The Healthy Twin Study, Korea (HT) is an ongoing multi-center cohort study that was initiated in 2005, based on a nation-wide twin and family database. Since its inception, the HT has recruited 815 pairs of adult twins and a total of 3,690 individual twins and their families as of July 2012. Here we summarize updates since the previous report in 2006. Besides the increase in size, the HT has been enriched in several aspects: a biobank was constructed for ongoing and future omics studies; and genome-wide single nucleotide polymorphism markers (Affymetrix GeneChip version 6.0, 1 M probes) have been analyzed for 2,200 individuals, which enabled gene identification studies for measured phenotypes. In addition, longitudinal study protocols were established through the HT and a second wave survey was finished in 2010 with >70% follow-up rate. The parallel genome research projects were recently launched, which would expedite multi-omics studies maximizing the twin potentials such as metagenomics and epigenetics studies, and endow us with resources for recruiting more participants. We submit this report to share updates and research opportunities from the HT.

Retrospective assessment of maternal smoking or substance use during pregnancy is sometimes unavoidable. The unusually close relationship of twin sister pairs permits comparison of self-report data versus co-twin informant data on substance use during pregnancy. Information about smoking during pregnancy has been gathered from a series of mothers from an Australian volunteer twin panel (576 women reporting on 995 pregnancies), supplemented in many cases by independent ratings of their smoking by twin sister informants (821 pregnancies). Estimates of the proportion of women who had never smoked regularly (56–58%), who had smoked but did not smoke during a particular pregnancy (16–21%), or who smoked throughout the pregnancy (16–18%), were in good agreement whether based on selfreport or twin sister informant data. However, informants underreported cases who smoked during the first trimester but then quit (1–3% versus 7–9% by self-report). Women who smoked throughout pregnancy (by informant report) rarely denied a history of regular smoking (< 1%), although a small proportion of apparent false negative cases were identified where they either denied smoking during a pregnancy (9%) or denied smoking beyond the first trimester (10%). We conclude that retrospective smoking data can safely be used to identify potential associations of later child outcomes with maternal smoking during pregnancy.

The effects on sleep pattern (‘short-sleep’ versus ‘long-sleep’) and subjective sleep disturbance of genotype, personality, symptoms of anxiety and depression, and lifestyle, were examined using survey data on a clinically unselected sample of adult Australian twin pairs, aged 17–88 years. When the effects of genotype, personality and symptoms were ignored, lifestyle variables appeared to account for roughly 4% of the variance in sleep disturbance, and 9% of the variance in sleep pattern. Significant genetic effects on sleep disturbance and sleep pattern were found, which were only partly explained by the effects of personality and symptoms of anxiety and depression. Much of the association between sleep disturbance and lifestyle appeared to be explained by separate effects of personality and symptoms of anxiety and depression on sleep and lifestyle (‘genotype – risk-factor correlation’). There was little evidence for genetically determined differences in sensitivity to the lifestyle variables (‘genotype × risk-factor interaction’).

Several common adult diseases appear to be related to impaired fetal growth and this may be caused either by nutritional inadequacies at particular stages of pregnancy or by variation in alleles at specific growth loci. Little is known about the genes involved in the underlying mechanism. This review proposes that at least some of the effects have their origins at imprinted loci, genes that are unusual because they are expressed from only one parental allele. Many imprinted genes are crucial for fetal growth and determine birthweight. They can be disrupted in the early embryo by environmental influences and these disruptions can be inherited through many cell cycles into adult tissues. Their disruption can affect specific organs during fetal development and disruption could affect adult disease in a variety of direct and indirect means. Imprinted genes may be particularly vulnerable to disruption as they are functionally haploid and their expression is regulated by different means from the rest of the genome. Thus many imprinted genes provide plausible candidates for programming adult disease and warrant further study in this context.

The physically active lifestyle is associated with low future morbidity and mortality, but the causality between physical activity and health is not always clear. As some inherited biological characteristics and childhood experiences may cause selection bias in observational studies, we sought to take them into account by identifying 16 twin pairs (7 MZ, 9 DZ, mean age 60 years) discordant for leisure time physical activity habits for thirty years. We conducted detailed health-related examinations among these twin pairs. Our main aims were to study the effects of physical activity and genes on fitness and body composition, with special reference to body fat compartments, metabolic syndrome components and related diseases and risk factor levels, status of arteries, structure and function of the heart, bone properties, and muscle and fat tissue-related mechanisms linked to physical activity and chronic disease development. Our physical activity assessments showed that inactive co-twins were on average 8.8 MET hours/day less active than their active co-twins through out their midlife (2.2 ± 2.3 vs. 11.0 ± 4.1 MET h/day, p < .001). Follow-up fitness tests showed that physically inactive co-twins were less fit than their active co-twins (estimated VO2peak 26.4 ± 4.9 vs. 32.5 ± 5.5 ml/kg/min, p < .001). Similar differences were found in both MZ and DZ pairs. On the basis of earlier epidemiological observations on nonrelated individuals, these physical activity and fitness differences are large enough to cause differences in many mechanisms and risk factors related to the development of chronic diseases and to permit future analyses.

In two studies, the General Factor of Personality (GFP) remained intact after controlling for the Lie scale from the Eysenck Personality Questionnaire, despite the Lie Scale showing significant correlations with the GFP defining traits. In Study 1, a re-analysis of 29 self-ratings from 322 pairs of twins (644 individuals) yielded a GFP both before and after controlling for social desirability. In Study 2, four measures of affect in 133 university students loaded on a GFP both before and after controlling for social desirability such that those high on the GFP were high in self-esteem and positive affect and low in depression and negative affect. These results join those from other studies failing to find evidence that the GFP is merely an artifact of evaluative bias.

Objective: The purpose of this article is to review the definition of twin-to-twin transfusion syndrome (TTTS) and the sonographic diagnostic assessment of these cases prior to therapy.

Materials and Methods: The article addresses the terminology used to refer to the condition and describes the systematic ultrasound assessment of the condition, including the ultrasound diagnosis, the staging of the disease, cervical assessment and pre-operative mapping.

Results: From an etymologic and medical point of view, the term ‘fetofetal transfusion’ is more appropriate than ‘TTTS’. However, as the latter, and its attendant acronym TTTS, have been widely adopted in the English language, it is impractical to change at this point. TTTS is defined sonographically in the combined presence of a maximum vertical pocket (MVP) of 8 cm or greater in one sac and 2 cm or less in the other sac, regardless of the gestational age at diagnosis. Staging of the condition using the Quintero staging system is practical, reproducible, and accepted. Transvaginal cervical length assessment should be an integral part of the ultrasound evaluation. Pre-operative mapping to anticipate the location of the placental vascular anastomoses and avoid injuring the dividing membrane is also discussed.

Conclusions: The term ‘TTTS’ can continue to be used in the English medical literature. The condition can be diagnosed and assessed following a systematic ultrasound methodology. The use of such ultrasound methodology breaks the examination into a distinct set of components, assuring a comprehensive examination and proper communication among caregivers.

A previous publication reported the etiology of mathematics performance in 7-year-old twins (Oliver et al., 2004). As part of the same longitudinal study we investigated low mathematics performance and normal variation in a representative United Kingdom sample of 1713 same-sex 9-year-old twins based on teacher-assessed National Curriculum standards. Univariate individual differences and DeFries-Fulker extremes analyses were performed. Similar to our results at 7 years, all mathematics scores at 9 years showed high heritability (.62–.75) and low shared environmental estimates (.00–.11) for both the low performance group and the full sample. Longitudinal analyses were performed from 7 to 9 years. These longitudinal analyses indicated strong genetic continuity from 7 to 9 years for both low performance and mathematics in the normal range. We conclude that, despite the considerable differences in mathematics curricula from 7 to 9 years, the same genetic effects largely operate at the two ages.

High density single nucleotide polymorphism (SNP) genotyping panels provide an alternative to microsatellite markers for genome scans. However, genotype errors have a major impact on power to detect linkage or association and are difficult to detect for SNPs. We estimated error rates with the Affymetrix GeneChip® SNP platform in samples from a family with a mixed set of monozygotic (MZ) and dizygotic (DZ) triplets using lymphocyte, buccal DNA and samples from whole genome amplification using the multiple displacement amplification (MDA) technique. The average call rate from 58,960 SNPs for five genomic samples was 99.48%. Comparison of results for the MZ twins showed only three discordant genotypes (concordance rate 99.995%). The mean concordance rate for comparisons of samples from lymphocyte and buccal DNA was 99.97%. Mendelian inconsistencies were identified in 46 SNPs with errors in one or more family members, a rate of 0.022%. Observed genotype concordance rates between parents, between parents and children, and among siblings were consistent with previously reported allele frequencies and Hardy–Weinberg equilibrium. Using the MDA technique, results for two samples had equivalent high accuracy to results with genomic samples. However, the SNP call rate for the remaining seven samples varied from 72.5% to 99.5%, with an average of 86.11%. Quality of the DNA sample following the MDA reaction appears to be the critical factor in SNP call rate for MDA samples. Our results demonstrate highly accurate and reproducible genotyping for the Affymetrix GeneChip® Human Mapping Set in lymphocyte and buccal DNA samples.

Asurge in the search for endophenotypes for psychiatric disorders has occurred in the past several years. An important criterion of an endophenotype is that it is heritable. Two of the most widely used executive cognitive functioning measures are the Wisconsin Card Sorting Test (WCST) and the Stroop Color-Word Test. Each has been considered as a possible endophenotype. However, research on the heritability of each of these measures is sparse, and in the case of the WCST, mixed. As part of a pilot twin study examining cognitive functioning and personality in adults, the WCST and the Stroop were administered to 80 monozygotic and 29 dizygotic twin pairs screened for absence of neurological disease and head injury. Results replicated and extended previous findings for moderate heritability of Stroop performance. However, the WCST showed little evidence of genetic influence, suggesting that it might not meet one of the criteria for an endophenotype.

Our objective was to examine the overlap between autistic traits and other behavioral problems in a general population sample, and explore the extent to which this overlap is due to genetic or environmental factors. Youth Self Report (YSR) data were collected in a general population sample of 424 twin pairs at 18 years of age, and their nontwin siblings. In 197 of these twin families, self-report ratings on the Autism-spectrum Quotient (AQ) were collected. Stepwise backward regression analyses revealed that of all 8 YSR syndrome scales, the Withdrawn Behavior (WB) and Social Problems (SOC) scale were the most important predictors of AQ scores, and together with sex, explained 23% of the variance in AQ scores. Genetic structural equation modeling showed that the overlap between AQ and WB and SOC was mainly due to genetic effects. About half of the genetic variance in AQ scores was specific to the AQ, with the remaining half shared with genetic variance in WB and SOC. Endorsement of autistic traits in a general population sample is associated with social and withdrawn behavioral problems and these problems partly share a common genetic etiology with autistic traits. However, most of the variance in AQ scores remains unexplained by YSR scores, and half of the genetic variance in AQ is unshared with WB and SOC. These results indicate that autistic traits have specific characteristics that are substantially genetically independent from other common but related behavioral domains such as social problems and withdrawn behavior.

The unique opportunity given by the “fiscal code”, an alphanumeric identification with demographic information on any single person residing in Italy, introduced in 1976 by the Ministry of Finance, allowed a database of all potential Italian twins to be created. This database contains up to now name, surname, date and place of birth and home address of about 1,300,000 “possible twins”. Even thought we estimated an excess of 40% of pseudo-twins, this still is the world's largest twin population ever collected. The database of possible twins is currently used in population-based studies on multiple sclerosis, Alzheimer's disease, celiac disease, and type 1 diabetes. A system is currently being developed for linking the database with data from mortality and cancer registries. In 2001, the Italian Government, through the Ministry of Health, financed a broad national research program on twin studies, including the establishment of a national twin registry. Among all the possible twins, a sample of 500,000 individuals are going to be contacted and we expect to enrol around 120,000 real twin pairs in a formal Twin Registry. According to available financial resources, a sub sample of the enrolled population will be asked to donate DNA. A biological bank from twins will be then implemented, guaranteeing information on future etiological questions regarding genetic and modifiable factors for physical impairment and disability, cancers, cardiovascular diseases and other age related chronic illnesses.

Our study examines the contribution of genetic and environmental factors (both shared and unique) to frailty, measured using the Rockwood Frailty Index (FI) in a sample of twins from the St Thomas’ UK Adult Twin Registry. The FI was based on 39 items of potential health deficit. Study participants were 3,375 volunteer adult twins (840 monozygotic and 802 dizygotic twin-pairs) 40.0–84.5 years old. First, we used structural equation modeling to estimate the relative contribution of genetics and of the shared and unique environment to variance in FI adjusted for age. In a second analysis, multiple linear regression was used to examine variance in FI as a function of father's occupational class (a component of shared environment and a measure of childhood socioeconomic status [SES]), adjusting for age, birth weight, marital status, and health behaviors (smoking, alcohol consumption, and physical activity). Statistical analyses were conducted using IBM SPSS® Version 22 software and Mx open source software. Findings showed that 45% (95% confidence intervals [CIs] 30–53%) of the inter-individual variation in FI was heritable and 52% (95% CIs 47–57%) was due to the individual's unique environment. Multiple linear regression also showed a small but statistically significant inverse association between father's occupational class and FI, mediated by one's own educational attainment and birth weight. Our results indicate that frailty is both genetically and environmentally determined. Thus, its prevention and management call for a multifaceted approach that includes addressing deleterious environmental factors, some of which, like childhood SES, may act across the life course.

The objective of this study was to determine if mothers' retrospective reports about events in their pregnancies with twins are reliable and stable. Six hundred and twenty-four mothers completed psychiatric interviews about their twins. These interviews also contained questions about the mothers' pregnancies, the perinatal period, and the child's early development. The mothers reported first on one twin and then on the other with interviews spaced from 3 days to 2 weeks apart. Thus mothers reported on the same pregnancy twice. Of these mothers, 47 were re-interviewed 6 to 18 months later by raters blind to the results of the initial interview. The twin design allowed us to compare the short-term reliability of the 624 mothers' reports of the same pregnancy. The re-interview of the 47 mothers enabled us to compare the stability of reports over a longer time period. Agreement between the reports was measured with the kappa statistic. Kappas were good to excellent for the short-term reports of pregnancy for each twin for the 624 mothers. Kappas were equally high for the 47 mothers that were re-interviewed 6 to 18 months later. Mothers show good reliability and stability of reporting about events during pregnancy.

In 1998, the Qingdao Twin Registry was initiated as the main part of the Chinese National Twin Registry. By 2005, a total of 10,655 twin pairs had been recruited. Since then new twin cohorts have been sampled, with one longitudinal cohort of adolescent twins selected to explore determinants of metabolic disorders and health behaviors during puberty and young adulthood. Adult twins have been sampled for studying heritability of multiple phenotypes associated with metabolic disorders. In addition, an elderly twin cohort has been recruited with a focus on genetic studies of aging-related phenotypes using twin modeling and genome-wide association analysis. Cross-cultural collaborative studies have been carried out between China, Denmark, Finland, and US cohorts. Ongoing data collection and analysis for the Qingdao Twin Registry will be discussed in this article.

We examined whether effortful control (EC), a temperament proposed by Rothbart and Bates (1998), has genetically coherent structure. A self- report measure of EC was administered to 450 Japanese twins (151 males and 299 females, ages 17 to 32 years) including 152 monozygotic and 73 dizygotic pairs. Univariate genetic analysis revealed that AE model fit best for the total EC as well as its subscales. The heritability estimate for total EC was 49%, and the estimates for subscales ranged between 32% and 45%. Multivariate genetic analysis revealed that the subscales of EC were genetically correlated to a high degree and environmentally correlated to a moderate degree. These results suggest that EC has substantial genetic basis and genetically coherent structure, supporting the validity of the construct. The implications to molecular genetic study and study of psychopathology were discussed.

The Wisconsin Twin Panel utilizes the resources of state birth records to study the etiology and developmental course of early emotions, temperament, childhood anxiety and impulsivity, the autism spectrum, and related psychobiological and behavioral phenotypes. The panel currently supports 5 active research studies which involve twins from birth to early adolescence. A range of research methods are employed, including questionnaires and structured interviews with caregivers, home and laboratory-based behavioral batteries, observer ratings, child self-report, psychophysiology, neuroendocrine measures, birth records, genotyping, and cognitive testing. The panel is in the early stages of generating longitudinal findings.

We describe the importance of the Norwegian Twin Registry (NTR) for research in public health and provide examples from several programs of twin research at the Norwegian Institute of Public Health (NIPH), including the Nordic Twin Study of Cancer, our epigenetics platform, and our large program of research in mental health. The NTR has become an integral component of a national strategy for maximizing the research potential from Norwegian registries and biobank-based studies. The information provided herein builds upon and complements our recent report describing the establishment of the NTR and the cohorts comprising it. Although Norway has a long tradition in twin research, the centralization and administration of the twin data through a single register structure is fairly recent. The NTR was established in 2009 and currently includes 47,989 twins covering birth years 1895–1960 and 1967–1979; 31,440 of these twins have consented to participate in medical research (comprising 5,439 monozygotic pairs, 6,702 dizygotic same-sexed pairs, and 1,655 dizygotic opposite-sexed pairs). DNA from approximately 4,800 twins is banked at the NIPH biobank and new studies continuously add new data to the registry. The value of NTR data is greatly enhanced through record linkage possibilities offered by Norway's many nation-wide registries (medical, demographic, and socio-economic) and several studies are already taking advantage of these linkage opportunities for research.

Although members of monozygotic twin pairs are identical in genome sequence, they may differ in patterns of gene expression. One early and irreversible process affecting gene expression, which can create differences within pairs of female monozygotic twins, is X inactivation — one twin can express mainly paternally-received genes on the X chromosome while the other twin expresses mainly maternally-received genes. It follows that non-identical X chromosome expression may cause female monozygotic twins to correlate less strongly than male monozygotic twins on complex behavioural traits affected by X-linked loci. We tested this hypothesis using data from around 4000 same-sex twin pairs on 9 social, behavioural and cognitive measures at ages 2, 3 and 4. Consistent with our hypothesis, monozygotic males were generally more similar than monozygotic females. Three of four significant differences were in traits showing higher correlations in males than females, and these traits — prosocial behaviour, peer problems, and verbal ability — have all been proposed previously in the literature as being influenced by genes on the X chromosome. Interestingly, dizygotic twins showed the reverse pattern of correlations for similar variables, which is also consistent with the X inactivation hypothesis; taken together, then, our monozygotic and dizygotic results suggest the presence of quantitative trait loci on the X chromosome.

This study aims to assess the validity of maternal recall for several perinatal variables 8–10 years after pregnancy in a twin sample. Retrospective information was collected 8–10 years after the delivery event in a cohort of mothers from the University of Southern California Twin Study (N = 611) and compared with medical records for validity analysis. Recall of most variables showed substantial to perfect agreement (κ = 0.60–1.00), with notable exceptions for specific medical problems during pregnancy (κ ≤ 0.40) and substance use when mothers provided continuous data (e.g., number of cigarettes per day; r ≤ 0.24). With the exception of delivery method, neonatal intensive care unit admission, birth weight, neonatal information, and post-delivery complications were also recalled with low accuracy. For mothers of twins, maternal recall is generally a valid measure for perinatal variables 10 years after pregnancy. However, caution should be taken regarding variables such as substance use, medical problems, birth length, and post-delivery complications.