Recent studies have claimed to detect interaction between candidate genes and specific environmental factors (Genotype × Environment interaction, G × E) in susceptibility to psychiatric disorder. The objective of the present study was to examine possible artifacts that could explain widely publicized findings. The additive effects of candidate genes and measured environment on liability to disorder were simulated under a model that allowed for mixture of distributions in liability conditional on genotype and environment. Simulated liabilities were dichotomized at a threshold value to reflect diagnosis of disorder. Multiple blocks of simulated data were analyzed by standard statistical methods to test for the main effects and interactions of genes and environment on outcome. The main outcome of this study was simulated liabilities and diagnoses of major depression and antisocial behavior. Analysis of the dichotomized data by logistic regression frequently detected significant G × E interaction even though none was present for liability. There is therefore reason to question the biological significance of published findings.

Linkage analysis (either parametric or nonparametric) is commonly applied to identify chromosomal regions using related individuals affected by disease. In complex disease the incomplete relationship between phenotype and genotype can be modeled using a phenocopy parameter, the probability that an individual is affected given they do not carry the disease mutation of interest, and a nonpenetrance parameter, the probability that an individual is not affected given they do carry the disease mutation of interest. If the linkage phase between multiple markers and a putative disease locus is known, then haplotypes carrying the mutation can, in principle, be identified by comparing the chromosome segments that are shared identical-by-descent (IBD) across affected individuals. We consider here the effect of a nonzero phenocopy rate on the linkage peak and hence upon the identification of disease haplotypes that are shared IBD between affected individuals. We show, by theory and computer simulation, that in diseases for which there is a nonzero phenocopy rate, the chromosomal regions identified may not include the true disease locus. We utilize a LOD-1 confidence interval for a widely used nonparametric linkage statistic. We find that in small/moderate samples this confidence interval may be inappropriate. We give specific examples where the phenocopy rates are nonnegligible in some complex diseases. The success of further work to identify the causal mutations underlying the linkage peaks in these diseases will depend on researchers allowing for the presence of phenocopies by examining appropriately wide regions around the initial positive linkage finding.

We investigated the extent to which cognitive dysfunction is shaped by genetic or environmental influences, and whether these factors differ in women and men. All members of the Swedish Twin Registry aged 65 and older were screened by telephone using the TELE, a brief cognitive assessment instrument (Gatz et al., 2002), and the Blessed Dementia Rating Scale (Blessed et al., 1968) from relatives of those who scored poorly on the TELE. Data were available for 4308 pairs where both members responded and 5070 pairs where only one member was alive and participated. To analyze all available data, we used a raw data method extended to ordinal data. As the prevalence of cognitive dysfunction increases with age, we incorporated age-adjusted thresholds. The best fitting model from biometric analyses indicated 35% of the variation in liability to cognitive dysfunction could be explained by heritable influences and the remaining 65% by nonfamilial environmental influences. Differences by gender were not significant. As this is a normative population including cognitively intact individuals, preclinical dementia cases and demented individuals, the relative magnitude of genetic and environmental effects is of particular interest in light of high heritabilities found for dementias such as Alzheimer's disease. The findings emphasize the extent to which research is needed to uncover nonfamilial environmental influences on cognitive dysfunction in later life.

The objective of this study was to estimate the magnitude of genetic and environmental influences to variation in adolescent neuroticism as a function of age and sex. Neuroticism was assessed using the Amsterdamse Biografische Vragenlijst (ABV): a self-report personality instrument similar in content to the Eysenck Personality Questionnaire. Genetic modeling procedures, including age as modifier, were fitted to the total sample of 3301 Dutch adolescent twins aged 12 to 17 years (mean age 15.5). Significant influences of additive genetic factors (.59, 95% confidence intervals [CI] .54–.63) and unshared environmental factors (.41, 95% CI .37–.45) were found. Our data did not support a role of shared environment. Results showed that different genes may influence variation in neuroticism between girls and boys. No interaction was found between the variance components and age. Results generally support prior findings in adults and young children that neuroticism is influenced principally by additive genetic and unique environmental factors. The magnitude of the genetic component appears higher in the present sample of adolescents than in most studies of adults. The present study suggests that, in adolescence, different genes are expressed in boys and girls.

The nature of Generalized Anxiety Disorder (GAD) and worry across the lifespan remains incompletely understood. We investigated genetic and environmental influences on GAD and the proportion of genetic and environmental variation in GAD that is shared with neuroticism in older adult twins. Participants included 1618 monozygotic and 2291 same-sexed dizygotic twin pairs from the Swedish Twin Registry aged 55 to 74. Participants provided personality information in 1973 and also participated in a telephone screening between 1998 and 2002 that included an assessment for lifetime GAD. Univariate biometric models indicated that both GAD and neuroticism were moderately heritable (.27 and .47, respectively), while the balance of variation reflected environmental factors unique to the individual. Bivariate analyses indicated that approximately one third of the genetic influences on GAD were in common with genetic influences on neuroticism, while individual specific environmental influences were virtually unshared between GAD and neuroticism. Analyses of sex effects suggested that men and women differed in the frequency of lifetime GAD and level of neuroticism; however, no sex differences for genetic and environmental influences for either trait were identified.

Conduct disorder (CD) symptoms and substance dependence commonly co-occur. Both phenotypes are highly heritable and a common genetic influence on the covariation has been suggested. The aim of this study was to determine the extent to which genes and environment contribute to the covariance between CD and drug dependence using twins from the Colorado Longitudinal Twin Sample and the Colorado Twin Registry. A total of 880 twin pairs (237 monozygotic [MZ] female, 195 MZ male, 116 dizygotic [DZ] female, 118 DZ male and 214 DZ opposite-sex) aged 13 to 18 (mean = 15.65) were included in the analysis. CD was assessed by lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) symptom count and a polysubstance dependence vulnerability index was developed from responses to the Composite International Diagnostic Interview — Substance Abuse Module. A bivariate Cholesky Decomposition model was used to partition the cause of variation and covariation of the two phenotypes. No sex-limitation was observed in our data, and male and female parameter estimates were constrained to be equal. Both CD symptoms and dependence vulnerability were significantly heritable, and genes, shared environment and nonshared environment all contributed to the covariation between them. Genes contributed 35% of the phenotypic covariance, shared environment contributed 46%, and nonshared environmental influences contributed the remaining 19% to the phenotypic covariance. Therefore, there appears to be pleiotropic genetic influence on CD symptoms and dependence vulnerability.

Simultaneous analysis of handedness data from 35 samples of twins (with a combined sample size of 21,127 twin pairs) found a small but significant additive genetic effect accounting for 25.47% of the variance (95% confidence interval [CI] 15.69–29.51%). No common environmental influences were detected (C = 0.00; 95% CI 0.00–7.67%), with the majority of the variance, 74.53%, explained by factors unique to the individual (95% CI 70.49–78.67%). No significant heterogeneity was observed within studies that used similar methods to assess handedness, or across studies that used different methods. At an individual level the majority of studies had insufficient power to reject a purely unique environmental model due to insufficient power to detect familial aggregation. This lack of power is seldom mentioned within studies, and has contributed to the misconception that twin studies of handedness are not informative.

It is often debated whether migraine with aura (MA) and migraine without aura (MO) are etiologically distinct disorders. A previous study using latent class analysis (LCA) in Australian twins showed no evidence for separate subtypes of MO and MA. The aim of the present study was to replicate these results in a population of Dutch twins and their parents, siblings and partners (N = 10,144). Latent class analysis of International Headache Society (IHS)-based migraine symptoms resulted in the identification of 4 classes: a class of unaffected subjects (class 0), a mild form of nonmigrainous headache (class 1), a moderately severe type of migraine (class 2), typically without neurological symptoms or aura (8% reporting aura symptoms), and a severe type of migraine (class 3), typically with neurological symptoms, and aura symptoms in approximately half of the cases. Given the overlap of neurological symptoms and nonmutual exclusivity of aura symptoms, these results do not support the MO and MA subtypes as being etiologically distinct. The heritability in female twins of migraine based on LCA classification was estimated at .50 (95% confidence intervals [CI] .27 – .59), similar to IHS-based migraine diagnosis (h2 = .49, 95% CI .19–.57). However, using a dichotomous classification (affected–unaffected) decreased heritability for the IHS-based classification (h2 = .33, 95% CI .00–.60), but not the LCA-based classification (h2 = .51, 95% CI .23–.61). Importantly, use of the LCA-based classification increased the number of subjects classified as affected. The heritability of the screening question was similar to more detailed LCA and IHS classifications, suggesting that the screening procedure is an important determining factor in genetic studies of migraine.

Both genetic and environmental factors affect smoking initiation and maintenance, but less is known about the genetic architecture of various other smoking-related behaviors. The aim of this study is to examine the genetic architecture of smoking behavior in a large twin cohort. Questionnaires with an extensive smoking history section were mailed to same-sex adult twins of the Finnish twin cohort. The final study population included 2923 monozygotic and 6018 dizygotic twin pairs aged 24 to 88 years. Two-stage bivariate genetic modeling of age at initiation with amount smoked (less than 20 cigarettes per day vs. 20 or more) and age at initiation with smoking cessation was done by using the Mx statistical package. For men the heritability estimate for age at initiation was .59 (95% confidence interval [CI] .49–.69), for amount smoked .54 (95% CI .45–.62) and for smoking cessation .58 (95% CI .50–.65). For women the heritability estimates were .36 (95% CI .28–.43), .61 (95% CI .46–.70) and .50 (95% CI .39–.60), respectively. The genetic correlations between age at initiation and amount smoked or smoking cessation were at most .22 in magnitude, indicating that genetic influences in age at initiation accounted for at most about 4% of the genetic factors in amount smoked or in cessation. Genetic factors are important in amount smoked and smoking cessation and they are largely independent of genetic influences on age at initiation. This has implications for defining phenotypes in searches for genes underlying smoking behaviors.

Previous studies have shown that Glutathione, a tripeptide found in blood, is involved in protecting against toxins. Glutathione levels are known to drop in response to cadmium. Using 15 twin pairs, we modeled the effect of cadmium on glutathione levels. The heritability of glutathione content was 91%. The application of cadmium significantly reduced the mean level of GSH. However, this reduction in GSH was not due to additive genetic influences in our sample.

The objective of the present study was to determine whether angiotensinogen G(–6)A polymorphism is associated with the elevation of blood pressure (BP) in the hypertensive disorders of pregnancy in Korean population. The subjects included 201 cases with the hypertensive disorders of pregnancy and 160 healthy controls. The medical records of subjects were reviewed. Cases were classified into the four subtypes (transient hypertension, preeclampsia, chronic hypertension, and preeclampsia superimposed on chronic hypertension) by the diagnostic criteria suggested by the National High Blood Pressure Education Program Working Group. Cases were also divided into the high and low BP group by the elevation of BP (diastolic BP greater than or equal to 110 mmHg). Maternal angiotensinogen G(–6)A polymorphism was determined by restriction fragment length polymorphism. Frequencies of AA genotype were significantly higher in the high than in the low BP group in the preeclampsia, superimposed preeclampsia, and the combined group (N = 201), suggesting that the angiotensinogen G(–6)A allele was significantly associated with the elevation of BP in the hypertensive disorders of pregnancy among South Korean women. The present findings imply that the elevation of BP can serve as an endophenotype for a spectrum of hypertensive conditions in pregnancy.

The purpose of this prospective cohort study of twins and triplets was to evaluate perinatal and early childhood outcomes through 18 months of age. The study population included 141 twin pregnancies (282 twin children) and 8 triplet pregnancies (24 triplet children) recruited between May, 1996 and June, 2001. Mothers of triplets versus twins were significantly more likely to have infertility treatments, to be overweight or obese before conception, to be admitted antenatally, and to deliver by cesarean section. Length of gestation for triplets was significantly shorter (–2.31 weeks, p < .0001), and more likely to be less than 35 weeks (Adjusted Odds Ratio [AOR] 9.38, 95% confidence interval [CI] 3.22–27.29). Average birthweight for triplets was significantly lighter (–495 grams, p < .0001), and more likely to be low birthweight (AOR 11.38, 95% CI 3.11–41.61). Triplets were also more likely to be admitted to neonatal intensive care (AOR 7.97, 95% CI 2.13–29.77), to require mechanical ventilation (AOR 5.67, 95% CI 2.05–15.65), to develop respiratory distress syndrome (AOR 12.50, 95% CI 3.89–40.20), or a major morbidity (retinopathy of prematurity, necrotizing enterocolitis, ventilator support, or grade III or IV intraventricular hemorrhage, AOR 5.67, 95% CI 2.05–15.65). Weight, length, and head circumference was significantly smaller at birth for triplets compared to twins, and these differences remained through 18 months of age, along with lower mental developmental scores at the oldest age. Compared to twins, triplets have greater neonatal morbidity, and through 18 months of age lower mental and motor scores, slower postnatal growth and more residual stunting, particularly of length and head circumference.

This project sought to examine 2 competing hypotheses: first, that twins are likely to be more prosocial by virtue of growing up with another same-age peer in the home, or second, that they are less prosocial because they have become more comfortable interacting with a same-age peer who is both genetically and environmentally similar to themselves and therefore they are less comfortable with other children who are dissimilar. Two studies were conducted to compare twins to singletons on measures of prosocial and aggressive behaviors. In Study 1, 5-year-olds (N = 91 twins and N = 152 singletons) engaged in a peer play situation with an unfamiliar, same-age, same-sex peer, and they were rated on items assessing prosocial and aggressive behaviors. Results showed that twins were less prosocial but not more aggressive than were singletons. In Study 2, which was a supplemented follow-up study of twins in Study 1, 10- to 15-year-old twins (N = 98) and singletons (N = 84) were rated by their parents on prosocial and aggressive behaviors. No significant differences were found between the groups on prosocial behavior, but twins were rated as more aggressive than singletons. Thus, in early childhood twins appear to exhibit fewer prosocial behaviors with unfamiliar peers, but this prosocial deficit was not aligned with parent-reported prosocial behaviors in adolescence. In adolescence, twins were rated by parents as more aggressive. These studies suggest that twins may be at risk for poorer social interactions in early and middle childhood.

This article conceptualizes the child as having active agency in the constructions of their social worlds, and reports on a study that understands the twin experiences from the perspectives of the twins. It examines how twins account for their relationships with their co-twins. The study drew on accounts of 60 twin children — 10 monozygotic (MZ), 10 dizygotic (DZ) same-sex, 10 DZ opposite-sex pairs — aged 5 to 10 years and their parent (n = 30). The children engaged in a sticker activity in which they represented their friendships, including their friendship with their co-twin. Using the task as a resource, the children were asked about their friends, the attributes of friendship and examples of everyday friendships encounters. These were audio-recorded and transcribed. Further, parents completed a questionnaire that provided demographic information and asked parents about the children's social experiences including twin children's time spent together, shared interests and their co-twin relationship. Using data from the pictorial representation from the sticker task and parent questionnaires, differences in relationship between MZ, DZ same-sex and DZ opposite-sex twins were examined and used to select a smaller sample for detailed study. DZ same-sex twins tended to view their co-twin less favorably and there was a nonsignificant trend in which conflict was elevated, compared to the other two groups. Based on these findings, the transcripts selected for analysis focuses on the DZ same-sex girls. The girls reported that they had differences of thought, activity and self-presentation. Conflict, competition and challenge as types of social interaction were described, suggesting that the everyday relationship of the twin with her co-twin is always being negotiated and realigned. Evident here is the complexity of social interactions in which the twins engaged everyday with each other.

Two observations suggest a genetic similarity among close friends: (1) the observed similarity among friends in certain traits and behaviors; (2) the evidence that many of these traits and behaviors have a genetic component. This hypothesis is tested using monozygotic (MZ) twins, dizygotic (DZ) twins, full biological siblings, and their best friends from the National Longitudinal Study of Adolescent Health (Add Health). Whether the resemblance between MZ twins' friends is larger than that between friends of DZ twins and full siblings is investigated with respect to 4 individual traits or behaviors: grade point average (GPA), AHPVT (the version Peabody Picture Vocabulary Test [PPVT] designed for Add Health), aggressive behavior, and depression. Our hypothesis is supported in analyses among same-sex friends (not among different-sex friends) for GPA, aggressive behavior, and AHPVT.

Behavioral problems in young children can be assessed by asking their parents or teachers to rate their behaviors. Genetic analyses of parental ratings show relatively large heritabilities for emotional and behavioral problems in young children, but data from teachers for this age group are scarce. Sources of variation in the Teacher's Report Form (TRF) problem scales were examined. The TRF was completed for 211 Dutch 5-year-old twin pairs and 4 single twins. Twins rated by different teachers had higher means and variances than twins rated by the same teacher, in addition twin correlations were lower in this group. In both groups monozygotic (MZ) correlations were generally higher than dizygotic (DZ) correlations. A model for twin resemblance was tested that allowed for these effects. For 5 problem scales (Withdrawn, Social Problems, Aggressive Behavior, Rule Breaking Behavior and Attention Problems) a model with genetic and unique environmental sources of variation fitted best to the data. For 3 problem scales (Anxious/Depressed, Thought Problems and Somatic Complaints) there were familial influences but it was not possible to distinguish between common environmental influences or genetic influences. Heritability was 63% for Attention problems, around 45% for Withdrawn, Social Problems, Aggressive Behavior and Rule Breaking Behavior, and around 30% for Anxious/Depressed, Thought Problems and Somatic Complaints.

Arecent large-scale study of Finnish adolescent twins (Pulkkinen et al., 2003) reported that individuals from opposite-sex twin pairs were more socially adaptive than individuals from same-sex pairs or singletons. This finding raised questions about the social learning effects of being an opposite-sex twin. The current article predicted on the basis of this finding, and evidence from singleton populations, that having an opposite-sex twin would yield social advantage. It sought to examine the social competencies of opposite-sex twins and compare them with same-sex twins and singletons. The study focused on the preschool years (age 3 to 6), a period in which the majority of children encounter their first large group, nonfamilial social experiences. The study obtained reports from parents and teachers of children aged 3 to 6 years: 72 children (36 pairs) who were dizygotic opposite-sex twins (DZOS), 50 children (25 pairs) who were dizygotic same-sex twins (DZSS), and 85 singletons of the same age and sex as the twins, who had at least one sibling. Reports were made using standardized measures of social competencies, behavior problems, language development and friendships. The main effects found were of differences in social competency between twins and singletons. Twins had lower social competency scores. No differences between same-sex and opposite-sex twins were found. The findings did not support the hypothesis of social advantage for opposite-sex twins in early childhood.

Research on twins has tended to focus around the question of heredity/environment. As part of this, attention has been paid to how twins' family environments impact upon them. By examining twinship as a social identity, this article considers the social experience of twinship as it is framed by parent–child relations and also actively shaped by twins themselves. Sameness constitutes one central defining component of ‘twin’ identity within Western societies. In preparing their twins' bodies for public presentation, parents play a key role in communicating twin identity on their children's behalf. However, children also construct and convey their own identities through presenting their bodies in certain ways. Drawing on findings from a small-scale qualitative study of twinship, this article examines how twin identity is created, modified and reproduced by parents and child twins. It highlights the active role that twins take in constructing their own identities and in shaping the ‘twin situation’.

Attention-deficit hyperactivity disorder (ADHD) is a common childhood disorder which occurs more often in twins than singletons. This article focuses on the psychosocial consequences of having a co-twin with ADHD. Specifically, the level of anxiety (generalized and separation) in non-ADHD children who have a co-twin with ADHD is examined using data from the Australian Twin ADHD Project (ATAP). Parental report data on 501 dizygotic (DZ) twin pairs aged 6 to 15 and their siblings were used to examine (i) anxiety symptoms in twin pairs discordant for ADHD, (ii) how the effects of an ADHD twin on their co-twin and siblings are related to the type of ADHD, and (iii) whether the effects are greater for the nonaffected twin than nontwin siblings. Results show that anxiety was high in co-twins of children with the combined subtype of ADHD, with increased symptoms of both generalized and separation anxiety. Inattentive ADHD had smaller effects, which were confined to generalized anxiety and were specific to the co-twin rather than other siblings. These results have clinical implications in managing the entire multiple birth family where one twin has ADHD, and also has implications for genetic analysis in modeling the relationship of ADHD to internalizing disorders.