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The objective of this study was to comprehensively assess fetal hemodynamic adaptions to occlusive procedures. Twin pregnancies complicated with acardiac twin and hydrops fetalis of the pump twin were recruited. The occlusive procedures - either alcoholization, radiofrequency ablation, coil embolization or occlusive glue - were performed under ultrasound guidance. Various hemodynamic parameters were assessed before, shortly after, then every 6 h for 48 h and 2-4 weeks after the procedures. Seven pregnancies were recruited. The median (range) gestational age of intervention was 21 (17-26) weeks of gestation. Before the procedures, all cases showed normal cardiac function. Just after the procedures, all cases showed an increase in Tei index and isovolumic relaxation time but returned to preocclusion levels within 6-48 h, except for two cases that were persistently high. Increased preload and poor shortening fraction were observed in two cases, leading to heart failure, with one recovery and one death in utero. Five out of the seven cases got through the critical period with a gradual return to normal hemodynamics, ending with the disappearance of hydrops and successful outcomes. It was concluded that the occlusive procedure could aggravate the overworked heart, leading to heart failure. Preocclusion preload index and Tei index may predict risk of heart failure due to the occlusion. This small series strongly suggests that the occlusion should be performed before the deterioration of cardiac function. [ABSTRACT FROM AUTHOR]

Twin studies can help us understand the relative contributions of genes and environment to phenotypic trait variation, including attentional and brain activation measures. In terms of applying methodologies such as electroencephalography (EEG) and eye tracking, which are key methods in developmental neuroscience, infant twin studies are almost nonexistent. Here, we describe the Babytwins Study Sweden (BATSS), a multi-method longitudinal twin study of 177 MZ and 134 DZ twin pairs (i.e., 622 individual infants) covering the 5-36 month time period. The study includes EEG, eye tracking and genetics, together with more traditional measures based on in-person testing, direct observation and questionnaires. The results show that interest in participation in research among twin parents is high, despite the comprehensive protocol. DNA analysis from saliva samples was possible in virtually all participants, allowing for both zygosity confirmation and polygenic score analyses. Combining a longitudinal twin design with advanced technologies in developmental cognitive neuroscience and genomics, BATSS represents a new approach in infancy research, which we hope to have impact across multiple disciplines in the coming years. [ABSTRACT FROM AUTHOR]

The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1-2 years), preschool (3-5 years), primary or elementary school (6-11 years), and adolescence (10-18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0-18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC. [ABSTRACT FROM AUTHOR]

Strong associations between neural tube defects (NTDs) and monozygotic (MZ) twinning have long been noted, and it has been suggested that NTD cases who do not present as MZ twins may be the survivors of MZ twinning events. We have recently shown that MZ twins carry a strong, distinctive DNA methylation signature and have developed an algorithm based on genomewide DNA methylation array data that distinguishes MZ twins from dizygotic twins and other relatives at well above chance level. We have applied this algorithm to published methylation data from five fetal tissues (placental chorionic villi, kidney, spinal cord, brain and muscle) collected from spina bifida cases (n = 22), anencephalic cases (n = 15) and controls (n = 19). We see no difference in signature between cases and controls, providing no support for a common etiological role of MZ twinning in NTDs. The strong associations therefore continue to await elucidation. [ABSTRACT FROM AUTHOR]

Accurate zygosity determination is a fundamental step in twin research. Although DNA-based testing is the gold standard for determining zygosity, collecting biological samples is not feasible in all research settings or all families. Previous work has demonstrated the feasibility of zygosity estimation based on questionnaire (physical similarity) data in older twins, but the extent to which this is also a reliable approach in infancy is less well established. Here, we report the accuracy of different questionnaire-based zygosity determination approaches (traditional and machine learning) in 5.5 month-old twins. The participant cohort comprised 284 infant twin pairs (128 dizygotic and 156 monozygotic) who participated in the Babytwins Study Sweden (BATSS). Manual scoring based on an established technique validated in older twins accurately predicted 90.49% of the zygosities with a sensitivity of 91.65% and specificity of 89.06%. The machine learning approach improved the prediction accuracy to 93.10%, with a sensitivity of 91.30% and specificity of 94.29%. Additionally, we quantified the systematic impact of zygosity misclassification on estimates of genetic and environmental influences using simulation-based sensitivity analysis on a separate data set to show the implication of our machine learning accuracy gain. In conclusion, our study demonstrates the feasibility of determining zygosity in very young infant twins using a questionnaire with four items and builds a scalable machine learning model with better metrics, thus a viable alternative to DNA tests in large-scale infant twin studies. [ABSTRACT FROM AUTHOR]

Selective termination is the term used for the elimination of an abnormal fetus. In contrast, multifetal pregnancy reduction refers to the termination of one or more members of a twin or higher-order multiple birth set, respectively, to reduce the high risks associated with these pregnancies. The procedure can also be used when a serious physical condition is detected prenatally in a member of a multiple birth set. In a minority of cases, selective termination has reduced two healthy fetuses to one when parents wanted just one additional child in the family. In the present article, the perspectives of a surviving twin whose family wished to terminate both healthy fetuses are examined. Next, past and present twin studies of primordial dwarfism, public service motivation, an analytical model, the global twinning rate and germline differences are summarized. The article concludes with a synopsis of twin-related news that covers twins and Dyngus Day, triplets born in an Austrian displaced persons' camp, the film Superior - about estranged identical twin sisters, a couple adopting their own twins after surrogacy and a new case of twins and primordial dwarfism, a condition introduced in the research reviews. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the genetic and environmental etiology of the association between childhood negative emotionality (NE) and hyperactivity/inattention problems (HIP) using South Korean elementary school twins (mean age = 10.19 years, SD = 1.79 years). Telephone interviews were given to mothers of 919 twins (229 monozygotic males: 112 pairs and 5 individuals; 148 dizygotic males: 73 pairs and 2 individuals; 180 monozygotic females: 87 pairs and 6 individuals; 103 dizygotic females: 50 pairs and 3 individuals; 259 opposite-sex dizygotic twins: 127 pairs and 5 individuals) to assess their children's NE and HIP. Consistent with prior studies, the phenotypic correlation between NE and the HIP was moderate (r = .29; 95% CI = .24, .34). Model-fitting analysis revealed that additive genetic and nonshared environmental influences on NE were .45 (95% CI [.34, .54]) and .55 (95% CI [.46, .66]), respectively, and that additive and nonadditive genetic, and nonshared environmental influences on HIP were .08 (95% CI [.03, .26]), .41 (95% CI [.21, .51]) and .51 (95% CI = .42, .61), respectively. In addition, the additive genetic correlation between NE and HIP was 1.0 (95% CI [.52, 1.00]), indicating that additive genetic factors are entirely shared between the two phenotypes. Nonadditive genetic influences were unique to HIP and not responsible for the NE-HIP association. Nonshared environmental correlation was significant but modest (re = .18, 95% CI [.06, .30]). [ABSTRACT FROM AUTHOR]

The objective of this study was to analyze differences in birth weight and overweight/obesity in a Shanghai twin cohort. We also wanted to study their association and explore possible risk factors for the discordance of overweight/obesity within twins. This was an internal case-control study designed for twins. The 2012 Shanghai Twin Registration System baseline survey data of a total of 3417 twin pairs were statistically analyzed using SPSS22 software. Results show that the body mass index (BMI) of the Shanghai twin population increased with age. Twins with a high birth weight had a higher BMI and a higher rate of overweight and obesity; 0- to 6-year-old twins, male twins and dizygotic (DZ) twins had higher rates of overweight/obesity than other groups. The greater the discordant birth weight rate of twins, the more obvious the difference in BMI (p < .05). There was a significant difference in overweight/obesity between twins with a relative difference of birth weight ≥15% in DZ twins (p < .05). DZ twins, male twins and 0- to 6-year-old twins were more likely to be discordant in overweight/obese than others. The discordant birth weight within twins was not a risk factor for discordant overweight/obesity. However, attention should be paid to childhood obesity, and appropriate interventions should be made at the appropriate time. Genetics may play an important role in the occurrence and development of overweight/obesity. In conclusion, discordant growth and development in the uterus early in life may not lead to discordant weight development in the future. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate how different obesity measures link to circulating metabolites, and whether the connections are due to genetic or environmental factors. A cross-sectional analysis was performed on follow-up survey data at the Chinese National Twin Registry (CNTR), which was conducted in four areas of China (Shandong, Jiangsu, Zhejiang and Sichuan) in 2013. The survey collected detailed questionnaire information and conducted physical examinations, fasting blood sampling and untargeted metabolomic measurements among 439 adult twins. Linear regression models and bioinformatics analysis were used to examine the relation of obesity measures, including body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) with serum metabolite levels and related pathways. A co-twin control study was additionally conducted among 15 obesity-discordant monozygotic (MZ) pairs (intrapair BMI difference >3 kg/m2) to examine any differences in metabolites controlling for genetic factors. Eleven metabolites were associated with BMI, WC and WHR after controlling for genetic and shared environmental factors. Pathway analysis identified pathways such as phenylalanine metabolism, purine metabolism, valine, leucine and isoleucine biosynthesis that were associated with obesity. A wide range of unfavorable alterations in the serum metabolome was associated with obesity. Obesity-discordant twin analysis suggests that these associations are independent of genetic liability. [ABSTRACT FROM AUTHOR]

A healthy diet is associated with the improvement or maintenance of health parameters, and several indices have been proposed to assess diet quality comprehensively. Twin studies have found that some specific foods, nutrients and food patterns have a heritable component; however, the heritability of overall dietary intake has not yet been estimated. Here, we compute heritability estimates of the nine most common dietary indices utilized in nutritional epidemiology. We analyzed 2590 female twins from TwinsUK (653 monozygotic [MZ] and 642 dizygotic [DZ] pairs) who completed a 131-item food frequency questionnaire (FFQ). Heritability estimates were computed using structural equation models (SEM) adjusting for body mass index (BMI), smoking status, Index of Multiple Deprivation (IMD), physical activity, menopausal status, energy and alcohol intake. The AE model was the best-fitting model for most of the analyzed dietary scores (seven out of nine), with heritability estimates ranging from 10.1% (95% CI [.02, .18]) for the Dietary Reference Values (DRV) to 42.7% (95% CI [.36, .49]) for the Alternative Healthy Eating Index (A-HEI). The ACE model was the best-fitting model for the Healthy Diet Indicator (HDI) and Healthy Eating Index 2010 (HEI-2010) with heritability estimates of 5.4% (95% CI [-.17, .28]) and 25.4% (95% CI [.05, .46]), respectively. Here, we find that all analyzed dietary indices have a heritable component, suggesting that there is a genetic predisposition regulating what you eat. Future studies should explore genes underlying dietary indices to further understand the genetic disposition toward diet-related health parameters. [ABSTRACT FROM AUTHOR]

There is a commonly observed association between chronic disease and psychological distress, but many potential factors could confound this association. This study investigated the association using a powerful twin study design that can control for unmeasured confounders that are shared between twins, including genetic and environmental factors. We used twin-paired cross-sectional data from the Adult Health and Lifestyle Questionnaire collected by Twins Research Australia from 2014 to 2017. Linear regression models fitted using maximum likelihood estimations (MLE) were used to test the association between self-reported chronic disease status and psychological distress, measured by the Kessler Psychological Distress Scale (K6). When comparing between twin pairs, having any chronic disease was associated with a 1.29 increase in K6 (95% CI: 0.91, 1.66; p < .001). When comparing twins within a pair, having any chronic disease was associated with a 0.36 increase in K6 (95% CI: 0.002, 0.71; p = .049). This within-pair estimate is of most interest as comparing twins within a pair naturally controls for shared factors such as genes, age and shared lived experiences. Whereas the between-pair estimate does not. The weaker effect found within pairs tells us that genetic and environmental factors shared between twins confounds the relationship between chronic disease and psychological distress. This suggests that associations found in unrelated samples may show exaggerated estimates. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of folic acid (FA) supplementation with birth weight, the risk of small for gestational age (SGA) and low birth weight (LBW) in singleton and twin pregnancy.Design: A population-based cross-sectional survey.Setting: Twenty counties and ten districts in Shaanxi Province of northwestern China, 2013.Participants: 28 174 pregnant women with their infants, covering 27 818 single live births and 356 twin live births.Results: The prevalence of FA supplementation in singletons and twins was 63·9 and 66·3 %. The mean birth weight was 3267 (sd 459·1) g, 2525 (sd 534·0) g and 2494 (sd 539·5) g; the prevalence of SGA was 14·3, 51·4 and 53·4 %; the prevalence of LBW was 3·4, 42·4 and 46·6 % among singleton, twin A and twin B, respectively. Compared with non-users, women with FA supplementation were (β 17·3, 95 % CI 6·1, 28·4; β 166·3, 95 % CI 69·1, 263·5) associated with increased birth weight, lower risk of SGA (OR 0·85, 95 % CI 0·80, 0·92; OR 0·45, 95 % CI 0·30, 0·68) and LBW (OR 0·82, 95 % CI 0·71, 0·95; OR 0·50, 95 % CI 0·33, 0·75) in singletons and twins, and more prominent effects in twins. Moreover, there were significant interactions between FA supplementation and plurality on birth weight, SGA and LBW.Conclusions: The present study suggests the association of periconceptional 0·4 mg/d FA supplementation with increased birth weight and reduced risk of SGA and LBW in both singletons and twins, and this association may be more prominent in twins. [ABSTRACT FROM AUTHOR]

We compare the power of two different approaches to detect passive genotype-environment (GE) covariance originating from cultural and genetic transmission operating simultaneously. In the traditional nuclear twin family (NTF) design, cultural transmission is estimated from the phenotypic covariance matrices of the mono- and dizygotic twins and their parents. Here, phenotyping is required in all family members. A more recent method is the transmitted-nontransmitted (T-NT) allele design, which exploits measured genetic variants in parents and offspring to test for effects of nontransmitted alleles from parents. This design requires two-generation genome-wide data and a powerful genome-wide association study (GWAS) for the phenotype in addition to phenotyping in offspring. We compared the power of both designs. Using exact data simulation, we demonstrate three points: how the power of the T-NT design depends on the predictive power of polygenic risk scores (PRSs); that when the NTF design can be applied, its power to detect cultural transmission and GE covariance is high relative to T-NT; and that, given effect sizes from contemporary GWAS, adding PRSs to the NTF design does not yield an appreciable increase in the power to detect cultural transmission. However, it may be difficult to collect phenotypes of parents and the possible importance of gene × age interaction, and secular generational effects can cause complications for many important phenotypes. The T-NT design avoids these complications. [ABSTRACT FROM AUTHOR]

We aimed to investigate whether the alterations of time intervals and velocity-time integrals (VTIs) of ductus venosus (DV) Doppler flow could predict evolving twin-to-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MD) twin pregnancies in the second trimester. DV Doppler waveforms of MD twin pregnancies were retrospectively analyzed. Time intervals and VTIs of the accelerating phase of S-wave (S1 and VTI-1), decelerating phase of S-wave (S2 and VTI-2) and phase of D-wave (D and VTI-diast) were measured in the recipient twins of TTTS and the larger twins of uncomplicated MD twins. Each parameter was normalized to total time intervals and VTIs. DV parameters of prerecipient twins in pre-TTTS conditions were analyzed. The pre-TTTS condition was defined as the condition within 2 weeks before when TTTS cases fulfilled the criteria. Both recipient twins in TTTS cases and prerecipient twins in pre-TTTS condition showed significantly shorter S1, longer S2, shorter D, smaller VTI-1, larger VTI-2 and smaller VTI-diast than did the larger twins in uncomplicated MD twins (p < .05). Receiver-operating characteristic curve analysis showed that VTI-2 had better performance, and VTI-2 >45.5% had 87.0% sensitivity, 90.9% specificity, 81.0% positive predictive value and 93.0% negative predictive value for detecting prerecipient twins. Recipient twins complicated with TTTS have characteristic alterations in time intervals and VTIs of DV Doppler flow, which is present even before fulfilling the TTTS criteria. Furthermore, VTI-2 >45.5% is a possible predictive parameter for TTTS in the second trimester. [ABSTRACT FROM AUTHOR]

Our current society is characterized by an increased availability of industrially processed foods with high salt, fat and sugar content. How is it that some people prefer these unhealthy foods while others prefer more healthy foods? It is suggested that both genetic and environmental factors play a role. The aim of this study was to (1) identify food preference clusters in the largest twin-family study into food preference to date and (2) determine the relative contribution of genetic and environmental factors to individual differences in food preference in the Netherlands. Principal component analysis was performed to identify the preference clusters by using data on food liking/disliking from 16,541 adult multiples and their family members. To estimate the heritability of food preference, the data of 7833 twins were used in structural equation models. We identified seven food preference clusters (Meat, Fish, Fruits, Vegetables, Savory snacks, Sweet snacks and Spices) and one cluster with Drinks. Broad-sense heritability (additive [A] + dominant [D] genetic factors) for these clusters varied between .36 and .60. Dominant genetic effects were found for the clusters Fruit, Fish (males only) and Spices. Quantitative sex differences were found for Meat, Fish and Savory snacks and Drinks. To conclude, our study convincingly showed that genetic factors play a significant role in food preference. A next important step is to identify these genes because genetic vulnerability for food preference is expected to be linked to actual food consumption and different diet-related disorders. [ABSTRACT FROM AUTHOR]

The present study aimed to explore secular trends in age at voice change (AVC), estimate heritability of AVC and investigate to what extent common genes influence the association between AVC and body mass index (BMI) in South Korean males. The sample of 955 male twins consisted of 241 pairs and 118 co-twin missing monozygotic (MZ) twins, 82 pairs and 50 co-twin missing dizygotic (DZ) twins and 141 male members of opposite-sex DZ twins who participated in telephone surveys in the South Korean Twin Registry. AVC was asked of twins during the surveys. The mean (SD) age of the sample was 18.92 (2.42) years (range: 16.00-29.25 years). The birth years of the twins were divided into two groups (1988-1993, 1994-2001). Kaplan-Meyer survival analyses were conducted to compute the mean age of AVC in the total sample as well as to test mean differences between the two birth cohorts. Maximum likelihood twin correlations and univariate and bivariate model-fitting analyses were performed. The mean AVC in the total sample was 14.19 (95% CI [14.09, 14.29]) years. The mean AVC significantly declined from 14.38 to 14.02 years from 1988 to 2001, confirming downward trends in AVC in recent years. Heritability for AVC was .59 (95% CI [.50, .67]), which was within the range reported in most Western twin studies. Although the phenotypic correlation between AVC and BMI was modest (r = -.14; 95% CI [-.07, -.21]), it was entirely mediated by common genes, similar to what has been found in females in prior twin studies. In conclusion, the present twin study underscores the importance of genetic influences on pubertal timing and its association with BMI in South Korean males. [ABSTRACT FROM AUTHOR]

The aim of the study was to examine the Family and School Psychosocial Environment (FSPE) questionnaire in relation to a possible genotype-environment correlation and genetic mediation between the FSPE variables and personality variables, assessed by the Junior Eysenck Personality Questionnaire. A sample of 506 Swedish children aged 10-20 years from 253 families were recruited via the Swedish state population and address register and SchoolList.Eu. The children were divided into 253 pairs: 46 monozygotic twin pairs, 42 dizygotic twin pairs, 140 pairs of full siblings and 25 pairs of half-siblings. The behavioral genetic analysis showed that both FSPE factors, Warmth and Conflicts, may be partly influenced by genetic factors (suggesting genotype-environment correlation) and that nonadditive genetic factors may mediate the relationship between FSPE factors and psychoticism/antisocial personality (P). An indication of a special shared monozygotic twin environment was found for P and Lie/social desirability, but based on prior research findings this factor may have a minor influence on P and L. P and L were negatively correlated, and the relationship seems to be partly mediated by nonadditive genetic factors. Nonshared environment and measurement errors seem to be the most influential mediating factors, but none of the cross-twin cross-dimension correlations suggest a common shared environmental mediating factor. [ABSTRACT FROM AUTHOR]

Loneliness is related to mental and somatic health outcomes, including borderline personality disorder. Here, we analyze the sources of variation that are responsible for the relationship between borderline personality features (including four dimensions, affective instability, identity disturbance, negative relationships, self-harm and a total score) and loneliness. Using genetically informative data from two large nonclinical samples of adult twin pairs from Australia and the Netherlands (N = 11,329), we estimate the phenotypic, genetic and environmental correlations between self-reported borderline personality features and loneliness. Individual differences in borderline personality and loneliness were best explained by additive genetic factors with heritability estimates h2 = 41% for the borderline personality total score and h2 = 36% for loneliness, with the remaining variation explained by environmental influences that were not shared by twins from the same pair. Genetic and environmental factors influencing borderline personality (total score and four subscales separately) were also partial causes of loneliness. The correlation between loneliness and the borderline personality total score was rph = .51. The genetic correlation was estimated at rg = .64 and the environmental correlation at re = .40. Our study suggests common etiological factors in loneliness and borderline personality features. [ABSTRACT FROM AUTHOR]

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

The Academic Development Study of Australian Twins was established in 2012 with the purpose of investigating the relative influence of genes and environments in literacy and numeracy capabilities across two primary and two secondary school grades in Australia. It is the first longitudinal twin project of its kind in Australia and comprises a sample of 2762 twin pairs, 40 triplet sets and 1485 nontwin siblings. Measures include standardized literacy and numeracy test data collected at Grades 3, 5, 7 and 9 as part of the National Assessment Program: Literacy and Numeracy. A range of demographic and behavioral data was also collected, some at multiple longitudinal time points. This article outlines the background and rationale for the study and provides an overview for the research design, sample and measures collected. Findings emerging from the project and future directions are discussed. [ABSTRACT FROM AUTHOR]

Life-course experiences have been postulated to program hypothalamus-pituitary-adrenal (HPA) axis activity, suggesting that HPA axis activity is, at least partially, stable over time. Yet, there is paucity of data on the long-term stability of cortisol production and metabolism. We performed a prospective follow-up study in twins recruited from a nationwide register to estimate the stability of cortisol production and metabolism over time, and the contribution of genetic and environmental factors to this stability. In total, 218 healthy mono- and dizygotic twins were included. At the ages of 9, 12 and 17 years, morning urine samples were collected for assessment (by gas chromatography-tandem mass spectrometry) of cortisol metabolites, enabling the calculation of cortisol metabolite excretion rate and cortisol metabolism activity. Our results showed a low stability for both cortisol metabolite excretion rate (with correlations <.20) and cortisol metabolism activity indices (with correlations of .25 to .46 between 9 and 12 years, -.02 to .15 between 12 and 17 years and .09 to .28 between 9 and 17 years). Because of the low stability over time, genetic and environmental contributions to this stability were difficult to assess, although it seemed to be mostly determined by genetic factors. The low stability in both cortisol production and metabolism between ages 9 and 17 years reflects the dynamic nature of the HPA axis. [ABSTRACT FROM AUTHOR]

Type 2 diabetes, which is caused by both genetic and environmental factors, may be diagnosed using the oral glucose tolerance test (OGTT). Recent studies demonstrated specific patterns in glucose curves during OGTT associated with cardiometabolic risk profiles. As the relative contribution of genetic and environmental influences on glucose curve patterns is unknown, we aimed to investigate the heritability of these patterns. We studied twins from the Danish GEMINAKAR cohort aged 18-67 years and free from diabetes at baseline during 1997-2000; glucose concentrations were measured three times during a 2-h OGTT. Heterogeneity of the glucose response during OGTT was examined with latent class mixed-effects models, evaluating goodness of fit by Bayes information criterion. The genetic influence on curve patterns was estimated using quantitative genetic modeling based on linear structural equations. Overall, 1455 twins (41% monozygotic) had valid glucose concentrations measured from the OGTT, and four latent classes with different glucose response patterns were identified. Statistical modeling demonstrated genetic influence for belonging to a specific class or not, with heritability estimated to be between 45% and 67%. During ∼12 years of follow-up, the four classes were each associated with different incidence of type 2 diabetes. Hence, glucose response curve patterns associated with type 2 diabetes risk appear to be moderately to highly heritable. [ABSTRACT FROM AUTHOR]

Work incapacity is a major public health challenge and an economic burden to both society and individuals. Understanding the underlying causes is becoming ever more relevant as many countries face an aging workforce. We examined stability and change in genetic and environmental factors influencing work incapacity from age 18 until retirement, and sex differences in these effects. The large population-based sample comprised information from 28,759 twins followed for up to 23 years combined with high-quality national registry data. We measured work incapacity as the total proportion of potential workdays lost due to sickness absence, rehabilitation and disability benefits. Structural equation modeling with twin data indicated moderate genetic influences on work incapacity throughout life in both men and women, with a high degree of genetic stability from young to old adulthood. Environmental influences were mainly age-specific. Our results indicate that largely the same genetic factors influence individual differences in work incapacity throughout young, middle and older adulthood, despite major differences in degree of work incapacity and probable underlying medical causes. [ABSTRACT FROM AUTHOR]

The Project Talent Twin and Sibling (PTTS) study includes 4481 multiples and their 522 nontwin siblings from 2233 families. The sample was drawn from Project Talent, a U.S. national longitudinal study of 377,000 individuals born 1942-1946, first assessed in 1960 and representative of U.S. students in secondary school (Grades 9-12). In addition to the twins and triplets, the 1960 dataset includes 84,000 siblings from 40,000 other families. This design is both genetically informative and unique in facilitating separation of the 'common' environment into three sources of variation: shared by all siblings within a family, specific to twin-pairs, and associated with school/community-level factors. We term this the GIFTS model for genetics, individual, family, twin, and school sources of variance. In our article published in a previous Twin Research and Human Genetics special issue, we described data collections conducted with the full Project Talent sample during 1960-1974, methods for the recent linking of siblings within families, identification of twins, and the design of a 54-year follow-up of the PTTS sample, when participants were 68-72 years old. In the current article, we summarize participation and data available from this 2014 collection, describe our method for assigning zygosity using survey responses and yearbook photographs, illustrate the GIFTS model applied to 1960 vocabulary scores from more than 80,000 adolescent twins, siblings and schoolmates and summarize the next wave of PTTS data collection being conducted as part of the larger Project Talent Aging Study. [ABSTRACT FROM AUTHOR]

The Wisconsin Twin Project encompasses nearly 30 years of longitudinal research that spans infancy to early adulthood. The twin sample was recruited from statewide birth records for birth cohorts 1989-2004. We summarize early recruitment, assessment, retention and recently completed twin neuroimaging studies. In addition to the focal twins, longitudinal data were also collected from two parents and nontwin siblings. Our adolescent and young adult neuroimaging sample (N = 600) completed several previous behavioral and environmental assessments, beginning shortly after birth. The extensive phenotyping is meant to support a range of empirical investigations with potentially differing theoretical perspectives. [ABSTRACT FROM AUTHOR]

The Pennsylvania Longitudinal Study of Parents and Children Twin Registry was developed to capture a representative sample of multiple births and their parents in the state of Pennsylvania. The registry has two main efforts. The first began in 2012 through recruitment of adolescents in Pennsylvania schools. The second effort began in January 2019 in partnership with the Pennsylvania Department of Health to capture the birth cohort of twins born from 2007 to 2017. Study recruitment, sample demographics, focus and measures are provided, as well as future directions. [ABSTRACT FROM AUTHOR]

The Mid-Atlantic Twin Registry (MATR) is a population-based registry of more than 60,000 twins primarily born or living in Virginia, North Carolina and South Carolina. Researchers may utilize the MATR for administration of research services, including study recruitment, data or sample (e.g., DNA) collection, archival dataset creation, as well as data collection through mailed, phone or online surveys. In addition, the MATR houses the MATR Repository, with over 1700 DNA samples primarily from whole blood available for researchers interested in DNA genotyping. For over 40 years MATR twins have participated in research studies with investigators from a range of scientific disciplines and institutions. These studies, which have resulted in numerous publications, explored diverse topics, including substance use, smoking behaviors, developmental psychopathology, bullying, children's health, cardiovascular disease, cancer, the human microbiome, epigenetics of aging, children of twins and sleep homeostasis. Researchers interested in utilizing twins are encouraged to contact the MATR to discuss potential research opportunities. [ABSTRACT FROM AUTHOR]

The Colorado Twin Registry (CTR) is a population-based registry formed from birth and school records including twins born between 1968 and the present. Two previous reports on the CTR [Rhea et al., (2006). Twin Research and Human Genetics, 9, 941-949; Rhea et al., (2013).Twin Research and Human Genetics, 16, 351-357] covered developments in the CTR through 2012. This report briefly summarizes previously presented material on ascertainment and recruitment and the relationships between samples and studies, discusses developments since 2012 for four previously described twin samples, describes two new samples and their complementary studies and expands on two subjects briefly mentioned in the last report: a history of genotyping efforts involving CTR samples, and a survey of collaborations and consortia in which CTR twins have been included. The CTR remains an active resource for both ongoing, longitudinal research and the recruitment of new twin samples for newly identified research opportunities. [ABSTRACT FROM AUTHOR]

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status. [ABSTRACT FROM AUTHOR]

This case study examined the hypothesis that longer outdoor time results in normal vision and refractive status, using unique genetically informative kinships. The participants were the members of 29-year-old doubly exchanged monozygotic male twin pairs from Bogotá, Colombia, in South America. Comprehensive ophthalmological examinations, including uncorrected and corrected visual acuity, refraction and keratometry, and visual life history interviews were undertaken; all examinations were conducted by two ophthalmologists blind to the hypothesis, relatedness, and rearing status of the four participants. Normal uncorrected vision and refractive status were present in the two rural-raised, unrelated brothers, relative to their urban-raised counterparts. Uncorrected visual acuities were 20/160 and 20/200 for the city-raised twins and 20/20 and 20/30 for the country-raised twins. Premature birth, low birth weight, computer use, and reading time could not explain these differences. It was concluded that time spent outdoors appears to be a significant factor in the development of myopia, reinforcing extant findings via a novel experimental approach. [ABSTRACT FROM AUTHOR]

A literature review was carried out to identify pre and perinatal characteristics associated with variation in Apgar scores in population-based studies. The parameters identified in the literature search were included in the classical twin design study to estimate effects of pre and perinatal factors shared and nonshared by twins and to test for a contribution of genetic factors in 1- and 5-min Apgar scores in a large sample of Dutch monozygotic (MZ) and dizygotic (DZ) twins. The sample included MZ and DZ twins (N = 5181 pairs) recruited by the Netherlands Twin Register shortly after birth, with data on prenatal characteristics and Apgar scores at first and/or fifth minutes. The ordinal regression and structural equation modeling were used to analyze the effects of characteristics identified in the literature review and to estimate genetic and nongenetic variance components. The literature review identified 63 papers. Consistent with the review, we observed statistically significant effects of birth order, zygosity and gestational age (GA) for 1- and 5-min Apgar scores of both twins. Apgar scores are higher in first-born versus second-born twins and DZ first-born versus MZ first-born twins. Birth weight had an effect on the 5-min Apgar of the first born. Fetal presentation and mode of delivery had different effects on Apgar scores of first- and second-born twins. Parental characteristics and chorionicity did not have significant main effects on Apgar scores. The MZ twins' Apgar correlations equaled the DZ Apgar correlations. Our analyses suggest that individual differences in 1- and 5-min Apgar scores are attributable to shared and nonshared pre and perinatal factors, but not to genotypic factors of the newborns. The main predictors of Apgar scores are birth order, zygosity, GA, birth weight, mode of delivery and fetal presentation. [ABSTRACT FROM AUTHOR]

The seasonality of demographic data has been of great interest. It depends mainly on the climatic conditions, and the findings may vary from study to study. Commonly, the studies are based on monthly data. The population at risk plays a central role. For births or deaths over short periods, the population at risk is proportional to the lengths of the months. Hence, one must analyze the number of births (and deaths) per day. If one studies the seasonality of multiple maternities, the population at risk is the total monthly number of confinements and the number of multiple maternities in a given month must be compared with the monthly number of all maternities. Consequently, when one considers the monthly rates of multiple maternities, the monthly number of births is eliminated and one obtains an unaffected seasonality measure of the rates. In general, comparisons between the seasonality of different data sets presuppose standardization of the data to indices with common means, mainly 100. If one assumes seasonality as 'non-flatness' throughout a year, a chi-squared test would be an option, but this test calculates only the heterogeneity and the same test statistic can be obtained for data sets with extreme values occurring in consecutive months or in separate months. Hence, chi-squared tests for seasonality are weak because of this arbitrariness and cannot be considered a model test. When seasonal models are applied, one must pay special attention to how well the applied model fits the data. If the goodness of fit is poor, nonsignificant models obtained can erroneously lead to statements that the seasonality is slight, although the observed seasonal fluctuations are marked. In this study, we investigate how the application of seasonal models can be applied to different demographic variables. [ABSTRACT FROM AUTHOR]

While snus has been the focus of increasing public health interest, twin studies have examined neither sources of individual variation for its use nor the sources of resemblance between snus and cigarette use. Twins from the Norwegian Institute of Public Health Panel were assessed by self-report questionnaire for the initiation of regular use and maximal quantity used for snus and cigarettes. Twin modeling was performed using OpenMx on data from 2767 twins including 856 complete pairs. Fitting univariate twin models produced similar results for cigarette initiation and quantity with estimates of additive genetic, shared environmental and unique environmental effects of approximately 77%, 0% and 23%, respectively. Estimates of snus initiation and quantity were, respectively, approximately 53%, 26% and 21%. Joint analyses suggested that the genetic, shared environmental and unique environmental correlations between cigarette and snus initiation and quantity were +.82, 0 and +.42, respectively. However, these results could not be statistically distinguished from a model which postulated that resemblance between cigarette initiation and quantity resulted from genetic and unique environmental correlations of +.47 and +.43. Compared with cigarette initiation and quantity of use in Norwegian twins, the role of genes was less prominent and shared environment more prominent for initiation and quantity of use of snus. Joint analyses of both tobacco phenotypes suggested, but did not confirm definitively, that genetic risk factors for cigarette and snus use were similar but not identical, while shared environmental factors existed that were specific to snus use. [ABSTRACT FROM AUTHOR]

Structural equation modeling (SEM) is an important research tool, both for path-based model specification (common in the social sciences) and also for matrix-based models (in heavy use in behavior genetics). We developed umx to give more immediate access, relatively concise syntax and helpful defaults for users in these two broad disciplines. umx supports development, modification and comparison of models, as well as both graphical and tabular outputs. The second major focus of umx, behavior genetic models, is supported via functions implementing standard multigroup twin models. These functions support raw and covariance data, including joint ordinal data, and give solutions for ACE models, including support for covariates, common- and independent-pathway models, and gene × environment interaction models. A tutorial site and question forum are also available. [ABSTRACT FROM AUTHOR]

Twinning is rare among humans, but there is much variability among populations. Several studies show that certain demographic and socioeconomic factors, such as maternal age, mother's educational level and income, influence twinning rate. There is no background of analytical studies of twins in Uruguay. To the best of our knowledge, this is the first study that has focused on describing and analyzing Uruguayan twinning rates over a period of 17 years (1999-2015). The birth data were collected from the website of Uruguay's Ministry of Public Health. Economic data were obtained from Uruguay's Instituto Nacional de Estadísti's website for the period 2001-2013, since these variables are defined specifically for that period of time. The statistical software R (The R Project for Statistical Computing) was used. The twinning rate varied from 8.51 to 13 in the studied period. Montevideo has the highest median and the smallest variability in comparison with the other departments. In Uruguay (1999-2015), the highest twinning rate (28.94%) was observed in women aged 45 and older. The analysis also showed a relationship between twin birth rates and the mother's educational level. In three regions of the country (West, Center and East), twin births show a random pattern but in the other two (North and Metropolitan), there is an increasing trend in the number of twins over time. In conclusion, this study recognizes social, economic and demographic factors that influence in the rate of twin births in Uruguay. [ABSTRACT FROM AUTHOR]

This study uses novel approaches to examine genetic and environmental influences shared between childhood behavioral inhibition (BI) and symptoms of preadolescent anxiety disorders. Three hundred and fifty-two twin pairs aged 9-13 and their mothers completed questionnaires about BI and anxiety symptoms. Biometrical twin modeling, including a direction-of-causation design, investigated genetic and environmental risk factors shared between BI and social, generalized, panic and separation anxiety. Social anxiety shared the greatest proportion of genetic (20%) and environmental (16%) variance with BI with tentative evidence for causality. Etiological factors underlying BI explained little of the risk associated with the other anxiety domains. Findings further clarify etiologic pathways between BI and anxiety disorder domains in children. [ABSTRACT FROM AUTHOR]

It has been suggested that the risk of adverse perinatal outcomes in twin pregnancies is exacerbated by concomitant gestational diabetes mellitus (GDM). This study aimed to assess the risk incurred by twin pregnancy and by a diagnosis of GDM, separately, on the development of poor perinatal outcomes. A retrospective cohort study was conducted on all pregnant women at a tertiary center between 2016 and 2017. The impact of GDM and twin pregnancies on perinatal outcomes - birth weight above the 90th centile for gestational age, cesarean delivery, clinical neonatal hypoglycemia, and premature delivery (before 37 weeks' gestation) - was assessed using univariate and multivariate analyses. Overall, 13,527 women were eligible for the study; 11,915 were uncomplicated singleton pregnancies; 1379 of these had GDM; 194 were twin pregnancies, and 39 of these had GDM. Univariate analyses showed that twin pregnancies were associated with a higher risk of all perinatal outcomes except macrosomia. In the multivariate analyses, twin pregnancy was a much higher predictor of cesarean delivery (OR 8.40, 95% CI [6.25, 11.49], p < .0001) and preterm birth (OR 58.82, 95% CI [31.25, 125], p < .0001) compared to GDM but GDM was a higher predictor of neonatal hypoglycemia (OR 4.87, 95% CI [3.74, 6.29], p < .0001). Twin pregnancy is more strongly associated with all adverse perinatal outcomes except macrosomia. GDM does not increase risk of adverse perinatal outcomes except for neonatal hypoglycemia. [ABSTRACT FROM AUTHOR]

Familial monozygotic (MZ) twinning reports are rare around the world, and we report a four-generation pedigree with seven recorded pairs of female MZ twins. Whole-genome sequencing of seven family members was performed to explore the featured genetic factors in MZ twins. For variations specific to MZ twins, five novel variants were observed in the X chromosome. These candidates were used to explain the seemingly X-linked dominant inheritance pattern, and only one variant was exonic, located at the 5'UTR region of ZCCHC12 (chrX: 117958597, G > A). Besides, consistent mitochondrial DNA composition in the maternal linage precluded roles of mitochondria for this trait. In this pedigree, autosomes also contain diverse variations specific to MZ twins. Pathway analysis revealed a significant enrichment of genes carrying novel SNVs in the epithelial adherens junction-signaling pathway (p = .011), contributed by FGFR1, TUBB6, and MYH7B. Meanwhile, TBC1D22A, TRIOBP, and TUBB6, also carrying similar SNVs, were involved in the GTPase family-mediated signal pathway. Furthermore, gene-set enrichment analysis for 533 genes covered by copy number variations specific to MZ twins illustrated that the tight junction-signaling pathway was significantly enriched (p < .001). Therefore, the novel changes in the X chromosome and the provided candidate variants across autosomes may be responsible for MZ twinning, giving clues to increase our understanding about the underlying mechanism. [ABSTRACT FROM AUTHOR]

In 1968, long before the publication of Stephen J. Gould's The Mismeasure of Man, Herrnstein and Murray's The Bell Curve, or Arthur Jensen's Bias in Mental Testing, Irving Gottesman published a book chapter that addressed head-on the issues that would define the relationship between the genetics of social behavior and large-scale social theory for the next 50 years. That he could do so with his characteristic scholarly thoroughness and scientific tough-mindedness without once lapsing into regressive hereditarianism is a testimony to the scope of his scientific knowledge and the generosity of his intellectual spirit. [ABSTRACT FROM AUTHOR]

Empathy plays a central role in prosocial behavior and human cooperation. Very few twin researchers have investigated innate and environmental effects in adult empathy, and twin research on gender differences in these effects is sparse. The goal of this study was to examine innate and environmental influences on three components of an empathy scale frequently used with adults - the expression of cognitive (CE), emotional (EE), and social skills (SS) empathy - and to explore gender differences in the influences. Study participants were ~1,700 twins (18-65 years) enrolled in the Italian Twin Registry. Empathy was assessed with the Italian version of the Empathy Quotient (EQ), for which the three-factor structure (i.e., CE, EE, and SS) was confirmed. Twin correlations in monozygotic and dizygotic pairs, and males and females were estimated for the total EQ and subscale scores, and univariate genetic model fitting was carried out. Women's empathy (i.e., total EQ as well as CE and EE subdimensions) was predominantly driven by genetic factors and individual experiences, whereas for males, no genetic contribution or important shared and individual environmental effects emerged. Although of large magnitude, the gender differences did not reach statistical significance. Age did not moderate empathy heritability in adulthood. Only for the SS subscale were genetic and environmental proportions of variance similar for men and women. This study suggests possible gender-specific innate and environmental influences on empathy and its cognitive and emotional components that need to be confirmed in future studies. [ABSTRACT FROM AUTHOR]

Twin pregnancies discordant for neural tube defects (NTD) is a management dilemma. Risks of preterm delivery from polyhydramnios must be balanced with the risks of selective termination (ST) of the anomalous fetus. We investigated the prevalence of twin pregnancies discordant for NTD and the rate of pregnancy complications in our institution over a 10-year period. Cases were obtained by searching the hospital ultrasound database and findings were confirmed by expert review of ultrasound images. Outcomes of ST and expectant management were assessed. Each unaffected co-twin was assigned to three consecutive twin pregnancy controls matched by chorionicity and maternal age. Primary outcome was birth before 34 weeks' gestation. Secondary outcomes were small for gestational age, mode of delivery, neonatal unit admission, and neonatal death. In total, 13 pregnancies were identified as potential cases. Of these, 11 were included in the analysis: 9 dichorionic diamniotic and 2 monochorionic diamniotic twins. Seven cases had ST and four were managed expectantly. We found 100% (4/4) of expectantly managed pregnancies delivered <34 weeks compared with 14% (1/7) of the ST group (p = .015). Polyhydramnios complicated three expectantly managed pregnancies and one pregnancy in the ST group. The birthweight SD score of all unaffected co-twins was ≥-2. The case-control analysis showed a higher rate of polyhydramnios in twin pregnancies discordant for NTD compared with controls, but little evidence for differences between groups in delivery rates <34 weeks, birthweight, neonatal unit admission, or neonatal death. ST warrants serious consideration to avoid potential complications to the unaffected co-twin. [ABSTRACT FROM AUTHOR]

Little is known about longitudinal changes of the first twin presentation in twin gestations. This is a retrospective cohort study including 411 women who were admitted consecutively and delivered live-born twins at 36 weeks of gestation or more. Longitudinal assessment of the first twin presentation was conducted during gestation and at birth in all cases. Gestational age at antenatal assessment was divided into two intervals: early-third trimester (28-31 weeks) and mid-third trimester (32-35 weeks). Fetal presentation was categorized as vertex or non-vertex. We analyzed change of fetal presentation between antepartum intervals and birth. First twin presentation at early-third trimester had the same presentation at birth in 87.6% (360/411) of the study population. In this 'no change' group, vertex presentation was seen in 95.6% (283/296) and non-vertex was seen in 67.0% (77/115) of cases. In total, 96.1% (395/411) of the study population maintained their presentation between mid-third trimester and birth. Vertex presentation was seen in 98.4% (310/315) and non-vertex was seen in 88.5% (85/96) of cases. When comparing vertex with non-vertex, vertex presentation during third trimester was a more reliable predictor of presentation at birth (p < .001). The only factor that contributed significantly to spontaneous version of the first twin during mid-third trimester and birth was a lower birth weight of the first twin compared with the second twin. In conclusion, first twin presentation with vertex during third trimester is not likely to change into non-vertex at birth. We concluded that vertex presentation in twin gestations at early- and mid-third trimester is very predictable. In contrast, a non-vertex first twin presentation is relatively unstable. [ABSTRACT FROM AUTHOR]

Twin registers are wonderful research resources for research applications in medical and behavioral genetics, epidemiology, psychology, molecular genetics, and other areas of research. New registers continue to be launched all over the world as researchers from different disciplines recognize the potential to boost and widen their research agenda. In this article, we discuss multiple aspects that need to be taken into account when initiating a register, from its preliminary sketch to its actual development. This encompasses aspects related to the strategic planning and key elements of research designs, promotion and management of a twin register, including recruitment and retaining of twins and family members of twins, phenotyping, database organization, and collaborations between registers. We also present information on questions unique to twin registers and twin-biobanks, such as the assessment of zygosity by SNP arrays, the design of (biomarker) studies involving related participants, and the analyses of clustered data. Altogether, we provide a number of basic guidelines and recommendations for reflection when planning a twin register. [ABSTRACT FROM AUTHOR]

Schooling differences between identical twins are often utilized as a natural experiment to estimate returns to education. Despite longstanding doubts about the truly random nature of within-twin-pair schooling discordance, such discordance has not yet been understood comprehensively, in terms of diverse between- and within-family peer, academic, familial, social, and health exposures. Here, a predictive analysis using national U.S. midlife twin data shows that within-pair schooling differences are endogenous to a variety of childhood exposures. Using discordance propensities, returns to education under a true natural experiment are simulated. Results for midlife occupation and income reveal differences in estimated returns to education that are statistically insignificant, suggesting that twin-based estimates of causal effects are robust. Moreover, identical and fraternal twins show similar levels of discordance endogeneity and similar responses to propensity weighting, suggesting that the identical twins may not provide demonstrably better leverage in the causal identification of educational returns. [ABSTRACT FROM AUTHOR]

The phenotypic relationships between body mass index (BMI) and cold-heat patterns have been frequently reported, but the etiology of these relationships remains unknown. We previously demonstrated that the cold pattern (CP) and the heat pattern (HP) were heritable traits. In the present study, we explored underlying genetic and environmental structures of the relationships among BMI and the CP and the HP. Twins (N = 1,752) drawn from the South Korean twin registry completed a cold-heat pattern questionnaire via a telephone interview. The phenotypic correlations among the three phenotypes were moderate but significant. Cross-twin, cross-trait correlations among BMI and the CP and the HP were consistently greater in monozygotic than in dizygotic twins, suggesting the presence of genetic effects on the relationships between BMI and the two patterns. A trivariate Cholesky model was applied to the raw data. The results indicated that the phenotypic relationship between the HP and BMI was completely determined by common genetic influences, while the relationship between the CP and BMI was explained by both common genetic and common individual-specific environmental influences. The genetic correlation between the HP and the CP was not significant, suggesting that the two patterns may be genetically independent from each other. Genetic correlations were 0.31 between the HP and BMI, and -0.22 between the CP and BMI. The individual-specific environmental correlation was -0.22 between HP and CP, and between CP and BMI. [ABSTRACT FROM AUTHOR]

Problem behaviors are of increasing public health concern. Twin studies have revealed substantial genetic and environmental influences on children's behavior, and examining birth-weight difference could allow the identification of the specific contribution of multiple non-shared prenatal environmental factors. The Twins and Multiple Births Association Heritability Study, a UK, volunteer-based study, recruited mothers of twins aged 18 months to 5 years; 960 twins (480 pairs) were included in the analysis. Twins' mothers answered questions relative to their pregnancy and their twins' characteristics, and completed the Child Behavior Checklist (CBCL) 1½-5. The association between the absolute birth-weight difference and each CBCL scale's score difference was analyzed by means of multiple linear regressions. Expected mean CBCL score differences were calculated. In monozygotic (MZ) twins, statistically and clinically significant associations were found between intrapair birth-weight difference and difference in total problems, internalizing problems, and emotional reactiveness. No significant results were observed neither in dizygotic (DZ) twins when analyzed as a separate group nor in MZ and DZ twins combined. The results of the present study suggest that with increasing the absolute birth-weight difference, the intrapair difference in total problems, internalizing behaviors and emotionality increases, with smaller twins being at major risk for later behavior problems. Moreover, these results suggest a causal association between birth weight and behavior development. [ABSTRACT FROM AUTHOR]

Monozygotic (MZ) and dizygotic (DZ) twins participate in research that partitions variance in health, disease, and behavior into genetic and environmental components. However, there are other innovative roles for twins in medical research. One such way is involving MZ and/or DZ twins in co-twin control-designed randomized controlled trials (RCTs). To our knowledge, no reviews have been conducted that summarizes the involvement of twins in RCTs. Therefore, we conducted a systematic literature search using the U.S. Clinical Trials Database, NHS electronic databases, MEDLINE, EMBASE, and PsychINFO for RCTs on publications involving MZ and/or DZ twins as RCT participants. Out of the 186,027 clinical trials registered in the U.S. clinical trial register ClinicaTrails.gov, only six RCTs used twins as participants. From 1,598 articles identified in our search, 50 peer-reviewed English language publications met our pre-defined inclusion criteria. Sample sizes for RCTs have ranged from a total number of participants from 2 to 1,162; however, 32 (64%) studies had a sample size of 100 or less, and of those, 12 (24%) had fewer than 10. Both MZ and DZ twins have been recruited to the RCTs. In most instances (33/50) each twin from a pair were assigned to different study arms. Most of those studies included MZ twins only. Despite the methodological advantages, the use of MZ and DZ twins as participants in interventional RCTs appeared limited. The continuous development of innovative twin designs, especially RCTs, indicates that twin research can extend beyond the more widely recognized heritability estimates. [ABSTRACT FROM AUTHOR]

A discordant twin gestation, in which one fetus is significantly growth restricted, compared to the other normal twin, is a unique model that can be used to elucidate the mechanism(s) by which the intrauterine environment affects fetal growth. In many model systems, placental transcription factor genes regulate fetal growth. Transcription factors regulate growth through their activation or repression of downstream target genes that mediate important cell functions. The objective of this study was to determine the expression of the placental HLX homeobox gene transcription factor and its downstream target genes in dizygotic twins with growth discordance. In this cross-sectional study, HLX and its downstream target genes' retinoblastoma 1 (RB1) and cyclin kinase D (CDKN1C) expression levels were determined in placentae obtained from dichorionic diamniotic twin pregnancies (n = 23) where one of the twins was growth restricted. Fetal growth restriction (FGR) was defined as small for gestational age with abnormal umbilical artery Doppler indices when compared with the normal control co-twin. Homeobox gene HLX expression was significantly decreased at both the mRNA and protein levels in FGR twin placentae compared with the normal control co-twin placentae (p < .05). Downstream target genes CDKN1C and RB1 were also significantly decreased and increased, respectively, at both the mRNA and protein levels in FGR twin placentae compared with normal control co-twin placentae (p < .05). Together, these observations suggest an important association between HLX transcription factor expression and abnormal human placental development in discordant twin pregnancies. [ABSTRACT FROM AUTHOR]

Until now, data have not been available to elucidate the genetic and environmental sources of comorbidity between all 10 DSM-IV personality disorders (PDs) and cocaine use. Our aim was to determine which PD traits are linked phenotypically and genetically to cocaine use. Cross-sectional data were obtained in a face-to-face interview between 1999 and 2004. Subjects were 1,419 twins (µage = 28.2 years, range = 19-36) from the Norwegian Institute of Public Health Twin Panel, with complete lifetime cocaine use and criteria for all 10 DSM-IV PDs. Stepwise multiple and Least Absolute Shrinkage and Selection Operator (LASSO) regressions were used to identify PDs related to cocaine use. Twin models were fitted to estimate genetic and environmental associations between the PD traits and cocaine use. In the multiple regression, antisocial (OR = 4.24, 95% CI [2.66, 6.86]) and borderline (OR = 2.19, 95% CI [1.35, 3.57]) PD traits were significant predictors of cocaine use. In the LASSO regression, antisocial, borderline, and histrionic were significant predictors of cocaine use. Antisocial and borderline PD traits each explained 72% and 25% of the total genetic risks in cocaine use, respectively. Genetic risks in histrionic PD were not significantly related to cocaine use. Importantly, after removing criteria referencing substance use, antisocial PD explained 65% of the total genetic variance in cocaine use, whereas borderline explained only 4%. Among PD traits, antisocial is the strongest correlate of cocaine use, for which the association is driven largely by common genetic risks. [ABSTRACT FROM AUTHOR]

The genetic and environmental contributions of negative valence systems (NVS) to internalizing pathways study (also referred to as the Adolescent and Young Adult Twin Study) was designed to examine varying constructs of the NVS as they relate to the development of internalizing disorders from a genetically informed perspective. The goal of this study was to evaluate genetic and environmental contributions to potential psychiatric endophenotypes that contribute to internalizing psychopathology by studying adolescent and young adult twins longitudinally over a 2-year period. This report details the sample characteristics, study design, and methodology of this study. The first wave of data collection (i.e., time 1) is complete; the 2-year follow-up (i.e., time 2) is currently underway. A total of 430 twin pairs (N = 860 individual twins; 166 monozygotic pairs; 57.2% female) and 422 parents or legal guardians participated at time 1. Twin participants completed self-report surveys and participated in experimental paradigms to assess processes within the NVS. Additionally, parents completed surveys to report on themselves and their twin children. Findings from this study will help clarify the genetic and environmental influences of the NVS and their association with internalizing risk. The goal of this line of research is to develop methods for early internalizing disorder risk detection. [ABSTRACT FROM AUTHOR]