The aim of this study is to characterize the relationship between major depression and the metabolic syndrome in a large community based sample of Australian men and women aged 26–90 years. A lifetime history of major depression was assessed by telephone interview following the DSM–III-R. A current history of metabolic syndrome was assessed following the United States National Cholesterol Education Program Adult Treatment Panel III (NCEP AP-III) guidelines 1 to 3 years later. Logistic regression was used to estimate the association between depression and the metabolic syndrome, and its component criteria, controlling for age, sex and alcohol dependence. There was no association between a lifetime history of major depression and the presence of the metabolic syndrome. There was a weak association between depression and low high-density lipoprotein cholesterol but not with other component criteria of the metabolic syndrome. Despite calls for interventions directed at depression to reduce the onset of the metabolic syndrome there are important failures to replicate in large samples such as this, no consensus regarding the threshold at which depression may pose a significant risk even allowing for heterogeneity across populations, and no consensus regarding confounders that may explain inter-study differences. The absence of any dosage effect of depression on the associated risk for the metabolic syndrome in other unselected samples does not support a direct causal relationship. The call for intervention studies on the basis of the currently published evidence base is unwarranted.

It has been long recognised that asthma and related phenoypes have an important hereditary nature, in which inheritance does not follow the classical Mendelian patterns and the exact mode of inheritance is not known. Linkage, association studies and genome-wide screening suggest that many genes are involved in the pathogenesis of asthma. Twin studies have contributed significantly to our understanding on the genetics of asthma, especially the large-scale twin studies in different parts of the world which have showed comparable results. With the shortcomings of the twin method borne in mind, more twin studies are needed to investigate the heredity component of the intermediate phenotypes of asthma, that is, bronchial hyperresponsiveness, total immunoglobulin E, skin test reactivity, specific IgE against different aeroallergens, and the variability of lung function. Twin studies are very suitable to unravel the intricate network of genes and environment which plays a role in asthma. Monozygotic twins and the co-twin control design are suitable for this purpose, while longitudinal twin studies are needed to solve the problem of the age related expression of genes which probably are involved in the pathogenesis of asthma. In the near future twin studies will play an important role in the detection of new, as yet undiscovered genes, but may be even more important in answering the most challenging of all questions: how do the environment interact with the genetics of asthma? Exchange of information and collaboration between the different research groups involved in the genetics of asthma will contribute to a better understanding of this condition.

This article discusses new latent variable techniques developed by the authors. As an illustration, a new factor mixture model is applied to the monozygotic–dizygotic twin analysis of binary items measuring alcohol-use disorder. In this model, heritability is simultaneously studied with respect to latent class membership and within-class severity dimensions. Different latent classes of individuals are allowed to have different heritability for the severity dimensions. The factor mixture approach appears to have great potential for the genetic analyses of heterogeneous populations. Generalizations for longitudinal data are also outlined.

The Early Growth and Development Study is a prospective adoption study of birth parents, adoptive parents, and adopted children (N = 359 triads) that was initiated in 2003. The primary study aims are to examine how family processes mediate or moderate the expression of genetic influences in order to aid in the identification of specific family processes that could serve as malleable targets for intervention. Participants in the study are recruited through adoption agencies located throughout the United States, following the birth of a child. Assessments occur at 6-month intervals until the child reaches 3 years of age. Data collection includes the following primary constructs: infant and toddler temperament, social behavior, and health; birth and adoptive parent personality characteristics, psychopathology, competence, stress, and substance use; adoptive parenting and marital relations; and prenatal exposure to drugs and maternal stress. Preliminary analyses suggest the representativeness of the sample and minimal confounding effects of current trends in adoption practices, including openness and selective placement. Future plans are described.

A multidimensional peer nomination inventory (MPNI; 30 items) and parallel versions – MPNI-Teacher and MPNI-Parental Rating Forms (37 items each) – were developed during a major new Finnish study of families with twins. The twins (477 girls and 467 boys) were 12 years old, representing subsets of three nationwide Finnish twin cohorts (b. 1983–1985). They were enrolled in 503 school classes, and the total number of children participating in peer nominations was 12 937. Three main factors were extracted from peer nominations and teacher and parental assessments. Intercorrelating sub-components were found, especially in parental assessments. Scales were formed, accordingly, for Behavioral Problems (including Hyperactivity-Impulsivity, Aggression, and Inattention), Emotional Problems (including Depression and Social Anxiety), and Adjustment (including Constructiveness, Compliance, and Social Activity). A framework for the development of the multidimensional inventory was a model of emotional and behavioural regulation. Peer nominations were most reliable, while parental assessments, although mostly satisfactory, were least reliable. Results provided evidence of concurrent validity of peer-referenced assessment, using teacher assessments as criteria; correlations between assessments of peers and parents were lower. The inventory has discriminative validity. Intra-pair correlations of monozygotic co-twins were higher than correlations of same-sex (SS) and opposite-sex (OS) dizygotic (DZ) co-twins for all scales across all three assessors, and peer nominations of both SS and OSDZ co-twins yielded correlations significantly greater than zero for all scales. All scales, except Depression and Social Anxiety, differentiated boys from girls.

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

Multivariate modelling of anxiety and depression data in twins has suggested that the two phenotypes are largely underpinned by one genetic factor, while other studies have indicated a relationship between these disorders and the neuroticism personality trait. As part of a study to identify quantitative trait loci for anxiety and depression, questionnaire responses and interviews of 15 027 Australian twins and 11 389 of their family members conducted during the past 20 years were reviewed to identify individuals with neuroticism, anxiety and depression scores in the upper or lower deciles of the population. This information was then used to identify extreme discordant and concordant (EDAC) sib pairs. 1373 high-scoring and 1571 low-scoring subjects (2357 sib pairs) were selected for participation, and extremely high participation rates were achieved, with over 90% of contactable prospective participants completing the interview phase, and over 90% of these providing blood or buccal samples. Participation bias arising from the nature of the selection variables was minimal, with only a small difference between rates of interview participation among prospective participants with high and low selection scores (89.4% vs 91.6%). The interview permitted the diagnosis of depression and several anxiety disorders (OCD, agoraphobia, panic disorder, generalised anxiety disorder) in this sample according to DSM-IV criteria. The methodology for selection of prospective subjects was demonstrated to be extremely successful, with highly significant differences in depression and anxiety disorder prevalence rates between individuals in the two selection groups. The success of this EDAC sampling scheme will enhance the power for QTL linkage and association analysis in this sample. Twin Research (2000) 3, 299–309.

Reports over the past seventy years show that twin gestations lead to an increased risk of hypertensive disorders. Numerous studies discuss the incidence of hypertensive disease in twin versus singleton gestations, as well as effects of parity, race, age, income level, smoking, zygosity and heritability on this condition. The range of relative risk of gestational hypertension, preeclampsia and eclampsia for twin compared to singleton gestations is 1.2 to 2.7, 2.8 to 4.4 and 3.4 to 5.1 respectively. Parity, African-American ethnicity, and young maternal age are all factors that increase the relative risk of acquiring hypertensive disease to 4.0, 1.8 and 1.5 in mothers of twin gestations. Factors such as maternal smoking, income level and zygosity have a negligible effect on the relative risk of acquiring hypertensive disease in twin gestations. In addition to twin mothers exhibiting a higher incidence of hypertensive disease compared to their singleton counterparts, they also exhibit an earlier onset of hypertensive disease at both 35 and 37 weeks of gestation comparatively. Uric acid levels measured at 30–31 weeks of gestation in twin mothers predicted the onset of preeclampsia with a sensitivity of 73% and a specificity of 74%. The range of risks presented in the literature is wide and the therapies avocated are diverse. We therefore decided to summarize the risks in a comparative fashion and to review current therapeutic strategies for the convenience of clinicians who confront increasing numbers of multiple pregnancies. The tables bring all recent published risks together in the first comparative analysis in which the data has been converted to relative risks and confidence intervals. Because the literature is relatively silent on specific management of hypertensive disease in twin pregnancies, general management recommendations for singleton gestations should be used by practitioners caring over twin gestations.

Women's mental health can be compromised during reproductive life, but to date there has been relatively little specific investigation of the links between multiple births and perinatal psychiatric illness. There has been more comprehensive examination of some of the psychological sequelae of multiple gestations and births, but many of the studies have small samples and are descriptive in nature. Most of the literature is drawn from investigations of the psychological aspects of multiple births following assisted conception. Current conceptualizations of the determinants of maternal perinatal mental health, with particular reference to multiple gestations and births are discussed and implications for clinical practice suggested.

Overall there is evidence that women with multiple gestation and multiple births may be at elevated risk for pregnancy anxiety, postpartum depression and complicated grief reactions. Much less is currently known about the associations between multiple birth and either maternity blues or postpartum psychosis. The relationships between personal or family psychiatric history, past experience of childhood abuse, intimate partner intimidation and psychological adjustment to multiple births are not known. The interactions between multiple births, operative delivery, prematurity, neonatal illness and separation of mother and infant as contributing factors to maternal postpartum mental health are not known. There is very limited evidence about the psychological functioning of fathers of multiple infants. Routine antenatal, intrapartum and postnatal health care for women with multiple infants needs to take into account the additional psychological demands they face.

In an extended twin study we estimated the heritability of fasting HbA1c and blood glucose levels. Blood glucose was assessed in different settings (at home and in the clinic). We tested whether the genetic factors influencing fasting blood glucose levels overlapped with those influencing HbA1c and whether the same genetic factors were expressed across different settings. Fasting blood glucose was measured at home and during two visits to the clinic in 77 healthy families with same-sex twins and siblings, aged 20 to 45 years. HbA1c was measured during the first clinic visit. A 4-variate genetic structural equation model was used that estimated the heritability of each trait and the genetic correlations among traits. Heritability explained 75% of the variance in HbA1c. The heritability of fasting blood glucose was estimated at 66% at home and lower in the clinic (57% and 38%). Fasting blood glucose levels were significantly correlated across settings (0.34 < r < 0.54), mostly due to a common set of genes that explained between 53% and 95% of these correlations. Correlations between HbA1c and fasting blood glucoses were low (0.11 < r < 0.23) and genetic factors influencing HbA1c and fasting glucose were uncorrelated. These results suggest that in healthy adults the genes influencing HbA1c and fasting blood glucose reflect different aspects of the glucose metabolism. As a consequence these two glycemic parameters can not be used interchangeably in diagnostic procedures or in studies attempting to find genes for diabetes. Both contribute unique (genetic) information.

The Colorado Twin Registry (CTR) is a population-based registry housed at the Institute for Behavioral Genetics at the University of Colorado. Recruitment began in 1982 and includes twins born from 1968 to the present. Four samples are currently drawn from the CTR: The Community Twin Sample, the Longitudinal Twin Sample, the Early Reading Development Sample, and the Colorado Learning Sample. Criteria for enrollment, recruitment strategies, demographic information, and zygosity assignment are explained for each sample. In addition, five studies in which CTR twins are now participating are highlighted. These include studies of cognition, learning ability, and vulnerability to substance abuse and antisocial behavior. The development of the CTR is an ongoing and evolving process, and it has proven to be a valuable registry, relatively representative of the population from which it was drawn.

The assessment of fetal growth is an essential component of good antenatal care, especially for twins. The aims of this study are to develop twin-specific intrauterine 'growth' charts, based on cross-sectional birthweight data, for monochorionic and dichorionic twins according to sex and parity, and to detect twins at risk for neonatal death by comparing the use of twin-specific and singleton charts. The study sample consisted of 76,471 singletons and 8454 twins (4227 pairs) born in East Flanders (Belgium). Birthweights were analyzed using a nonlinear Gaussian regression. After 33 weeks of gestation, the birthweights of twins started to deviate from singletons (difference of 900 grams at 42 weeks). Birthweights of dichorionic twins continued to increase, whereas those of monochorionic twins decreased after week 40 (difference of more than 300 g at 42 weeks). After 31 weeks of gestation, neonatal mortality increased as centile decreased, and was especially high if birthweight was below the twin-specific third centile: .032 (below) versus .007 (above). Using singleton centiles, this was less obvious. In conclusion, twin-specific growth charts, taking chorionicity into account, are more accurate to detect twins at risk for neonatal death. Therefore the presented charts, based on cross-sectional birthweight data, enable an improved assessment of twin growth.

The present study deals with the determination of zygosity in twins of childhood age by simple questionnaire. The subjects were 224 twin pairs and their mothers, consisting of 159 monozygotic and 65 same-sex dizygotic pairs, identified by genetic markers including DNA samples. Mothers of twins responded to 19 questionnaire items dealing with twin similarity in 16 items about physical features and 3 items about the degree of similarity and frequency of being mistaken (confusion of identity) when twins were about 1 year of age. The twins themselves responded to three questionnaire items dealing with only confusion of identity items. The results of stepwise logistic regression analysis were as follows: the total accuracy of the mothers' questionnaire was 91.5% when using only the items dealing with confusion of identity. This accuracy was slightly lower than that obtained by twins' self-reports dealing with nearly the same question items of confusion of identity, answered by both twins separately with 93.3% accuracy. The total accuracy of mothers' questionnaire responses rose to 95.1% when we used all 19 items. In addition to ‘the frequency of being mistaken‘, two physical features, namely ‘shape of fingers’ and ‘shape of eyebrow’, were very informative. In conclusion, twin zygosity can be estimated by the use of the mothers' simple questionnaire with sufficient accuracy even in very young twins about 1 year of age.

The Early Growth and Development Study (EGDS) is a prospective adoption study of birth parents, adoptive parents and adopted children (n = 561 adoptees). The original sample has been expanded to include siblings of the EGDS adoptees who were reared by the birth mother and assessed beginning at age 7 years (n = 217 biological children), and additional siblings in both the birth and adoptive family homes, recruited when the adoptees were 8–15 years old (n = 823). The overall study aims are to examine how family, peer and contextual processes affect child and adolescent adjustment, and to examine their interplay (mediation, moderation) with genetic influences. Adoptive and birth parents were originally recruited through adoption agencies located throughout the USA following the birth of a child. Assessments are ongoing and occurred in 9 month’s intervals until the adoptees turned 3 years of age, and in 1 to 2 year intervals thereafter through age 15. Data collection includes the following primary constructs: child temperament, behavior problems, mental health, peer relations, executive functioning, school performance and health; birth and adoptive parent personality characteristics, mental health, health, context, substance use, parenting and marital relations; and the prenatal environment. Findings highlight the power of the adoption design to detect environmental influences on child development and provide evidence of complex interactions and correlations between genetic, prenatal environmental and postnatal environmental influences on a range of child outcomes. The study sample, procedures and an overview of findings are summarized and ongoing assessment activities are described.

This study examined cross-validation and test-retest reliability of questions and questionnaire indices commonly used for twin zygosity classification. Mothers of 58 monozygotic (MZ) and 52 dizygotic (DZ) same sex twin pairs were interviewed by telephone to answer questions regarding the similarity of their twins (mean age = 14.6 ± 2.8 years). A logistic regression equation correctly classified 91% of both MZ and DZ twin pairs in our sample using 7 of the 12 zygosity questions. The internal consistency for the total questionnaire (Cronbach's alpha) was 0.88. The median two month temporal stability estimate for the individual questions was r = .56 and r = .79 for the test total. For the cross-validation, zygosity classification indices taken from 9 previous studies were applied to our sample and compared to classification according to DNA microsatellite analyses (agreement range = 44 to 100%). The accuracy of the classification indices was significantly lower than the original studies for 62% of the comparisons. If zygosity determination with DNA markers or blood group typing for all subjects is not feasible, rather than using classification indices based on other studies, an optimal classification scheme can be achieved by using a zygosity questionnaire of which the reliability and validity of the questions is established in a random subsample of the same twin cohort.

Molecular epidemiological studies confirm a substantial contribution of individual genes to variability in susceptibility to disease and death for humans. To evaluate the contribution of all genes to susceptibility and to estimate individual survival characteristics, survival data on related individuals (eg twins or other relatives) are needed. Correlated gamma-frailty models of bivariate survival are used in a joint analysis of survival data on more than 31 000 pairs of Danish, Swedish and Finnish male and female twins using the maximum likelihood method. Additive decomposition of frailty into genetic and environmental components is used to estimate heritability in frailty. The estimate of the standard deviation of frailty from the pooled data is about 1.5. The hypothesis that variance in frailty and correlations of frailty for twins are similar in the data from all three countries is accepted. The estimate of narrow-sense heritability in frailty is about 0.5. The age trajectories of individual hazards are evaluated for all three populations of twins and both sexes. The results of our analysis confirm the presence of genetic infiuences on individual frailty and longevity. They also suggest that the mechanism of these genetic infiuences may be similar for the three Scandinavian countries. Furthermore, results indicate that the increase in individual hazard with age is more rapid than predicted by traditional demographic life tables.

Weight discordance is very rare in monozygotic (MZ) twin pairs; when found, however, such pairs are advantageous in the search for either environmental or epigenetic causes and consequences of obesity. We analyzed the growth patterns of young adult MZ pairs discordant and concordant for obesity. Screening 5 consecutive birth cohorts (1975–1979) of 22- to 27-year-old Finnish twins (the FinnTwin16 study), we found 14 obesity discordant (Body Mass Index [BMI] difference ≥ 4 kg/m2) MZ pairs out of 658. Ten pairs participated in clinical studies. Nine concordant pairs (BMI difference ≤ 2 kg/m2) were examined as controls. Lifetime measured heights and weights recorded in hospitals and health centers were traced manually. Height development was similar in all the co-twins of both groups. The weight differences between the co-twins of the discordant pairs began to emerge at 18 years leading to an average discordance of 16.4 kg, 5.6 kg/m2(p for both = .005) at 25.7 years. The heavier co-twin weighed 221 g (p = .066), 1.0 kg/m2 (p = .01) more already at birth than the leaner, but the differences waned by 6 months of age and reappeared only after adolescence. Both the leaner and the heavier co-twins of the discordant pairs weighed more than expected by the singleton reference values (Cole et al., 1998) after 8 years. The concordant co-twins, on the other hand, grew similarly and after 6 months, their mean growth was not distinguishable from the singleton patterns. Young adulthood represents a critical period of gaining weight irrespective of genetic background in this twin sample.

For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.

A number of studies have provided evidence of a significant familial aggregation for both asthma and hay fever, and have reported a substantial comorbidity between the two conditions. However, far fewer, especially in Italy, have aimed at clarifying the origins of such comorbidity. The main aims of the present study were (a) to estimate heritability of asthma and hay fever, (b) to measure the association between asthma and hay fever at the individual level, and (c) to assess the extent to which genetic and environmental factors, shared by the two conditions, mediate this association. The twin method was used. The study sample was derived from the Italian Twin Registry, and included 392 twin pairs aged 8 to 17 years. Data collection was performed through parent self-administered questionnaire. Bivariate structural equation twin modeling was applied to asthma and hay fever. Genetic factors accounted for 92% and 78% of the variance in liability to asthma and hay fever, respectively, with the remaining contributions due to unique environmental influences. The within-individual association between asthma and hay fever was substantial. The genetic correlation between the two conditions was .58, whereas no evidence of overlapping unique environmental effects was found. In conclusion, this study showed a high heritability of asthma and hay fever in the Italian child and adolescent population. It also indicated that asthma and hay fever share, to a large extent, a common genetic background, and environmental factors are not relevant to explain the comorbidity.

That the zona pellucida (ZP) plays a prominent role in the physiology of some human twinning is an attractive, albeit incompletely proven, medical hypothesis. Indeed, an association has been proposed between manipulation of the ZP and/or native ZP microarchitecture and monozygotic (MZ) twins. Ovulation induction also has been theoretically linked to in vivo ZP alterations facilitating MZ twin development. In vitro fertilization (IVF) relies on necessary (and, in some cases extended) embryo culture techniques potentially creating subtle ZP changes and subsequent MZ twinning. With growing experience in the assisted reproductive technologies and particularly IVF, some preliminary reports have noted an increased frequency of MZ twins after procedures that artificially breach the ZP (i.e., intracytoplasmic sperm injection [ICSI], or ‘assisted hatching’). Such ZP manipulations ostensibly enhance oocyte fertilization or facilitate blastocyst hatching, thus improving pregnancy rates for couples undergoing fertility treatment. Evidence exists both to challenge and support the connection between these phenomena and MZ twins. This report outlines the fundamental embryological processes believed responsible for these conflicting observations; the current literature on the subject of human ZP micro-manipulation and MZ twins is also discussed. Twin Research (2000) 3, 217–223.