Obesity is associated with blood pressure (BP), but the associations between different obesity indicators and BP have not reached agreement. Besides, both obesity and BP are influenced by genetic and environmental factors. Whether they share the same genetic or environmental etiology has not been fully understood. We therefore analyzed the relationship between different obesity indicators and BP components as well as the genetic and environmental contributions to these relationships in a Chinese adult twin sample. Twins aged 18–79 years (n = 941) were included in this study. Body mass index (BMI) was used as the index of general obesity, whereas waist circumference (WC), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR) were used as the indicators of central obesity. BP components included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Linear regression models and bivariate structural equation models were used to examine the relation of various obesity indicators with BP components, and genetic or environmental influences on these associations, respectively. A strong association of BP components with BMI—and a somewhat weaker association with WC, WHtR, and WHR—was found in both sexes, independent of familial factors. Of these phenotypic correlations between obesity indicators and BP components, 60–76% were attributed to genetic factors, whereas 24–40% were attributed to unique environmental factors. General obesity was most strongly associated with high BP in Chinese adult twins. There were common genetic backgrounds for obesity and BP, and unique environmental factors also played a role.

This study was designed to evaluate the degree of placenta share discordance in relation to the betamethasone-induced return of positive end-diastolic flow in monochorionic twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery Doppler. Monochorionic twins with sIUGR was defined as one twin having an estimated fetal weight below the 10th percentile combined with an estimated fetal weight discordance >25%. The umbilical artery Doppler directly prior to (D0) and 24 hours (D1) and 48 hours (D2) after the first dose of betamethasone administration was recorded. The estimated individual placental weight in monochorionic twins was obtained by cutting the placenta along the vascular equator into two territories; the placenta share discordance was calculated as [(estimated individual placental weight of appropriated for gestational age twin- estimated individual placental weight of growth restricted twin)/estimated individual placental weight of appropriated for gestational age twin] × 100%. Six (23.1%) of the 26 included cases achieved betamethasone-induced return of positive umbilical artery end-diastolic flow. The difference of placenta share discordance and birth weight discordance were not significantly different between twins with and without betamethasone-induced return of positive umbilical artery end-diastolic flow. Thus, according to our study results, it was proposed that although the placenta share discordance correlated with the abnormal umbilical artery Doppler in the IUGR fetus in monochorionic twin, the betamethasone-induced return of positive umbilical artery end-diastolic flow, however, did not reveal the similar relationship with the severity of placenta share discordance.

Major depression is a complex disorder with no single, direct causal mechanism. Morbidity has been linked to genetic processes, developmental history, and unique environmental exposures. Epigenetic mechanisms, especially DNA methylation, are also likely important factors in the pathogenesis of major depressive disorder (MDD). A community-based twin sample has many advantages for epigenetic studies, given the shared genetic and developmental histories of same-sex twin pairs. This article describes the rationale and study design for the Mood and Methylation Study in which 133 twin pairs (101 monozygotic and 32 dizygotic), both discordant and concordant for lifetime history of MDD, were evaluated on a large number of variables related to MDD. The twins also provided blood samples for an epigenome-wide association study of differentially methylated regions (DMR) relevant to MDD. Although MDD is typically considered a disorder of the central nervous system, it is unfeasible to obtain a large sample of brain tissues. However, epigenetic variation is not limited to the affected tissue but can also be detected in peripheral blood leukocytes. Thus, this study focused on monocytes for the major analyses. Additional plans for the study include gene expression analysis from the same set of twins using RNA-seq and validation of significant DMRs in postmortem brain tissues from a separate sample. Moreover, sufficient samples have been collected to perform future ‘multi-omic’ analyses, including metabolome, microbiome, and transcriptome. Our long-term goal is to understand how epigenomic and other ‘omic’ factors can be manipulated for diagnostic, preventive, and therapeutic purposes for MDD and its related conditions.

In order to estimate the influence of genetic and environmental factors on ‘crying without a cause’ and ‘being easily upset’ in 2-year-old children, a large twin study was carried out. Prospective data were available for ~18,000 2-year-old twin pairs from the Netherlands Twin Register. A bivariate genetic analysis was performed using structural equation modeling in the Mx software package. The influence of maternal personality characteristics and demographic and lifestyle factors was tested to identify specific risk factors that may underlie the shared environment of twins. Furthermore, it was tested whether crying without a cause and being easily upset were predictive of later internalizing, externalizing and attention problems. Crying without a cause yielded a heritability estimate of 60% in boys and girls. For easily upset, the heritability was estimated at 43% in boys and 31% in girls. The variance explained by shared environment varied between 35% and 63%. The correlation between crying without a cause and easily upset (r = .36) was explained both by genetic and shared environmental factors. Birth cohort, gestational age, socioeconomic status, parental age, parental smoking behavior and alcohol use during pregnancy did not explain the shared environmental component. Neuroticism of the mother explained a small proportion of the additive genetic, but not of the shared environmental effects for easily upset. Crying without a cause and being easily upset at age 2 were predictive of internalizing, externalizing and attention problems at age 7, with effect sizes of .28–.42. A large influence of shared environmental factors on crying without a cause and easily upset was detected. Although these effects could be specific to these items, we could not explain them by personality characteristics of the mother or by demographic and lifestyle factors, and we recognize that these effects may reflect other maternal characteristics. A substantial influence of genetic factors was found for the two items, which are predictive of later behavioral problems.

The relationship between self-report abilities and measured intelligence was examined at both the phenotypic (zero-order) level as well as at the genetic and environmental levels. Twins and siblings (N = 516) completed a timed intelligence test and a self-report ability questionnaire, which has previously been found to produce 10 factors, including: politics, interpersonal relationships, practical tasks, intellectual pursuits, academic skills, entrepreneur/business, domestic skills, vocal abilities, and creativity. At the phenotypic level, the correlations between the ability factor scores and intelligence ranged from 0.01 to 0.42 (between self-report academic abilities and verbal intelligence). Further analyses found that some of the phenotypic relationships between self-report ability scores and measured intelligence also had significant correlations at the genetic and environmental levels, suggesting that some of the observed relationships may be due to common genetic and/or environmental factors.

The Russian School Twin Registry (RSTR) was established in 2012, supported by a grant from the Government of the Russian Federation. The main aim of the registry is to contribute to Progress in Education through Gene-Environment Studies (PROGRESS). The formation of the registry is ongoing and it is expected that most schools in the Russian Federation (approximately 50,000 schools) will contribute data to the registry. With a total of 13.7 million students in Grades 1–11 (ages 7–18), the potential number of twin pairs exceeds 100,000. Apart from the large sample size and its representative nature, the RSTR has one unique feature: in collaboration with the International Advisory Committee to the Registry, genetically sensitive cross-cultural investigations are planned, aided by the use of the common assessment instruments. Other strengths of the registry include the assessment of a large sample of non-twin school children, including those studying in the same classes as the twins in the registry. It is hoped that the RSTR will provide an important research platform for national and international educationally relevant research.

A threefold increase for testicular carcinoma has been reported in male dizygotic twins. In this comment we suggest the hypothesis that over-exposure to endogenously hypersecreted Follicle Stimulating Hormone (FSH) may underlie the pathogenesis. This is supported by several findings. 1) FSH hypersecretion in mothers of dizygotic twins is most likely an autosomal trait implicating the possibility of male offspring with the same hormone characteristic. 2) In testicular carcinoma higher levels of cyclin D2 are found. This is an FSH dependent stimulatory regulator of mitosis. 3) There is a marked similarity between geographical distribution in occurence of dizygotic twinning and testicular carcinoma. 4) Men undergoing surgery for testicular carcinoma have higher FSH concentrations and males with Down syndrome have higher FSH levels and are more at risk to develop testicular carcinoma. We suggest to study FSH secretion in males of familial dizygotic twins and furthermore the risk of developing testicular carcinoma in males with elevated FSH. These men with one testicle and/or with dysfunctioning Sertoli/Leydig cells.

The objective of this study was to compare length of gestation, fetal growth, and birthweight by race/ethnicity and pregravid weight groups in twin pregnancies. Three thousand and thirty-six twin pregnancies of 28 weeks or more gestation were divided by race/ethnicity (White, Black and Hispanic), and pregravid body mass index (BMI) groups (less than 25.0 vs. 25.0 or more). Outcomes were modeled using multiple regression, controlling for confounders, with White non-Hispanic women as the reference group. Hispanic women had the highest average birthweight and the longest gestation, as well as the lowest proportions of low birthweight, very low birthweight, preterm and early preterm births of the 3 race/ethnicity groups. In the multivariate analyses, Hispanic women had significantly longer gestations (by 7.8 days) and faster rates of fetal growth midgestation (20 to 28 weeks, by 17.4 g/week) and late gestation (after 28 weeks, by 5.3 g/week), whereas Black women had significantly slower rates of fetal growth (by 5.7 g/week and by 4.5 g/week, respectively). These findings in twins reflect the racial and ethnic disparities previously shown in singletons, including the Hispanic paradox of longer gestations and higher rates of fetal growth.

Studies have reported that refractive errors are associated with premature births. As twins have higher prevalence of prematurity than singletons, it is important to assess similarity of the prevalence of refractive errors in twins and singletons for proper interpretations and generalizations of the findings from twin studies. We compared refractive errors and diopter hours between 561 pairs of twins and 3757 singletons who are representative of school-age children (7–15 years) residing in an urban area of southern China. We found that the means and variances of the continuous measurement of spherical equivalent refractive error and diopter hours were not significantly different between twins and singletons. Although the prevalence of myopia was comparable between twins and singletons, that of hyperopia and astigmatism was slightly but significantly higher in twins than in singletons. These results are inconsistent with those of adult studies that showed no differences in refractive errors between twins and singletons. Given that the sample size of twins is relatively small and that this study is the first to demonstrate minor differences in refractive errors between twins and singletons, future replications are necessary to determine whether the slightly higher prevalence of refractive errors in twins than in singletons found in this study was due to a sampling error or to the developmental delay often observed in twins in childhood.

Purpose: To further understand genetic factors that contribute to congenital cataracts, we sought to identify early post-twinning mutational and epigenetic events that may account for the discordant phenotypes of a twin pair. Methods: A patient with a congenital cataract and her twin sister were assessed for genetic factors that might contribute to their discordant phenotypes by mutation screening of 11 candidate genes (CRYGC, CRYGD, CRYAA, CRYAB, CRYBA1, CRYBB1, CRYBB2, MIP, HSF4, GJA3, and GJA8), exome analysis followed by Sanger sequencing of 10 additional candidate genes (PLEKHO2, FRYL, RBP3, P2RX2, GSR, TRAM1, VEGFA, NARS2, CADPS, and TEKT4), and promoter methylation analysis of five representative genes (TRAM1, CRYAA, HSF4, VEGFA, GJA3, DCT) plus one additional candidate gene (FTL). Results: Mutation screening revealed no gene mutation differences between the patient and her twin sister for the 11 candidate genes. Exome sequencing analysis revealed variations between the twins in 442 genes, 10 of which are expressed in the eye. However, these differential variants could not be confirmed by Sanger sequencing. Furthermore, epigenetic discordance was not detected in the twin pair. Conclusions: The genomic DNA mutational and epigenetic events assessed in this study could not explain the discordance in the development of phenotypic differences between the twin pair, suggesting the possible involvement of somatic mutations or environmental factors. Identification of possible causes requires further research.

Deciphering the relative importance of genetic and environmental factors, which play a major role in the prevalence of early childhood caries (ECC), can help clinicians with planning a long-term preventive treatment. The objective of the study was to determine the prevalence and heritability of ECC among monozygotic (MZ) and dizygotic (DZ) twins in Chennai, India, in the year 2013. A cross-sectional study was designed to estimate the prevalence of ECC among twins. Zygosity classification for the survey framework was adapted from a highly accurate parental report questionnaire pertaining to the physical similarity between twins. The associated heritability index was estimated. The Decayed, Missing, Filled Surface (DMFS) Index was used as the diagnostic criterion for dental caries. The prevalence of ECC was estimated at 18.7%. The correlation coefficient between the twin pair showed significant correlation. The heritability index for ECC was estimated at 15% higher prevalence of ECC found among children in the age group 25–36 months. The heritability estimate indicated a relatively low genetic influence for early childhood caries among twins. There was no significant difference detected in the concordance rate for the MZ and DZ twins. Further research could be directed toward the prevalence of ECC among higher age group children to explore the role of genetic and environmental factors.

The Louisville Twin Study (LTS) is nationally recognized as one of the largest and most comprehensive studies of child development related to multiple birth status. The LTS is unique because of the extensive longitudinal face-to-face assessments, the frequency of data collection, the inclusion of data on additional family members (i.e., parents, siblings, grandparents; and later, twins’ own spouses and children), and the variety of data collection methods used. Data preservation efforts began in 2008 and are largely complete, although efforts are ongoing to obtain funding to convert the electronic data to a newer format. A pilot study was completed in the summer of 2018 to bring the twins, who are now middle-aged, back for testing. A grant is currently under review to extend the pilot study to include all former participants who are now ≥40 years of age. Opportunities for collaboration are welcome.

The phenomenon of paternally dependent familial twinning has been known in human and animal genetics since the 1920s, but still remains without any theoretical explanation and is indeed a neglected field of inquiry. Over the last two decades investigations in reproduction biology have discovered the significant role of multiple paternally dependent errors in fertilization including androgenic triploidy and moles. We suggest the hypothesis that the fathers of twins in the relevant families carry gene variants that increase the probability of dispermy, diplospermy and male pronucleus heterochrony as well as involvement of two male pronuclei in the fertilization of two female meiotic products. Any resulting twins would be an exceptional intermediate between MZ and DZ twins — and might properly be described as “sesquizygotic” (SZ). Paternal familial twinning may also go together with infertility due to triploidy, moles and chimerism. The hypothesis: (i) places the curiosities of paternally derived twinning within the framework of current knowledge of reproductive genetics and verifiable phenomena; (ii) predicts the existence of families in which twinning is associated with reproductive abnormalities; (iii) predicts an occurrence in relevant families of the third and intermediate category of SZ twins. Families with paternal twinning may thus provide the natural selective system for the search of unusual cases of primary chimeras, the frequency of which is still unknown.

Objective: The incidence of preterm delivery has been increasing, and our aim was to estimate the influence of fetal sex on the risk of preterm delivery in dichorionic twins after spontaneous conception. Methods: 125 spontaneously conceived dichorionic twin gestations, with viable fetuses, born after 24 weeks and delivered spontaneously before 37 weeks, were enrolled. The impact of fetal sex, previous preterm delivery, maternal age, body-mass-index, smoking, and parity on gestational age at birth were evaluated. Results: Despite similar baseline characteristics in all three groups, women with one or two male fetuses delivered significantly more often before 34 weeks than patients with two female fetuses, 48% (23/48) and 43% (19/44) vs 21% (7/33), p = .04. Regression analyses, including fetal sex, maternal age, maternal body-mass-index, smoking, previous preterm delivery and parity, revealed that only fetal sex was significantly associated with spontaneous preterm delivery (p = .03). Conclusion: Fetal sex appears to be a risk factor for preterm delivery in spontaneously conceived dichorionic twin gestations. Twin pregnancies with one or two male fetuses seem to be at higher risk for spontaneous preterm delivery than those with only females.

This study aimed to examine differences in multiple maternities by neighborhood-income levels in Toronto, Canada. Hospital records were used to perform secondary analysis of 144,731 maternities resulting in single or multiple infants live-born to mothers residing in the City of Toronto 1996 to 2001. The independent variable was neighborhood income, defined as mean household neighborhoodincome quintiles. Multiple logistic regression analysis was used to compute adjusted odds ratios (AORs) and 95% confidence intervals (CIs). Differences by income levels were found in twin maternities but not in higher order maternities. Twin maternities were more likely to occur in the richest neighborhood-income quintile compared to the rest of the population (AOR: 1.25, 95% CI: 1.10-1.41), after adjustment for potential confounders. The positive association between high neighborhood income and twin maternities found in this study suggests that the richest neighborhoods select families whose characteristics pose them at increased risk of having twins. Further studies are needed to clarify the underlying mechanisms leading to socioeconomic differences in multiple births.

Twinning rates have changed substantially over time for reasons that are only partly known. In this study we studied smoking, coffee and alcohol intake, and their possible interaction with obesity as potential determinants of twinning rates using data from the Danish National Birth Cohort between 1996 and 2002. We identified 82,985 pregnancies: 81,954 singleton and 1031 twins. For the twins we had data to classify 121 as monozygotic, 189 dizygotic (same sex), 313 dizygotic (opposite sex) but, 408 were of the same sex but with unknown zygosity. All mothers were interviewed about their prepregnancy weight and height, coffee and alcohol intake, smoking habits, and potential confounding factors at early stages of pregnancy. We identified smoking (> 10 cigarettes/day) as a possible determinant of twinning, particularly for dizygotic twinning rates (same sex) and furthermore corroborated that obesity and the mother's age are strong correlates of twinning. Others have found coffee intake to increase twinning rates but that is not seen in these data.

A twin design was used to examine the developmental nature of genetic, environmental, and phenotypic variations in hyperactivity and inattention problems (HIP). Mothers of 662 complete pairs of twins (273 monozygotic [MZ] pairs and 389 dizygotic [DZ] pairs) aged from 3 to 13 years (mean [SD] age = 8.3 [2.9] years) responded to the items of the HIP scale of the Strengths and Difficulties questionnaire via a telephone interview. Maximum likelihood MZ and DZ twin correlations in the total sample were 0.47 (95% CI: 0.37–0.55) and −0.01 (95% CI: −0.11–0.09). A standard univariate model incorporating age as a modifier was applied to the raw data. Results of model-fitting analyses showed that the phenotypic variation of HIP monotonically increased from age 3 to age 12 and that this increase was completely due to an increase in genetic variance, suggesting that it is genes that expand individual difference in ADHD symptoms with age during childhood. Child-specific environmental variance was constant during this age period. In terms of relative influences, total genetic factors increased from 33% (95% CI: 27–44%) at age 3 to 51% (95% CI: 28–71%) at age 13 and this increase was accompanied by a decrease in relative influences of child-specific environmental factors from 67% (95% CI: 56–73%) at age 3 to 49% (95% CI: 29–72%) at age 13. These estimates of genetic influences were somewhat lower than those found in most twin studies of ADHD symptoms. However, the increasing trend of genetic influences with age during childhood was consistent with the results of a recent meta-analysis of ADHD symptoms.

Objective: The aim of this study was to compare the neurodevelopmental outcome at 12–18 months’ corrected age between multiples and singleton preterm infants. Methods: We designed a prospective study of preterm infants (≤32 weeks gestation) born and hospitalized in the neonatal intensive care unit between November 2008 and November 2009, whose assessments were performed at 12–18 months’ corrected age. Neurodevelopmental impairment was defined as the presence of any one of the following: moderate or severe cerebral palsy, severe bilateral hearing loss or bilateral blindness, mental developmental index score, or psychomotor developmental index score less than 70. Results were compared for both multiples and singleton infants. Results: One hundred and fifty-nine multiples and 211 singleton infants were assessed at 12–18 months’ corrected age. The neurodevelopmental outcome including all parameters at 12–18 months’ corrected age in multiples was not significantly different from singleton preterm infants. Conclusions: Multiple gestation in preterm infants is not associated with an increased risk of neurodevelopmental impairment at 12–18 months’ corrected age compared with singleton preterm infants. For further information, long term and high participation in neurodevelopmental follow-up and evaluation at pre-school age will be needed.

Diseases of the myoneural junction and muscle are disabling and some are life-threatening. Recent successes in the identification of the underlying genetic mechanisms have had profound implication for their diagnostics, treatment and classification. We define familial risks for siblings who were hospitalized for or deceased from diseases of the myoneural junction and muscle. A nationwide database on diseases of the myoneural junction and muscle was constructed by linking the Multigeneration Register on 0- to 69-year-old siblings to the Hospital Discharge Register and the Causes of Death Register from years 1987 to 2001. Standardized risk ratios (SIRs) were calculated for affected sibling pairs by comparing to those whose siblings had no diseases of myoneural junction and muscle. Among a total of 2307 patients, myasthenia gravis, muscular dystrophy and myotonic disorders were commonest diagnoses. The sibling risks for these disease were 22, 190 and 198, respectively, when a sibling was diagnosed with any disease of the myoneural junction and muscle. The concordant SIRs, both siblings presenting the same disease, were 42 for myasthenia gravis, 737 for muscular dystrophy, 2000 for congenital myopathy, 1211 for myotonic disorder, 909 for periodic paralysis and 209 for unspecified myopathy. Only a few discordant sibling pairs were noted. The very high overall SIRs for the diseases of the myoneural junction and muscle imply that the sporadic forms of these diseases are relatively rare and these diseases are overwhelmingly heritable.

Questionnaire-based dimensional measures are often employed in epidemiological studies to predict the presence of psychiatric disorders. The present study sought to determine how accurately 4 dimensional mental health measures, the 12-item General Health Questionnaire (GHQ-12), Neuroticism (EPQ-N), the high positive affect and anxious arousal scales from the Mood and Anxiety Symptoms Questionnaire (MASQ-HPA and MASQ-AA) and a composite of all 4, predicted psychiatric caseness as diagnosed by the University of Michigan Composite International Diagnostic Interview (UM-CIDI). Community subjects were recruited through general practitioners; those who agreed to participate were sent a questionnaire containing the above measures. Subsequently, the UM-CIDI was administered by telephone to 469 subjects consisting of sibling pairs who scored most discordantly or concordantly on a composite index of the 4 measures. Logistic Regression and Receiver Operating Characteristic (ROC) curve analyses were carried out to assess the predictive accuracy of the dimensional measures on UM-CIDI diagnosis. A total of 179 subjects, 62 men and 117 women with an average age of 42 years, were diagnosed with at least one of the following psychiatric disorders: depression, dysthymia, generalized anxiety disorder (GAD), social phobia, agoraphobia and panic attack. The six disorders showed high comorbidity. EPQ-N and the Composite Index were found to be very strong and accurate predictors of psychiatric caseness; they were however unable to differentiate between specific disorders. The results from the present study therefore validated the four mental health measures as being predictive of psychiatric caseness.