The influence of zygosity and chorion type on fat distribution in young adult twins consequences for twin studies.

An adverse intra-uterine environment has been associated with abdominal fat distribution in singletons. Twins often have a low birth weight and a short gestation. Therefore, they may have an increased risk to develop abdominal obesity. Furthermore, monozygotic monochorionic twins (MZ MC) have a larger intra-pair birth weight difference compared to monozygotic dichorionic twins (MZ DC). If adult anthropometry is programmed in utero, this may affect the intra-pair correlations in adulthood and, consequently, also the results from the classic twin method to estimate genetic and environmental influences. In the present study, we compared the absolute values, the intra-pair differences, and the intra-pair correlations of body mass, height, BMI, and abdominal fat distribution of 424 MZ MC, MZ DC and dizygotic (DZ) twin pairs (aged 18-34 yrs). DZ, MZ DC and MZ MC twins did not differ for most anthropometric characteristics. Only MZ women tended (p = 0.03) to accumulate more abdominal fat compared to DZ twins. Overall, the contribution of zygosity and chorion type to adult anthropometry was rather low (< or = 1.7%). Although the intra-pair birth weight difference of MZ MC pairs (10.5% in men, 12.3% in women) was significantly larger compared to that of MZ DC pairs (6.9% and 9.2% resp.), the intra-pair differences in adult anthropometry were similar for both MZ twin types. Also the intra-pair correlations of MZ MC and MZ DC pairs were strikingly alike, suggesting no significant influence of the prenatal environment on adult concordance. In conclusion, the substantial difference in the prenatal environment of MZ MC and MZ DC twins did not result in a difference in intra-pair concordance of adult anthropometry and fat distribution. Therefore, we suggest that the chorion type of MZ twins does not bias the twin design and the estimation of the genetic contribution to adult anthropometry.     

The effects of chorion type on variation in IQ in the NCPP twin population.

The 7-year IQ scores (WISC) of 116 white and 143 black nonmalformed twins of known zygosity and placental type were ascertained from the NINCDS Collaborative Perinatal Project (NCPP). The type of chorion and zygosity had no significant effect on the mean IQ or among-pair variation. In white monozygotic twins, however, analysis of variance revealed a significantly greater within-pair mean square for dichorionic twins than monochorionic twins. On the other hand, the white dichorionic monozygotic (MZ) and dizygotic (DZ) within-pair mean squares were quite similar. These findings were not evident in blacks for either of the within-pair comparisons. In addition, estimates of genetic variance were dependent upon MZ chorion type in both races. These data suggest to us that (1) in white twin pairs dichorionic placentas are of greater influence than the similarity or dissimilarity of genomes with regard to intrapair IQ development, and (2) failure to consider chorion type may introduce a serious bias in the interpretation of genetic variance estimates of IQ variability.     

The East Flanders Prospective Twin Survey (Belgium): a population-based register.

The East Flanders Prospective Twin Survey (EFPTS), started in 1964, is unique among the 17 major European twin registers because it is population based, the twins (and higher order births) are ascertained at birth, basic perinatal data are collected, chorion type is established and, when appropriate, genetic markers including DNA fingerprints, are determined. The total number of sets is 5089 twin, 158 triplet and 14 of higher order. Zygosity has been diagnosed on the basis of sex, placental structure and genetic markers in more than 95% of pairs. The EFPTS is the only large register that includes placental data and allows differentiation of three subtypes of monozygotic twins based on the time of the initial zygotic division: the dichorionic-diamnionic pairs (early), the monochorionic-diamnionic pairs (intermediate), and the monochorionic-monoamnionic pairs (late). Methodology and basic results in twins are considered in this article; detailed studies will be reported later. The sex proportion in dizygotic (DZ) twins is the same as in singletons, whereas monozygotic (MZ) twins number more girls than boys. The difference in perinatal mortality between DZ and MZ twins is limited to the monochorionic MZ subgroup. Birth weight is highest in DZ twins and diminishes stepwise in MZ dichorionic and MZ monochorionic twins. Duration of pregnancy follows the same trend but is limited to a few days. Iatrogenic pregnancies are increasing to the point of representing almost 50% of the twin births in 1997.     

Twins and non-twin siblings: different estimates of shared environmental influence in early childhood.

Twin studies typically indicate shared environmental influence for cognitive abilities, especially in early childhood. However, across studies, DZ twin correlations tend to be greater than non-twin sibling correlations, suggesting that twin estimates of shared environment are to some extent specific to twins. We tested this hypothesis in a sample of more than 1800 MZ and 1800 same-sex DZ pairs from the Twins Early Development Study (TEDS), a study of twins born in England and Wales in 1994 and 1995. For this analysis, we obtained comparable data from more than 130 same-sex younger siblings of the twins. Twins and their younger siblings were assessed for language, cognitive abilities and behavior problems by their parents at 2 and 3 years of age. For language and cognitive measures at both 2 and 3 years, but not for behavior problems, estimates of shared environment were more than twice as large for twins as compared to non-twin siblings. We conclude that about half of twin study estimates of shared environment for cognitive abilities in early childhood are specific to twins. Although many possibilities exist for explaining the special shared environment effect for twins, we suggest that cognitive-relevant experiences that are not shared by siblings are shared by twins because they are exactly the same age.     

Placentation in multiple births.

Outcomes of multifetal pregnancy in prenatal life are markedly affected by chorionicity. Several disease processes are found in monochorionic (MC) twins that do not occur in dichorionic (DC) twins. Improvements in prenatal outcomes will depend on reliable first trimester diagnosis of chorionicity, allowing early monitoring for complications of MC placentation. Particular structures and functions of MC twin placentas affect outcomes and can be targeted for specific treatments, especially in twin-twin transfusion. The causes of severe DC twin fetal growth discordance are clarified. In post-natal life, zygosity is a determining effect in genetic predisposition to many chronic diseases, including neoplasia. Few MC twins know that they are monozygotic (MZ). Few twin researchers realize that MZ twins may be genetically discordant. Abandonment of the word "identical" for MZ twins would assist in clarifying these issues of zygosity, concordance and discordance.     

Does higher concordance in monozygotic twins than in dizygotic twins suggest a genetic component?

It is widely regarded that twins can be used as a natural experiment to subject hypotheses to empirical testing regarding the contributions of genetic factors to phenotypic variability in human traits, especially behavioral traits. In genetic epidemiology, a higher concordance rate in monozygotic (MZ) twins than in dizygotic (DZ) twins is often taken as prima facie evidence for a genetic component. While twins studies have been used to estimate the contributions of genetic factors to phenotypic variability in human traits, the corresponding methodology that allows the estimation entails several crucial assumptions. The most critical is that MZ and DZ twins are equally similar environmentally. Although MZ twins are genetically more similar than DZ twins, they are often environmentally more similar. This paper demonstrates that, even in the complete absence of any genetic factor and of any biases, the greater environmental similarity alone in MZ twins can result in higher concordance rate in MZ twins than in DZ twins. This is especially true when there are multiple environmental factors, which may have multiple exposure levels and/or interact strongly, although each of them may be of low risk. This may serve as a sobering antidote to the uncritical reliance on twin studies without examining the validity of the underlying assumptions.     

Happy families: a twin study of humour.

The objective of this study was to estimate how much of an individual's appreciation of humour is influenced by genetic factors, the shared environment or the individual's unique environment. A population-based classical twin study of 127 pairs of female twins (71 monozygous (MZ) and 56 dizygous (DZ) pairs) aged 20-75 from the St Thomas' UK Adult Twin Registry elicited responses to five 'Far Side' Larson cartoons on a scale of 0-10. Within both MZ and DZ twin pairs, the tetrachoric correlations of responses to all five cartoons were significantly greater than zero. Furthermore, the correlations for MZ and DZ twins were of similar magnitude and in some cases the DZ correlation was greater than that of the MZ twins. This pattern of correlations suggests that shared environment rather then genetic effects contributes to cartoon appreciation. Multivariate model-fitting confirmed that these data were best explained by a model that allowed for the contribution of the shared environment and random environmental factors, but not genetic effects. However, there did not appear to be a general humour factor underlying responses to all five cartoons and no effect of age was seen. The shared environment, rather than genetic factors, explains the familial aggregation of humour appreciation as assessed by the specific 'off the wall' cognitive type of cartoons used in this study.     

Effects of chorion type on variation in cord blood cholesterol of monozygotic twins.

Cholesterol levels were measured in the cord blood of 30 pairs of monochorionic and 22 pairs of dichorionic monozygotic (MZ) twins. Cholesterol levels were found to be significantly higher in female twins when data was combined over chorion type. The type of chorionic development had no significant effect on variation among twin pairs. Chorion type did, however, have a significant effect on the within-pair variation. The variation within dichorionic pairs was more than five times that within monochorionic pairs (P less than .01). This result suggests that the variation in placentation has a significant effect on within-pair variation in serum cholesterol of newborn MZ twins.     

A finite mixture distribution model for data collected from twins.

Most analyses of data collected from a classical twin study of monozygotic (MZ) and dizygotic (DZ) twins assume that zygosity has been diagnosed without error. However, large scale surveys frequently resort to questionnaire-based methods of diagnosis which classify twins as MZ or DZ with less than perfect accuracy. This article describes a mixture distribution approach to the analysis of twin data when zygosity is not perfectly diagnosed. Estimates of diagnostic accuracy are used to weight the likelihood of the data according to the probability that any given pair is either MZ or DZ. The performance of this method is compared to fully accurate diagnosis, and to the analysis of samples that include some misclassified pairs. Conventional analysis of samples containing misclassified pairs yields biased estimates of variance components, such that additive genetic variance (A) is underestimated while common environment (C) and specific environment (E) components are overestimated. The bias is non-trivial; for 10% misclassification, true values of Additive genetic: Common environment: Specific Environment variance components of.6:.2:.2 are estimated as.48:.29:.23, respectively. The mixture distribution yields unbiased estimates, while showing relatively little loss of statistical precision for misclassification rates of 15% or less. The method is shown to perform quite well even when no information on zygosity is available, and may be applied when pair-specific estimates of zygosity probabilities are available.     

Long-term effect of placental type on anthropometrical and psychological traits among monozygotic twins: a follow up study.

The long-term effect of differences in placentation in MZ twins is a controversial subject. An effect has been clearly established for birth weight but data on psychological traits are still under debate. We studied 20 pairs of monochorionic MZ (MC MZ) and 24 pairs of dichorionic MZ (DC MZ) twins. A chorion effect was observed for Block Design (WISC-R) confirming a previous report: MC MZ co-twins were more similar that DC MZ co-twins. For anthropometrical measures, an expected effect in the opposite direction was found. No chorion effect was significant for the other variables. A follow up was undertaken 3 years later using cognitive, national academic evaluations, and personality variables. The sample included 16 pairs of MC MZ and 22 pairs of DC MZ twins. Again a chorion effect was observed on anthropometrical variables but results on the Block Design were not replicated. However, the MC MZ co-twins were more similar than the DC MZ co-twins for two other cognitive variables: Perceptual Organization Index from the WISC-R and Global Visualisation from a Belgian reasoning test. Among the personality variables only one was sensitive to a chorion effect. The discussion focuses on the need for larger samples to achieve adequate power in statistical comparisons.     

Between twins; research summaries; in the real world.

Research on unusually long birth intervals between twin and triplet deliveries is reviewed. A recent multicentre study reported gestational and survival data for 35 multiple birth sets from 12 centers, and evaluated conservative treatment strategies for mothers delivering one twin fetus. Next, findings from three recent twin studies are reviewed: effects of close inter-twin communication on longevity; case report of dizygous twins with a single chorion; and a case of discordance for hemihypertrophy in an MZ female twin pair. The article concludes with summaries of three interesting and informative anecdotal accounts of twins.     

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.     

Analysis of functional abilities for elderly Danish twins using GEE models.

In this work we present a new method for genetic analysis of twin data which is based on generalized estimating equations and allows for analysis of various response types (e.g., continuous, binary, counts) combined with estimation of residual correlations. The new approach allows for control of covariates of any kind (e.g., continuous, counts) by modeling the dependence of mean and variance on background variables. The proposed method was applied to identify the covariates that have a significant influence on elderly people's functional abilities, and find the estimates for the correlation coefficients of residuals for MZ and DZ twins in a sample of 2401 Danish twin 75 years of age or older. The bootstrap method was used to obtain standard errors for correlation coefficients. It was shown, that the chosen covariates have similar effects on MZ and DZ twins, and that the residual correlation in MZ twins is significantly higher than in DZ twins, which indicates that genetic factors play an etiological role in the determination of physical status of elderly people, controlled for 10 background variables.     

Observed frequency of monozygotic twinning in Holstein dairy cattle

Bonnier's equation is used to mathematically estimate the frequency of monozygotic (MZ) twinning in epidemiologic studies of twinning in dairy cattle; however, no empirical determination of MZ twinning has been reported in the literature. Our objectives were to empirically determine the frequency of MZ twinning in lactating Holstein cows and to compare this result with published estimates predicted using Bonnier's equation. Ear biopsies were collected from 107 sets of Holstein twins from six Wisconsin dairies resulting in 40 opposite-sex twins, 29 same-sex male twins, and 38 same-sex female twins. To empirically determine the frequency of MZ twinning, DNA extracted from ear biopsies collected from the 67 same-sex twins was PCR amplified using primers for a minimum of 5 polymorphic microsatellite DNA markers. Opposite-sex twins were classified as dizygotic (DZ) as well as same-sex twins differing in at least one microsatellite DNA marker. Same-sex twins were classified as MZ when all genotypes for a minimum of five markers were identical. Of the 67 same-sex twins, 62 were classified as DZ and 5 MZ resulting in a MZ twinning frequency of 7.5% of same-sex twins and 4.7% of all twins. The estimated frequency of MZ twinning in this population of twin calves using Bonnier's equation was 39.5% of same-sex twins and 24.7% of all twins. We concluded that MZ twinning occurred infrequently in Holstein cattle and perhaps less frequently than that reported in studies using Bonnier's equation to estimate MZ twinning.     

Parent ratings of temperament in twins: explaining the 'too low' DZ correlations.

Twin studies of child temperament using objective measures consistently suggest moderate heritability for most dimensions. However, parent rating measures produce unusual patterns of results. Intraclass correlations for identical (MZ) twins are typically high, whereas fraternal (DZ) twin intraclass correlations are much lower than would be predicted from an additive genetic model. The 'too low' DZ correlations can be explained by parent-rating biases that either exaggerate the differences between DZ twins (contrast effects) or that inflate the similarity of MZ twins (assimilation effects), or by the presence of non-additive genetic variance. To evaluate the three possible explanations, we used model-fitting procedures applied to parent-rating data averaged across 14, 20, 24, and 36 months of age in a sample of 196 twin pairs participating in the MacArthur Longitudinal Twin Study. The data were best described by a model that included contrast effects. Implications for non-twin research are discussed.     

Excess of twins among affected sibling pairs with autism: implications for the etiology of autism

It is widely accepted that genes play a role in the etiology of autism. Evidence for this derives, in part, from twin data. However, despite converging evidence from gene-mapping studies, aspects of the genetic contribution remain obscure. In a sample of families selected because each had exactly two affected sibs, we observed a remarkably high proportion of affected twin pairs, both MZ and DZ. Of 166 affected sib pairs, 30 (12 MZ, 17 DZ, and 1 of unknown zygosity) were twin pairs. Deviation from expected values was statistically significant (P<10(-6) for all twins); in a similarly ascertained sample of individuals with type I diabetes, there was no deviation from expected values. We demonstrate that to ascribe the excess of twins with autism solely to ascertainment bias would require very large ascertainment factors; for example, affected twin pairs would need to be, on average, approximately 10 times more likely to be ascertained than affected non-twin sib pairs (or 7 times more likely if "stoppage" plays a role). Either risk factors (related to twinning or to fetal development) or other factors (genetic or nongenetic) in the parents may contribute to autism.     

Genetic effects in human skeletal muscle fiber type distribution and enzyme activities

The purpose of the study was to estimate the genetic effect for skeletal muscle characteristics using pairs of nontwin brothers (n = 32), dizygotic (DZ) twins (n = 26), and monozygotic (MZ) twins (n = 35). They were submitted to a needle biopsy of the vastus lateralis for the determination of fiber type distribution (I, IIa, IIb) and the following enzymes were assayed for maximal activity: creatine kinase, hexokinase, phosphofructokinase (PFK), lactate dehydrogenase, malate dehydrogenase, 3-hydroxyacyl CoA dehydrogenase, and oxoglutarate dehydrogenase (OGDH). For the percentage of type I fibers, intraclass correlations were 0.33 (p less than 0.05), 0.52 (p less than 0.01), and 0.55 (p less than 0.01) in brothers and DZ and MZ twins, respectively. MZ twins exhibited significant within-pair resemblance for all enzyme activities (0.30 less than or equal to r less than or equal to 0.68). In spite of these correlations, genetic analyses performed with the twin data alone indicated that there was no significant genetic effect for muscle fiber type I, IIa, and IIb distribution and fiber areas. Although there were significant correlations in MZ twins for all muscle enzyme activities, the often nonsignificant intraclass coefficients found in brothers and DZ twins suggest that variations in enzyme activities are highly related to common environmental conditions and nongenetic factors. However, genetic factors appear to be involved in the variation of regulatory enzymes of the glycolytic (PFK) and citric acid cycle (OGDH) pathways and in the variation of the oxidative to glycolytic activity ratio (PFK/OGDH ratio). Data show that these genetic effects reach only about 25-50% of the total phenotypic variation when data are adjusted for age and sex differences.     

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.     

Genetic and environmental contributions to population group differences on the Raven's Progressive Matrices estimated from twins reared together and apart

We carried out two studies to test the hypothesis that genetic and environmental influences explain population group differences in general mental ability just as they do individual differences within a group. We estimated the heritability and environmentality of scores on the diagrammatic puzzles of the Raven's Coloured and/or Standard Progressive Matrices (CPM/SPM) from two independent twin samples and correlated these estimates with group differences on the same items. In Study 1, 199 pairs of 5- to 7-year-old monozygotic (MZ) and dizygotic (DZ) twins reared together provided estimates of heritability and environmentality for 36 puzzles from the CPM. These estimates correlated with the differences between the twins and 94 Serbian Roma (both rs=0.32; Ns=36; ps<0.05). In Study 2, 152 pairs of adult MZ and DZ twins reared apart provided estimates of heritability and environmentality for 58 puzzles from the SPM. These estimates correlated with the differences among 11 diverse samples including (i) the reared-apart twins, (ii) another sample of Serbian Roma, and (iii) East Asian, White, South Asian, Coloured and Black high school and university students in South Africa. In 55 comparisons, group differences were more pronounced on the more heritable and on the more environmental items (mean rs=0.40 and 0.47, respectively; Ns=58; ps<0.05). After controlling for measurement reliability and variance in item pass rates, the heritabilities still correlated with the group differences, although the environmentalities did not. Puzzles found relatively difficult (or easy) by the twins were those found relatively difficult (or easy) by the others (mean r=0.87). These results suggest that population group differences are part of the normal variation expected within a universal human cognition.