Genetic and Environmental Causes of Covariation in Interview Assessments of Disruptive Behavior in Child and Adolescent Twins

Multirater, face-to-face, interview data relating to conduct disorder (CD), oppositional-defiant disorder (ODD), and inattentive, impulsive, and hyperactive components of attention-deficit hyperactivity disorder (ADHD) in a population-based sample of 1376 pairs of 8- to 16-year-old MZ and DZ twins are analyzed to examine (1) the genetic and environmental causes of correlation among ratings of ODD and CD symptoms and (2) the pattern of genetic and environmental correlation among the three components of ADHD. Parental ratings of ADHD showed marked sibling contrast effects, specific within raters but partly common across components. After these effects were removed, there was a modest genetic correlation between maternal and paternal ratings, but genetic effects were virtually uncorrelated across boys and girls. Genetic correlations among inattention, impulsivity, and hyperactivity were all large but fell well short of unity. There was little evidence that counts of symptoms of CD and ODD were genetically independent but the genetic correlations among ratings of twins, mothers, and fathers were all relatively modest. ODD and CD showed much higher genetic correlations across sexes than did the measures of ADHD. There was no evidence of rater contrast effects or of shared family environment influences in the twin resemblance for ODD and CD.     

Genetic and Cultural Transmission of Smoking Initiation: An Extended Twin Kinship Model

BACKGROUND: Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a significant role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent-offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. METHODS: We examined the role of genetic and environmental factors for smoking initiation using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission. A dichotomous lifetime smoking measure was obtained from twins and relatives in the Virginia 30,000 sample. RESULTS: Results demonstrate that both genetic and environmental factors play a significant role in the liability to smoking initiation. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission and resulting genotype-environment covariance. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent-offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (i) age x gene interaction, and (ii) social homogamy. Neither mechanism provided a significantly better explanation of the data, although age regression was significant. CONCLUSIONS: This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on smoking initiation.     

Genetic and environmental influences on birthweight in a sample of Korean twins

This study is the first report of genetic and environmental influences on birthweight using Korean twins. The sample consisted of 255 monozygotic (MZ) and 178 dizygotic (DZ) twin pairs drawn from the Seoul Twin Family Study. Intraclass twin correlations were computed for the twins' birthweights obtained from parents (typically mothers) of the twins. To estimate genetic and shared and nonshared environmental influences on birthweight, standard univariate model-fitting analyses were performed using a software, Mx. For each gender, MZ twin correlations were higher than DZ twin correlations, suggesting existence of genetic influences on birthweight; however, DZ twin correlations were higher than half the MZ twin correlations, indicating that shared environmental factors are also important. For each zygosity, twin correlations were not significantly different between males and females, implicating that genes and environments that cause individual differences in birthweight may not vary between males and females. Model-fitting analyses based on the data pooled across gender yielded estimates of 17% for genetic, 60% for shared environmental, and 23% for nonshared environmental influences on birthweight.     

Multivariate path analysis of cognitive ability measures in reading-disabled and control nuclear families and twins

Matrix notation is used to formulate a multivariate path model of familial resemblance in nuclear families, monozygotic (MZ) twin pairs, and dizygotic (DZ) twin pairs. The model incorporates multivariate genetic and environmental influences, cultural transmission, assortative mating, and environmental influences shared by offspring, and it permits the estimation of genetic and environmental correlations. The model is applied to data from nuclear families, MZ twin pairs, and DZ twin pairs in which at least one child was diagnosed as being reading disabled and to data from control families and twins. Three cognitive ability measures (Reading, Coding Speed, and Spatial Ability) were analyzed simultaneously. Results indicate that genetic influences are moderate, with significant genetic correlations among characters. Cultural transmission is negligible, as are the environmental correlations. Assortative mating is significant only for the Reading measure. There is no evidence for sibling shared environmental influences; however, there are significant twin shared environmental effects for each measure but not between measures.This work was supported by grants from the Spencer Foundation and the NICHD (HD-11681) to J. C. DeFries and by NIMH Postdoctoral Training Grant MH-17104.     

Genetic and Environmental Factors in Relative Body Weight and Human Adiposity

We review the literature on the familial resemblance of body mass index (BMI) and other adiposity measures and find strikingly convergent results for a variety of relationships. Results from twin studies suggest that genetic factors explain 50 to 90% of the variance in BMI. Family studies generally report estimates of parent–offspring and sibling correlations in agreement with heritabilities of 20 to 80%. Data from adoption studies are consistent with genetic factors accounting for 20 to 60% of the variation in BMI. Based on data from more than 25,000 twin pairs and 50,000 biological and adoptive family members, the weighted mean correlations are .74 for MZ twins, .32 for DZ twins, .25 for siblings, .19 for parent–offspring pairs, .06 for adoptive relatives, and .12 for spouses. Advantages and disadvantages of twin, family, and adoption studies are reviewed. Data from the Virginia 30,000, including twins and their parents, siblings, spouses, and children, were analyzed using a structural equation model (Stealth) which estimates additive and dominance genetic variance, cultural transmission, assortative mating, nonparental shared environment, and special twin and MZ twin environmental variance. Genetic factors explained 67% of the variance in males and females, of which half is due to dominance. A small proportion of the genetic variance was attributed to the consequences of assortative mating. The remainder of the variance is accounted for by unique environmental factors, of which 7% is correlated across twins. No evidence was found for a special MZ twin environment, thereby supporting the equal environment assumption. These results are consistent with other studies in suggesting that genetic factors play a significant role in the causes of individual differences in relative body weight and human adiposity.     

Genetic Analysis of Anger: Genetic Dominance or Competitive Sibling Interaction

The knowledge of the causes and development of anger is still scarce. Previous studies on the sources of variance on Type A Behavior Pattern (TABP) related measures found variable heritability estimates ranging from 0.12 to 0.68, and large differences between MZ and DZ correlations. Some authors considered dominance genetic effects, competitive sibling interaction and sex differences as possible mechanisms to explain the results, but most studies lacked power. The present study uses a large sample of more than 2500 families, with longitudinal data from MZ and DZ pairs as well as their parents, to disentangle the sources of variance on anger. Model Fitting results showed that the sources of variance differ across sexes. For males 23% of the variance is due to additive genetic effects, and 26% to dominance genetic effects. For females 34% of the variance is due to additive genetic effects, and no dominance effects are found. There was no consistent evidence to confirm the presence of competitive sibling interaction as an alternative explanation for the low correlations in DZ males. The focus of research on the prediction of coronary heart disease (CHD) risk through psychological characteristics has recently changed from the multidimensional TABP to its emotional component: Anger. Understanding the sources of individual differences on anger can help to clarify the mechanisms that link it with CHD and its possible implications for treatment and prevention.     

Widespread Evidence for Non-Additive Genetic Variation in Cloninger’s and Eysenck’s Personality Dimensions using a Twin Plus Sibling Design

Studies using the classical twin design often conclude that most genetic variation underlying personality is additive in nature. However, studies analyzing only twins are very limited in their ability to detect non-additive genetic variation and are unable to detect sources of variation unique to twins, which can mask non-additive genetic variation. The current study assessed 9672 MZ and DZ twin individuals and 3241 of their siblings to investigate the environmental and genetic architecture underlying eight dimensions of personality: four from Eysenck’s Personality Questionnaire and four from Cloninger’s Temperament and Character Inventory. Broad-sense heritability estimates from best-fitting models were two to three times greater than the narrow-sense heritability estimates for Harm Avoidance, Novelty Seeking, Reward Dependence, Persistence, Extraversion, and Neuroticism. This genetic non-additivity could be due to dominance, additive-by-additive epistasis, or to additive genetic effects combined with higher-order epistasis. Environmental effects unique to twins were detected for both Lie and Psychoticism but accounted for little overall variation. Our results illustrate the increased sensitivity afforded by extending the classical twin design to include siblings, and may provide clues to the evolutionary origins of genetic variation underlying personality.     

Bigger Families Fare Better: A Novel Method to Estimate Rater Contrast Effects in Parental Ratings on ADHD Symptoms

Many twin studies on parental ratings of attention deficit hyperactivity disorder (ADHD) symptoms report low or negative DZ correlations. The observed differences in MZ and DZ variances indicate sibling contrast effects, which appear to reflect a bias in parent ratings. Knowledge of the factors that contribute to this rater contrast effect is, however, limited. Using parent-rated ADHD symptoms from the Twins’ Early Development Study and a novel application of a twin model, we explored a range of socio-demographic variables (ethnicity, socio-economic status, and family size), as potential contributors to contrast effects and their interactive effect with gender composition of twin pairs. Gender did moderate contrast effects but only in DZ opposite-sex twin pairs. Family size also showed a moderating effect on rater contrast effects, which was further modified by gender. We further observed an effect of rating scale, with the DSM-IV ADHD subscale of the Revised Conners’ Parent Rating Scale more resistant to contrast effects than shorter scales of ADHD symptoms. The improved identification of situations where the accuracy of the most common informant of childhood ADHD symptoms—parents—is compromised as a result of rater bias, might have implications for future research on ADHD.     

Heredity,environment, and the Thurstone Temperament Schedule

Correlations on scales of the Thurstone Temperament Schedule are examined in two twin studies (Michigan and Veterans twin samples), an adoption study (Texas), and an unpublished twin-family study. It is concluded that the joint evidence suggests (1) an appreciable effect of additive genes, differing across scales; (2) a negligible influence of shared environments, except possibly for monozygotic (MZ) twins; (3) a possible contrast effect among dizygotic (DZ) twins on temperament and personality traits, but shared interests; and (4) a causally ambiguous elevation of MZ twin correlations, which could be due either to nonadditive genetic effects or to a special sharing of environments (or self-concepts) in this group.This work was supported in part by Grant BNS-7902918 from the National Science Foundation.     

The Impact of Variation in Twin Relatedness on Estimates of Heritability and Environmental Influences

By taking advantage of the natural variation in genetic relatedness among identical (monozygotic: MZ) and fraternal (dizygotic: DZ) twins, twin studies are able to estimate genetic and environmental contributions to complex human behaviors. Recently concerns have been raised about the accuracy of twin studies in light of findings of genetic and epigenetic changes in twins. One of the concerns raised is that MZ twins are not 100% genetically and epigenetically similar because they show variations in their genomes and epigenomes leading to inaccurate estimates of heritability. This article presents findings from a simulation study that examined the degree of bias in estimates of heritability and environmentality when the genetic and epigenetic similarity of MZ twins differs from 1.00 and when the genetic and epigenetic similarity of DZ twins differs from 0.50. The findings suggest that in the standard biometric model when MZ or DZ twin similarity differs from 1.00 or 0.50, respectively, the variance that should be attributed to genetic influences is instead attributed to nonshared environmental influences, thus deflating the estimates of genetic influences and inflating the estimates of nonshared environmental influences. Although estimates of genetic and nonshared environmental influences from the standard biometric model were found to deviate from “true” values, the bias was usually smaller than 10% points indicating that the interpretations of findings from previous twin studies are mostly correct.     

Genetic analysis of the resting electroencephalographic power spectrum in human twins

Most twin studies have provided evidence for genetic effects on the electroencephalogram (EEG). In two twin studies, monozygotic (MZ) cotwin covariance for EEG power was greater than expected for additive gene actions, as compared with dizygotic (DZ) cotwin covariance. These findings were attributed to complex gene interactions, termed emergenesis. In the present study of 53 MZ and 38 DZ twin pairs departures from the additive genetic model were tested on resting EEG power. Total spectral power and the quotient of (beta band power)/(total power) both fit gene interaction models significantly better than did additive genetic models. These findings support the previous findings of MZ covariance for EEG power as much greater than DZ covariance; these findings can be explained entirely by the additive effects of genes. This pattern of twin covariances could be due to gene interactions but also to greater MZ than DZ environmental covariance.     

Fetal alcohol syndrome in twins of alcoholic mothers: Concordance of diagnosis and IQ

The effects of teratogens can be modified by genetic differences in fetal susceptibility and resistance. Twins of alcoholic mothers provide a unique opportunity to study this phenomenon with respect to alcohol teratogenesis. Sixteen pairs of twins, 5 MZ and 11 DZ, all heavily exposed to alcohol prenatally, were evaluated. They represented all available twins of alcohol-abusing mothers who were on the patient rolls of the authors. The rate of concordance for diagnosis was 5/5 for MZ and 7/11 for DZ twins. In two DZ pairs, one twin had fetal alcohol syndrome (FAS), while the other had fetal alcohol effects (FAE). In 2 other DZ pairs, one twin had no diagnosis while one had FAE. IQ scores were most similar within pairs of MZ twins and least similar within pairs of DZ twins discordant for diagnosis. Despite equivalent alcohol exposure within twin pairs, alcohol teratogenesis appears to be more uniformly expressed in MZ than in DZ twins. These data are interpreted as reflecting the modulating influence of genes in the expression of the teratogenic effects of alcohol. © 1993 Wiley-Liss, Inc.     

A Note on the Statistical Power in Extended Twin Designs

The power to detect sources of genetic and environmental variance varies with sample size, study design, effect size and the statistical significance level chosen. We explored whether the power of the classical twin study may be increased by adding non-twin siblings to the classical twin design. Sample sizes to detect genetic and shared environmental variation were compared for kinships with only twins, kinships consisting of twins and one additional sibling, and kinships with twins and two additional siblings. The effect of adding siblings to the classical twin design was considered for univariate and bivariate analyses. For the univariate case, adding one non-twin sibling resulted in a decrease in sample size needed to detect additive genetic influences in the presence of environmental influences. However, adding two additional siblings did not decrease the number of subjects as compared to the classical twin design. The sample size required to detect common environmental factors was also greatly decreased by adding one non-twin sibling. Adding two non-twin siblings resulted in a small additional decrease. In models including additive genetic, dominant genetic, and unique environmental effects, adding one sibling to a twin family decreased the required sample size to detect dominant genetic influences. Adding two siblings to a twin family resulted in only a slight additional decrease in sample size. In the bivariate case a similar pattern of results was found, in addition to the observation that the overall required sample size, as expected, was lower than in the univariate case. The decrease in sample size from bivariate testing was more pronounced in a design with one or two additional siblings, as compared to a design with twins only. It is concluded that a well considered choice of family design, i.e. including families with twins and one or two additional siblings increases the statistical power to detect sources of variance due to additive and non-additive genetic influences, and common environment.     

Heritability of reproductive hormones in adult male twins

BACKGROUND: Proper functioning of the male reproductive axis depends on complex feedback systems between several hormones. In this study, the genetic contribution of various endocrine components of the hypothalamic-pituitary-testicular axis is evaluated and previously observed differences in FSH and inhibin B levels between mono- (MZ) and dizygotic (DZ) twins are re-investigated. METHODS: Inhibin B, FSH, LH, sex hormone-binding globulin (SHBG) and testosterone levels were assayed in 128 adult males (20 MZ twin pairs, 7 single MZ twins, 10 DZ twin pairs, 27 single DZ twins and 34 siblings of twins, constituting 10 sibling pairs), aged 15.6-68.7 years. Hormone levels were compared across zygosity groups and heritability estimates were obtained using maximum likelihood variance component analysis. RESULTS: Heritability estimates ranged from 56% (testosterone) to 81% (inhibin B and SHBG). For LH and FSH, the heritability was estimated at 68% and 80% respectively. No mean differences in hormone levels were observed across groups. CONCLUSIONS: All measured hormones are highly heritable. A difference in the FSH-inhibin B feedback system between DZ twin males and MZ twin males could not be confirmed.     

Neuropathologic Assessment of Dementia Markers in Identical and Fraternal Twins

Twin studies are an incomparable source of investigation to shed light on genetic and non‐genetic components of neurodegenerative diseases, as Alzheimer's disease (AD). Detailed clinicopathologic correlations using twin longitudinal data and post‐mortem examinations are mostly missing. We describe clinical and pathologic findings of seven monozygotic (MZ) and dizygotic (DZ) twin pairs. Our findings show good agreement between clinical and pathologic diagnoses in the majority of the twin pairs, with greater neuropathologic concordance in MZ than DZ twins. Greater neuropathologic concordance was found for β‐amyloid than tau pathology within the pairs. ApoE4 was associated with higher β‐amyloid and earlier dementia onset, and importantly, higher frequency of other co‐occurring brain pathologies, regardless of the zygosity. Dementia onset, dementia duration, difference between twins in age at dementia onset and at death, did not correlate with AD pathology. These clinicopathologic correlations of older identical and fraternal twins support the relevance of genetic factors in AD, but not their sufficiency to determine the pathology, and consequently the disease, even in monozygotic twins. It is the interaction among genetic and non‐genetic risks which plays a major role in influencing, or probably determining, the degeneration of those brain circuits associated with pathology and cognitive deficits in AD.     

Genetic and environmental contributions to allergen sensitization in a Chinese twin study

Background Allergic disease is on the rise worldwide. Effective prevention of allergic disease requires comprehensive understanding of the factors that contribute to its intermediate phenotypes, such as sensitization to common allergens. Objective To estimate the degree of genetic and environmental contributions to sensitization to food and aeroallergens. Methods Sensitization was defined as a positive skin prick test to an allergen. We calculated the zygosity‐specific concordance rates and odds ratios (ORs) for sensitization to food and aeroallergens in 826 Chinese twin pairs [472 monozygotic (MZ) and 354 dizygotic (DZ)] aged 12–28 years. We also applied structural equation modelling procedures to estimate genetic and environmental influences on sensitization. Results The concordance rates and risk of sensitization in one twin given the presence vs. the absence of sensitization in the other twin were higher in MZ twins than those in DZ twins. However, a large number of MZ twins were discordant in sensitization to common allergens. These observations suggest both genetic and environmental factors influence sensitization. Consistently, the estimated heritability and individual environmental components of the liability to sensitization ranged from 0.51 to 0.68 and 0.32 to 0.49, respectively, based on the best‐fitted structural equation model. We also observed high phenotypic correlations between sensitization to two aeroallergens (cockroach and dust mite: 0.83) and two food allergens (peanut and shellfish: 0.58), but only moderate correlations for the pairs between sensitization to a food and an aeroallergen (0.31–0.46). The shared genetic and environmental factors between paired sensitizations contribute to the observed correlations. Conclusion We demonstrated that sensitization to common food and aeroallergens were influenced by both genetic and environmental factors. Moreover, we found that paired allergen sensitizations might share some common sets of genes and environmental factors. This study underscores the need to further delineate unique and/or pleiotropic genetic and environmental factors for allergen sensitization.     

Twin study of genetic and aging effects on X chromosome inactivation

To investigate the genetic influence on X chromosome inactivation and on age-related skewing of X inactivation, in particular, we analysed the X inactivation pattern (XIP) in peripheral blood cells from 118 young monozygotic (MZ) twin pairs (18-53 years), 82 elderly MZ twin pairs (55-94 years), 146 young dizygotic (DZ) twin pairs (20-54 years) and 112 elderly DZ twin pairs (64-95 years). Elderly twins had a higher frequency of skewed X inactivation (34%) than young twins (15%) (P<0.001). Our data suggest that the increase in skewing occurs after age 50-60 years. The intraclass correlation was 0.61 and 0.58 in young and elderly MZ twin pairs, and 0.08 and 0.09 in young and elderly DZ twin pairs. Biometric analysis showed that dominant genetic effects accounted for 63 and 58% of the variance of XIP in the young and elderly twin pairs, respectively. The dominant genetic effect and the shared environment for monochorionic MZ twins may explain the high intraclass correlation for the MZ twin pairs compared to the DZ twin pairs. We did not observe a significant decrease in the intraclass correlation in elderly MZ twins compared to young MZ twins, which would be expected if age-related skewing were due to stochastic factors. We conclude that the increased skewing with age implies that a genetically dependent selection of blood cells take place.     

Multiple raters of disruptive child behavior: Using a genetic strategy to examine shared views and bias

Most research on child behavior incorporates information from different individuals. While agreement between informants is generally only modest, there is little understanding of the processes underlying disagreement. In twin studies, differential agreement among raters for MZ and DZ twins is of particular concern. The processes underlying differences among mother, father, and child ratings of oppositional and conduct disorder symptoms are explored. Evidence in favor of a shared parental view of behavior is presented. Parental ratings give higher intrapair correlations, which could be due to either parents rating their twins more similarly or twins contrasting themselves. Rater bias and situational specificity are among the possible explanations of differential ratings. The effects of incorporating multiple raters of behavior on estimates of genetic and environmental effects are explored. These suggest that genetic influences are greater for the shared (multiple-rater) phenotype than for individual ratings; reduction in measurement error is only a partial explanation.     

Toddler see,toddler do? Genetic and environmental influences on laboratory-assessed elicited imitation

The imitative performance of 311 pairs of 24-month old twins (143 MZ, 168 same-sex DZ) was assessed via three multi-step imitative sequences. Composite imitation score correlations suggested the presence of genetic influences on imitation, with MZ correlations significantly exceeding DZ correlations. Univariate model-fitting procedures supported this finding. Substantial broad heritability was found for imitative performance, with no evidence for shared environment. However, we are unable to say with certainty to what extent this heritability is represented by additive and nonadditive genetic variance. Estimates of heritability derived from both ACE and ADE model-fitting procedures accounted for approximately 50% of the total variance, with the remaining variance in imitative performance attributable to nonshared environmental factors. Edited by Dorret Boomsma & John K Hewitt     

Biometrical genetic models of self-reported delinquent behavior: A twin study

Adolescent twins reported delinquent acts on an anonymous questionaire. Intraclass correlations and mean squares were obtained by analysis of variance. Monozygotic (MZ) twins were more alike in their rates of antisocial behavior (ABS) than dizygotic (DZ) twins, and this result held for both sexes (rs MZ, 0.62–0.74; rs DZ, 0.46–0.52). Biometrical models were fitted to ASB (untransformed and log-transformed) mean squares. Only models containing a parameter for additive genetic variability fitted; the purely environmental common environment (CE) specific environment (SE) model was rejected. Several tests supported the equal environments assumption, indicating that the inference of genetic influence was legitimate. However, antisocial behavior was a complex “phenotype.” A correlation between pair means/differences showed that influences common to twin partners interacted with SE. This result suggested that random evironmental opportunities which may be present for one twin but not the other had an effect on delinquency rates. Twins also commited delinquent acts with one another. This result provides a different interpretation for the “common-environment” parameter; this parameter may reflect the influence of one twin on the other, rather than aspects of home environment determined by the twins' parents.