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.

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.

Depression and fatigue have previously been suggested to share an underlying genetic contribution. The present study aims to investigate and characterize the familiality and genetic relationship between depression and fatigue. The familiality of depression and fatigue was assessed by calculating relative risks, measured by the prevalence ratio, within 643 monozygotic (MZ) and 577 dizygotic (DZ) twin pairs. Bivariate twin modeling was utilized to assess the magnitude of shared heritability between depression and fatigue. Finally, the relationship between depression and fatigue was investigated using the co-twin control method, to determine whether the association is explained by causal or non-causal models. We observed an increased risk of fatigue in co-twins of probands with depression and increased risk of depression in co-twins of probands with fatigue. Higher risks were observed in MZ compared to DZ twin pairs, and bivariate heritability analyses indicated significant genetic components for depression and fatigue, with heritability estimates of 48% and 41%, respectively. Importantly, a significant additive genetic correlation of 0.71 [95% CI = 0.51–0.92) and bivariate heritability of 21% [95% CI = 10–35%] was observed between depression and fatigue. Furthermore, results from the co-twin control method indicate a non-causal genetic relationship that likely explains the association between depression and fatigue. Notably, the contribution of shared genetic factors remained significant, independent of the overlapping symptoms, indicating that the relationship between co-occurring depression and fatigue is primarily due to shared genetic factors rather than overlapping symptomatology.

Depression and anxiety are highly comorbid due to shared genetic risk factors, but less is known about whether burnout shares these risk factors. We aimed to examine whether the covariation between major depressive disorder (MDD), generalized anxiety disorder (GAD), and burnout is explained by common genetic and/or environmental factors. This cross-sectional study included 25,378 Swedish twins responding to a survey in 2005–2006. Structural equation models were used to analyze whether the trait variances and covariances were due to additive genetics, non-additive genetics, shared environment, and unique environment. Univariate analyses tested sex limitation models and multivariate analysis tested Cholesky, independent pathway, and common pathway models. The phenotypic correlations were 0.71 (0.69–0.74) between MDD and GAD, 0.58 (0.56–0.60) between MDD and burnout, and 0.53 (0.50–0.56) between GAD and burnout. Heritabilities were 45% for MDD, 49% for GAD, and 38% for burnout; no statistically significant sex differences were found. A common pathway model was chosen as the final model. The common factor was influenced by genetics (58%) and unique environment (42%), and explained 77% of the variation in MDD, 69% in GAD, and 44% in burnout. GAD and burnout had additive genetic factors unique to the phenotypes (11% each), while MDD did not. Unique environment explained 23% of the variability in MDD, 20% in GAD, and 45% in burnout. In conclusion, the covariation was explained by an underlying common factor, largely influenced by genetics. Burnout was to a large degree influenced by unique environmental factors not shared with MDD and GAD.

Utilizing a newly released cognitive Polygenic Score (PGS) from Wave IV of Add Health (n = 1,886), structural equation models (SEMs) examining the relationship between PGS and fertility (which is approximately 50% complete in the present sample), employing measures of verbal IQ and educational attainment as potential mediators, were estimated. The results of indirect pathway models revealed that verbal IQ mediates the positive relationship between PGS and educational attainment, and educational attainment in turn mediates the negative relationship between verbal IQ and a latent fertility measure. The direct path from PGS to fertility was non-significant. The model was robust to controlling for age, sex, and race; furthermore, the results of a multigroup SEM revealed no significant differences in the estimated path coeficients across sex. These results indicate that those predisposed towards higher verbal IQ by virtue of higher PGS values are also predisposed towards trading fertility against time spent in education, which contributes to those with higher PGS values producing fewer offspring at this stage in their life course.

Behavioral traits generally show moderate to strong genetic influence, with heritability estimates of around 50%. Some recent research has suggested that trust may be an exception because it is more strongly influenced by social interactions. In a sample of over 7,000 adolescent twins from the United Kingdom's Twins Early Development Study, we found broad sense heritability estimates of 57% for generalized trust and 51% for trust in friends. Genomic-relatedness-matrix restricted maximum likelihood (GREML) estimates in the same sample indicate that 21% of the narrow sense genetic variance can be explained by common single nucleotide polymorphisms for generalized trust and 43% for trust in friends. As expected, this implies a large amount of unexplained heritability, although power is low for estimating DNA-based heritability. The missing heritability may be accounted for by interactions between DNA and the social environment during development or via gene–environment correlations with rare variants. How these genes and environments correlate seem especially important for the development of trust.

Because of recent concerns about the replication of published results in the behavioral and biomedical sciences (Ioannidis, PLoS Medicine, Vol. 2, 2005, p. e124; Open Science Collaboration, Science, Vol. 349, 2015, p. 943; Pashler & Wagenmakers, Perspectives on Psychological Science, Vol. 7, 2012, pp. 528–530), we have conducted a replication of our recently published analyses of longitudinal reading performance and attention deficit-hyperactivity disorder data from twin pairs selected for reading difficulties (Wadsworth et al., Twin Research and Human Genetics, Vol. 18, 2015, pp. 755–761). Results obtained from univariate and bivariate (DeFries & Fulker, Behavior Genetics, Vol. 15, 1985, pp. 467–473; Acta Geneticae Medicae et Gemellologiae: Twin Research, Vol. 37, 1988, pp. 205–216) analyses of data from a subset of twin pairs tested in the International Longitudinal Twin Study of Early Reading Development at post-4th grade, and its continuation into high school at post-9th grade, were compared to those from our previous report. Similar measures of reading performance, the same measures of inattention and hyperactivity/impulsivity, and similar selection criteria were used in the two studies. In general, the patterns of results obtained from these two independent studies were highly similar. Thus, these results clearly illustrate the principle that findings from studies in quantitative behavioral genetics often replicate (Plomin et al., Perspectives on Psychological Science, Vol. 11, 2016, pp. 3–23).

Introduction: Literature suggests that male hormones influence fetal growth in singleton pregnancies. We hypothesized that the same phenomenon is seen in twin gestations. Objectives: (1) to identify the impact of gender associated with fetal birth weight, head circumference, and birth length for twins; (2) to examine the effect of gender on standardized fetal growth at birth, according to gestational age and birth order; (3) to examine the effect of gender on placenta weight and dimensions. Methodology: This was a population-based retrospective cohort study of twins (4,368 twins, 2,184 pairs) born in British Columbia, Canada from 2000–2010. We excluded twins with stillbirth, congenital anomalies, and those delivered with cesarean section. We also controlled for confounding factors, including birth order, gestational age, maternal anthropometric measures, maternal smoking habits, and obstetric history. A subsample of this population was analyzed from Children and Women Hospital to obtain chorionicity information. Results: Male–male twins were heavier than male–females and female–female twin pairs (p=.01). Within sex-discordant twin pairs, males were also heavier than females (p=.01). Regression analysis suggested that gender affects birth weight independent of birth order and gestational age. Other newborn anthropometric measures were not found to be dependent on gender. In analyzing a subsample with chorionicity data, birth weight was the only anthropometric measure that was both statistically and clinically affected by sex, even after adjustment for gestational age, chorionicity, birth order, and maternal age. Conclusion: Birth weight was affected by gender while head circumference and birth length were not.

The German twin family study ‘TwinLife’ was designed to enhance our understanding of the development of social inequalities over the life course. The interdisciplinary project investigates mechanisms of social inequalities across the lifespan by taking into account psychological as well as social mechanisms, and their genetic origin as well as the interaction and covariation between these factors. Main characteristics of the study are: (1) a multidimensional perspective on social inequalities, (2) the assessment of developmental trajectories in childhood, adolescence, and young adulthood in a longitudinal design by using (3) a combination of a multi-cohort cross-sequential and an extended twin family design, while (4) capturing a large variation of behavioral and environmental factors in a representative sample of about 4,000 German twin families. In the present article, we first introduce the theoretical and empirical background of the TwinLife study, and second, describe the design, content, and implementation of TwinLife. Since the data will be made available as scientific use file, we also illustrate research possibilities provided by this project to the scientific community.

The aim of this study was to investigate the twinning rates (TWRs) in isolates relative to the TWRs in the surrounding populations. It is not uncommon that the TWR shows extreme values (high or low rates) within isolated subpopulations. Starting from the isolated populations of the Åland Islands in Finland (high rates), we enlarged our studies to other isolated subpopulations in other countries: the island of Gotland (high rates), the county of Älvsborg located in the southwestern part of Sweden (low rates), and mountain villages in Norway. In our statistical analyses, we paid special attention to the robustness of the variance formula of the TWR and to alternative confidence intervals for the TWR. Particularly, we show how to obtain the most precise confidence intervals for the twinning rates. These statistical methods are crucial when the extreme TWRs within subpopulations are compared with the TWRs within the general population. One must decide whether the differences are real or caused by random fluctuations within the small isolates.

The present study investigates the twinning rates in the city of São Paulo, Brazil, during the years 2003–2014. The data were drawn from the Brazilian Health Department database of Sistema de Informações de Nascidos Vivos de São Paulo—SINASC (Live Births Information System of São Paulo). In general, more information is available on the incidence of twinning in developed countries than in developing ones. A total of 24,589 twin deliveries and 736 multiple deliveries were registered in 140 hospitals of São Paulo out of a total of 2,056,016 deliveries during the studied time period. The overall average rates of singleton, twin, and multiple births per 1,000 maternities (‰) were 987.43, 11.96 (dizygotic (DZ) rate was 7.15 and monozygotic (MZ) 4.42), and 0.36, respectively. We further regressed maternal age and historical time period on percentage of singleton, twin, and multiple birth rates. Our results indicated that maternal age strongly positively predicted twin and multiple birth rates, and negatively predicted singleton birth rates. The historical time period also positively, although weakly, predicted twin birth rates, and had no effect on singleton or multiple birth rates. Further, after applying Weinberg's differential method, we computed regressions separately for the estimated frequencies of DZ and MZ twin rates. DZ twinning was strongly positively predicted by maternal age and, to a smaller degree, by time period, while MZ twinning increased marginally only with higher maternal age. Factors such as increasing body mass index or air pollution can lead to the slight historical increase in DZ twinning rates. Importantly, consistent with previous cross-cultural and historical research, our results support the existence of an age-dependent physiological mechanism that leads to a strong increase in twinning and multiple births, but not singleton births, among mothers of higher age categories. From the ultimate perspective, twinning and multiple births in later age can lead to higher individual reproductive success near the end of the reproductive career of the mother.

The Brazilian Twin Registry (BTR) was established in 2013 and has impelled twin research in South America. The main aim of the initiative was to create a resource that would be accessible to the Brazilian scientific community as well as international researchers interested in the investigation of the contribution of genetic and environmental factors in the development of common diseases, phenotypes, and human behavior traits. The BTR is a joint effort between academic and governmental institutions from Brazil and Australia. The collaboration includes the Federal University of Minas Gerais (UFMG) in Brazil, the University of Sydney and University of Melbourne in Australia, the Australian Twin Registry, as well as the research foundations CNPq and CAPES in Brazil. The BTR is a member of the International Network of Twin Registries. Recruitment strategies used to register twins have been through participation in a longitudinal study investigating genetic and environmental factors for low back pain occurrence, and from a variety of sources including media campaigns and social networking. Currently, 291 twins are registered in the BTR, with data on demographics, zygosity, anthropometrics, and health history having been collected from 151 twins using a standardized self-reported questionnaire. Future BTR plans include the registration of thousands of Brazilian twins identified from different sources and collaborate nationally and internationally with other research groups interested on twin studies.

Background: Monochorionic diamniotic (MCDA) twin pregnancies are associated with adverse perinatal outcome. Intertwin discordances at the time of nuchal translucency (NT) screening may have a value in the prediction of fetal loss or twin-to-twin transfusion syndrome. We aimed to determine the ability of intertwin NT and crown rump length (CRL) discordances among MCDA twins to predict adverse outcomes. Material and Methods: All MCDA twins with a documented routine ultrasound at 11 to 13+6 weeks’ gestation, and known pregnancy outcome between August 2003 and August 2012 were included. Receiver operating characteristic curves were used to determine the ideal NT and CRL discordances cut-off points that maximized the ability to predict adverse outcome, which was defined as any of: death of one or both twins, twin-to-twin transfusion syndrome, or estimated fetal weight or birth weight discordances ≥25%. Results: Of the 89 cases, 20 (22.5%) had at least one adverse outcome. NT discordance was more discriminatory of adverse outcome than was CRL discordance. The optimal values for predicting any adverse outcomes for NT were >23.7% and for CRL >3.5%. The positive predictive values for NT (52.4%) and CRL (29.8%) screening were relatively low; however, the lack of either NT or CRL discordances was more reassuring, with negative predictive values of 86.8% and 86.4%, respectively. Conclusions: NT discordance is more predictive for adverse fetal outcome in MCDA twins than CRL discordance. Neither NT nor CRL discordance are likely to modify the intensive monitoring required for these very high-risk pregnancies.

The aim of the present work was to determine maternal and fetal outcomes of intrahepatic cholestasis of pregnancy (ICP) in twin pregnancies. All twin pregnancies delivered above 28 gestational weeks in West China Second University Hospital from January 2013 to May 2015 were included. Data on maternal demographics and obstetric complications together with fetal outcomes were collected. The risk of adverse maternal and fetal outcomes were determined in relation to ICP by crude odds ratios (OR) and adjusted ORs (aOR) with 95% confidence intervals (CI). Subgroup analysis concentrated on the effect of assisted reproductive technology (ART), ICP severity, and onset time. A total of 1,472 twin pregnancies were included, of which 362 were cholestasis patients and 677 were conceived by ART. Higher rates of preeclampsia (aOR 1.96; 95% CI 1.35, 2.85), meconium-stained amniotic fluid (aOR 3.10; 95% CI 2.10, 4.61), and preterm deliveries (aOR 3.20; 95% CI 2.35, 4.37) were observed in ICP patients. Subgroup analysis revealed higher incidences of adverse outcomes in severe and early onset ICP groups. In conclusion, adverse maternal and fetal outcomes were strongly associated with ICP in twin patients. Active management and close antenatal monitoring are needed, especially in the early onset and severe groups.

Dr Irving I. Gottesman, a colleague, friend, and long-time member of the International Society of Twin Studies passed away on June 29, 2016. His contributions to twin research and some personal reflections are presented to honor both the man and the memory. This tribute is followed by short reviews of twin research concerning differences between cosmetic surgical techniques, the rearing of preterm twins, behavioral observations of dichorionic fetal twins, and the outcomes of co-bedding twins with reference to stress reduction. Interesting and informative articles in the media describe identical co-twins who delivered infants on the same day, educational policies regarding twins in Bosnia and the United Kingdom, unusual practices of twin auctioneers, and a theatrical production, Sister, featuring identical twins in the leading roles.