Inheritance of hypodontia in twins

The aim of this study was to establish prevalence of hypodontia in the twin sample and to assess the degree of its heritability. A study was performed in a sample of 96 twin pairs, 38 pairs being monozygotic (MZ) and 58 pairs dizygotic (DZ), from north-west Croatia. The sample included 25.82% of all twins born in the region during a ten-year period. The twin zygosity was determined according to the WHO recommendations (1996). A revised Holzinger's index (Hc') according to Allen was applied to calculate the degree of heritability. Hypodontia was found in 22 out of the total of 192 twins analyzed (11.5%). Among 96 pairs of twins, hypodontia was observed in 17 pairs (7 MZ and 10 DZ pairs). Among the MZ, 4 pairs were found to be concordant for hypodontia, among the DZ one pair only. The heritability index was 0825. A prevalence of hypodontia in twins observed in this study is significantly higher than in the general population. A high index of heritability (Hc' = 0.825) points to a high genetic determination.     

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.     

Cooperation and Competition as a Function of Zygosity in 7- to 9-Year-Old Twins

A study of 31 monozygotic (MZ) and 24 dizygotic (DZ) Singapore twin pairs (aged 7.6 to 9.7 years) is reported. MZ and DZ twins differed in cooperative and competitive behaviors measured by within-pair reactions to payoff structures designed to elicit simultaneous cooperation (SCO) or reciprocal altruism (RA) on a marble-pull task. Reciprocation entailed turn-taking in rewards. DZ twins showed greater competition than MZ twins when competing for marbles in the RA condition, as predicted. Unexpectedly, however, MZ twins were markedly more competitive than DZ twins under the SCO condition, when success on the task always rewarded both twins. The competition arose over which end of the apparatus was to be used on a given trial. This interaction between condition and zygosity could not be related to differences in parents’ reported treatment of their children or zygosity beliefs, nor did it appear to be related to differences in factors such as time spent together and shared activities. An explanation in terms of uncertain or unstable dominance in MZ twinships is suggested.     

Determination of Zygosity in Adult Chinese Twins Using the 450K Methylation Array versus Questionnaire Data

Previous studies have shown that both single nucleotide polymorphisms (SNPs) and questionnaires-based method can be used for twin zygosity determination, but few validation studies have been conducted using Chinese populations. In the current study, we recruited 192 same sex Chinese adult twin pairs to evaluate the validity of using genetic markers-based method and questionnaire-based method in zygosity determination. We considered the relatedness analysis based on more than 0.6 million SNPs genotyping as the golden standards for zygosity determination. After quality control, qualified twins were left for relatedness analysis based on identical by descent calculation. Then those same sex twin pairs were included in the zygosity questionnaire validation analysis. Logistic regression model was applied to assess the discriminant ability of age, sex and the three questions in zygosity determination. Leave one out cross-validation was used as a measurement of internal validation. The results of zygosity determination based on 65 SNPs in 450k methylation array were all consistent with genotyping. Age, gender, questions of appearance confused by strangers and previously perceived zygosity consisted of the most predictable model with a consistency rate of 0.8698, cross validation predictive error of 0.1347. For twin studies with genotyping and\or 450k methylation array, there would be no need to conduct other zygosity testing for the sake of costs consideration.     

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.     

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.     

Genetic influences in self-reported symptoms of obstructive sleep apnoea and restless legs: a twin study.

Sleep disorders, such as obstructive sleep apnoea (OSA) and restless legs syndrome (RLS), are very common. The relative importance of genetic and nongenetic (environmental) influences on the symptomatology of these conditions has not been well studied. This study uses the twin design to examine this by evaluating OSA and RLS symptoms in monozygotic (MZ) and dizygotic (DZ) twins. Six thousand six hundred unselected female twin pairs, identified from a national volunteer twin register, were asked to complete a medical questionnaire. This questionnaire included questions on OSA and RLS symptoms, as well as questions on subject demographics, past medical history, smoking history and menopausal status. Responses were obtained from 4503 individuals (68% response rate). A total of 1937 twin pairs were evaluable: 933 MZ pairs (mean [range] age 51 [20-76] years) and 1004 DZ pairs (age 51 [20-80] years). Concordance rates were higher for MZ than DZ twins for OSA and RLS symptoms. Multifactorial liability threshold modeling suggests that additive genetic effects combined with unique environmental factors provide the best model for OSA and RLS symptoms. Heritability was estimated to be 52% (95% confidence interval 36% to 68%) for disruptive snoring, 48% (37% to 58%) for daytime sleepiness, 54% (44% to 63%) for restless legs, and 60% (51% to 69%) for legs jerking. These estimates dropped only slightly after adjustment for potential confounding influences on the symptoms of snoring and daytime sleepiness. These results suggest a substantial genetic contribution to the symptomatology of OSA and RLS. More research is needed to identify the genes responsible, and may ultimately lead to new therapies.     

Effective Noninvasive Zygosity Determination by Maternal Plasma Target Region Sequencing

Background

Currently very few noninvasive molecular genetic approaches are available to determine zygosity for twin pregnancies in clinical laboratories. This study aimed to develop a novel method to determine zygosity by using maternal plasma target region sequencing.

Methods

We constructed a statistic model to calculate the possibility of each zygosity type using likelihood ratios (L_i) and empirical dynamic thresholds targeting at 4,524 single nucleotide polymorphisms (SNPs) loci on 22 autosomes. Then two dizygotic (DZ) twin pregnancies,two monozygotic (MZ) twin pregnancies and two singletons were recruited to evaluate the performance of our novel method. Finally we estimated the sensitivity and specificity of the model in silico under different cell-free fetal DNA (cff-DNA) concentration and sequence depth.

Results/Conclusions

We obtained 8.90 Gbp sequencing data on average for six clinical samples. Two samples were classified as DZ with L values of 1.891 and 1.554, higher than the dynamic DZ cut-off values of 1.162 and 1.172, respectively. Another two samples were judged as MZ with 0.763 and 0.784 of L values, lower than the MZ cut-off values of 0.903 and 0.918. And the rest two singleton samples were regarded as MZ twins, with L values of 0.639 and 0.757, lower than the MZ cut-off values of 0.921 and 0.799. In silico, the estimated sensitivity of our noninvasive zygosity determination was 99.90% under 10% total cff-DNA concentration with 2 Gbp sequence data. As the cff-DNA concentration increased to 15%, the specificity was as high as 97% with 3.50 Gbp sequence data, much higher than 80% with 10% cff-DNA concentration.

Significance

This study presents the feasibility to noninvasively determine zygosity of twin pregnancy using target region sequencing, and illustrates the sensitivity and specificity under various detecting condition. Our method can act as an alternative approach for zygosity determination of twin pregnancies in clinical practice.     

Contribution of familial factors to the occurrence of cancer before old age in twin veterans

In an earlier report, we evaluated familial factors in deaths from all causes before age 62 among the 31,848 white male twin veterans who were followed during 1946–1978 through the National Academy of Sciences-National Research Council Twin Registry. We now report data for this group on twin concordances and heritabilities of cancer recorded on the death certificate as an underlying or associated cause. The study subjects have a mortality from cancer 0.88 times, and one from all causes 0.84 times, that of U.S. white males [12], but this is very similar to the mortality of other U.S. veterans [9].

Among 11,350 monozygotic (MZ) and 14,450 dizygotic (DZ) individuals in twin pairs alive on January 1, 1946, 1,162 MZ and 1,646 DZ individuals died before January 1, 1979. Cancer was diagnosed for 223 MZ and 323 DZ twins as an underlying or associated cause of death. Among the latter were 176 MZ and 274 DZ pairs with the only death in the pair a cancer death, 10 MZ and eight DZ pairs concordant for cancer, and 12 MZ and 14 DZ pairs in which the first death in the pair from cancer was followed by death of the other twin from another cause. When account is taken of the three MZ and two DZ pairs concordant for lung cancer, most likely related to cigarette smoking, the twin cancer death concordance rates are very low, and they are not appreciably different between the two zygosity groups.

Genetic factors may be important in some specific forms of cancer. However, these data suggest that genetic factors and early familial environment, generally shared by twin-pair members, do not contribute much to mortality from most cancers between 30 and 60 years of age.

     

Familial factors in early deaths: Twins followed 30 years to ages 51–61 in 1978

Summary Subjects in the National Academy of Sciences-National Research Council Twin Registry of 31,848 male twin veterans were followed for mortality from 1 January 1946, or from the date of entry into military service if that was later, to 31 December 1978. During this time 3,573 deaths occurred among them, 837 due to trauma and 2,712 due to disease.Mortality from all causes for the entire follow-up period was 10.2% among 11,350 monozygotic (MZ) twins and 11.4% among 14,450 dizygotic (DZ) twins. Mortality of veterans is known to be favorable compared to U.S. males. Among U.S. males of the same ages as the two respective twin zygosity groups, a mortality of 13.9% would have been expected during this time period. Observed mortality from trauma was 2.3% for MZ twins and 2.5% for DZ twins, with 3.0% expected in either group. Observed mortality from all disease was 7.9% for MZ twins and 8.8% for DZ twins, with 10.9% expected in either group.For total mortality, the case twin concordance rates, based on individual deaths, were 28.2% among MZ twins and 17.7% among DZ twins. For trauma, respectively by zygosity, these concordance rates were 6.9% and 3.9%. In this sample, familial factors appear to be of little consequence in trauma deaths. For all disease the concordance rates were 30.1% and 17.4%. Estimating heritability of liability to death from disease, as proposed by Edwards (1969), provides values of h ²=r=0.51 for MZ twins, h ²=2r=0.48 for DZ twins, and h ₂=2(r _MZ–r _DZ=0.54 using data for the two zygosity groups combined.Presented in abbreviated form at The Third International Congress of Twin Studies, Jerusalem, Israel, 19 June 1980     

Interaction between the ABO and Rh-Hr blood group systems in pairs of monozygotic (MZ) and dizygotic (DZ) twins

Previous studies have revealed significant deviations of twin pairs' blood group distributions. A comparison between monozygotic (MZ) and dizygotic (DZ) pairs in a sample of 688 twin pairs as to interaction between ABO and Rh indicates that the main contribution to total deviation comes from the MZ pairs, thus confirming a different behaviour of the two twin types in this respect.     

Contribution of genetic and environmental factors to variation in body compartments--a twin study in adults

This study aimed at analyzing the contribution of genetic and environmental factors on phenotypic variation of various traits of body composition. Subjects were 30 same-sexed pairs of twins including 20 monozygous (MZ) and 10 dizygous (DZ) pairs, aged 19-62 years. Zygosity was determined by DNA typing and morphological diagnosis. Body composition parameters (fat mass FM, lean body mass LBM, body cell mass BCM, extracellular mass ECM, total body water TBW, extracellular water ECW, and intracellular water ICW) were estimated by tetrapolar bioelectrical impedance analysis. Potential environmental factors influencing body composition (number of children, sporting activity and smoking behaviour) were determined by questionnaires. Heritabilities for traits of body composition were calculated by use of the twin method. Intraclass correlation is > 0.80 for the variation of LBM, BCM, ECM, TBW, ECW, and ICW in both MZ and DZ twins. Estimated heritability (h2) for FM, LBM, BCM, ECW, TBW, ECW, and ICW is 65%, 77%, 79%, 83%, 76%, 68%, and 82%, respectively. The h2 values for FM and LBM are consistent with those reported in other twin studies. For BCM, ECM, ECW and ICW, no comparative h2 estimates exist. Within-pair differences in body compartments do not change with increasing age in MZ and DZ twin pairs (p > 0.05). Stepwise multiple regression analyses indicate that zygosity, age, sex, number of children, sporting level and smoking behaviour do not significantly predict within-pair differences for weight, BMI, FM, LBM, TBW, ECW and ICW (each, p > 0.05). In contrast, sex and the number of children explain together 27% of observed within-pair differences for BCM. Zygosity is the only significant predictor of within-pair differences for ECM and height, explaining 20% (p = 0.008) and 36% of variance, respectively (p < 0.0001). Results indicate that genetic factors exert stronger influences on body composition than the considered environmental traits.     

On the food favoritism of twins

In the present study, there is a continuation of the authors' earlier investigations concerning food preference/refusal patterns in a group of Hungarian adult MZ and DZ twin pairs. A "Food Like/Dislike Chart" (FLDC), adapted to local nutritional habits, was applied. In order to characterize the degree of intra-pair concordance referring to the food favoritism, the concept of the "Taste Concordance Point" (TCP) was introduced. On the basis of the comparison of the TCP values obtained for the MZ and DZ pairs the conclusion can be drawn that gustatory habits are presumably influenced also by genetic factors. The results allow the possibility of applying TCP to testing zygosity.     

Diagnosis of twin zygosity by mailed questionnaire

A deterministic questionnaire method for zygosity determination is developed for use in epidemiological studies of adult twins. It is based on the answers of both members of a twin pair to two questions on similarity and confusion in childhood. The algorithm of the method is used to determine the zygosity status of a twin pair at two different levels of certainty. The validity of the method is tested by making blood marker determinations of 11 polymorphic marker systems fro a random sample of 104 twin pairs. The agreement between questionnaire and blood marker diagnosis was 100%, but the stricter level of certainty left 8.7% in the nonclassified group. The genetical representativeness of the sample is tested by the allele distribution of the markers as compared to the Finnish population data as well as by the distribution of the number of intra-pair differences in blood markers.     

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.     

Zygosity diagnosis in young twins by parental report.

This study reports on zygosity determination in twins of childhood age. Parents responded to questionnaire items dealing with twin similarity in physical characteristics and frequency of mistaking one twin for another by parents, relatives and strangers. The accuracy of zygosity diagnosis was evaluated across twins aged 6, 8, and 10 and across parents. In addition, it was examined whether the use of multiple raters and the use of longitudinal data lead to an improvement of zygosity assignment. Complete data on zygosity questions and on genetic markers or blood profiles were available for 618 twin pairs at the age of 6 years. The method used was predictive discriminant analyses. Agreement between zygosity assigned by the replies to the questions and zygosity determined by DNA markers/blood typing was around 93%. The accuracy of assignment remained constant across age and parents. Analyses of data provided by both parents and collected over multiple ages did not result in better prediction of zygosity. Details on the discriminant function are provided.     

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.     

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.