According to the Sasang theory, humans can be categorized into one of the four Sasang constitution (SC) types. The four SC types are Tae-Yang (TY), Tae-Eum (TE), So-Yang (SY), and So-Eum (SE), which are determined mainly on the basis of anthropometric characteristics, personality, and the balance of the physiological functions of the major organ systems. There is a growing recognition in the complementary and alternative medicine area that SC types have the potential to be a useful scientific tool for the prevention, diagnosis, and treatment of diseases (Cooper, Evidence Based Complementary and Alternative Medicine, Vol. 6 (Suppl. 1), 2009, pp. 1–3). The main purposes of the present study are to estimate genetic and environmental influences on SC types, and to explore genetic and environmental correlations that affect phenotypic associations among the SC types. In total, 1,742 (365 monozygotic male, 173 dizygotic male, 675 monozygotic female, 271 dizygotic female, and 258 opposite-sex dizygotic) twins (mean age = 19.1 ± 3.1 year) completed a Sasang questionnaire. Univariate and multivariate model-fitting analyses were performed. Total (additive and non-additive) genetic influences were 71% for males and 81% for females in TE, 70% for males and 71% for females in SE, and 47% for both sexes in SY. Non-additive genetic effects were substantial, and shared environmental influences were negligible in most SC types. Multivariate model-fitting analysis revealed that non-additive genetic and individual-specific environmental correlations between TE and SE were -0.92 (95% CI [-0.89, -0.93]) and -0.62 (95% CI [-0.57, -0.68]), respectively. The corresponding estimates were -0.55 (95% CI [-0.48, -0.61]) and -0.44 (95% CI [-0.37, -0.51]) between TE and SY and 0.19 (95% CI [0.09, 0.29]) and -0.40 (95% CI [-0.32, -0.47]) between SE and SY. These results suggest that the phenotypic associations among SC types may be mediated by pleiotropic mechanism of genes.

Genetic and environmental influences on predictors of decline in daily functioning, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), handgrip, and five-times-sit-to-stand test (FTSST), have not been addressed in the aging Chinese population. We performed classical twin modeling on FEV1, FVC, handgrip, and FTSST in 379 twin pairs (240 MZ and 139 DZ) with median age of 50 years (40–80 years). Data were analyzed by fitting univariate and bivariate twin models to estimate the genetic and environmental influences on these measures of physical function. Heritability was moderate for FEV1, handgrip, and FTSST (55–60%) but insignificant for FVC. Only FVC showed moderate control, with shared environmental factors accounting for about 50% of the total variance. In contrast, all measures of pulmonary function and muscle strength showed modest influences from the unique environment (40–50%). Bivariate analysis showed highly positive genetic correlations between FEV1 and FVC (rG = 1.00), and moderately negative genetic correlations between FTSST and FEV1 (rG = −0.33) and FVC (rG = −0.42). FEV1 and FVC, as well as FEV1 and handgrip, displayed high common environmental correlations (rC = 1.00), and there were moderate correlations between FVC and handgrip (rC = 0.44). FEV1 and FVC showed high unique environmental correlations (rE = 0.76) and low correlations between handgrip and FEV1 (rE = 0.17), FVC (rE = 0.14), and FTSST (rE = −0.13) with positive or negative direction. We conclude that genetic factors contribute significantly to the individual differences in common indicators of daily functioning (FEV1, handgrip, and FTSST). FEV1 and FVC were genetically and environmentally correlated. Pulmonary function and FTSST may share similar sets of genes but in the negative direction. Pulmonary function and muscle strength may have a shared environmental background.

Trends in the civil registration of fetal death in multiple gestations that has occurred before, but expelled from the womb after, 24 weeks' gestation are examined using England and Wales 1993–2004 registration obtained from the Office for National Statistics. Count was made of fetal death registrations in which fetus papyraceous, fetal death before 24 weeks' gestation or fetocide before 24 weeks' gestation was recorded. There were 3700 fetal death registrations among 217,595 twin, triplet and higher order multiple births in England and Wales between 1993 and 2004. In 354 (9.6%) of these fetal deaths, death was recorded as having occurred before 24 weeks' gestation. There has been a threefold increase in such fetal death registrations. It is a legal requirement of parents to register a fetal death. The definition of a fetal death that meets formal registration criteria is that the fetus is expelled from the womb after 24 weeks' gestation. However, if the fetal death occurs before 24 weeks, there is confusion, nationally and internationally, whether or not registration is legally required. Fetal death in a multiple gestation has serious clinical implications for a surviving co-conceptus and failure to inform parents of an early death in a multiple gestation may have important repercussions. Legal definition for the registration of fetal death requires international agreement and application.

In the course of twin studies whose main focus was elucidation of genetic and environmental factors on behavioral traits, many twin researchers became aware of the strong tendency for dizygotic (DZ) twinning to run in families. Over four decades, Nick Martin and others initiated hormone and ultrasound studies, performed segregation and pedigree analyses, tested candidate genes, carried out linkage projects in sister pairs and formed large collaborations to illuminate the genetics of DZ twinning by genome-wide association studies and meta-analysis. This article summarizes the early work on hormone and genetic studies and describes the meta-analyses that have at last met with success in finding the first genes that predispose to DZ twinning, which also appear to influence many other female reproductive traits.

It has been proposed that low birth weight is associated with high levels of blood pressure in later life. The aim of this study was to assess the relationship of blood pressure to birth weight and current body size during growth and adulthood. A total of 711 female multiple births, with one group of 244 in their growth phase mean age 12.0 (2.3)(SD) years and the other of 467 adults (mean age 35.2 (12.6) years), had height, weight and both systolic (SBP) and diastolic (DBP) blood pressures measured, and self-reported their birth weight. Regression analyses were performed to assess the cross-sectional and within-pair associations of blood pressure to birth weight, with and without adjustments for current body size. Within-pair analysis was based on 296 twin pairs. Cross-sectionally, a reduction in birth weight of 1 kg was associated with 2 to 3 mm Hg higher age-adjusted SBP, which was of marginal significance and explained about 2% of the population variance. Adjustment for body mass index did not significantly change this association. Within-pair analyses found no association between birth weight and SBP or DBP, even after adjusting for current body size. After age, current body size was the strongest predictor of systolic BP. The weak association of blood pressure to birth weight cross-sectionally is of interest, but any within-pair effect of birth weight on blood pressure must be minimal compared with the effect of current body size.

This study aims to determine whether fetal growth is related to insulin-like growth factor-1 in dichorionic and monochorionic twins and also aims to investigate the correlation of insulin-like growth factor-1 to birthweight discordance in twins. We studied 100 women with twin pregnancies. The correlation tests of 36 discordant twins (15 monochorionic, 21 dichorionic) showed correlation between insulin-like growth factor-1 difference and birthweight discordance (insulin-like growth factor-1 vs. birthweight of first twin, r = +0.915, at 0.01 level, IGF-1 vs birthweight of second twin r = +0.790, at 0.01 level). In 49 monochorionic twins, independent of discordance, there was a correlation between birthweight discordance and insulin-like growth factor-1 difference (r = .538, at the 0.01 level). This correlation was not significant in dichorionic twins, r = .144, p = .01. These data suggest that growth discordances of twins exposed to the same maternal environment may be due to variations in IGF-1, depending upon the genetic similarity.

We analyzed depressive and psychosomatic symptoms in relation to parental preference in 419 twins at the age of 22 to 30 years. Depressiveness was elicited with Children's Depression Inventory and reported as a total score and three subscales (low self-confidence, anhedonia and sadness) based on factor analysis as reported in a previous epidemiological study conducted in Finland. Items assessing nervous complaints and somatic symptoms were adapted from Finnish studies of juvenile health habits. Twins reported the preference in two directions: experienced parental preference towards either twin, and twin's own preference towards either parent. About half of the twins were from pairs where both twins experienced having been equally close to both parents, while about 30% were from ‘equal and mother's’ pair, where one twin evaluated having been preferred by the mother and the co-twin evaluated having been equally close to both parents. According to the twins' own preference, about one third of the twin pairs were ‘both equal’, one third ‘both mother's’ and one third ‘equal and mother's’. Those male twins who were equally close to both parents (experienced parental preference) had least total depressiveness, while females in the intermediate situation had the highest self-confidence and least anhedonia and nervousness. According to twins' own preference, twins who felt equally close to both parents had the least depressiveness and anhedonia. The intermediate position seems to be the best alternative, as these twins had the least symptoms.

The Florida State Twin Registry has existed for nearly two decades, and it grew primarily over 10 years as part of the Florida Learning Disability Research Center at Florida State University. The registry contains 2753 sets of twins and other multiples in Florida. The mean age of the sample currently is 17.96 years (SD = 2.05). The registry is diverse in terms of race and ethnicity (49% White, 19% African American, 24% Hispanic and 8% mixed or other). The characteristics of the samples and measures in the studies that served to build the registry are outlined.

The aim of the present work was to estimate the risk of monochorionic twin (MCT) pregnancies in in vitro fertilization (IVF) cycles using data from a prenatal diagnosis unit. This was a retrospective cross-sectional study reporting on the frequency of IVF pregnancies among women attending a prenatal diagnosis service specifically dedicated to the management of monochorionic pregnancies. The observed rate was compared with the local regional rate of IVF births (2.2%). A binomial distribution model was used to calculate the 95% CI of proportions. One hundred and forty-five monochorionic pregnancies were selected. Ten of these were achieved with IVF, corresponding to a rate of 6.9% (95% CI: 3.5–11.8), significantly higher than the background rate in the local population of 2.2%. When considering exclusively monochorionic pregnancies achieving delivery of two viable newborns (n = 132), the number of IVF pregnancies was nine (6.8%, 95% CI: 3.7–12.5). We did not detect major differences in pregnancy outcome between IVF and natural monochorionic pregnancies, with the exception of the proportion of newborns with a neonatal birth < 2,500 g (100% vs. 80%, p = .03). In conclusion, data obtained from the perspective of a prenatal diagnosis unit suggest that women undergoing IVF face a 3- to 4-fold increased risk of monochorionic pregnancies.

Variation in human cognitive ability is of consequence to a large number of health and social outcomes and is substantially heritable. Genetic linkage, genome-wide association, and copy number variant studies have investigated the contribution of genetic variation to individual differences in normal cognitive ability, but little research has considered the role of rare genetic variants. Exome sequencing studies have already met with success in discovering novel trait-gene associations for other complex traits. Here, we use exome sequencing to investigate the effects of rare variants on general cognitive ability. Unrelated Scottish individuals were selected for high scores on a general component of intelligence (g). The frequency of rare genetic variants (in n = 146) was compared with those from Scottish controls (total n = 486) who scored in the lower to middle range of the g distribution or on a proxy measure of g. Biological pathway analysis highlighted enrichment of the mitochondrial inner membrane component and apical part of cell gene ontology terms. Global burden analysis showed a greater total number of rare variants carried by high g cases versus controls, which is inconsistent with a mutation load hypothesis whereby mutations negatively affect g. The general finding of greater non-synonymous (vs. synonymous) variant effects is in line with evolutionary hypotheses for g. Given that this first sequencing study of high g was small, promising results were found, suggesting that the study of rare variants in larger samples would be worthwhile.

From 1964 to 1971, twins and singleton controls were followed from 10 to 16 years of age in Swedish schools. It was a nationally representative sample of 323 twin pairs, and 1193 classmate controls. In 1991 a follow-up was made of this sample with the purpose of investigating genetic influences on experienced family and school environments, as well as coping ability at the age of 35. The follow-up also evaluated the relation between coping ability at mid-life and family environment, as well as coping ability and school environment at adolescence for males and females. Genetic influences on perceived family and school environments, as well as on self-reported coping ability, have been investigated by means of comparisons of MZ and DZ twin pairs. A stepwise linear regression analysis was performed to assess environmental influences on coping ability at mid-life. The findings indicated that coping ability at mid-life is influenced by both genetic and environmental factors. Different environmental factors were operating for males and females, however. The results demonstrate that early environmental factors and genetic disposition have a long-term effect on coping ability.

Dr Nick Martin has made enormous contributions to the field of behavior genetics over the past 50 years. Of his many seminal papers that have had a profound impact, we focus on his early work on the power of twin studies. He was among the first to recognize the importance of sample size calculation before conducting a study to ensure sufficient power to detect the effects of interest. The elegant approach he developed, based on the noncentral chi-squared distribution, has been adopted by subsequent researchers for other genetic study designs, and today remains a standard tool for power calculations in structural equation modeling and other areas of statistical analysis. The present brief article discusses the main aspects of his seminal paper, and how it led to subsequent developments, by him and others, as the field of behavior genetics evolved into the present era.

To evaluate the accuracy of ultrasound in early detection of chorionicity and amnionicity in twin pregnancies and evaluate the role of operator-experience, a prospective follow up of 87 consecutive twin pregnancies was performed. Chorionicity and amnionicity were determined by 17 different observers, divided in 2 groups on the basis of their experience, using a composite of US markers at the first US examination confirming a viable intrauterine twin pregnancy. Accuracy of prediction was determined for both groups by comparison with postnatal pathology. From the 87 pregnancies examined at 10.1 (minimum 5.5 weeks, maximum 26.0) weeks of gestation, pathology was available in 82 cases and a correct prediction of chorionicity was made in all but two cases, both being diagnosed as monochorionic while dichorionic by observers belonging the more experienced group. No monochorionic pregnancy was missed and amnionicity was correctly diagnosed in all cases, including two monoamniotic twins. We conclude that use of a composite of ultrasound markers for early detection of chorionicity and amnionicity is reliable in a clinical setting where physicians with a variable degree of experience perform ultrasound examination.

Intelligence and educational attainment are strongly genetically correlated. This relationship can be exploited by Multi-Trait Analysis of GWAS (MTAG) to add power to Genome-wide Association Studies (GWAS) of intelligence. MTAG allows the user to meta-analyze GWASs of different phenotypes, based on their genetic correlations, to identify association's specific to the trait of choice. An MTAG analysis using GWAS data sets on intelligence and education was conducted by Lam et al. (2017). Lam et al. (2017) reported 70 loci that they described as ‘trait specific’ to intelligence. This article examines whether the analysis conducted by Lam et al. (2017) has resulted in genetic information about a phenotype that is more similar to education than intelligence.

Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term ‘metabolomics’ refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented.

We compared the accuracy of genotyping for DNA extracted from lymphocytes to that of DNA amplified from buccal epithelial cells. Amplification was via a rolling circle/φ29 DNA polymerase commercial kit. Paired buccal and lymphocyte DNA samples were available from 30 individuals. All samples were genotyped for 12 SNPs, 5 microsatellites and 2 VNTRs. The accuracy of genotyping (no-call proportions, reproducibility, and concordance) was similar for DNA from lymphocytes in comparison to amplified DNA from buccal samples. If used with caution, these data suggest that rolling-circle whole-genome amplification can be used to increase the DNA mass available for large-scale genotyping projects based on DNA from buccal cells.

Several studies have explored the impact of marital bereavement on mortality, while increasing emphasis has recently been placed on genetic factors influencing longevity — in this paper, we study the impact of losing the spouse and losing the co-twin, for twins aged 50 to 70. We use data from the Danish Twin Registry and the Population Register of Denmark for the period 1968 through 1999. Firstly, we use survival analysis to study mortality after the death of the spouse or the co-twin. We find that the risk of dying is highest in the first year after the death of the spouse, as well as in the second year after the death of the co-twin. We then use event history analysis techniques to show that there is a strong impact of the event ‘losing the co-twin' even after controlling for age, sex and zygosity and that this effect is significantly higher in the second year of bereavement. The effect is similar for men and women, and it is higher for monozygotic twins. The latter confirms the influence of genetic factors on survival, while the mortality trajectory with a peak in the second year after the death of the co-twin is consistent with the existence of a twin bereavement effect.