Suchergebnisse

AbstractThe 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.

The number of rubella cases has increased in Japan, especially among adults. Rubella infection in pregnant females can lead to congenital rubella syndrome (CRS). The Japanese government is promoting vaccination to prevent CRS. This study performs a cost-effectiveness analysis of the following four methods: (1) females who wished to become pregnant and partners, with an antibody-titer test; (2) females only, with an antibody-titer test; (3) females and males, without an antibody-titer test; (4) females only, without an antibody-titer test. A decision tree model with a hypothetical cohort of 500 males and 500 females was used for the analysis, and the parameters were obtained from previous studies. The number of avoidances of CRS was defined as the effect. Compared to the case where methods were not implemented, the number of CRS cases that can be prevented by implementing the methods was 0.0115589 by (1) and (3) and 0.0147891 by (2) and (4). The cost effectiveness of (1) to (4) was 287,413,677 JPY, 135,050,529 JPY, 388,524,974 JPY, and 197,744,219 JPY, respectively (1 JPY = 0.00963247 USD). Method (2) was the most cost-effective and did not change by sensitivity analysis. We conclude that the vaccination for females only with an antibody-titer test is recommended.

AbstractPhenotypic variation is the result of gene expression based on complex interaction between genetic and environmental factors. It is well known that genetic and environmental factors influence gene expression, but our understanding of their relative importance remains limited. To obtain a hint for the understanding of their contributions, we took advantage of monozygotic twins, as they share genetic and shared environmental factors but differ in nonshared factors, such as environmental differences and stochastic factors. In this study, we performed cap analysis of gene expression on three pairs of twins and clustered each individual based on their expression profiles of annotated genes. The dendrogram of annotated gene transcripts showed a monophyletic clade for each twin pair. We also analyzed the expression of retrotransposons, such as human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs), given their abundance in the genome. Clustering analyses demonstrated that HERV and LINE expression diverged even within monozygotic twin pairs. Thus, HERVs and LINEs are more susceptible to nonshared factors than annotated genes. Motif analysis of differentially expressed annotated genes suggests that specificity protein/Krüppel-like factor family transcription factors are involved in the expression divergence of annotated gene influenced by nonshared factors. Collectively, our findings suggest that expressions of annotated genes and retrotransposons are differently regulated, and that the expression of retrotransposons is more susceptible to nonshared factors than annotated genes.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.

A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.