A twin study of genetic and environmental influences on psychological traits of eating disorders in a Japanese female sample.

The purpose of the present study was to clarify genetic and environmental origins of psychological traits of eating disorders using a Japanese female twin sample. Participants were 162 pairs of female twins consisting of 116 pairs of monozygotic (MZ) twins and 46 pairs of dizygotic (DZ) twins in their adolescence. Psychological traits of eating disorders were assessed with five subscales of the Eating Disorder Inventory (EDI). As a result of using univariate twin analyses, among five subscales of EDI (maturity fears, ineffectiveness, interpersonal distrust, interoceptive awareness, and perfectionism), perfectionism showed significant additive genetic contributions and individual specific environmental effects. On the other hand, maturity fears, ineffectiveness, interoceptive awareness, and interpersonal distrust indicated significant shared environment contributions and individual specific environment effects. The results suggest the importance of both genetic and shared environmental influences on psychological traits of eating disorders in the present study.     

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.     

Genetic and environmental influences on expression of recurrent headache as a function of the reporting age in twins.

To explore age-related mechanisms in the expression of recurrent headache, we evaluated whether genetic and environmental influences are a function of the reporting age using questionnaire information that was gathered in 1973 for 15- to 47-year-old Swedish twins (n = 12,606 twin pairs). Liability to mixed headache (mild migraine and tension-type headache) was explained by non-additive genetic influences (49%) in men aged from 15 to 30 years and additive genetic plus shared environmental influences (28%) in men aged from 31 to 47 years. In women, the explained proportion of variance, which was mainly due to additive genetic effects, ranged from 61% in adolescent twins to 12% in twins aged from 41 to 47 years, whereas individual specific environmental variance was significantly lower in twins aged from 15 to 20 years than in twins aged from 21 to 30 years. Liability to migrainous headache (more severe migraine) was explained by non-additive genetic influences in men, 32% in young men and 45% in old men, while total phenotypic variance was significantly lower in young men than in old men. In women, the explained proportion of variance ranged from 91% in the youngest age group to 37% in the oldest age group, with major contributions from non-additive effects in young and old women (15-20 years and 41-47 years, respectively) and additive genetic effects in intermediate age groups (21-40 years). While total variance showed a positive age trend, genetic variance tended to be stable across age groups, whereas individual specific environmental variance was significantly lower in adolescent women as compared to older women.     

Genetic and environmental contributions to prosocial behaviour in 2- to 9-year-old South Korean twins

Although over 50 twin and adoption studies have been performed on the genetic architecture of antisocial behaviour, far fewer studies have investigated prosocial behaviour, and none have done so on a non-western population. The present study examined mothers' ratings of prosocial behaviour in 514 pairs of 2- to 9-year-old South Korean monozygotic and dizygotic twins. Correlational analyses showed a tendency of increasing genetic effects and decreasing shared environmental effects with age although shared family environment effects and the moderating effects of age did not attain statistical significance in model-fitting analyses. The best-fitting model indicated that 55% (95% CI: 45-64%) of the variance in the 2- to 9-year-olds' prosocial behaviour was due to genetic factors and 45% (95% CI: 36-55%) was due to non-shared environmental factors. It is concluded that genetic and environmental influences on prosocial behaviour in young South Koreans are mostly similar to those in western samples.     

Causes of blood methylomic variation for middle-aged women measured by the HumanMethylation450 array

To address the limitations in current classic twin/family research on the genetic and/or environmental causes of human methylomic variation, we measured blood DNA methylation for 479 women (mean age 56 years) including 66 monozygotic (MZ), 66 dizygotic (DZ) twin pairs and 215 sisters of twins, and 11 random technical duplicates using the HumanMethylation450 array. For each methylation site, we estimated the correlation for pairs of duplicates, MZ twins, DZ twins, and siblings, fitted variance component models by assuming the variation is explained by genetic factors, by shared and individual environmental factors, and by independent measurement error, and assessed the best fitting model. We found that the average (standard deviation) correlations for duplicate, MZ, DZ, and sibling pairs were 0.10 (0.35), 0.07 (0.21), -0.01 (0.14) and -0.04 (0.07). At the genome-wide significance level of 10^?7, 93.3% of sites had no familial correlation, and 5.6%, 0.1%, and 0.2% of sites were correlated for MZ, DZ, and sibling pairs. For 86.4%, 6.9%, and 7.1% of sites, the best fitting model included measurement error only, a genetic component, and at least one environmental component. For the 13.6% of sites influenced by genetic and/or environmental factors, the average proportion of variance explained by environmental factors was greater than that explained by genetic factors (0.41 vs. 0.37, P value <10^?15). Our results are consistent with, for middle-aged woman, blood methylomic variation measured by the HumanMethylation450 array being largely explained by measurement error, and more influenced by environmental factors than by genetic factors.     

Genetic and environmental influences on bilateral dental asymmetry in Northwest Indian twins

The role of genetic and environmental factors on dental asymmetry (in maximum crown dimensions) was examined using 58 pairs of twins (23 MZ and 35 DZ) from Chandigarh, India. The t'-test for equality of means by zygosity showed only one variable significantly different among 56: this is ascribable to Type 1 error. Heterogeneity of MZ-DZ total variance was observed in 42.9% of traits of the two types (fluctuating and directional) of bilateral asymmetry. In general, MZ twins showed higher total variance than DZ pairs. MZ twins also showed stronger environmental covariance for a majority of the traits. Dental asymmetry measures thus yielded consistently low genetic variance ratios and indicated predominantly complex environmental determinism. Since fluctuating asymmetry is widely believed to be an environmental stress indicator, this data set allows confirmation of methods for detecting unequal environmental influences on the zygosities which bias estimates of genetic variance and heritability.     

Investigating the genetic and environmental structure of Cloninger's personality dimensions in adolescence.

In this study we examined the genetic and environmental structure of four dimensions from Cloninger's personality system: novelty-seeking (NS), harm-avoidance (HA), reward-dependence (RD), and persistence (PS). Although adult twin studies suggest that these personality dimensions are moderately heritable, this is the first twin study of Cloninger's personality dimensions in adolescence--a period marked by significant physiological and social changes. Study participants included 1851 adolescent twins between the ages of 11 and 18 years; 878 complete twin pairs and 95 singleton-responding twins. Subjects were participants in two community-based samples of twins residing in the state of Colorado. Results indicated that cross-sectional mean levels for NS, HA and RD tended to show modest increases across the adolescent years, while PS showed modest mean decreases. Consistent sex differences in means were found only for RD. Univariate biometrical twin models were used to decompose trait variance into genetic and environmental sources. Results indicated that for NS, HA and RD additive genetic influences and unique environmental effects were sufficient to explain the data. PS, however, could be explained by unique and common environmental effects only, with different patterns of common environmental effects for males and females. We found moderate heritability estimates for NS, HA and RD ranging from .28 to .36--with no evidence for sex-limitation in those influences.     

Glucocorticoid receptor binding in twin pairs is affected by shared environment but not by shared genes

We set out to determine whether glucocorticoid receptor activity is affected mainly by genetic or environmental factors. The affinity and capacity of the glucocorticoid receptor was measured using dexamethasone binding in whole leukocytes from 53 monozygotic and 48 dizygotic twin pairs. Receptor binding characteristics assayed from twin pairs on the same day were highly correlated within twin pairs irrespective of zygosity. Apparent Kd was negatively correlated with environmental temperature (R²=0.13, P<0.0001) but this did not confound the intra-pair correlation, suggesting a strong familial component independent of zygosity. Receptor binding parameters were not more closely correlated in monozygotic twins than dizygotic twin pairs indicating that there is no major genetic contribution to receptor binding and that environmental influences predominate. The close similarity in binding between twin pairs in adulthood raises the possibility that familial, non-genetic, factors such as shared early life environment may programme the glucocorticoid receptor.     

The heritability of human longevity: A population-based study of 2872 Danish twin pairs born 1870–1900

The aim of this study was to explore, in a large and non-censored twin cohort, the nature (i.e., additive versus non-additive) and magnitude (i.e., heritability) of genetic influences on inter-individual differences in human longevity. The sample comprised all identified and traced non-emigrant like-sex twin pairs born in Denmark during the period 1870–1900 with a zygosity diagnosis and both members of the pairs surviving the age of 15 years. A total of 2872 pairs were included. Age at death was obtained from the Danish Central Person Register, the Danish Cause-of-Death Register and various other registers. The sample was almost non-censored on the date of the last follow-up (May 1, 1994), all but 0.6% had died, leaving a total of 2872 pairs for analysis. Proportions of variance attributable to genetic and environmental factors were assessed from variance-covariance matrices using the structural equation model approach. The most parsimonious explanation of the data was provided by a model that included genetic dominance (non-additive genetic effects caused by interaction within gene loci) and non-shared environmental factors (environmental factors that are individual-specific and not shared in a family). The heritability of longevity was estimated to be 0.26 for males and 0.23 for females. The small sex-difference was caused by a greater impact of non-shared environmental factors in the females. Heritability was found to be constant over the three 10-year birth cohorts included. Thus, longevity seems to be only moderately heritable. The nature of genetic influences on longevity is probably non-additive and environmental influences non-shared. There is no evidence for an impact of shared (family) environment.     

Etiology of individual differences in birth weight of twins as a function of maternal smoking during pregnancy.

Birth weight is in large extent influenced by gestational age. In addition genetic and environmental factors determine intrauterine growth and birth weight. The contributions of these factors may be influenced by maternal smoking during pregnancy. We examined birth weight and maternal smoking in a sample of 2930 twin pairs from the Netherlands Twin Register using structural equation modelling. Gestational age accounted for 27-44% of the variance in birth weight. A lower variability of birth weight and a lower association of birth weight with gestational age was found in twins whose mothers smoked during pregnancy. The variance not associated with gestational age was independent of maternal smoking during pregnancy. A systematic smaller part of the variability in birth weight was associated with variability in gestational age in second born twins compared to first born twins. The heritability of interindividual differences in birth weight was modest (10% for twins with non-smoking mothers and 11% for twins with smoking mothers). Common environmental influences other than gestational age accounted for a slightly larger part of the variance not associated with gestational age (17-20%).     

Heritability of eleven metabolic phenotypes in Danish and Chinese twins: A cross‐population comparison

Objectives : A twin‐based comparative study on the genetic influences in metabolic endophenotypes in two populations of substantial ethnic, environmental, and cultural differences was performed. Design and Methods : Data on 11 metabolic phenotypes including anthropometric measures, blood glucose, and lipids levels as well as blood pressure were available from 756 pairs of Danish twins (309 monozygotic and 447 dizygotic twin pairs) with a mean age of 38 years (range: 18‐67) and from 325 pairs of Chinese twins (183 monozygotic and 142 dizygotic twin pairs) with a mean age of 40.5 years (range: 18‐69). Twin modeling was performed on full and nested models with the best fitting models selected. Results : Heritability estimates were compared between Danish and Chinese samples to identify differential genetic influences on each of the phenotypes. Except for hip circumference, all other body measures exhibited similar heritability patterns in the two samples with body weight showing only a slight difference. Higher genetic influences were estimated for fasting blood glucose level in Chinese twins, whereas the Danish twins showed more genetic regulation over most lipids phenotypes. Systolic blood pressure was more genetically controlled in Danish than in Chinese twins. Conclusions : Metabolic endophenotypes show disparity in their genetic determinants in populations under distinct environmental conditions.     

Application of multiparametric procedures for assessing the heritability of circadian health

At present, the measurement of circadian system status under free-living conditions by the use of sensors is a relatively new technique. The data obtained using these methods are influenced by strong environmental masking factors and artifacts that can affect its recording. Therefore, the use of integrative variables such as TAP, a measure that includes temperature, activity and position that reduces these drawbacks and the number of parameters obtained is necessary. However, the relative genetic contribution to this circadian marker is unknown. The aim of our study was to ascertain the relative importance of genetic influences in TAP, and for each of its components using classical twin models. The study was performed in 53 pairs of female twins [28 monozygotic (MZ) and 25 dizygotic (DZ)] with mean age 52 ± 6 years. Circadian patterns were studied by analyzing temperature, body position and activity for 1 week every 1 min with “Circadianware®.”. Genetic influences affecting the variability of each of the measurements were estimated by comparing the observed data in twin pairs. MZ twins showed higher intrapair correlations than DZ twins for most of the parameters. Genetic factors (broad sense heritability) were responsible for about 40–72% of TAP variance in parameters such as mesor, acrophase, amplitude, Rayleigh test, percentage of rhythmicity and circadian function index. We found more homogeneous heritability estimates of the circadian system when using an integrative technique such as TAP than with individual variables alone, suggesting that this measurement can be more reliable and less subject to environmental artifacts.     

Genetic influences on osteoarthritis in women: a twin study.

OBJECTIVES--To assess the relative contribution of genetic and environmental factors to common forms of osteoarthritis of the hands and knees. DESIGN--Classic twin study with unselected twins who were screened radiologically for osteoarthritis. SUBJECTS--130 identical and 120 non-identical female twins aged 48-70 recruited from a London based twin register and through a national media campaign. MAIN OUTCOME MEASURES--Similarity in identical compared with non-identical twin pairs for radiographic changes at the interphalangeal and first carpometacarpal joints of the hands and the tibiofemoral joint and patellofemoral joint of the knee expressed as intraclass correlations. RESULTS--The intraclass correlations of radiographic osteophytes and narrowing at most sites and the presence of Heberden''s nodes and knee pain were higher in the identical pairs. The intraclass correlation of the total radiographic osteoarthritis score in identical pairs (rMZ) was 0.64 (SE 0.05) compared with 0.38 (0.08) in non-identical pairs. The proportion of genetic variance of total osteoarthritis score (osteophytes and narrowing) with modelling techniques was estimated at 0.54 (95% confidence interval 0.43 to 0.65) and ranged from 0.39 to 0.65 for different sites and features (p < 0.001) after adjustment for age and weight. CONCLUSIONS--These results demonstrate for the first time a clear genetic effect for radiographic osteoarthritis of the hand and knee in women, with a genetic influence ranging from 39-65%, independent of known environmental or demographic confounders. The results of this study should lead to further work on isolating the gene or genes involved in the pathogenesis of the common disabling disease.     

Chorion type as a possible influence on the results and interpretation of twin study data.

The estimation of genetic effects from twin studies usually relies upon the equal environment assumption--that monozygous (MZ) and dizygous (DZ) twin pairs experience equal similarity of their environments from prenatal experiences through adulthood. However, the sharing of a chorion may make a subset of identical twins more similar, or in some cases, more different, than twins that do not share a chorion. Recent studies suggest monochorionic MZ twins resemble one another more than dichorionic MZ twins in cognitive abilities, personality, and risk for psychiatric disorder. To the extent that prenatal environment affects these characteristics, the traditional twin method will yield biased estimates of genetic and environmental influences. We develop models for quantifying this bias and estimating the influence of chorion type on estimates of heritability.     

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.     

The heritability of mortality due to heart diseases: a correlated frailty model applied to Danish twins.

Data of the Danish Twin Registry on monozygotic and dizygotic twins are used to analyse genetic and environmental influences on susceptibility to heart diseases for males and females, respectively. The sample includes 7955 like-sexed twin pairs born between 1870 and 1930. Follow-up was from 1 January 1943 to 31 December 1993 which results in truncation (twin pairs were included in the study if both individuals were still alive at the beginning of the follow-up) and censoring (nearly 40% of the study population was still alive at the end of the follow-up). We use the correlated gamma-frailty model for the genetic analysis of frailty to account for this censoring and truncation. During the follow-up 9370 deaths occurred, 3393 deaths were due to heart diseases in general, including 2476 deaths due to coronary heart disease (CHD). Proportions of variance of frailty attributable to genetic and environmental factors were analyzed using the structural equation model approach. Different standard biometric models are fitted to the data to evaluate the magnitude and nature of genetic and environmental factors on mortality. Using the best fitting model heritability of frailty (liability to death) was found to be 0.55 (0.07) and 0.53 (0.11) with respect to heart diseases and CHD, respectively, for males and 0.52 (0.10) and 0.58 (0.14) for females in a parametric analysis. A semi-parametric analysis shows very similar results. These analyses may indicate the existence of a strong genetic influence on individual frailty associated with mortality caused by heart diseases and CHD in both, males and females. The nature of genetic influences on frailty with respect to heart diseases and CHD is probably additive. No evidence for dominance and shared environment was found.     

Genetic Influences on Changes in Body Mass Index: A Longitudinal Analysis of Women Twins

AUSTIN, MELISSA A, YECHIEL FRIEDLANDER, BETH NEWMAN, KAREN EDWARDS, ELIZABETH J MAYER-DAVIS, MARY-CLAIRE KING. Genetic influences on changes in body mass index: a longitudinal analysis of women twins. Numerous studies have demonstrated genetic influences on body fat, but there also may be genetic effects on its intraindividual variation over time. This study examined changes in body mass index (BMI) using longitudinal data from two examinations of the Kaiser Permanente Women Twins Study, performed a decade apart. The analysis included 630 women, 185 monozygotic and 130 dizygotic twin pairs, with average ages of 41 years and 51 years at the two examinations, respectively. Age adjusted heritability estimates for the change in BMI over the decade ranged from 0.57 to 0.86 (all ρ≤0.001) using three different statistical analysis approaches, indicating that at least half, and possibly as much as 85%, of the variance in the change in BMI is attributable to genetic influences under a polygenic model. These estimates remained statistically significant after adjusting for environmental factors (ranging from 0.57 to 0.78) and with additional adjustment for BMI at baseline (ranging from 0.41 to 0.79), although dizygotic intraclass correlations were low after these adjustments. Thus, in addition to known environmental and behavioral influences, these results provide evidence for genetic influences on changes in BMI over a decade in women.     

Estimating Modifying Effect of Age on Genetic and Environmental Variance Components in Twin Models

Twin studies have been adopted for decades to disentangle the relative genetic and environmental contributions for a wide range of traits. However, heritability estimation based on the classical twin models does not take into account dynamic behavior of the variance components over age. Varying variance of the genetic component over age can imply the existence of gene–environment (G × E) interactions that general genome-wide association studies (GWAS) fail to capture, which may lead to the inconsistency of heritability estimates between twin design and GWAS. Existing parametric G × E interaction models for twin studies are limited by assuming a linear or quadratic form of the variance curves with respect to a moderator that can, however, be overly restricted in reality. Here we propose spline-based approaches to explore the variance curves of the genetic and environmental components. We choose the additive genetic, common, and unique environmental variance components (ACE) model as the starting point. We treat the component variances as variance functions with respect to age modeled by B-splines or P-splines. We develop an empirical Bayes method to estimate the variance curves together with their confidence bands and provide an R package for public use. Our simulations demonstrate that the proposed methods accurately capture dynamic behavior of the component variances in terms of mean square errors with a data set of >10,000 twin pairs. Using the proposed methods as an alternative and major extension to the classical twin models, our analyses with a large-scale Finnish twin data set (19,510 MZ twins and 27,312 DZ same-sex twins) discover that the variances of the A, C, and E components for body mass index (BMI) change substantially across life span in different patterns and the heritability of BMI drops to ∼50% after middle age. The results further indicate that the decline of heritability is due to increasing unique environmental variance, which provides more insights into age-specific heritability of BMI and evidence of G × E interactions. These findings highlight the fundamental importance and implication of the proposed models in facilitating twin studies to investigate the heritability specific to age and other modifying factors.     

Inheritance of human finger and palm dermatoglyphic characteristics]

The degree of genetic determination of 25 quantitative dermatoglyphic characteristics has been studied on family: twin material: 45 pairs of MZ and 75 single-sex DZ twins; and 53 single-sex "parent-child" pairs. Approximating formulae were used to estimate main components of phenotypic variance due to additive interaction of genetic factors, to non-linear effects (intralocus dominance) and to the effect of total-familiar and random environmental factors. All the finger dermatoglyphic characteristics studied had a high degree of genetic determination (G greater than 0,80), and for most of them the contribution into the large variance of intralocus dominance effects was comparable with that of additive gene interaction, included in the determination of these characters. There are some palm dermatoglyphic characteristics ("ad" distance "cd" comb counting, "bad", "adt" and "cda" angles), which degree of genetic determination is low (G less than 0,35). At least ten quantitative finger and palm dermatogliphic characteristics with a high degree of genetic determination can be used for special studies in frames of multidimentional genetical analysis, including determination of twin zygosity type. Earlier described "indices" (using twin data) of relative role of genetic and environment factors in the determination of populational variability of quantitative characters are considered. None of them is shown to be a reliable estimate of the coefficient of genetic character determination. The use of these indices in practical studies can result in wrong conclusions on the degree and the character of genetic determination of quantitative characters.     

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.