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.     

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 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.     

Parent- and Observer-Rated Positive Affect in Early Childhood: Genetic Overlap and Environmental Specificity

The sources of individual differences in both observed and parent-rated positive affect (PA) were examined in a sample of 304 3-year-old twin pairs (140 MZ, 164 DZ). Based on model-fitting analyses, individual differences in observed PA were attributed to moderate genetic and high nonshared environmental factors, but not shared environmental factors. In contrast, shared environmental effects accounted for over half of the variance in parent-rated PA and genetic and nonshared environmental effects were more modest. The genetic correlation across the two measures was high, indicating substantial overlap between genetic factors influencing the two. It was these overlapping genetic effects that fully explained the phenotypic correlation between both measures. There was no significant covariance between the environmental influences on parent rated and observed PA. Thus, the two measures of PA in early childhood have common genetic underpinnings, whereas environmental influences are measure-specific. Measurement implications are discussed.     

Family Matters: Happiness in Nuclear Families and Twins

Biometric studies have shown that happiness is strongly affected by genes. The findings are mainly based on twin data, however, and the full validity of the results has been debated. To overcome some limitations in classical twin research, we examined aetiological sources of subjective well-being (SWB), using two independent population-based samples, one including nuclear families (N = 54,540) and one including twins (N = 6,620). Biometric modelling using R was conducted to test for a data structure implying either non-additive genetic effects or higher environmental co-twin correlation in MZ than DZ pairs (violation of the EEA). We also estimated non-random mating, cultural transmission and shared environments specific for regular siblings and twins. Two sets of nested models were fitted and compared. The best explanatory model shows that family matters for happiness predominantly due to quantitative sex-specific genetic effects, a moderate spousal correlation and a shared twin environment. Upper limits for broad-sense heritability were estimated to be 0.33 (females) and 0.36 (males). Our study constitutes the most elaborate biometric study of SWB to date and illustrates the utility of including responses from multiple types of relatives in quantitative genetic analyses.     

Genetic and environmental influences on psychological distress in the population: General Health Questionnaire analyses in UK twins

BACKGROUND: The General Health Questionnaire (GHQ) is the most popular screening instrument for detecting psychiatric disorders in community samples. Using longitudinal data of a large sample of UK twin pairs, we explored (i) heritabilities of the four scales and the total score; (ii) the genetic stability over time; and (iii) the existence of differential heritable influences at the high (ill) and low (healthy) tail of the distribution. METHOD: At baseline we assessed the GHQ in 627 MZ and 1323 DZ female pairs and at a second occasion (3.5 years later) for a small subsample (90 MZ and 270 DZ pairs). Liability threshold models and raw ordinal maximum likelihood were used to estimate twin correlations and to fit longitudinal genetic models. We estimated extreme group heritabilities of the GHQ distribution by using a model-fitting implementation of the DeFries-Fulker regression method for selected twin data. RESULTS: Heritabilities for Somatic Symptoms, Anxiety, Social Dysfunction, Depression and total score were 0.37, 0.40, 0.20, 0.42 and 0.44, respectively. The contribution of shared genetic factors to the correlations between time points is substantial for the total score (73%). Group heritabilities of 0.48 and 0.43 were estimated for the top and bottom 10% of the total GHQ score distribution, respectively. CONCLUSION: The overall heritability of the GHQ as a measure of psychosocial distress was substantial (44%), with all scales having significant additive genetic influences that persisted across time periods. Extreme group analyses suggest that the genetic control of resilience is as important as the genetic control of vulnerability.     

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.     

Profile comparisons of physical growth for monozygotic and dizygotic twin pairs

Three different methods of analysing similarity of physical growth curves within MZ and DZ twin pairs are compared. The concordance of the curves for each pair can be measured by either a multiple regression coefficient (R2) or the square root of the sum of squared differences between corresponding deviation points (D). The latter seems to be a more appropriate measure of profile contour similarity, mainly because the distance between curves is allowed for. An intra-class correlation based on a longitudinal analysis of variance seems to be a useful measure of average profile similarity for comparing groups of individuals. The distributions of the D measures, calculated for all MZ and DZ twin pairs, show MZ pairs to have significantly smaller D-values for both height and weight, on average, than DZ pairs. The intra-class correlations also show a higher concordance in developmental profile for MZ in comparison to DZ.     

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.     

Hay fever – a Finnish nationwide study of adolescent twins and their parents

Background Like other atopic diseases, hay fever is known to cluster in families. This clustering is due either to effects of a shared family environment or to genetic inheritance. By comparing the occurrence of hay fever among monozygous (MZ) and dizygous (DZ) twin pairs, we were able t o estimate the contribution of genetic and environmental factors in the development of hay fever.
Methods A questionnaire mailed to a nationwide sample of 2483 families with 16-year-old twins furnished data for the cumulative incidence of physician-diagnosed hay fever among these adolescents and their parents. Results Among the 1765 twin pairs with data available for analysis, hay fever was reported for 14.1% of boys (95% CI = 12.4-15.8%) and 10.0% of girls (95% CI=8.6-11.4%). The MZ twin pairs (probandwise concordance rate=60.3%, 95% CI=52-68%) were significantly more concordant for hay fever than were DZ twin pairs (31.5%, 95% Cl=26-36%). Genetic factors accounted for 74-82% of the interindividual variability in liability to hay fever, variation in shared family environment for 7% at most, and unique (individual) environment for 18%.
Conclusions Familial occurrence of hay fever is mainly due to genes predisposing to the trait. Environmental exposures shared in common by family members but varying between families appear to account for at most a modest proportion of the variability in risk of developing hay fever.     

Familial association between allergic disorders and depression in adult Finnish twins

Clinical studies have shown a relationship between allergic disorders and depression, panic disorder, attention deficit/hyperactivity disorder, and social anxiety for a significant subset of patients with these disorders. The nature of the relationship, whether due to shared environmental or biologic vulnerabilities or as a result of the stress of chronic illness, has been less clear. By examining the covariance of atopic disorders and depressive symptoms in a community sample of monozygotic (MZ) and dizygotic (DZ) twins, the contribution of genetic and/or shared environmental etiological factors can be established. A Finnish sample of 1337 MZ and 2506 DZ twin pairs, ages 33-60 years, was sent questionnaires inquiring about history of asthma, eczema, and atopic rhinitis, as well as the Beck Depression Inventory (BDI). The nature of the covariation between twins of these symptoms was investigated by fitting competing genetic and environmental models. Within-person correlation between atopic symptoms and BDI was 0.103 (P < 0.001) for the total sample. Using the Mx statistical modeling program to fit the data to competing quantitative genetic models, the best fitting model estimated that 64% of the association between atopy and BDI was due to shared familial vulnerability, primarily additive genetic influences. Although the measures for allergic disorders and depression are crude, this study supports the hypothesis that there is a small shared genetic risk for atopic and depressive symptoms, and if replicated, may open research for common mechanisms between allergic and depressive disorders. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:146-153, 2000.     

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.     

Sexual orientation,sexual identity,and sex-dimorphic behaviors in male twins

Sexual orientation, sexual identity, and sex-dimorphic behaviors were assessed concurrently and retrospectively, for childhood, in 95 pairs of male monozygotic (MZ) twins and 63 pairs of dizygotic (DZ) twins. There was a significantly higher rate of adult homosexuality among the MZ than among DZ twins. We employed a model-fitting approach using LISREL to test for genetic and environmental influences on variation for each trait singly and on the covariation among all six traits (three for childhood and three for adulthood). Univariate analyses confirmed the presence of familial factors for five of the six variables but were generally unable to distinguish shared environmental from genetic influences. Hierarchial tests of multivariate models supported the existence of an additive genetic factor contributing to the covariance among the variables. More restrictive multivariate models yielded a significant genetic influence on sexual orientation. Because of the different rates of orientation by zygosity and because of the restrictive nature of some of the multivariate models, our results are best considered tentative but do suggest that further biometrically oriented studies of sexual orientation and its correlates would be worthwhile.The study was supported by the New South Wales Institute of Psychiatry and by NIH Grant MH47227-01.     

Heritability of different measures of smooth pursuit eye tracking dysfunction: a study of normal twins

Research studies have found that smooth pursuit eye movement dysfunction may serve as an index of genetic liability to develop schizophrenia. The heritability of various measures of smooth pursuit eye tracking proficiency and the saccades that occur during smooth pursuit was examined in 64 monozygotic (MZ) and 48 dizygotic (DZ) twin pairs. Two age cohorts were assessed (11-12 and 17-18 years of age). Intraclass correlations indicated significant similarity in the MZ twins for almost all measures in both age cohorts, whereas few of the DZ twin correlations attained significance. Biometrical modeling indicated that genetic mechanisms influence performance on both global and specific eye tracking measures, accounting for about 40% to 60% of the variance. These findings suggest that the underlying brain systems responsible for smooth pursuit and saccade generation during pursuit are under partial genetic control.     

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.     

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     

Narcolepsy-like symptoms among adult twins

The genetic architecture of narcolepsy is poorly known. Genetic and environmental components of symptoms characteristic of narcolepsy, excessive sleepiness and cataplexy were assessed in a population-based sample of middle-aged like-sexed twin pairs. Questionnaire assessment of the 11-item Ullanlinna Narcolepsy Scale (UNS), a validated screening instrument for narcolepsy [ J. Sleep Res . (1994) 3 , 52–59] and two subscales (sleepiness and cataplexy-like symptoms) was obtained from both twins of 3785 pairs aged 33–60 y (541 male MZ pairs, 1089 male DZ pairs, 781 female MZ and 1374 female DZ pairs) from the population-based Finnish Twin Cohort. For the UNS scores, the intraclass correlation for male MZ pairs was 0.365 and for male DZ pairs 0.072, while for female pairs the MZ correlation was 0.375 and for DZ pairs 0.155. Structural equation model fitting indicated that a model with additive and non-additive genetic effects, and idiosyncratic environmental effects best accounted for the pattern of twin resemblance in both men and women. Genetic effects accounted for 35% (in men) and for 39% (in women) of total phenotypic variance in UNS. Analysis of the subscales suggested that there may be a greater genetic component to the sleepiness subscale, while environmental components play more of a role in the development of cataplexy-like symptoms. Further investigation of the complex genetic architecture of narcolepsy and its symptoms is warranted.     

ADHD: sibling interaction or dominance: an evaluation of statistical power

Sibling interaction effects are suggested by a difference in phenotypic variance between mono-zygotic (MZ) twins and dizygotic (DZ) twins, and a pattern of twin correlations that is inconsistent with additive genetic influences. Notably, negative sibling interaction will result in MZ correlations which are more than twice as high as DZ correlations, a pattern also seen in the presence of genetic dominance. Negative sibling interaction effects have been reported in most genetic studies on Attention Deficit Hyperactivity Disorder (ADHD) and related phenotypes, while the presence of genetic dominance is not always considered in these studies. In the present paper the statistical power to detect both negative sibling interaction effects and genetic dominance is explored. Power calculations are presented for univariate models including sources of variation due to additive genetic influences, unique environmental influences, dominant genetic influences and a negative sibling interaction (i.e., contrast effect) between phenotypes of twins. Parameter values for heritability and contrast effects are chosen in accordance with published behavior genetic studies on ADHD and associated phenotypes. Results show that when both genetic dominance and contrast effects are truly present and using a classical twin design, genetic dominance is more likely to go undetected than the contrast effect. Failure to detect the presence of genetic dominance consequently gives rise to slightly biased estimates of additive genetic effects, unique environmental effects, and the contrast effect. Contrast effects are more easily detected in the absence of genetic dominance. If the significance of the contrast effect is evaluated while also including genetic dominance, small contrast effects are likely to go undetected, resulting in a relatively large bias in estimates of the other parameters. Alternative genetic designs, such as adding pairs of unrelated siblings reared together to a classical twin design, or adding non-twin siblings to twin pairs, greatly enhances the statistical power to detect contrast effects as well as the power to distinguish between genetic dominance and contrast effects.     

Individual Differences in Handedness and Specific Speech and Language Impairment: Evidence Against a Genetic Link

Data from two twin studies were used to address two related questions. First, is there any association between handedness and specific speech and language impairment (SSLI) in children? Second, is there genetic influence on individual differences in handedness and, if so, are the same genes implicated in the cause of SSLI? The first study used data from 58 MZ and 26 DZ pairs previously recruited for an investigation into the genetic origins of SSLI. All pairs contained at least one child with SSLI. Handedness was assessed using a preference inventory and a tapping task from which a laterality quotient (LQ) was derived. There were no handedness differences between these twins and 172 singleborn controls, and neither measure revealed any association between handedness and SSLI. The data were equally well-fitted by a CE model (no genetic influence) and an AE model (no effect of shared environment) for both hand preference and tapping LQ. Nonshared environment was the largest influence on handedness for both measures. Bivariate analysis indicated no overlapping genetic influences on SSLI and handedness. In the second study, handedness was assessed in a general population sample of 48 MZ and 44 DZ twin pairs, aged 7 to 13 years, using a preference inventory and a peg-moving task. A subset of children was also given a test that assessed persistence of hand preference when reaching across the midline. The latter was the only measure to relate to children's language status, with language-impaired children showing less midline crossing. This appears to reflect neurodevelopmental immaturity, rather than a stable trait. To investigate familial transmission of handedness, inventory data for parents and their twins were combined for both samples. The most parsimonious model was one that accounted for parent-child resemblance solely in terms of cultural transmission. Overall, there was no evidence that genes play a role in determining stable individual differences in hand preference. Insofar as there are links between handedness and speech and language difficulties, these reflect delayed neuromotor maturation.