Twin researchers face the challenge of accurately determining the zygosity of twins for research. As part of the annual questionnaire between 1999 and 2006, 8,307 twins from the TwinsUK registry were asked to complete five questions (independently from their co-twin) to ascertain their self-perceived zygosity during childhood on up to five separate occasions. This questionnaire is known as the ‘peas in the pod’ questionnaire (PPQ), but there is little evidence of its validation. Answers were scored and classified as monozygotic (MZ), dizygotic (DZ), or unknown zygosity (UZ) and were compared with 4,484 twins with genotyping data who had not been selected for zygosity. Of these, 3,859 individuals (46.5% of those who had a zygosity from PPQ) had zygosity classified by both the PPQ and genotyping. Of the 708 individual twins whose answers meant that they were consistently classed as MZ in the PPQ, 683 (96.5%) were MZ within the genotype data. Of the 945 individual twins consistently classed as DZ within questionnaire, 936 (99.0%) were DZ in the genotype data. Where both twins scored MZ consistently across multiple questionnaires, 99.6% were MZ on genotyping, 99.7% were DZ on genotyping if both twins consistently scored DZ. However, for the initial questionnaire, 88.6% of those scoring as MZ were genotypically MZ and 98.7% DZ. For twin pairs where both scored UZ, 94.7% were DZ. Using the PPQ on a single occasion provided a definitive classification of whether the twin was MZ or DZ with an overall accuracy of 86.9%, increasing to 97.9% when there was a consistent classification of zygosity across multiple questionnaires. This study has shown that the PPQ questionnaire is an excellent proxy indicator of zygosity in the absence of genotyping information.

Behavior genetics has convincingly shown the importance of genetic factors in objective tests of memory function. However, self-report memory tests have received little attention. This study used items from the Multifactorial Memory Questionnaire (MMQ) to estimate the heritability of self-reported memory contentment and ability in 909 monozygotic (MZ) and 1034 dizygotic (DZ) twin pairs aged between 20 and 84 years from the St Thomas' Adult UK Twin Register. Heritability estimates ranged between 37% and 64% for contentment (e.g., reporting to worry about one's memory) and approximately 45% for ability (e.g., reporting a tendency to forget keys). Shared family environmental influences (between 32% and 33%) were found for some abilities (e.g., learning to use a new gadget). Given their clinical significance and ease of administration, these tests could prove to be useful in examining memory functioning in large-scale population studies.

The Thought–Problem scale (TP) of the CBCL assesses symptoms such as hallucinations and strange thoughts/behaviors and has been associated with other behavioral disorders. This study uses parental reports to examine the etiology of variation in TP, about which relatively little is known, in 7-year-old twins. Parental ratings on TP were collected in 8,962 7-year-old twin pairs. Because the distribution of TP scores was highly skewed scores were categorized into 3 classes. The data were analyzed under a threshold liability model with genetic structural equation modeling. Ratings from both parents were simultaneously analyzed to determine the rater agreement phenotype (or common phenotype [TPc]) and the rater specific phenotype [TPs] that represents rater disagreement caused by rater bias, measurement error and/or a unique view of the parents on the child's behavior. Scores on the TP-scale varied as a function of rater (fathers rated fewer problems), sex (boys scored higher) and zygosity (DZ twins scored higher). The TPc explained 67% of the total variance in the parental ratings. Variation in TPc was influenced mainly by the children's genotype (76%). Variance in TPs also showed a contribution of genetic factors (maternal reports: 61%, paternal reports: 65%), indicating that TPs does not only represent rater bias. Shared environmental influences were only found in the TPs. No sex differences in genetic architecture were observed. These results indicate an important contribution of genetic factors to thought problems in children as young as 7 years.

The first twin study in Serbia began in 2011 as a part of the research project, ‘Psychological Foundations of Mental Health: Hereditary and Environmental Factors’. At the same time, the research team from the Faculty of Philosophy and Faculty of Medicine in Novi Sad established the first Serbian twin registry. The registry is intended primarily for the purpose of the research in behavioral genetics, as well as potential future studies in human genetics. It includes information on 1658 volunteers, including twin-pairs, their parent and siblings. The behavioral genetic study of adult twins has been focused on the hereditary and environmental sources of variance of different psychological characteristics, such as personality traits, cognitive abilities, executive functions and aggression, as well as some anthropometric measures and aspects of mental and physical health. Certain molecular genetic analyses have also been performed. The research team is currently starting the longitudinal twin study of children, which will be focused on different indicators of emotional, cognitive and physical development.

Sweden has, as a whole nation, the oldest continuous population register of births, including twin and higher multiple maternities, starting in the 17th century. Until the 1920s, the rates of multiple maternities in Sweden were among the highest known among Europeans. Strong secular and regional fluctuations were noted. Some of the eastern counties showed especially marked decreasing trends. The twinning rate had no clear associations with the anthropometric and serological data. In this paper we study the temporal and regional variations of the twinning rate in the 25 counties of Sweden from 1751 to 1960. Different statistical methods were applied in order to test the hypothesis that, irrespective of the initial levels, the twinning rates for the counties converge towards a common low level. We present and interpret a geometrical model for the trends of the regional twinning rates. We also analyze the regional heterogeneity using the ranges and the coefficients of variation of the regional twinning rates. All the methods gave consistent results, supporting our convergence hypothesis that the regional differences in the twinning rate are gradually disappearing. In addition, this study supports our earlier findings that the regional heterogeneity cannot be explained by differences in the distribution of maternal age and parity. We suggest that the convergence may be caused by increased urbanization and industrialization and by the increased interregional migration of citizens as a consequence of better communications, which lead to the breaking up of isolates and decreased endogamy.

Disorders of eye development such as microphthalmia and anophthalmia (small and absent eyes respectively), anterior segment dysgenesis where there may be pupillary and iris anomalies, and associated cataract and glaucoma, often lead to visual impairment or blindness. Currently treatment options are limited, as much is unknown about the molecular pathways that control normal eye development and induce the aberrant processes that lead to ocular defects. Mutation detection rates in most of the known genes are generally low, emphasizing the genetic heterogeneity of developmental ocular defects. Identification of the disease genes in these conditions improves the clinical information available for affected individuals and families, and provides new insights into the underlying biological processes for facilitation of better treatment options. Investigation of chromosomal rearrangements associated with an ocular phenotype has been especially powerful for disease gene identification. Molecular characterization of such rearrangements, which pinpoints the region by physically disrupting the causative gene or its regulatory sequences, allows for rapid elucidation of underlying genetic factors that contribute to the phenotype. Genes including PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4 have been identified in this way to be associated with developmental eye disorders. More recently, new methods in chromosomal analysis such as comparative genomic hybridization (CGH) microarray, have also enhanced our ability in disease gene identification.

Background: This study aims to assess whether the associations between burnout and sick leave due to stress-related mental disorders, other mental disorders, and somatic conditions are influenced by familial (genetic and shared environmental) factors. Methods: In this prospective cohort study, 23,611 Swedish twins born between 1959 and 1985, who answered a web-based questionnaire, including the Pines Burnout Measure 2004–2006, were included. Registry data on sick leave spells from the response date until December 31, 2010 were obtained from the Swedish Social Insurance Agency. Logistic regression analysis was performed to assess odds ratios with 95% confidence intervals for the association between burnout and sick leave for the whole sample, while conditional logistic regression of the same-sex discordant twin pairs was used to estimate the association between burnout and sick leave, adjusting for familial confounding. The Bivariate Cholesky models were used to assess whether the covariation between burnout and sick leave was explained by common genetic and/or shared environmental factors. Results: Burnout was a risk factor for sick leave due to stress-related and other mental disorders, and these associations were explained by familial factors. The phenotypic correlation between burnout and sick leave due to somatic conditions was 0.07 and the association was not influenced by familial factors. The phenotypic correlations between burnout and sick leave due to stress-related (0.26) and other mental disorders (0.30) were completely explained by common genetic factors. Conclusions: The association between burnout and sick leave due to stress-related and other mental disorders seems to be a reflection of a shared genetic liability.

Twins, due to their unique genetic and environmental relationships, have provided crucial insight in our understanding of genetic contributions to numerous etiologically complex disorders in developed countries. As the leading cause of death and adult disability, cardio- and cerebrovascular diseases are common in China, followed by cancer. Obesity and psychological disorders are increasing. The overall goal of this program is to develop a resource for genetic epidemiologic studies of these and other common and complex diseases in China. Our initial focus is to delineate the genetic and environmental determinants of vascular diseases in general, coronary artery disease (CAD) and stroke in particular. To date, we have over 4500 twin pairs registered and about 700 twin pairs studied for various metabolic traits (e.g., lipids, glucose, insulin, etc.). The long-term plan of this program is to (1) establish a population-based twin registry from several selected regions in China for future studies of specific common complex diseases; (2) conduct detailed phenotyping for clinical and intermediate traits related to cardiovascular diseases; (3) expand studies of twins to twin families by including their parents, siblings, and offspring for genetic linkage and association studies; and (4) follow up twins in the registry longitudinally. The goals of the program are health education and promotion of healthy behavior, early identification of cases to provide timely medical attention, and the evaluation of long-term effects of identified risk factors. We want to develop collaborations with investigators who have expertise in cancer, psychological disorders, and other disease areas.

Information about linkage disequilibrium (LD) is important in understanding the genome structure and has its applications in association studies. Here we present the first genome-wide LD study based on a founder population (East Finland). The LD data consist of 118 unrelated individuals and around 480,000 SNP pairs genotyped with the Affymetrix 100K genotyping assay. Using the minor allele frequency (MAF) limit of .05, the squared correlation coefficient between two loci (r2) was .48, .37, .28, and .20 for distances of 5, 10, 20, and 40 kb respectively. MAF had a significant effect on the mean r2 so that the extent of useful LD (r2 > .3) varied from 17 kb to 80 kb depending on the limit set for the MAF. For D' the effect of MAF was smaller but reflected the possible age of the mutation: SNPs with high MAF had lower D' than those with low MAF. The X chromosome showed higher D' values than autosomes and the extent of useful LD (r2 > .3) was twice as long on the X chromosome than on the autosomes. Based on the results, LD varies across the genome and is correlated to local recombination rate between and within chromosomes. However, the recombination rate does not explain all the variation found in LD. We also report a number of long chromosomal regions where exceptionally high or low LD were detected.

The Sri Lankan Twin Registry began as a volunteer register in 1997. Previously, we have shown door-to-door surveys as the best option to build a population-based twin register of older, adult twins. Our aim was to build a population-based twin register in the Colombo district and use it for twin studies on common mental disorders. We aimed to identify a random sample of 4000 twins ascertained through the twin census. The Colombo district is divided into 13 divisional secretariat divisions (DSDs) and each division is further divided into Grama Niladari divisions administratively. Grama niladaris (GNs) are civil servants and visit each household in order to update the electoral register. GNs were used to do a census of twins while they updated the electoral register. The correlation between population density and twin rate among DSDs was .81, and between twin rate and the percentage of returned forms (from each DSD) was .74. We received 9648 forms notifying about twins and multiples. After removing the duplicates and information about twins who live in other districts, there were 17,406 multiples remaining. After incorporating twins and multiples from various other feasibility studies we now have 19,040 multiples with 8.46 twins per 1000 people in the Colombo district.

Epidemiological studies have consistently shown a positive association between size at birth (i.e. birth weight or birth length) and height in children, adolescents and adults. To examine whether this association is explained by genetic or nongenetic (intra-uterine) factors, we investigated birth weight, birth length and height in 60 dizygotic and 68 monozygotic adolescent twin pairs still living with their parents. Birth weight of the twins was obtained from their mothers. Height was measured in a standardised way. The mean age was 17±1.7 years for the dizygotic twins and 16±1.8 years for the monozygotic twins. Both dizygotic and monozygotic twins with the lowest birth weight from each pair had a height that was lower compared to their co-twins with the highest birth weight (dizygotic twins: 172.2±7.9 vs. 173.8±9.4 cm [p = 0.05]; monozygotic twins: 171.1±9.4 vs. 171.8±9.5 cm [p = 0.01]). Similarly, both dizygotic and monozygotic twins with the shortest birth length from each pair had a height that was lower compared to their co-twins with the longest birth length (dizygotic twins: 172.3±7.9 vs. 174.9±9.7 cm [p < 0.05]; monozygotic twins: 168.9±10.6 vs. 169.9±10.2 cm [p < 0.01]). In addition, intra-pair differences in birth weight and birth length were significantly associated with differences in height in both dizygotic twins (regression coefficient: 4.3 cm/kg [95% confidence interval: 1.0 to 7.5] and 0.96 cm/cm [0.17 to 1.74], respectively) and monozygotic twins (2.8 cm/kg [1.4 to 4.1] and 0.73 cm/cm [0.40 to 1.06], respectively). These associations were stronger in dizygotic than in monozygotic twins, but this difference was not statistically significant (for birth weight p = 0.4; and for birth length p = 0.6). However, genetic model fitting indicated that models incorporating a genetic source of the covariance gave a better description of the observed association of birth weight and length with height in later life than models not incorporating this genetic source. The results were similar for data on adult height after 12 years of follow-up in a subgroup of these twin pairs. These data suggest that the association between size at birth and height in later life is influenced by non-genetic intra-uterine and by genetic factors.

Our aims were to assess the incidence of birthweight discordance of twins, to explore risk factors and its impact on perinatal mortality, and to quantify the risks at different severity of birthweight discordance in Japan, by using a nationwide obstetric database. There were 10,828 pairs of twins, born from 2001 to 2005 recorded in the database of the national Perinatal Health Care Project, fully enrolled. The overall incidence of birthweight discordance was 47.34%. The incidence of mild, severe and extremely severe discordance was 19.26%, 10.21% and 17.87%, respectively. The incidence of birthweight discordance in Japan is much higher than that in other countries, particularly at higher severity level. By linear regression model, our study added independent factors of primiparity (p < .001), sex composition (p < .001), chorionicity (p < .001), gestational age (p < .001), and delivery mode (p < .001) in determining birthweight discordance percentage. Maternal age and application of assisted reproduction technologies (ART) didn't significantly influence the birthweight discordance. The birthweight discordance is closely associated with gestational age and affected discharge mortality. From 25% of birthweight discordance, risk to discharge mortality tended to significantly increase, suggesting it should be added as a reference for clinical practices.

We identified the genetic variants for eye color by Genome-Wide Association Study (GWAS) in a Dutch Caucasian family-based population sample and examined the genetic correlation between hair and eye color using data from unrelated participants from the Netherlands Twin Register. With the Genome-wide Complex Trait Analysis software package, we found strong genetic correlations between various combinations of hair and eye colors. The strongest positive correlations were found for blue eyes with blond hair (0.87) and brown eyes with dark hair (0.71), whereas blue eyes with dark hair and brown eyes with blond hair showed the strongest negative correlations (-0.64 and -0.94, respectively). Red hair with green/hazel eyes showed the weakest correlation (-0.14). All analyses were corrected for age and sex, and we explored the effects of correcting for principal components (PCs) that represent ancestry and describe the genetic stratification of the Netherlands. When including the first three PCs as covariates, the genetic correlations between the phenotypes disappeared. This is not unexpected since hair and eye colors strongly indicate the ancestry of an individual. This makes it difficult to separate the effects of population stratification and the true genetic effects of variants on these particular phenotypes.

Aim: To determine whether or not the change in cervical length (CL) over time is valuable in predicting spontaneous preterm delivery (SPTD) in asymptomatic twin pregnancies with a normal mid-trimester CL (>25 mm). Methods: This was a prospective study including 190 consecutive asymptomatic twin gestations with a CL > 25 mm at 20–24 weeks. The women underwent an initial CL measurement at the time of routine ultrasound examination between 20 and 24 weeks’ gestation, followed 4–5 weeks later by a repeat CL measurement. The primary outcome measure was SPTD at <32 completed weeks’ gestation. Multicollinearity was a concern in the multivariable model since change in CL and follow-up CL were highly correlated. Results: The rate of SPTD at <32 weeks was 4.2%. Multiple logistic regression analyses demonstrated that the change in CL and the follow-up CL were significantly associated with SPTD before 32 weeks after adjusting for baseline covariate such as in vitro fertilization. The best cut-off values for the prediction of SPTD at <32 weeks’ gestation were 13% for the change in CL with a sensitivity of 87.5% and a specificity of 63.2%. There was no significant difference in the area under the receiver operating characteristic curves between the change in CL and the follow-up CL. Conclusions: A greater change in CL is a good predictor of SPTD in asymptomatic twin pregnancies with a normal mid-trimester CL. However, the change in CL cannot provide data beyond the follow-up CL. In the setting of a normal mid-trimester CL, a follow-up CL measurement should be considered in asymptomatic twin pregnancies.

The Osaka University Twin Registry was originally established as a registry of older twins but was subsequently expanded to include twins of all ages. The Center for Twin Research at Osaka University Graduate School of Medicine has been managing this registry, as well as collecting research information and bioresources from twin participants. Based on the resources, multidisciplinary research projects have been conducted in collaboration with researchers from institutions both inside and outside Japan. One of the main aims of the center is to collect research information as well as biological resources from registered twins, and to establish a biobank and databases of these data and bioresources. Although data availability may vary, the following data have been collected: physical data (e.g., height, body weight, blood pressure, theoretical visceral fat, pulse wave velocity and bone density); epidemiological data (e.g., medical history, lifestyle, quality of life, mood status, cognitive function and nutritional status); electrocardiography, ultrasonography (carotid artery and thyroid); dentistry, dermatological assessment; positron emission tomography; magnetoencephalographam; brain magnetic resonance imaging (MRI); and functional MRI. In addition to these in-person survey data, microbiome data have been collected from some participants. As for bioresources, peripheral blood is obtained from the participants for isolation of serum and extraction of DNA and RNA, then stored in deep freezers for further analyses. A variety of research projects are in progress and more are on the way both in Japan and internationally using these data.

Migraine and tension-type headache (TTH) are often viewed as distinct entities and defined as such in the International Classification of Headache Disorders, 2nd edition (ICHD-II) criteria, although there is also empirical evidence to suggest they may be etiologically similar. This study aims to investigate whether migraine and TTH are etiologically related conditions. First, we explored whether migraine and TTH were associated with the same environmental and lifestyle risk factors at the population level. Second, we examined comorbidity of migraine and TTH in a twin design. By comparing the associations in monozygotic (MZ) and dizygotic (DZ) twin pairs, we investigated whether the comorbidity can be explained by genetic factors that influence both conditions. Results indicated that migraine and TTH were largely associated with the same environmental and lifestyle factors, including younger age, female sex, higher body mass index, more depression, stress at home, and less participation in regular exercise, with consistently stronger effects for migraine than for TTH. Migraine in one twin was significantly associated with TTH in the other twin. A stronger cross-trait, cross-twin association in MZ than DZ twins suggested that this comorbidity may also be partly due to shared genetic factors, although the difference in associations was not significant. In conclusion, our findings are consistent with the hypothesis that migraine and TTH have partly shared etiologies. For both treatment and research, it may be advisable not to make a rigid distinction, but to treat migraine and TTH as related conditions.

Accumulating evidence suggests that the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria for cannabis abuse and dependence are best represented by a single underlying factor. However, it remains possible that models with additional factors, or latent class models or hybrid models, may better explain the data. Using structured interviews, 626 adult male and female twins provided complete data on symptoms of cannabis abuse and dependence, plus a craving criterion. We compared latent factor analysis, latent class analysis, and factor mixture modeling using normal theory marginal maximum likelihood for ordinal data. Our aim was to derive a parsimonious, best-fitting cannabis use disorder (CUD) phenotype based on DSM-IV criteria and determine whether DSM-5 craving loads onto a general factor. When compared with latent class and mixture models, factor models provided a better fit to the data. When conditioned on initiation and cannabis use, the association between criteria for abuse, dependence, withdrawal, and craving were best explained by two correlated latent factors for males and females: a general risk factor to CUD and a factor capturing the symptoms of social and occupational impairment as a consequence of frequent use. Secondary analyses revealed a modest increase in the prevalence of DSM-5 CUD compared with DSM-IV cannabis abuse or dependence. It is concluded that, in addition to a general factor with loadings on cannabis use and symptoms of abuse, dependence, withdrawal, and craving, a second clinically relevant factor defined by features of social and occupational impairment was also found for frequent cannabis use.

Though twinning rates have been rapidly increasing in Japan, the problem of zygosity misclassification at birth has been paid little attention. By analyzing four independent samples, the authors found that at a constant rate about 25–30% of monozygotic twins were misclassified as dizygotic twins at birth. This percentage is in very good accordance with that of monozygotic twins having dizygous placenta. Generally the obstetricians informed twins' parents about their children's zygosity. The number of placentas, as informed by obstetricians, was very strongly associated with zygosity. Concluding, even now many monozygotic twins in Japan may be misclassified as dizygotic at birth by obstetricians based solely on the number of placenta.

There are conflicting studies associating twin pregnancies derived from assisted reproductive technology (ART) with preterm birth, low birthweight, and other negative outcomes. This work investigates whether ART is linked with any placental pathology, given that placentation significantly influences fetal development. A 5-year, retrospective cohort study was conducted on placentas from twin pregnancies. The placental information from 417 patients was divided into two groups: placentas derived from ART and placentas derived from spontaneous pregnancies (non-ART). Available clinical information and pathologic findings from both groups then were compared. There was no statistical difference in the prevalence of placental pathology between the non-ART and ART cohorts (i.e., cord insertion, single umbilical artery, cord knot, retroplacental hemorrhage, infarction, vasculopathy, vascular anastomoses, chorangiosis, villitis, deciduitis, chorioamnionitis, meconium staining). However, 8% of ART multiple pregnancies were monochorionic. While monochorionicity is a known risk factor for adverse obstetric and neonatal outcomes, the rate of monochorionic placentation did not increase as a result of ART. Nevertheless, it is interesting to note that this small percentage of monochorionic placentation occurred in the ART cohort despite the implantation of individual embryos. Overall, the data suggests that ART does not have a role in the pathologic placentation of twin pregnancies.

Systolic and diastolic blood pressure, pulse pressure (PP), and body mass index (BMI) are heritable traits in human metabolic health but their common genetic and environmental backgrounds are not well investigated. The aim of this article was to explore the phenotypic and genetic associations among PP, systolic blood pressure (SBP), diastolic blood pressure (DBP), and BMI. The studied sample contained 615 twin pairs (17–84 years) collected in the Qingdao municipality. Univariate and multivariate structural equation models were fitted for assessing the genetic and environmental contributions. The AE model combining additive genetic (A) and unique environmental (E) factors produced the best fit for each four phenotypes. Heritability estimated in univariate analysis ranged from 0.42 to 0.74 with the highest for BMI (95% CI 0.70–0.78), and the lowest for PP (95% CI 0.34–0.49). The multivariate model estimated (1) high genetic correlations for DBP with SBP (0.87), PP with SBP (0.75); (2) low–moderate genetic correlations between PP and DBP (0.32), each BP component and BMI (0.24–0.37); (3) moderate unique environmental correlation for PP with SBP (0.68) and SBP with DBP (0.63); (4) there was no significant unique environmental correlation between PP and BMI. Overall, our multivariate analyses revealed common genetic and environmental backgrounds for PP, BP, and BMI in Chinese twins.