Quantitative genetic analysis of internalising and externalising problems in a large sample of 3-year-old twins.

For a quantitative genetic study of pre-school problem behaviours, we have collected data with the Child Behavior Checklist for 2 and 3-year-old children (CBCL 2/3). Questionnaires were completed by mothers of 3620 twin pairs: 633 monozygotic males, 581 dizygotic males, 695 monozygotic females, 519 dizygotic females and 1192 dizygotic opposite sex twin pairs. The genetic and environmental influences on the Externalising and Internalising Problem scales were estimated, simultaneously with sex differences and sibling interaction effects. Genetic factors explained most of the observed variance for both Externalising and Internalising Problems. Cooperative sibling interactions were found for Externalising Problems, indicating that twins reinforce each other's behaviour. Sex differences in genetic architecture were found for Externalising Problems. Genetic factors explained 75% of the variance in girls and 50% in boys. Shared environmental influences were only of importance in boys. For both problem scales, non-shared environmental factors accounted for 25 to 32% of the variance. The observed variances of Internalising Problems could be adequately explained by genetic and nonshared environmental factors, with genetic factors accounting for 68% of the variance.     

Sex differences in the prevalence of human birth defects: a population-based study.

BACKGROUND: Sex differences in the prevalence of several human birth defects have often been reported in the literature, but the extent of sex differences for most birth defects is unknown. To determine the full extent of sex differences in birth defects in a population, we examined population-based data from the Metropolitan Atlanta Congenital Defects Program (MACDP). METHODS: MACDP records were analyzed for 1968 through 1995. We determined the sex-specific prevalence of all major birth defects, using the total number of live births by sex during these years as the denominator. For each specific defect, we calculated a relative risk with regard to sex on the basis of the ratio of prevalence among males to prevalence among females. Male-female relative risks were also determined for total major birth defects and for several broad categories of defects. RESULTS: The overall prevalence of major defects at birth was 3.9% among males and 2.8% among females. All but two of the major categories of birth defects (nervous system defects and endocrine system defects) had a higher prevalence among males. Defects of the sex organs were eight and one-half times more prevalent among males and accounted for about half of the increased risk of birth defects among males relative to females. Urinary tract defects were 62% more prevalent among males, and gastrointestinal tract defects were 55% more prevalent among males. Among specific defect types, twofold or greater differences in prevalence by sex were common. CONCLUSIONS: Our data indicate that sex differences in the prevalence of specific human birth defects are common, and male infants are at greater risk for birth defects than female infants. Several mechanisms have been proposed to account for these differences.     

Twins,triplets, and cerebral palsy in births in Western Australia in the 1980s.

OBJECTIVES--To examine the rate of cerebral palsy in twins and triplets in births from 1980 to 1989 in Western Australia and to identify factors associated with increase in risk. DESIGN--Pluralities for all births in Western Australia were identified through the standardised midwives'' notification system, and cases of cerebral palsy were identified from the Western Australian cerebral palsy register. MAIN OUTCOME MEASURES--Multiple births, cerebral palsy, excluding postneonatal cause. RESULTS--The prevalence of cerebral palsy in triplets, of 28 per 1000 survivors to 1 year (95% confidence interval 11 to 63) exceeded that in twins (7.3; 5.2 to 10) and singletons (1.6; 1.4 to 1.8). Although twins and triples were more likely than singletons to be low in birth weight, their risks of cerebral palsy if low in birth weight were similar. In contrast, in normal birthweight categories twins had a higher rate of cerebral palsy (4.2; 2.2 to 7.7) than singletons (1.1; 1.0 to 1.3). The prevalence of cerebral palsy was similar in twins of unlike sex pairs, all of whom are dizygotic, and in like sex pairs. A twin pair in which one member died in utero was at higher risk of cerebral palsy: 96 per 1000 twin pairs (36 to 218) compared with 12 (8.2 to 17) for twin pregnancies in which both survived. There was a similar but non-significant trend for death of one triplet to be associated with increased risk of cerebral palsy in the survivors of the set. CONCLUSION--Triplet pregnancies produced a child with cerebral palsy 47 times more often than singleton pregnancies did and twin pregnancies eight times more often. Eighty six per cent of cerebral palsy in multiple births was in twins. As multiple births are increasing mainly because of personal and medical decisions the increased risk of cerebral palsy in multiple births is of concern.     

Correlations between live and stillbirth outcomes in twin pairs

A relationship has been proposed to exist between individual outcomes (live or stillbirth) of twins in the same set. Here, we analyze this association between live births and stillbirths among individuals in different twin pairs. When national birth registers are analyzed, individuals in opposite-sex twin sets can be identified and the correlation between individual outcomes estimated. However, full information about the individuals in same-sex twin sets is not, as a rule, available, and consequently, correlation coefficients cannot be estimated, but upper and lower limits of the correlation coefficients can be obtained. The methods introduced here were applied to data from Sweden (1869-1967), the Aland Islands (Finland) (1750-1949), the Kingdom of Saxony (1881-1900), and England and Wales (1940-2003). Comparisons between the correlation coefficients among opposite-sex twins and the lower bound (minimum) of correlation coefficients among same-sex twins indicate that in all populations studied a stronger association exists between twins in same-sex rather than opposite-sex twin sets or pairs. For opposite-sex twin sets no general association between the correlation coefficient and the stillbirth rate was identified.     

Otitis media: genetic factors and sex differences.

Although genetic factors are recognised as major contributors to otitis media, the presence of sex differences in heritability needs clarification. The aim of this study was to estimate the relative contribution of genetic and environmental effects in otitis media liability with particular focus on sex differences. Data from a cohort of Norwegian twins born between 1967 and 1979 with repeated measures on recurrent childhood otitis media were analysed. Altogether the sample included 4247 twin pairs. The tetrachoric correlations for monozygotic twins were .71 and .65 for males and females respectively. In dizygotic twins the correlations were .35 and .25 for males and females, respectively, and was.34 in opposite sexed pairs. The contribution of genetic and environmental effects was analyzed using structural equation modeling. The best fitting model showed that additive genetic effects explained 72% and 61% of the variance in males and females, respectively. The remaining variance was attributed to individual environmental effects. A model specifying equal heritability estimates for males and females yielded an almost equivalent fit. We found substantial genetic effects for liability to otitis media. There is no evidence that different sets of genes influence liability in males and females, but there may be sex differences in the relative importance of genetic effects.     

Comparing sensory experience in bitter taste perception of phenylthiocarbamide within and between human twins and singletons: intrapair differences in thresholds and genetic variance estimates

BACKGROUND: Quantitative genetic studies revealed that not all of the phenotypic variance in PTC taste perception is heritable. AIM: To study quantitative variations in PTC tasting ability in twins and to estimate heritability of PTC taste perception on the taste of twin data on males and females sexes separately. SUBJECTS AND METHODS: The data for PTC taste sensitivity following the classic method of Harris & Kalmus (1949) were collected on a sample of 141 twin pairs (66 MZ and 75 DZ) and 275 singletons (128 males and 147 females) from Chandigarh, India. Genetic analyses were performed following Christian (1979), Donner (1986) and Sham (1998). RESULTS: Frequency of non-tasters was similar in twins (33 %) and singletons (32 %), but significant sex differences were observed. No differences were found between zygosities for mean thresholds. Similarly, no evidence of variance heterogeneity and environmental covariance was seen between zygosities. Since no basic assumption of the twin method was found violated, within-pair estimates of genetic variance would be unbiased. These estimates were highly significant in both males and females. However, dominance and additive components of genetic variance were found to differ between sexes. CONCLUSION: PTC thresholds do not seem to be significantly affected by environmental factors as no variance inequality was observed between twin zygosities. Intensity of bitterness (scalar dimensions) of PTC is a separate trait having no commonality with the genetic basis of recognition threshold for PTC tasting ability. The receptors recognizing bitter taste are different from the receptors determining intensity of taste. The absolute difference between co-twins in PTC thresholds can be used as a simple tool in the twin zygosity diagnosis. The results show that none of the MZ co-twins had manifested difference of more than 3 in their PTC threshold.     

Sex difference in heritability of BMI in South Korean adolescent twins

Twin studies of BMI on the basis of Asian twins are extremely rare. Eight hundred eighty-eight pairs of twins [279 monozygotic (MZ) and 82 dizygotic (DZ) pairs of male twins, 319 MZ and 82 DZ pairs of female twins, and 126 opposite-sex pairs of DZ twins] completed items concerning height and weight through a mail and a telephone survey. A general sex-limitation model was applied to the data. Heritability estimate was greater among women than among men. However, there was little evidence of sex-specific genes. Under the best-fitting model, additive genetic variances were 82% [95% confidence interval (CI): 72% to 95%] for men and 87% (95% CI: 77% to 99%) for women; shared environmental variances were negligible in both men and women. These estimates of genetic and environmental factors in BMI found among South Korean adolescent twins were broadly in the range of those reported in previous studies of BMI based on Western twin samples.     

Effects of birth weight on later intelligence

Abstract

Identical twins are used to show the long‐term effects of birth weight when genetic and many environmental factors are controlled. Female twins between the ages of 6 and 10 are evaluated for performance IQ and other measures of activity. No relationship was found between any of these measures and birth weight except for IQ. The heavier cotwin had the higher IQ score even when the birth weight of each twin was above 2,500 grams. Birth order was not associated with intelligence within the twin pairs.     

Heritability of human brain functioning as assessed by electroencephalography.

To study the genetic and environmental contributions to individual differences in CNS functioning, the electroencephalogram (EEG) was measured in 213 twin pairs age 16 years. EEG was measured in 91 MZ and 122 DZ twins. To quantify sex differences in the genetic architecture, EEG was measured in female and male same-sex twins and in opposite-sex twins. EEG was recorded on 14 scalp positions during quiet resting with eyes closed. Spectral powers were calculated for four frequency bands: delta, theta, alpha, and beta. Twin correlations pointed toward high genetic influences for all these powers and scalp locations. Model fitting confirmed these findings; the largest part of the variance of the EEG is explained by additive genetic factors. The averaged heritabilites for the delta, theta, alpha and beta frequencies was 76%, 89%, 89%, and 86%, respectively. Multivariate analyses suggested that the same genes for EEG alpha rhythm were expressed in different brain areas in the left and right hemisphere. This study shows that brain functioning, as indexed by rhythmic brain-electrical activity, is one of the most heritable characteristics in humans.     

Genetic and environmental effects on age at menarche,and its relationship with reproductive health in twins

INTRODUCTION:

Menarche or first menstrual period is a landmark in reproductive life span and it is the most prominent change of puberty. The timing of menarche can be under the influence of genes as well as individual environmental factors interacting with genetic factors.

OBJECTIVE:

Our study objectives were (a) to investigate the heritability of age of menarche in twins, (b) to obtain the association between age of menarche and childhood factors, and reproductive events/behavior, (c) to examine whether or not having a male co-twin affects early/late menarche.

METHODOLOGY:

A group of female-female identical (n = 108, 54 pairs), non-identical twins (n = 68, 34 pairs) and 17 females from opposite-sex twin sets were identified from twin registries of Malaysia and Iran. Genetic analysis was performed via two methods of Falconers’ formula and maximum likelihood.

RESULTS:

Heritability was found to be 66% using Falconers’ formula and 15% using univariate twin analysis. Model analysis revealed that shared environmental factors have a major contribution in determining the age of menarche (82%) followed by non-shared environment (18%).

DISCUSSION:

Result of this study is consistent with that of the literature. Timing of menarche could be under the influence of shared and non-shared environmental effects. Hirsutism was found to have a higher frequency among subjects with late menarche. There was no significant difference in age of menarche between females of opposite-sex twins and females of same-sex twins.

CONCLUSION:

It is concluded that twin models provide a powerful means of examining the total genetic contribution to age of menarche. Longitudinal studies of twins may clarify the type of environmental effects that determine the age of menarche.     

Intrauterine growth restriction in like-sex twins discordant for structural defects

BACKGROUND: An increased risk for intrauterine growth restriction in the affected member of like-sex twin pairs discordant for hypospadias has been reported. The purpose of this study was to document patterns of birth weight disparities in like-sex twins discordant for a variety of structural defects in order to determine if this is a general phenomenon seen in twins who are discordant for any malformation, is seen only in pairs discordant for certain specific malformations, or is unique to hypospadias. METHODS: Data were extracted from the Latin American Collaborative Study of Congenital Malformations (ECLAMC). Between 1967 and 1999, all like-sex twin pairs discordant for hypospadias or any other isolated defect that met the criteria of at least 5 discordant pairs for which birth weight was available on both twins were selected. All nonmalformed like-sex twin pairs in the ECLAMC data base collected over the same study years were selected as controls. RESULTS: A total of 216 discordant malformed like-sex twin pairs in 13 defect categories and 328 nonmalformed like-sex twin pairs met the criteria for inclusion. The proportion of affected infants who were > or =20% smaller than their co-twin was statistically significantly different from controls for hypospadias, heart defects, anencephaly, and esophageal atresia. CONCLUSIONS: Intrauterine growth restriction seen in the affected member of like-sex twin pairs discordant for hypospadias is not unique, but occurs as well in at least 3 additional structural malformations.     

Twin concordance for a binary trait. II. Nested analysis of ever-smoking and ex-smoking traits and unnested analysis of a "committed-smoking" trait

Twin concordance rates for a binary trait can provide information about causes of trait variation. However, if trait prevalence varies with age (or birth cohort) or between the sexes, trait concordance rates will be artificially inflated because of the matching within pairs of twins. Our previous paper showed how to minimize the effects of such confounding by using logistic regression to model trait prevalence as a function of age and sex and that the binary correlation coefficient was useful as a measure of concordance that can be adjusted for trait prevalence. This method is extended here to allow for nested analyses and is applied to the smoking habits of a sample of 3,807 pairs of adult twins. For monozygotic (MZ) twins, the correlation coefficients for the binary trait of "ever-smoking" (males: .50 +/- .04; females: .60 +/- .02) were significantly greater than for dizygotic (DZ) twins (males: .37 +/- .05; females: .31 +/- .04; unlike-sex pairs: .21 +/- .03). For "giving-up smoking," given that both twins were previously smokers, the correlations for MZ twins (males: .37 +/- .07; females: .29 +/- .05) were also greater than for DZ twins (males: .11 +/- .09; females: .26 +/- .08; unlike-sex pairs: .13 +/- .06), although the difference was not statistically significant for females. Current smokers who had been smoking for at least 10 years were arbitrarily defined as "committed-smokers." The binary trait of "committed-smoking" was more strongly correlated in MZ twins (males: .41 +/- .06; females: .41 +/- .04) than in DZ twins (males: .22 +/- .08; females: .18 +/- .05; unlike-sex pairs: .16 +/- .05). These observations suggest that as well as depending on socially determined environmental factors, smoking behavior is influenced by genetic factors and/or by environmental factors unique to the MZ twin environment, which are of particular importance as determinants of "committed-smoking." There is a need for further research to investigate the personal characteristics of "committed-smokers" and to seek intervention strategies that are more suited to the needs of individual smokers.     

Twin births to mothers who are twins: a registry based study.

OBJECTIVES: To estimate the risk of having twin infants for mothers who are twins; to investigate the genetic influence on twinning. DESIGN: Retrospective study of multiple births in two nationwide registries. SETTING: Sweden. SUBJECTS: Multiple births among 31,586 deliveries between 1973 and 1991 to women who were twins. MAIN OUTCOME MEASURES: Numbers of monozygotic and dizygotic twin births expected and estimated. RESULTS: Women who are dizygotic twins have a moderately increased risk of having twins (relative risk 1.30, 95% confidence interval 1.14 to 1.49) which seems to be completely the result of dizygotic twinning. When a mother is a monozygotic twin, her risk of having twins of the same sex is significantly increased (1.47; 1.10 to 1.97). This is the result of an excess of monozygotic twins (39 pairs estimated, 18 expected). CONCLUSIONS: Women who are twins have an increased risk of giving birth to twins. Genetic components of monozygotic and dizygotic twinning seem to be independent.     

Individual differences in adolescent religiosity in Finland: familial effects are modified by sex and region of residence.

Data from 16-year-old Finnish twin pairs were used to estimate familial effects on religiosity and the modification of those effects by sex and residential region. The sample of 2265 twin boys and 2521 twin girls formed 779 monozygotic and 1614 dizygotic pairs, 785 of the same sex and 829 of opposite sex. We compared religiosity scores of twins living in more rural and traditional northern Finland with those living in the more urban and secular southern region. Girls had higher religiosity scores than did boys, and twins living in northern Finland had higher religiosity scores than those resident in southern Finland. Correlations for monozygotic twins were slightly higher than those for dizygotic twins, and covariance modeling found modest heritability of religiosity [11% (95% CI 0-24) for girls; 22% (95% CI 6-38) for boys], and substantial shared environmental effects [60% (95% CI 49-69) and 45% (95% CI 31-57)] among girls and boys, respectively. The correlation between shared environmental effects in boys and girls was estimated to be 0.84 (95% CI 0.73-0.99). In analyses distinguishing region of residence, girls living in southern Finland were found to have significantly higher unshared environmental effects than girls in northern Finland, while boys living in the urban south appeared to have lower shared environmental effects, and higher additive genetic effects, than boys living in the rural north.     

Plantar pressures in identical and non-identical twins

Identifying environmental risk factors for musculoskeletal disorders is challenging due to the number of potential confounders. Twins are of particular interest for researchers interested in studying these types of problems due to their inherent control for the influence of genetic factors. In twin studies, this population can allow environmental risk factors to be more easily identified, and this type of study design may allow the role of biomechanics in injury and disease to be further explored. At present, it is unclear if foot function displays more similarity between certain types of twins. In this study, we hypothesized that the plantar pressures of monozygotic (identical) twins would be more similar between pairs than dizygotic (non-identical) twins. We measured static and dynamic plantar pressures from five pairs of each twin type. Statistical parametric modeling was used to compare pressure distributions at the sensor level. For >80% of stance phase, the pixel level analysis indicated that monozygotic twins had less variation in plantar pressure between pairs. The average z-statistic across the entire trial was 0.88 for the monozygotic group and 1.13 for the dizygotic group. In this study we provide evidence of greater similarity of plantar pressures in monozygotic twin pairs compared to dizygotic twins. This finding supports the use of co-twin studies investigating potentially modifiable environmental and biomechanical risk factors for musculoskeletal conditions that affect the foot and ankle.     

Comparing blood pressure of twins and their singleton siblings: being a twin does not affect adult blood pressure.

The hypothesis was tested that monozygotic (MZ) and dizygotic (DZ) twins, with their lower average birth weight, have higher adult blood pressure than their singleton brothers or sisters. From the Netherlands Twin Registry, 261 twin families were recruited from a young adult and an older adult cohort with mean ages of 26.2 and 50.4 respectively. These families yielded 204 MZ twins with 71 singleton siblings and 271 DZ twins with 103 of their singleton siblings. Anti-hypertensive medication use of these 649 participants was assessed twice with a two-year interval. Resting blood pressure was measured thrice during a standardized laboratory protocol. In spite of a significant difference in birth weight (1036 gram), no differences were found in anti-hypertensive medication use at both time points between twins and singletons nor between their resting laboratory diastolic or systolic blood pressure. These results applied to each gender and to both age cohorts. Limiting the analyses to matched twin-sibling pairs of the same families and taking current weight and height into account did not change the results; no evidence was found for a twin-singleton difference. It was concluded that estimates of genetic and environmental contributions to blood pressure deriving from twin studies do not appear to be biased and may be generalized to singletons. Our results suggest that the lower birth weight in twins does not reflect the intrauterine disadvantage described by the Barker hypothesis.     

X chromosome inactivation patterns correlate with fetal-placental anatomy in monozygotic twin pairs: implications for immune relatedness and concordance for autoimmunity.

BACKGROUND: Monozygotic (MZ) twinning is a poorly understood phenomenon that may result in subtle biologic differences between twins, despite their identical inheritance. These differences may in part account for discordant expression of disease in MZ twin pairs. Due to their stochastic nature, differences in X chromosome inactivation patterns are one source of such variation in female MZ twins. MATERIALS AND METHODS: We investigated X chromosome inactivation patterns in the blood of 41 MZ twin pairs based on methylation of the androgen receptor gene using a Hpa II-PCR assay. Twenty-six female MZ twin pairs with autoimmune disease (rheumatoid arthritis or multiple sclerosis) were studied. In addition, we studied 15 newborn female MZ twin pairs who were characterized at birth with respect to the anatomy of chorionic membranes (dichorionic versus monochorionic). RESULTS: We found a strong correlation between dichorionic fetal anatomy and differences in X chromosome inactivation patterns between members of an MZ twin pair. In contrast, all monochorionic twin pairs had closely correlated patterns of X chromosome inactivation. X chromosome inactivation patterns did not distinguish between MZ twin pairs who were concordant or discordant for autoimmune disease. CONCLUSIONS: The highly similar patterns of X chromosome inactivation among monochorionic twin pairs may result from their shared placental blood supply during intrauterine life. Alternatively, these patterns may indicate that X chromosome inactivation occurs before the twinning event in this anatomic subgroup of MZ twins. The data further suggest that these factors do not make a major contribution to the high discordance rates for autoimmune disease in MZ twin pairs.     

Potential bias regarding birth weight in historical and contemporary twin data bases.

In this study we examine the hypothesis that monozygotic (MZ) twins in historical databases are less discordant for birth weight due to negative selection of severely discordant MZ twins. Furthermore, we test the hypothesis that MZ twins are less discordant for birth weight when comparing a volunteer based twin registry with a population based twin registry, due to selective registration. Data were available on 3927 twin pairs from the volunteer Australian Twin Registry born before 1964, 3059 volunteer twin pairs from the Netherlands Twin Register born 1987-1989 and 454 Belgian twin pairs from The East Flanders Prospective Twin Survey born 1987-1989. Intrapair relative birth weight differences (RBWD) were computed for MZ and dizygotic (DZ) twins from each twin registry. Comparing birth weight differences between MZ and DZ twins provides support for the hypothesis that MZ twins are subject to a negative selection in historical databases. Furthermore, Australian MZ twins have a lower RBWD compared to Dutch MZ twins when corrected for the RBWD of Australian and Dutch DZ twins, indicating circumstances which only affect MZ twins. Our hypothesis that MZ twins are less discordant for birth weight in a volunteer based twin registry compared to a population based twin registry had to be rejected. We suggest that investigators using historical databases to test the fetal origins hypothesis should be aware of this increased likelihood of selective exclusion of individuals with extreme morphometric parameters at time of birth.     

The risk of birth defects in dichorionic twins conceived by assisted reproductive technology.

The purpose of this study was to examine whether dichorionic twins conceived by assisted reproductive technology (ART; intracytoplasmic sperm injection [ICSI], in vitro fertilization [IVF], gamete-intrafallopian tube transfer [GIFT]) have a higher risk of birth defects compared to dichorionic twins conceived naturally. We reviewed the medical records of 406 mothers with dichorionic twin pregnancies, who received continuous antenatal care from < or = 20 weeks of gestation and gave birth to infants after > or = 24 weeks of gestation in our institute. Birth defects were diagnosed at the time of hospital discharge according to the International Classification of Diseases, 10th Revision. Occurrence of birth defects was compared between twins conceived by ART and those conceived naturally using logistic regression analysis. Overall, 51 of 812 infants (51/812 = 6.2%) had birth defects. The incidence of birth defects in ART-conceived twins was significantly higher than that of naturally conceived twins with an odds ratio of 6.9 (95% confidence interval [CI] 2.1, 22.5), 3.7 (95% CI 1.2, 12.0), and 4.3 (95% CI 1.4, 14.3) for ICSI, IVF, and GIFT, respectively. The higher frequency of birth defects in ART-conceived twins was still significant after adjusting for higher maternal age in the ART group, with an adjusted odds ratio of 6.7 (95% CI 2.1, 21.9), 3.6 (95% CI 1.1, 11.5), and 3.7 (95% CI 1.2-11.8) for ICSI, IVF, and GIFT, respectively. Dichorionic twins conceived by ART, compared to dichorionic twins conceived naturally, had a much higher risk for birth defects diagnosed at hospital discharge.     

Genetic and environmental influences on Anxious/Depression during childhood: a study from the Netherlands Twin Register

For a large sample of twin pairs from the Netherlands Twins Register who were recruited at birth and followed through childhood, we obtained parental ratings of Anxious/Depression (A/D). Maternal ratings were obtained at ages 3 years (for 9025 twin pairs), 5 years (9222 pairs), 7 years (7331 pairs), 10 years (4430 pairs) and 12 years (2363 pairs). For 60-90% of the pairs, father ratings were also available. Multivariate genetic models were used to test for rater-independent and rater-specific assessments of A/D and to determine the genetic and environmental influences on individual differences in A/D at different ages. At all ages, monozygotic twins resembled each other more closely for A/D than dizygotic twins, implying genetic influences on variation in A/D. Opposite sex twin pairs resembled each other to same extent as same-sex dizygotic twins, suggesting that the same genes are expressed in boys and girls. Heritability estimates for rater-independent A/D were high in 3-year olds (76%) and decreased in size as children grew up [60% at age 5, 67% at age 7, 53% at age 10 (60% in boys) and 48% at age 12 years]. The decrease in genetic influences was accompanied by an increase in the influence of the shared family environment [absent at ages 3 and 7, 16% at age 5, 20% at age 10 (5% in boys) and 18% at age 12 years]. The agreement between parental A/D ratings was between 0.5 and 0.7, with somewhat higher correlations for the youngest group. Disagreement in ratings between the parents was not merely the result of unreliability or rater bias. Both the parents provided unique information from their own perspective on the behavior of their children. Significant influences of genetic and shared environmental factors were found for the unique parental views. At all ages, the contribution of shared environmental factors to variation in rater-specific views was higher for father ratings. Also, at all ages except age 12, the heritability estimates for the rater-specific phenotype were higher for mother ratings (59% at age 3 and decreasing to 27% at age 12 years) than for father ratings (between 14 and 29%). Differences between children, even as young as 3 years, in A/D are to a large extent due to genetic differences. As children grow up, the variation in A/D is due in equal parts to genetic and environmental influences. Anxious/Depression, unlike many other common childhood psychopathologies, is influenced by the shared family environment. These findings may provide support for why certain family therapeutic approaches are effective in the A/D spectrum of illnesses.