Low birth weight (LBW) can have an impact on health outcomes in later life, especially in relation to pre-disposition to metabolic disease. Several studies suggest that LBW resulting from restricted intrauterine growth leaves a footprint on DNA methylation in utero, and this influence likely persists into adulthood. To investigate this further, we performed epigenome-wide association analyses of blood DNA methylation using Infinium HumanMethylation450 BeadChip profiles in 71 adult monozygotic (MZ) twin pairs who were extremely discordant for birth weight. A signal mapping to the IGF1R gene (cg12562232, p = 2.62 × 10−8), was significantly associated with birth weight discordance at a genome-wide false-discovery rate (FDR) of 0.05. We pursued replication in three additional independent datasets of birth weight discordant MZ pairs and observed the same direction of association, but the results were not significant. However, a meta-analysis across the four independent samples, in total 216 birth-weight discordant MZ twin pairs, showed a significant positive association between birth weight and DNA methylation differences at IGF1R (random-effects meta-analysis p = .04), and the effect was particularly pronounced in older twins (random-effects meta-analysis p = .008, 98 older birth-weight discordant MZ twin pairs). The results suggest that severe intra-uterine growth differences (birth weight discordance >20%) are associated with methylation changes in the IGF1R gene in adulthood, independent of genetic effects.

Strabismus represents a complex oculomotor disorder characterized by the deviation of one or both eyes and poor vision. A more sophisticated understanding of the genetic liability of strabismus is required to guide searches for associated molecular variants. In this classical twin study of 1,462 twin pairs, we examined the relative influence of genes and environment in comitant strabismus, and the degree to which these influences can be explained by factors in common with refractive error. Participants were examined for the presence of latent (‘phoria’) and manifest (‘tropia’) strabismus using cover–uncover and alternate cover tests. Two phenotypes were distinguished: eso-deviation (esophoria and esotropia) and exo-deviation (exophoria and exotropia). Structural equation modeling was subsequently employed to partition the observed phenotypic variation in the twin data into specific variance components. The prevalence of eso-deviation and exo-deviation was 8.6% and 20.7%, respectively. For eso-deviation, the polychoric correlation was significantly greater in monozygotic (MZ) (r = 0.65) compared to dizygotic (DZ) twin pairs (r = 0.33), suggesting a genetic role (p = .003). There was no significant difference in polychoric correlation between MZ (r = 0.55) and DZ twin pairs (r = 0.53) for exo-deviation (p = .86), implying that genetic factors do not play a significant role in the etiology of exo-deviation. The heritability of an eso-deviation was 0.64 (95% CI 0.50–0.75). The additive genetic correlation for eso-deviation and refractive error was 0.13 and the bivariate heritability (i.e., shared variance) was less than 1%, suggesting negligible shared genetic effect. This study documents a substantial heritability of 64% for eso-deviation, yet no corresponding heritability for exo-deviation, suggesting that the genetic contribution to strabismus may be specific to eso-deviation. Future studies are now needed to identify the genes associated with eso-deviation and unravel their mechanisms of action.

Do genetically identical children experience the same classroom differently? Are nonshared classroom experiences associated with differences in achievement? We designed a telephone diary measure which we administered every school day for 2 weeks to 122 10-year-olds in 61 monozygotic (MZ) twin pairs. Each pair shared genes, a classroom, peers and a teacher. We found that MZ twins did experience their classrooms differently (rMZ < 0.65 for all measures of classroom experience). Furthermore, MZ differences in peer problems were significantly associated with MZ differences in Mathematics achievement (ES = 8%); differences in positivity about school were significantly associated with differences in Mathematics (ES = 15%) and Science (ES = 8%) achievement; and differences in ‘flow’ in Science lessons were associated with differences in Science achievement (ES = 12%). In a multiple regression analysis, MZ differences in positivity about school significantly predicted MZ differences in Mathematics achievement (R2 = 0.16, p < .01) and MZ differences in ‘flow’ in Science significantly predicted MZ differences in Science achievement (R2 = 0.10, p < .05). These results indicate that MZ twins experience the classroom differently and that differences in their experience are associated with differences in their achievement.

It has been over 5 years since the last special issue of Twin Research and Human Genetics on ‘Twin Registries Worldwide: An Important Resource for Scientific Research’ was published. Much progress has been made in the broad field of twin research since that time, and the current special issue is a follow-up to update the scientific community about twin registries around the globe. The present article builds upon our 2013 Registry description by summarizing current information on the Washington State Twin Registry (WSTR), including history and construction methods, member characteristics, available data, and major research goals. We also provide a section with brief summaries of recently completed studies and discuss the future research directions of the WSTR. The Registry has grown in terms of size and scope since 2013; highlights include recruitment of youth pairs under 18 years of age, extensive geocoding work to develop environmental exposures that can be linked to survey and administrative health data such as death records, and expansion of a biobank with specimens collected for genotyping, DNA methylation, and microbiome based-studies.

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.

The prevalence of overweight and obesity is growing rapidly in many countries. Socioeconomic inequalities might be important for this increase. The aim of this study was to determine associations of body mass index (BMI), overweight and obesity with educational level and marital status in Chinese twins. Participants were adult twins recruited through the Chinese National Twin Registry (CNTR), aged 18 to 79 years, and the sample comprised 10,448 same-sex twin pairs. Current height, weight, educational attainment, and marital status were self-reported. Regression analyses and structural equation models were conducted to evaluate BMI, overweight, and obesity associated with educational level and marital status in both sexes. At an individual level, both educational level and marital status were associated with higher BMI and higher risk of being overweight and obesity in men, while in women the effects of educational level on BMI were in the opposite direction. In within-Monozygotic (MZ) twin-pair analyses, the effects of educational level on BMI disappeared in females. Bivariate structural equation models showed that genetic factors and shared environmental confounded the relationship between education and BMI in females, whereas marital status was associated with BMI on account of significant positive unique environmental correlation apart in both sexes. The present data suggested that marital status and BMI were associated, independent of familiar factors, for both sexes of this study population, while common genetic and shared environmental factors contributed to education-associated disparities in BMI in females.

The roles of genetic and environmental influences on stressful life events were examined in 3938 twin pairs (MZ, same-sex DZ, and opposite-sex DZ) using a sex-limitation model. Life events were assessed by personal interview, and were categorized as being either personal (i.e., events that occur directly to the individual) or network (i.e., events that occur to someone within the individual's social network, thus affecting the individual indirectly). Consistent with previous reports, genetic factors were found to exert more influence on personal events than network events. Genetic correlations between males and females suggest that many of the same genetic factors are acting within both genders.

Identification of individuals within pairs of monozygotic (MZ) twins remains unresolved using common forensic DNA typing technology. For some criminal cases involving MZ twins as suspects, the twins had to be released due to inability to identify which of the pair was the perpetrator. In this study, we performed a genome-wide scan on whole blood-derived DNA from four pairs of healthy phenotypically concordant MZ twins using the methylated DNA immunoprecipitation sequencing technology to identify candidate DNA methylation markers with capacity to distinguish MZ twins within a pair. We identified 38 differential methylation regions showing within-pair methylation differences in all four MZ pairs. These are all located in CpG islands, 17 of which are promoter-associated, 17 are intergenic islands, and four are intragenic islands. Genes associated with these markers are related with cell proliferation, differentiation, and growth and development, including zinc finger proteins, PRRX2, RBBP9, or are involved in G-protein signaling, such as the regulator of G-protein signaling 16. Further validation studies on additional MZ twins are now required to evaluate the broader utility of these 38 markers for forensic use.

The Genesis 12–19 (G1219) Study is an ongoing longitudinal study of a sample of UK twin pairs, non-twin sibling pairs, and their parents. G1219 was initially designed to examine the role of gene–environment interplay in adolescent depression. However, since then data have continued to be collected from both parents and their offspring into young adulthood. This has allowed for longitudinal analyses of depression and has enabled researchers to investigate multiple phenotypes and to ask questions about intermediate mechanisms. The study has primarily focused on emotional development, particularly depression and anxiety, which have been assessed at multiple levels of analysis (symptoms, cognitions, and relevant environmental experiences). G1219 has also included assessment of a broader range of psychological phenotypes ranging from antisocial behaviors and substance use to sleep difficulties, in addition to multiple aspects of the environment. DNA has also been collected. The first wave of data collection began in the year 1999 and the fifth wave of data collection will be complete before the end of 2012. In this article, we describe the sample, data collection, and measures used. We also summarize some of the key findings to date.

Most studies on lung function heritability have been conducted in smokers and non-smokers using cross-sectional study design. Smoking patterns may, however, confound the contribution of genetic factors. We investigated heritability of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio longitudinally, excluding the effects of smoking. A sample of never smoking female twins (n = 374), aged 63–76 at baseline, answered health questionnaires and attended spirometry in years 2000 and 2003. Bivariate structural equation modeling, restricted to adequate spirometry performances (baseline n = 339, follow-up n = 252), was used to estimate genetic and environmental influences on consecutive measurements of FEV1, FVC, and FEV1/FVC. The best-fitting models included additive genetic and non-shared environmental effects. Heritability estimates of 32% and 36% for FEV1, 41% and 37% for FVC, while 46% and 16% for FEV1/FVC were found at baseline and at follow-up. Genetic correlation between FEV1 and FEV1/FVC heritability estimates approached unity, whereas correlation between FVC estimates was 0.80. Environmental correlations were 0.69 for FEV1, 0.62 for FVC, and 0.07 for FEV1/FVC. In never smokers, additive genetic and non-shared environmental effects explain the inter-individual variations in FEV1, FVC, and FEV1/FVC. One third of the variation in FEV1 and FVC is explained by genetic and two thirds by environmental effects. Between 2000 and 2003, environmental effects on FEV1/FVC changed, and the proportion of variance explained by environmental effects increased remarkably. Genetic effects on FEV1 and FEV1/FVC are common to consecutive measurements, whereas at follow-up, new genetic factors explained 14% of the observed variance in FVC.

Since our last report on the voluntary Hungarian Twin Registry (HTR) in 2012, the number of pairs or multiplets included increased from 310 to 1044. Efforts to turn the registry into a population-based one are on the way. Nearly 128,000 twins living in Hungary (98,500 adults) will be mailed information on how to register on the new HTR website. Twins will be asked to invite their spouses and immediate family members. Meanwhile, strong cooperation through exchange programs has been developed with other foreign twin registries. Current research focuses on radiogenomics, musculoskeletal, cardiovascular and respiratory diseases, gut microbiome as well as basic molecular research and yielded new awards and further publications.

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.

People differ markedly in their risk for developing posttraumatic stress symptoms (PTSS) after exposure to traumatic events. Twin studies suggest that the trauma-PTSS relationship is moderated by genetic and environmental influences. The present study tested for specific types of genetic and environmental interaction effects on PTSS. A sample of 222 monozygotic and 184 dizygotic twin pairs reported on lifetime frequency of assaultive and nonassaultive trauma and associated PTSS. Biometric analyses indicated that in the case of nonassaultive trauma, PTSS were directly affected by environmental factors that also influence exposure to nonassaultive trauma. For assaultive trauma both genetic and non-shared environmental influences jointly affected PTSS, and the number of traumatic events moderated the severity of PTSS. Genetic factors were found to become less important beyond some threshold (e.g., 3 or 4 types of serious trauma) suggesting that genetic factors — which may confer either risk or resilience to PTSS — modify these symptoms within a range of human experience, beyond which environmental effects supervene.

Background: Twin pregnancies are at increased physiological and psychosocial risks. Objective: To investigate the prevalence of major depression in twin pregnancies and correlate with stress and social support. Method: The study included 51 pregnant women under specialized prenatal care who were evaluated by a Portuguese version of the semi-structured questionnaire Primary Care Evaluation of Mental Disorders (PRIME-MD) for Major Depression, and the Prenatal Psychosocial Profile (PPP) for evaluation of stress and social support. Results: Major depression was found in 33.3% of pregnant women, and prevailing symptoms were fatigue or loss of energy (100%), insomnia or hypersomnia (82.4%), changes in appetite (82.4%), decreased interest in daily activities (82.4%), and psychomotor agitation or retardation (82.4%). Among pregnant women who were diagnosed depressive, 76.5% also had a high level of stress and 47.1% complained about lack of social support. Statistical significance was found when correlating depression with perception of negative aspects of having twins and belief in significant body changes during pregnancy (p = .005 and .03, respectively). Marital status, occupation, and pregnancy planning were not significantly associated with the diagnosis of depression. Conclusion: Major depression occurs in one-third of pregnant women expecting twins and is associated with higher levels of stress and lack of social support. A multidisciplinary approach in these cases is fundamental to minimize further risks and complications.

The Yoruba are an important ethnic group mainly occupying Southwestern Nigeria. Mainly for genetic reasons, this very large tribe happens to present the highest dizygotic twinning rate in the world (4.4 % of all maternities). The high perinatal mortality rate associated with such pregnancies has contributed to the integration of a special twin belief system within the African traditional religion of this tribe. The latter is based on the concept of a supreme deity called Olodumare or Olorun, assisted by a series of secondary gods (Orisha) while Yoruba religion also involves immortality and reincarnation of the soul based on the animistic cult of ancestors. Twins are therefore given special names and believed to detain special preternatural powers. In keeping with their refined artistic tradition, the Yoruba have produced numerous wooden statuettes called Ibejis that represent the souls of deceased newborn twins and are involved in elaborate rituals. Among Yoruba traditional beliefs and lore some twin-related themes are represented which are also found in other parts of the world. Basic features of the original Yoruba beliefs have found their way into the religious traditions of descendants of African slaves imported in the West Indies and in South America.

We examined the genetic architecture of functional brain connectivity measures in resting state electroencephalographic (EEG) recordings. Previous studies in Dutch twins have suggested that genetic factors are a main source of variance in functional brain connectivity derived from EEG recordings. In addition, qualitative descriptors of the brain network derived from graph analysis — network clustering and average path length — are also heritable traits. Here we replicated previous findings for connectivity, quantified by the synchronization likelihood, and the graph theoretical parameters cluster coefficient and path length in an Australian sample of 16-year-old twins (879) and their siblings (93). Modeling of monozygotic and dizygotic twins and sibling resemblance indicated heritability estimates of the synchronization likelihood (27–74%) and cluster coefficient and path length in the alpha and theta band (40–44% and 23–40% respectively) and path length in the beta band frequency (41%). This corroborates synchronization likelihood and its graph theoretical derivatives cluster coefficient and path length as potential endophenotypes for behavioral traits and neurological disorders.

The possibility of genotype–environment interaction for memory performance and change was examined in 150 monozygotic (MZ) twin pairs from the Swedish Adoption Twin Study of Aging (SATSA). We used an MZ twin pair difference approach to examine the possibility that genotype was associated with intrapair variability and thus suggestive of genotype–nonshared environment interactions. Multiple ‘variability genes’ were found for longitudinal change in a semantic memory task including candidates coding for apolipoprotein E (APOE) and estrogen receptor alpha (ESR1) as well as serotonin candidates (HTR2A and 5HTT). One candidate also related to variability in change in episodic memory (5HTT). Of the significant associations observed, generally results indicated that MZ pairs who carry putative risk alleles were less variable than noncarriers, suggesting that noncarriers may be more sensitive to environmental contexts. We sought to ‘contextualize’ the possible nonshared environmental influences for found gene–environment (G × E) effects by considering intrapair differences in measured social and stress factors, including social support, life events and depressive symptoms. Results suggested that nonshared environmental influences associated with depressive symptoms may moderate the G × E relationship observed for ESR1 and APOE and longitudinal semantic memory change whereby noncarriers of putative risk alleles may be relatively more sensitive to depressionevoking environmental contexts than carriers of the risk allele. Thus, the contexts that facilitate or reduce depressive symptoms may affect semantic memory resiliency dependent on genotype. Further work ought to consider larger sample sizes as well as consider additional social and contextual factors.

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.

The East Flanders Prospective Twin Survey (EFPTS), started in 1964, is unique among the 17 major European twin registers because it is population based, the twins (and higher order births) are ascertained at birth, basic perinatal data are collected, chorion type is established and, when appropriate, genetic markers including DNA fingerprints, are determined. The total number of sets is 5089 twin, 158 triplet and 14 of higher order. Zygosity has been diagnosed on the basis of sex, placental structure and genetic markers in more than 95% of pairs. The EFPTS is the only large register that includes placental data and allows differentiation of three subtypes of monozygotic twins based on the time of the initial zygotic division: the dichorionic—diamnionic pairs (early), the monochorionic—diamnionic pairs (intermediate), and the monochorionic—monoamnionic pairs (late). Methodology and basic results in twins are considered in this article; detailed studies will be reported later. The sex proportion in dizygotic (DZ) twins is the same as in singletons, whereas monozygotic (MZ) twins number more girls than boys. The difference in perinatal mortality between DZ and MZ twins is limited to the monochorionic MZ subgroup. Birth weight is highest in DZ twins and diminishes stepwise in MZ dichorionic and MZ monochorionic twins. Duration of pregnancy follows the same trend but is limited to a few days. Iatrogenic pregnancies are increasing to the point of representing almost 50% of the twin births in 1997.

The study endeavored to assess the epidemiology, postnatal survival, and growth pattern of multiple births in Sub-Saharan Africa (SSA). It was based on the data of 25 demographic health surveys conducted in the subcontinent since 2008. The records of 213,889 children born in the preceding 59 months of the surveys were included. The multiple birth rate was computed as the number of multiple confinements per 1,000 births. Factors associated with multiple births were identified using logistic regression and their survival pattern was assessed using the Kaplan–Meier method. The multiple birth rate was 17.1 (95% confidence interval: 17.7–16.6) and showed considerable variation across the 25 countries included in the study. Odds of multiple births were significantly increased with advanced maternal age, parity, and maternal height but not with wealth index, age at first birth, and month of birth. At the end of the fourth year of age, the cumulative survival probability was as low as 0.77 in multiple births as compared to 0.93 in their counterparts. The odds of neonatal, infant and under-five mortality were 5.55, 4.39, and 3.72 times increased in multiple births, respectively. Multiple births tend to be malnourished than singletons and the odds of wasting, stunting, and underweight were 1.31, 1.83, and 1.73 times raised, consecutively. Nevertheless, multiple births regain their weight-for-age (WFA) and height-for-age (HFA) deficits by the end of the fourth year of age. Counseling pregnant mothers with multiple gestation to give birth at a health institution and providing close medical follow-up during and after the neonatal period can improve the survival of multiple births.