There is evidence that tamoxifen treatment of BRCA1 and BRCA2 carriers for prior breast cancer increases risk of endometrioid subtype endometrial cancer (EC), and suggestive evidence that BRCA1 and BRCA2 mutation carriers may be predisposed to EC in the absence of tamoxifen exposure. We assessed the association of EC with BRCA1 or BRCA2 mutation status in Australasian breast-ovarian families. Report of at least one case of EC was significantly greater in BRCA1-positive families (35/218 (16%); p = .03) and non-significantly greater in BRCA2-positive families (23/189 (12%); p = .6), compared to high-risk breast cancer families without a BRCA1/2 mutation (86/796 (11%)). EC was the first/concurrent cancer for 41% of EC cases with multiple cancer diagnoses from BRCA1/2 families, and early onset for most of these diagnoses. Mutation status was imputed for ungeno-typed individuals from 57 BRCA1/2 pedigrees reporting EC using BRCAPRO. Effects of genotype on EC diagnosis age, and interaction with tamoxifen therapy, were assessed using Cox proportional hazards regression analysis. EC risk was non-significantly marginally greater for BRCA1 carriers (hazard ratio = 1.25, 95%CI = 0.65–2.41), and BRCA2 carriers (HR = 1.12, 95%CI = 0.51–2.45), compared to non-carrier family members. Tamoxifen therapy was highly significantly associated with EC (HR = 6.68, 95%CI = 3.12–15.15; p = 1.7 x 10-6) in BRCA1/2 families, with no evidence for interaction between tamoxifen therapy and BRCA1/2 genotype. Our family-based study supports a 7-fold increase in EC risk with tamoxifen exposure for female family members from BRCA1/2 families. Early onset EC in carriers without tamoxifen use suggests that further study is required to assess association of modest EC risk with BRCA1/2 mutation status alone.

The longitudinal stability of IQ is well-documented as is its increasing heritability with age. In a longitudinal twin study, we addressed the question to what extent heritability and stability differ for full scale (FSIQ), verbal (VIQ), and performance IQ (PIQ) in childhood (age 9–11 years), and early adolescence (age 12–14 years). Genetic and environmental influences and correlations over time were evaluated in an extended twin design, including Dutch twins and their siblings. Intelligence was measured by the Wechsler Intelligence Scale for children — Third version (WISC III). Heritability in childhood was 34% for FSIQ, 37% for VIQ, and 64% for PIQ, and increased up to 65%, 51%, and 72% in early adolescence. The influence of common environment decreased between childhood and early adolescence from explaining 43% of the phenotypic variance for FSIQ to 18% and from 42% for VIQ to 26%. For PIQ common environmental influences did not play a role, either in childhood or in early adolescence. The stability in FSIQ and VIQ across the 3-year interval (rp) was .72 for both measures and was explained by genetic and common environmental correlations across time (FSIQ, rg = .96, rc = 1.0; VIQ, rg =.78, rc = 1.0). Stability of PIQ (rp =.56) was lower and was explained by genetic influences (rg = .90). These results confirm the robust findings of increased heritability of general cognitive abilities during the transition from childhood to adolescence. Interestingly, results for PIQ differ from those for FSIQ and VIQ, in that no significant contribution of environment shared by siblings from the same family was detected.

Myasthenia gravis (MG) is an autoimmune disorder in which patients experience muscular fatigability due to the presence of anti-acetylcholine receptor (AChR) antibodies which inhibit signal transduction across the neuro-muscular junction. Like all complex disorders, disease is caused by an interaction between genetic and environmental factors. Although several genes have been identified which appear to be associated with MG, both classic twin studies and current multi-gene models are insufficient to explain either disease pathogenesis or inheritance. We examined the literature on MG to determine both mono- and dizygotic twin concordance rates, and used this data to (1) estimate the proportion of the population with underlying genetic predisposition to MG and the frequency of the environmental component and (2) derive the number of inherited genetic regions that are required to confer predisposition to MG. Using a MZ twin concordance rate of 35.5%, and a dizygotic rate of approximately 4–5% (based on family data), the probability of encountering environmental components necessary to develop MG in an individual with genetic predisposition is approximately 52.4%, making the frequency of predisposition (1:5240) roughly twice the rate of incidence. Furthermore, the number of genetic regions co-inherited between affected individuals is between two and four, which may be large haplotypes with interacting activity. Determining these haplotypes, by fully sequencing associated regions in cases and controls to identify mutations present, may therefore be a practically step toward the understanding of complex disease.

Twin studies have long provided a means to separate the contributions of genetic and environmental factors. A recent pioneering report by Baranzini et al. presented an analysis of the complete genomes and epigenomes of a monozygotic (MZ) twin pair discordant for multiple sclerosis. This failed to find any difference between the twins, raising doubts regarding the value of whole-genome twin studies for defining disease susceptibility alleles. However, the study was carried out with DNA extracted from blood. In many cases, the hematopoietic lineages of MZ twins are chimeric due to twin-to-twin exchange of hematopoietic stem cells during embryogenesis. We therefore wondered how chimerism might impact the ability to identify genetic differences. We inferred the blood chimerism rates and profiles of more than 30 discordant twin cases from a wide variety of medical conditions. We found that the genotype compositions of the twins were highly similar. We then benchmarked the performance of SNP callers to detect discordant variations using high-throughput sequencing data. Our analysis revealed that chimerism patterns, well within the range normally observed in MZ twins, greatly reduce the sensitivity of SNP calls. This raises questions regarding any conclusions of genomic homogeneity that might be drawn from studies of blood-derived twin DNA.

Our aim in this study is to describe the characteristics of sexual development in twins and estimate the role of heritability and environmental factors as causes of certain sexual disorders. Two hundred and ten adult same-sex twin pairs (92 monozygotic [MZ] female, 41 MZ male, 55 dizygotic [DZ] female and 22 DZ male pairs) were involved in the study. Data were collected in 1982 by self-administered questionnaires that included items on sexual maturation, sexual life, contraception, mutual sexual activity within twin pairs and alcohol use. The ratio of married to unmarried twins was nearly the same in MZs and DZs, with the exception that the divorce rate was higher in MZ female twins (14%), and DZ and male twins were slightly more likely to be single. Menarche was later in twins compared to non-twin Hungarian women. 57% of MZs experienced menarche within 3 months of each other, 77% within 6 months while it occurred for 30% and 43% respectively in DZs. The first seminal emission indicated some delay in male twins compared with the Hungarian general population sample. MZ first kisses occurred later than DZ's first kisses. The same was true for the first petting, masturbation and first sexual intercourse. Anorgasmy is 27% heritable but the estimate is not statistically significant. Concordance rate for premature ejaculation in MZs was greater than in DZs but the structural equation model showed significant misfit. Age at menarche appeared to be strongly heritable.

Few studies have examined differences of civil status of twins and singletons and the conclusions are contradictory. In the present study, based on a linkage between the Danish Twin Register, a random 5% sample of the total Danish population, and administrative register databases, the authors compare rates of marriage and divorce in a sample of 35,975 twins and 81,803 singletons born 1940–1964. Cox-regressions are used in order to control for potential confounders. We find that compared with singletons twins have significantly lower marriage rates: (males: 15–19 years: Hazard Ratio (HR) = 0.66 (95%CI: 0.58–0.76); 20–24 years: 0.85 (0.82–0.88); 25 years or more: 0.96 (0.93–0.98) and females: 15–19 years: 0.70 (0.67–0.75); 20–24 years: 0.83 (0.80–0.85); 25 years or more: 0.94 (0.91–0.97)). There is no difference in divorce rates for males, but a significantly lower divorce rate for female twins compared with singletons (HR=0.87, 95%CI: 0.83–0.90). These differences offset each other, thus 57% of both populations remain in their first marriage until censoring. The interpretation may be that since twins have a partner from birth, they do not have the same need for marriage as singletons but have more experience in maintaining a relationship if they do marry.

The Dark Triad of personality, comprising Machiavellianism, narcissism, and psychopathy, was investigated in relation to the Supernumerary Personality Inventory (SPI) traits, because both sets of variables are predominantly distinct from the Big Five model of personality. Correlational and principal factor analyses were conducted to assess the relations between the Dark Triad and SPI traits. Multivariate behavioral genetic model-fitting analyses were also conducted to determine the correlated genetic and/or environmental underpinnings of the observed phenotypic correlations. Participants were 358 monozygotic and 98 same-sex dizygotic adult twin pairs from North America. As predicted, results revealed significant correlations between the Dark Triad and most SPI traits, and these correlations were primarily attributable to common genetic and non-shared environmental factors, except in the case of Machiavellianism, where shared environmental effects emerged. Three correlated factors were extracted during joint factor analysis of the Dark Triad and SPI traits, as well as a heritable general factor of personality — results that clarified the structure of the Dark Triad construct. It is concluded that the Dark Triad represents an exploitative and antisocial construct that extends beyond the Big Five model and shares a theoretical space with the SPI traits.

Molecular genetic research has provided some evidence for the association between depression and metabolic disorders. We sought to determine if molecular findings are reflected in twin analyses testing if common genetic and environmental risk factors contribute to the co-occurrence of diabetes and depression. Data to derive depression and diabetes were collected from 1,237 male-male twins who participated in the 2005 Vietnam Era Twin Study of Aging (VETSA). The 1,237 twins were comprised of 347 MZ pairs, 3 MZ singletons, 267 DZ pairs and 6 unpaired twins. Depression was defined as a score below 46 on the Short Form-36 mental component summary score. Diabetes was defined by self report, use of anti-diabetic medications and insulin. Twin models were fit to estimate the correlation of genetic and environmental contributions to depression and diabetes. Consistent with other studies these data support the association between depression and diabetes (OR = 1.7; 95%CI: 1.1–2.7). Genetic vulnerability accounted for 50% (95%CI: 32%–65%) of the variance in risk for depression and 69% (95%CI: 52%–81%) of the variance in risk for diabetes. The genetic correlation between depression and diabetes was r = 0.19 (95%CI: 0–0.46) and the non-shared environmental correlation was r = 0.09 (95% CI: 0–0.45). Overall there is little evidence that common genetic and environmental factors account for the co-occurrence of depression and diabetes in middle aged men. Further research in female twins and larger cohorts is warranted.

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.

The purpose of this study was to estimate the number of siblings in each Japanese family with multiple birth children using two sets of census data, from 1990 and 1995. The mean number of siblings for singletons was 2.3 in 1990 (2.4 in 1995), 2.9 (2.9) for one set of twins, 4.6 (4.5) for two sets of twins, and 3.5 (3.3) for one set of triplets. For birth order of multiples, the highest mean sibling number was 4.4 for one set of twins (the middle), 7.5 for two sets of twins (the middle-middle), and 4.3 for one set of triplets (the last). The mean sibling number was slightly higher for like-sexed twins and triplets than in unlike-sexed twins and triplets. The mean sibling number was highest in the Okinawa District, among nine districts (0.4 for singletons, 0.6 for one set of twins, 1.0 for two sets of twins and 0.6 for triplets). The current study of the number of siblings in each family with multiple birth children will help provide data for designing programs to help support multiple-birth families. The method of using census data on multiple births might result in a system to analyze nationwide data on multiple birth children if there is no national registry of multiple births after live births in any country.

We analyzed whether motor development in early life is different between singletons and triplets in Japan. The motor development was reported by mothers by postal questionnaire for 1,121 triplet children and in regular health check-ups for 13,906 singleton children. Children who were suspected of having neurological abnormality or disability were excluded from the analysis. The ages of milestone achievements were significantly higher in triplets for each outcome compared to singletons. Further, after adjustment for gestational age, birthweight, and birth length, the differences were significant for maintaining head, sitting alone and standing holding on. In children with birthweight of 2 kg or more, the ages of milestone achievements were significantly higher in triplets for each outcome compared to singletons, except walking holding on. Moreover, after adjustment for the confounding factors, the differences were significant for sitting alone and walking independently. On the contrary, singletons attained motor development facilitating crawling, walking holding on, and walking independently slower than triplets among those children with birthweight of 2 kg or less after adjustment for gestational age. In conclusion, triplets are overall at higher risk for the delay of gross motor milestones as compared to singletons independently of birth-related factors. In contrast, among children with a birthweight of less than 2 kg, singletons showed slower motor development than triplets after adjusting for gestational age. There is an obvious need to apply developmental standards that consider at least both multiple birth status (singleton, twin or triplet) and birthweight.

This study was conducted to investigate the relationship among umbilical venous volume flow, birthweight and placental share in monochorionic twins with or without selective growth restriction. Having excluded cases complicated with twin-to-twin transfusion syndrome and one co-twin suffering intrauterine fetal death, a total of 51 monochorionic twin pregnancies were divided into two groups as with (group 1) and without (group 2) selective intrauterine growth restriction. Umbilical venous volume flow was calculated by multiplying the umbilical vein cross-sectional area by half of the maximal velocity around mid-trimester. The placentas were cut along the vascular equator into two individual placental masses. The discordance of birthweight was calculated as [(birthweight of larger twin—birthweight of smaller twin)/birthweight of larger twin 100%]. The discordances of umbilical venous volume flow and placental share were calculated in a similar fashion. The median umbilical venous volume flow discordances (68.4% and 15.3% in groups 1 and 2 monochorionic twins, respectively) were similar and correlated well with the placental share discordances (66.6% and 18.5% in groups 1 and 2 monochorionic twins, respectively) but not with the birthweight discordance (28.6% and 6.4% in groups 1 and 2 monochorionic twins, respectively) in both groups. We concluded that the umbilical venous volume flow discordance reflects the placental share discordance rather than the birthweight discordance in monochorionic twin pregnancies.

This report presents the uncommon case of a 154-day delayed delivery in a spontaneous twin pregnancy associated with uterine atony. After abortion of the first fetus at 16 weeks, a healthy male was born at 38 weeks. Postpartum hemorrhage due to uterine atony, which was successfully treated with prostaglandins, occurred.

This study was conducted for the purpose of assessing, in the light of results of other research carried out in the present researchers' clinic and in Turkey, the status of twin pregnancies in Turkey, the incidence of twin births, perinatal and mortality rates associated with twin pregnancies, and the problems experienced in Turkey in cases of multiple and twin pregnancies. Materials and Methodology: The outcomes of twin births that occurred at the researchers' clinic during the period 2001–2009 were studied retrospectively. Seventeen studies conducted in Turkey on multiple and twin pregnancies during the years 1991–2010 were included in the study. Findings: It was observed that the mean multiple pregnancy rate in Turkey is 1.9% and the mean twin birth rate is 1.7%. It was also observed that a large majority (80–97.3%) of multiple pregnancies in Turkey are twin pregnancies. It was noted from Turkish literature that the mean gestational age of twins at birth varies between 33–36.2 weeks and that mean birthweights are 2065–2327 grams for the first-born twin and 1887–2262 grams for the second-born. These findings were observed to be lower than what is indicated in the literature. Perinatal and neonatal mortality, at 58–156/1000 and 40–98/1000 respectively, were seen to be higher than in the literature. Conclusion: It can be seen that preterm birth rates for twin pregnancies in Turkey are higher than what is indicated in the literature and that prenatal and neonatal mortality rates are also similarly higher.

The relative contributions of genetic and environmental factors to unintentional injuries are of interest to families with young twins. A recent study found that childhood injuries are explained mostly by child-specific environmental factors. Next, twin research reviews of the association between periodontal disease and cancer, secular trends in gestational age and birthweight, and language development in hearing and deaf co-twins are also summarized. Interesting reports of newborn twins, twin-like relationships, twin interactions and missed twin relationships are presented.