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

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

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

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

Neuropathologic Assessment of Dementia Markers in Identical and Fraternal Twins

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

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

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

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 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.     

Manual performance and laterality in twins of known chorion type

Manual performance, direction, and degree of laterality were tested in monozygotic (MZ) twins (8–12 years old) of known chorion type and dizygotic (DZ) twins. Three manual tasks rarely employed in twin studies were used: dot-filling, tapping, and peg-moving tasks. No chorion effect was observed: the monochorionic and dichorionic MZs differed neither for frequency of discordant pairs nor for handedness, laterality measurements, and manual performance. The pooled MZs and DZs were then compared in a classic twin design. The within-pair resemblance was not higher in MZs than in DZs for variables measuring level of manual performance. For laterality scores intraclass correlations were close to zero in MZ and DZ twin groups.     

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.     

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.     

Assortative Mating for Cigarette Smoking and for Alcohol Consumption in Female Australian Twins and their Spouses

Background Non-random mating affects population variation for substance use and dependence. Developmentally, mate selection leading to positive spousal correlations for genetic similarity may result in increased risk for substance use and misuse in offspring. Mate selection varies by cohort and thus, assortative mating in one generation may produce marked changes in rates of substance use in the next. We aim to clarify the mechanisms contributing to spousal similarity for cigarette smoking and alcohol consumption.Methods Using data from female twins and their male spouses, we fit univariate and bivariate twin models to examine the contribution of primary assortative mating and reciprocal marital interaction to spousal resemblance for regular cigarette smoking and nicotine dependence, and for regular alcohol use and alcohol dependence.Results We found that assortative mating significantly influenced regular smoking, regular alcohol use, nicotine dependence and alcohol dependence. The bivariate models for cigarette smoking and alcohol consumption also highlighted the importance of primary assortative mating on all stages of cigarette smoking and alcohol consumption, with additional evidence for assortative mating across the two stages of alcohol consumption.Conclusions Women who regularly used, and subsequently were dependent on cigarettes or alcohol were more likely to marry men with similar behaviors. After mate selection had occurred, one partner’s cigarette or alcohol involvement did not significantly modify the other partner’s involvement with these psychoactive substances.An erratum to this article can be found at     

Genetic contribution to DZ twinning

The genetic contribution to dizygotic (DZ) twinning was investigated using 6,596 twin pairs from the Australian Twin Registry who provided information on other twins in their families. Responses were classified by the zygosity (DZ; monozygotic [MZ]) of the proband twins and by the relationship and zygosity of related twins. MZ probands and MZ twins reported by DZ probands were used as controls and assumed to be independent of any genetic influence. Significantly higher proportions of DZ twins were found in the families of DZ probands compared to the families of MZ probands for the following relationships: sibs of probands, proband mothers, offspring of sisters of proband mothers, and offspring of female probands (P < 0.001 in each case). The latter 2 relationships were used to estimate risk ratios of 1.7 for sisters of mothers of DZ twins, and 2.5 for offspring of female DZ twins. No greater tendency to DZ twinning in close relatives was found in mothers who bore DZ twins at a younger age than at an older age. © 1996 Wiley-Liss, Inc.     

Caffeine intake, toxicity and dependence and lifetime risk for psychiatric and substance use disorders: an epidemiologic and co-twin control analysis

BACKGROUND: Although caffeine is the most commonly used psychoactive substance and often produces symptoms of toxicity and dependence, little is known, especially in community samples, about the association between caffeine use, toxicity and dependence and risk for common psychiatric and substance use disorders. METHOD: Assessments of lifetime maximal caffeine use and symptoms of caffeine toxicity and dependence were available on over 3600 adult twins ascertained from the population-based Virginia Twin Registry. Lifetime histories of major depression (MD), generalized anxiety disorder (GAD) and panic disorder, alcohol dependence, adult antisocial behavior and cannabis and cocaine abuse/dependence were obtained at personal interview. Logistic regression analyses in the entire sample and within monozygotic (MZ) twin pairs were conducted in SAS. RESULTS: In the entire sample, measures of maximal caffeine use, heavy caffeine use, and caffeine-related toxicity and dependence were significantly and positively associated with all seven psychiatric and substance use disorders. However, within MZ twin pairs, controlling for genetic and family environmental factors, these associations, while positive, were all non-significant. These results were similar when excluding twins who denied regular caffeine use. CONCLUSIONS: Maximal lifetime caffeine intake and caffeine-associated toxicity and dependence are moderately associated with risk for a wide range of psychiatric and substance use disorders. Analyses of these relationships within MZ twin pairs suggest that most of the observed associations are not causal. Rather, familial factors, which are probably in part genetic, predispose to both caffeine intake, toxicity and dependence and the risk for a broad array of internalizing and externalizing disorders.     

Intra-pair similarity in IQ of monozygotic and dizygotic male twins at 12 and 18 years of age

Verbal and inductive test results have been collected for a group of male twins in grade 5 at 12 years of age and at enrolment to military service at 18 years of age. MZ twin pairs tend to get progressively more concordant for both verbal and inductive ability from age 12 to 18. DZ twins, on the other hand, get progressively more concordant for inductive ability, while they tend to get less concordant for verbal ability. The results are interpreted with reference to a model taking heredity-environment interaction into account. The discordant trend found when comparing intra-pair similarity in verbal ability for MZ and DZ twins thus seems to indicate the presence of interactional and correlational effects.

For inductive ability, however, the difference between within-pair correlations for MZ and DZ twins tends to be of the same magnitude at both 12 and 18 years of age. Probably this type of test is less differentially influenced by the environments being sampled, at least under present circumstances, when children are not specifically trained to solve the kind of items included in the inductive test.

Regression effects for the two tests and possible explanations to the increase from age 12 to 18 in both MZ and DZ within-pair similarity for inductive test scores are discussed.     

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.     

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 variance in age‐related changes in running performance and growth during adolescence: A longitudinal twin study

The purpose of this study was to assess an effect of genotype on the patterns of age‐related changes in running performance and physical growth during adolescence. The total sample was 14 pairs of male and 25 pairs of female monozygotic (MZ) twins and 19 pairs of male and 15 pairs of female dizygotic (DZ) twins. Performance on the 50‐m dash and endurance run (1,500 m for boys and 1,000 m for girls, respectively) and stature and body mass were measured at yearly intervals from 12 to 17 years of age. A principal component analysis was applied to the longitudinal data, and within‐pair resemblance in the scores on the first, the second, and the third principal components was compared between MZ and DZ twins. The analysis was conducted with both sexes pooled because of the limited number of twin pairs. The first two principal components explained at least 87% of the total variance, while the third principal component (PC3) explained a smaller portion of the total variance (more than 5%) in the dash and the endurance run. However, the total variance was explained almost entirely (more than 96%) by the first two components in height and mass. The first principal component (PC1), which explained 67–84% of the total variance, was a good indicator of average performance/body size of individuals during the period of observation. The second (PC2) and the third components (PC3) could be considered as indicators of the “shape” of developmental/growth curves, which were not related to inter‐individual differences in the average performance/body size. Intraclass correlations (r_i) of the scores on PC1 were consistently higher for MZ than for DZ twins, and estimated genetic variance was significant in endurance run, stature and body mass. The situation was the same for the scores on PC2 and/or PC3. However, such a between‐genotype difference in r_i and a significant genetic variance were not observed in the dash. It was concluded that MZ twins are more similar in the patterns of age‐related changes in the performance of endurance run and physical growth during adolescence than DZ twins, suggesting a genetic contribution, while there was no evidence of a genetic contribution in the dash. Am. J. Hum. Biol. 13:71–80, 2001. © 2001 Wiley‐Liss, Inc.     

Genetic and Social Determinants of Initiation and Age at Onset of Smoking in Australian Twins

Retrospective data on age at onset of smoking, reported by 3810 adult Australian twin pairs, were analyzed to determine the role of genetic and environmental factors in the onset of smoking. Results of nonmetric multidimensional scaling supported a two-process model in which different etiologic factors determined which individuals were at risk of becoming smokers and the age at onset of smoking in those who were at risk. Parametric model-fitting confirmed this difference. For female twins and younger male twins (aged 30 years or less), the onset of smoking was strongly influenced by genetic factors, with shared and nonshared environmental effects having a more modest impact. For older male twins, shared environmental influences on onset of smoking were very important, and the influence of genetic predisposition was slight. The age at which smoking onset occurred, however, was influenced by both genetic and nonshared environmental effects, but not by shared environmental effects, in both sexes and both cohorts.     

Twinning causative origin investigated by Sartwell's biometrical method

Sartwell's biometrical model is useful to test potential causal factors at the origin of biological phenomena of unknown etiology. It postulates a lognormal distribution of the incubation time. The method has been applied in the past to infectious and neoplastic diseases and, only lately, to genetic diseases. We report here an application to unlike-sex and like-sex twins in an attempt to infer causal origin from a family of potentially related factors. Two hypotheses are tested: the maternal prenatal origin of unlike-sex twins, and the menopausal basis of like-sex twins. The hypotheses are respectively grounded in the presumed genetic origin of DZ twinning, and in the ovarian-dysfunction origin of MZ twinning. The study is population-based; it proceeds from a matched control group and considers various time windows (induction periods) of possible etiologic significance—namely, age at onset of twins, the time window from the first birth to the twin birth, and the time window from the twin birth to the last birth. The study of lognormality has been carried out with the Box-Cox transformations, Fisher's cumulants method, and the normal probability plots. Results show clearly that unlike-sex (presumably DZ) twins have their causal origin in the maternal prenatal period as age of onset is definitely lognormal. Median induction time is 31 ± 6 years. This is interpreted as a multiplicative age-related causal process involving hypophyseal hormones. The menopausal origin of like-sex twins, a mixture of MZ and DZ, is less clear-cut, as the fit of the distribution of the time window until last birth to a lognormal model is less than perfect. In spite of the heterogeneity of the like-sex twin group, there is evidence that some cases of MZ twins may be menopause-related. But this complex question needs more study.     

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.     

The Speed of Progression to Tobacco and Alcohol Dependence: A Twin Study

We investigated the etiological role of genetic and environmental influences for two milestones of tobacco and alcohol use: age of initiation, and speed of progression to dependence (latency). Study participants included 1352 monozygotic and 1422 dizygotic twins (mean age at assessment?=?24.31). Earlier ages of initiation significantly increased the likelihood of developing dependence, but were associated with longer dependence latencies for tobacco and alcohol. Latencies to dependence were heritable traits for tobacco (a²?=?0.63) and alcohol (a²?=?0.64). Genetic influences contributing to early age of initiation were associated with faster latencies to dependence but sometimes were counteracted by environmental factors, the extent to which depended on substance and, sometimes, sex. Our findings may have important implications for public policy and add to the literature by characterizing the genetic and environmental contributions to the speed of progression to tobacco and alcohol dependence.