 141 twin pregnancies (282 twin children) and 8 triplet pregnancies (24 triplet children) recruited between May, 1996 and June, 2001. Mothers of triplets versus twins were significantly more likely to have infertility treatments, to be overweight or obese before conception, to be admitted antenatally, and to deliver by cesarean section. Length of gestation for triplets was significantly shorter (–2.31 weeks, p < .0001), and more likely to be less than 35 weeks (Adjusted Odds Ratio [AOR] 9.38, 95% confidence interval [CI] 3.22–27.29). Average birthweight for triplets was significantly lighter (–495 grams, p < .0001), and more likely to be low birthweight (AOR 11.38, 95% CI 3.11–41.61). Triplets were also more likely to be admitted to neonatal intensive care (AOR 7.97, 95% CI 2.13–29.77), to require mechanical ventilation (AOR 5.67, 95% CI 2.05–15.65), to develop respiratory distress syndrome (AOR 12.50, 95% CI 3.89–40.20), or a major morbidity (retinopathy of prematurity, necrotizing enterocolitis, ventilator support, or grade III or IV intraventricular hemorrhage, AOR 5.67, 95% CI 2.05–15.65). Weight, length, and head circumference was significantly smaller at birth for triplets compared to twins, and these differences remained through 18 months of age, along with lower mental developmental scores at the oldest age. Compared to twins, triplets have greater neonatal morbidity, and through 18 months of age lower mental and motor scores, slower postnatal growth and more residual stunting, particularly of length and head circumference.

It has been suggested that twinning may influence handedness through the effects of birth order, intra-uterine crowding and mirror imaging. The influence of these effects on handedness (for writing and throwing) was examined in 3657 Monozygotic (MZ) and 3762 Dizygotic (DZ) twin pairs (born 1893–1992). Maximum likelihood analyses revealed no effects of birth order on the incidence of left-handedness. Twins were no more likely to be left-handed than their singleton siblings (n = 1757), and there were no differences between the DZ co-twin and siblingtwin covariances, suggesting that neither intra-uterine crowding nor the experience of being a twin affects handedness. There was no evidence of mirror imaging; the co-twin correlations of monochorionic and dichorionic MZ twins did not differ. Univariate genetic analyses revealed common environmental factors to be the most parsimonious explanation of familial aggregation for the writing-hand measure, while additive genetic influences provided a better interpretation of the throwing hand data.

With the changing patterns of morbidity and mortality in China, noncommunicable chronic diseases have become the major threats to the health of the Chinese population. The causes of chronic diseases include genetic factors and behavioral risk factors such as the use of tobacco, alcohol, and other drugs, unhealthy dietary behaviors, and lack of physical activity. Twin studies offer a unique opportunity to disentangle the genetic and environmental risk and protective factors for chronic disease. The Qingdao Twin Registry (QTR) was initiated in 1998 as part of the National Chinese Twin Registry. Over 11,000 pairs of twins and multiples of all ages have been recruited into the registry. Several studies of physical and mental health are underway. Many of the adult twins have completed health and behavioral risk factor surveys, and the adolescent twins are participating in a study of gene–environment interactions in tobacco and alcohol use. Studies of the heritability of personality factors have been conducted. In 2002, Qingdao established the Qingdao Twin Health Promotion Association, a nonprofit organization that supports health services for twins and their parents, organizes special events and health-related activities for twins, and raises funds to conduct twin health examinations. The QTR will be a useful resource for future studies of population genetics in human health and disease.

Behavioral problems in young children can be assessed by asking their parents or teachers to rate their behaviors. Genetic analyses of parental ratings show relatively large heritabilities for emotional and behavioral problems in young children, but data from teachers for this age group are scarce. Sources of variation in the Teacher's Report Form (TRF) problem scales were examined. The TRF was completed for 211 Dutch 5-year-old twin pairs and 4 single twins. Twins rated by different teachers had higher means and variances than twins rated by the same teacher, in addition twin correlations were lower in this group. In both groups monozygotic (MZ) correlations were generally higher than dizygotic (DZ) correlations. A model for twin resemblance was tested that allowed for these effects. For 5 problem scales (Withdrawn, Social Problems, Aggressive Behavior, Rule Breaking Behavior and Attention Problems) a model with genetic and unique environmental sources of variation fitted best to the data. For 3 problem scales (Anxious/Depressed, Thought Problems and Somatic Complaints) there were familial influences but it was not possible to distinguish between common environmental influences or genetic influences. Heritability was 63% for Attention problems, around 45% for Withdrawn, Social Problems, Aggressive Behavior and Rule Breaking Behavior, and around 30% for Anxious/Depressed, Thought Problems and Somatic Complaints.

Chorion type is an important variable that can affect the prenatal environment of monozygotic (MZ) twin pairs, leading to differences in growth and development. In particular, vascular anastomoses between monochorionic (MC) MZ twin pairs can lead to an imbalance in nutrition between co-twins. One objective of this study was to determine whether maternal reports, hospital records or birthweight discordances found in MZ co-twins provide reliable indications of monochorionicity. The other objective was to test the hypotheses that in MZ twin pairs of known chorion type, MC twin pairs would show greater birthweight differences and greater within-pair variability in permanent tooth size than dichorionic (DC) twin pairs, reflecting greater differences in intrauterine environment between MC MZ pairs. Birthweights and tooth size data were recorded for 170 pairs of MZ Australian twins enrolled in an ongoing study of dentofacial growth and development. Chorion type based on maternal reports was compared with that based on hospital records for a subsample of 68 pairs of these MZ twins. Maternal reports were found to be unreliable for determining chorion type and hospital records often did not provide enough information to be certain about chorionicity. For 27 twin pairs with confirmed chorion type, associations were tested between birthweight discordances in MZ twin pairs and chorion type, and also between intrapair variances for tooth size and chorion type. A significant association was noted between birthweight discordance and chorion type (p <.05), with greater discordances occurring more often in MC twin pairs. Although significant heterogeneity of intrapair variances for tooth size was found in only 5 of 48 comparisons, intrapair variances for crown dimensions were greater significantly more often in MC pairs than DC pairs (p <.05). Our findings indicated that neither maternal reports nor often hospital records can be relied upon for information on chorion type. However, when analyses were performed on data for MZ twin pairs of known chorion type, we found evidence of a significant association between intrapair birthweight differences and chorion type and also between intrapair variances of dental crown measurements and chorion type. Consistent with our hypotheses, large birthweight discordances were found to occur more often in MC twin pairs than DC twin pairs, and intrapair variances for tooth size in MC twin pairs exceeded those in DC twin pairs more often than expected due to chance.