Dominance and environmental variances: their effect on heritabilities estimated from twin data

A method for partitioning genetic variance estimated from twin data into additive and dominance variances was presented using Falconer's variance component model. The effects of dominance and environmental variances on a number of heritability estimates were also reviewed. A heritability estimate, based on the analysis of variance and the genetic variance estimates presented by HASEMAN and ELSTON and CHRISTIAN et al. which utilizes all available information from twin data, was proposed and discussed. This estimate seems to be the least affected by fluctuations in the magnitudes of dominance and environmental variances.     

Parakeet: a digital twin software pipeline to assess the impact of experimental parameters on tomographic reconstructions for cryo-electron tomography

In cryo-electron tomography (cryo-ET) of biological samples, the quality of tomographic reconstructions can vary depending on the transmission electron microscope (TEM) instrument and data acquisition parameters. In this paper, we present Parakeet, a ‘digital twin’ software pipeline for the assessment of the impact of various TEM experiment parameters on the quality of three-dimensional tomographic reconstructions. The Parakeet digital twin is a digital model that can be used to optimize the performance and utilization of a physical instrument to enable in silico optimization of sample geometries, data acquisition schemes and instrument parameters. The digital twin performs virtual sample generation, TEM image simulation, and tilt series reconstruction and analysis within a convenient software framework. As well as being able to produce physically realistic simulated cryo-ET datasets to aid the development of tomographic reconstruction and subtomogram averaging programs, Parakeet aims to enable convenient assessment of the effects of different microscope parameters and data acquisition parameters on reconstruction quality. To illustrate the use of the software, we present the example of a quantitative analysis of missing wedge artefacts on simulated planar and cylindrical biological samples and discuss how data collection parameters can be modified for cylindrical samples where a full 180° tilt range might be measured.     

Genetic influences on premature parturition in an Australian twin sample.

We investigated possible genetic influences on women's liability to preterm birth, using data from a large sample of Australian female twin pairs. In a 1988-90 questionnaire survey, both members of 905 parous twin pairs (579 monozygotic and 326 dizygotic) reported on whether deliveries had been more than two weeks preterm. Tetrachoric twin pair correlations for first birth were rMZ = 0.20+/-0.11 and rDZ = -0.03+/-0.14, and for any birth were rMZ = 0.30+/-0.08 and rDZ = 0.03+/-0.11. Best-fitting models to data contained only additive genetic influences and individual environmental effects. Heritability was 17% for preterm delivery in first pregnancy, and 27% for preterm delivery in any pregnancy. In the former case, however, we could not reject a model without genetic influences. Although our data did not allow for differentiation of the varying aetiologies of premature parturition, results from this exploratory analysis suggest that further investigation of genetic influences on specific reasons for preterm birth is warranted.     

A bivariate frailty model with a cure fraction for modeling familial correlations in diseases

We suggest a cure-mixture model to analyze bivariate time-to-event data, as motivated by the article of Chatterjee and Shih (2001, Biometrics 57, 779-786), but with a simpler estimation procedure and the correlated gamma-frailty model instead of the shared gamma-frailty model. This approach allows us to deal with left-truncated and right-censored lifetime data, and accounts for heterogeneity, as well as for an insusceptible (cure) fraction in the study population. We perform a simulation study to evaluate the properties of the estimates in the proposed model and apply it to breast cancer incidence data for 5857 Swedish female monozygotic and dizygotic twin pairs from the so-called old cohort of the Swedish Twin Registry. This model is used to estimate the size of the susceptible fraction and the correlation between the frailties of the twin partners. Possible extensions, advantages, and limitations of the proposed method are discussed.     

Hypertensive disease in twin pregnancies: a review.

Reports over the past seventy years show that twin gestations lead to an increased risk of hypertensive disorders. Numerous studies discuss the incidence of hypertensive disease in twin versus singleton gestations, as well as effects of parity, race, age, income level, smoking, zygosity and heritability on this condition. The range of relative risk of gestational hypertension, preeclampsia and eclampsia for twin compared to singleton gestations is 1.2 to 2.7, 2.8 to 4.4 and 3.4 to 5.1 respectively. Parity, African-American ethnicity, and young maternal age are all factors that increase the relative risk of acquiring hypertensive disease to 4.0, 1.8 and 1.5 in mothers of twin gestations. Factors such as maternal smoking, income level and zygosity have a negligible effect on the relative risk of acquiring hypertensive disease in twin gestations. In addition to twin mothers exhibiting a higher incidence of hypertensive disease compared to their singleton counterparts, they also exhibit an earlier onset of hypertensive disease at both 35 and 37 weeks of gestation comparatively. Uric acid levels measured at 30-31 weeks of gestation in twin mothers predicted the onset of preeclampsia with a sensitivity of 73% and a specificity of 74%. The range of risks presented in the literature is wide and the therapies avocated are diverse. We therefore decided to summarize the risks in a comparative fashion and to review current therapeutic strategies for the convenience of clinicians who confront increasing numbers of multiple pregnancies. The tables bring all recent published risks together in the first comparative analysis in which the data has been converted to relative risks and confidence intervals. Because the literature is relatively silent on specific management of hypertensive disease in twin pregnancies, general management recommendations for singleton gestations should be used by practitioners caring over twin gestations.     

Mapping precursor-binding site on TatC subunit of twin arginine-specific protein translocase by site-specific photo cross-linking

A number of secreted precursor proteins of bacteria, archaea, and plant chloroplasts stand out by a conserved twin arginine-containing sequence motif in their signal peptides. Many of these precursor proteins are secreted in a completely folded conformation by specific twin arginine translocation (Tat) machineries. Tat machineries are high molecular mass complexes consisting of two types of membrane proteins, a hexahelical TatC protein, and usually one or two single-spanning membrane proteins, called TatA and TatB. TatC has previously been shown to be involved in the recognition of twin arginine signal peptides. We have performed an extensive site-specific cross-linking analysis of the Escherichia coli TatC protein under resting and translocating conditions. This strategy allowed us to map the recognition site for twin arginine signal peptides to the cytosolic N-terminal region and first cytosolic loop of TatC. In addition, discrete contact sites between TatC, TatB, and TatA were revealed. We discuss a tentative model of how a twin arginine signal sequence might be accommodated in the Tat translocase.     

Statistical Analyses of Twins Birth Data from a Nigerian Sample

In this paper, both the linear logistic model and its analogous linear model (weighted least squares) are fitted to twin birth data from a Nigerian sample. The logits of the observed perinatal mortality rates are fitted against the birthweight of breech infants for both first born and second born twins. Results show that a quadratic response model fits the data very well, and that the WLS procedure gives a better fit. The results further show that breech births necessarily result in 7.7% and 11.2% mortality rates respectively for first born and second born twins. The results of a log-linear model analysis on the 2×2×4 contingency table formed by the factors, ‘mode of birth’, and twins with the response variable ‘Apgar Scores’-an index of morbidity-also show that both factors play significant roles in explaining the variation of the response variable. It was found that the most important factor effecting the ability of a twin infant to survive as measured by the Apgar scores is the variable ‘mode of birth’ (vertex or breech). In other words, a vertex first twin infant has the best survival chance.     

The use of linear mixed models to estimate variance components from data on twin pairs by maximum likelihood.

It is shown that maximum likelihood estimation of variance components from twin data can be parameterized in the framework of linear mixed models. Standard statistical packages can be used to analyze univariate or multivariate data for simple models such as the ACE and CE models. Furthermore, specialized variance component estimation software that can handle pedigree data and user-defined covariance structures can be used to analyze multivariate data for simple and complex models, including those where dominance and/or QTL effects are fitted. The linear mixed model framework is particularly useful for analyzing multiple traits in extended (twin) families with a large number of random effects.     

Psychobiological and evolutionary perspectives on coping and health characteristics following loss: a twin study.

An analysis of coping, grief and health characteristics is reported for a bereaved monozygotic (MZ) and dizygotic (DZ) same-sex twin sample. The data were examined with reference to psychobiological and evolutionary perspectives on behavior. A Coping Scale, included as part of a comprehensive Twin Loss Survey (TLS), assessed coping with daily responsibilities and activities 1-2 months before the co-twin's death, 1-2 months following the co-twin's death and currently. A Grief Intensity Scale obtained judgments of grief 1-2 months following the loss, and currently. Information on physical symptoms was available from the Somatization Scale of the Grief Experience Inventory. Psychobiological and evolutionary perspectives specified hypotheses for two twin groups: one model was specified to reflect bereavement experiences immediately following loss of the co-twin (retrospective twin group); a second model represented present bereavement response (current twin group). Consistent with psychobiological theory, twins' social closeness showed a positive association with grief intensity which, in turn, affected somatic symptoms and coping efficacy in predicted directions. With respect to evolutionary psychological theory, the effect of zygosity on current grief implicated correlates of genetic relatedness as factors in the bereavement process.     

Sex differences in birth defects: a study of opposite-sex twins

BACKGROUND: Sex differences in structural birth defects are often confounded by environmental risk factors. Opposite-sex twins provide a unique model for detecting sex differences in birth defects while maximally controlling environmental risk factors in a natural setting. METHODS: Population data from the Florida Birth Defects Registry were analyzed. A total of 4,768 pairs of twins who were discordant for sex and born between 1996 and 2001 were analyzed. The McNemar test was used to compare the differences between a male twin and his twin sister for the risk of developing specific defects and organ-system defects. RESULTS: Of 4,768 twin pairs, 225 males (4.72%) and 175 females (3.67%) had birth defects. Among opposite-sex twin pairs, males had a 29% higher risk for birth defects than their twin sisters. Compared to their twin sisters, males had a 5.4 times higher risk for pyloric stenosis and a 2.4 times higher risk for obstructive genitourinary defect, but only one-tenth the risk for congenital hip dislocation. CONCLUSIONS: Sex differences in birth defects exist between opposite-sex twins.     

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.     

Longevity studies in GenomEUtwin.

Previous twin studies have indicated that approximately 25% of the variation in life span can be attributed to genetic factors and recent studies have also suggested a moderate clustering of extreme longevity within families. Here we discuss various definitions of extreme longevity and some analytical approaches with special attention to the challenges due to censored data. Lexis diagrams are provided for the Danish, Dutch, Finnish, Italian, Norwegian, and Swedish Twin registries hereby outlining possibilities for longevity studies within GenomEUtwin. We extend previous analyses of lifespan for the Danish 1870-1900 twin cohorts to include the new 1901-1910 cohorts, which are consistent with the previous findings. The size of the twin cohorts in GenomEUtwin and the existence of population-based, nationwide health and death registers make epidemiological studies of longevity very powerful. The combined GenomEUtwin sample will also allow detailed age-specific heritability analyses of lifespan. Finally, it will provide a resource for identifying unusual sibships (i.e., dizygotic twin pairs) where both survived to extreme ages, as a basis for discovering genetic variants of importance for extreme survival.     

Using bivariate models to understand between- and within-cluster regression coefficients, with application to twin data

In the regression analysis of clustered data it is important to allow for the possibility of distinct between- and within-cluster exposure effects on the outcome measure, represented, respectively, by regression coefficients for the cluster mean and the deviation of the individual-level exposure value from this mean. In twin data, the within-pair regression effect represents association conditional on exposures shared within pairs, including any common genetic or environmental influences on the outcome measure. It has therefore been proposed that a comparison of the within-pair regression effects between monozygous (MZ) and dizygous (DZ) twins can be used to examine whether the association between exposure and outcome has a genetic origin. We address this issue by proposing a bivariate model for exposure and outcome measurements in twin-pair data. The between- and within-pair regression coefficients are shown to be weighted averages of ratios of the exposure and outcome variances and covariances, from which it is straightforward to determine the conditions under which the within-pair regression effect in MZ pairs will be different from that in DZ pairs. In particular, we show that a correlation structure in twin pairs for exposure and outcome that appears to be due to genetic factors will not necessarily be reflected in distinct MZ and DZ values for the within-pair regression coefficients. We illustrate these results in a study of female twin pairs from Australia and North America relating mammographic breast density to weight and body mass index.     

Resolution of genetic and cultural inheritance in twin families by path analysis: application to HDL-cholesterol.

A path model and associated statistical method for the analysis of data on twin families are introduced and applied to high density lipoprotein cholesterol (HDL-c) observations in the Swedish Twin Family Study. The proposed path model incorporates both genetic and environmental sources of familial resemblance, maternal environmental effects, intergenerational differences in heritabilities, marital resemblance due to either primary or secondary phenotypic homogamy, and twin residual environmental correlations. Application of the model to HDL-c levels resulted in parameter estimates consistent with those reported in earlier reviews and in the analysis of nuclear family and twin data. Genetic heritability was estimated as h2 = .363 +/- .243, cultural heritability as c2 = .187 +/- .082, and the proportion of phenotypic variance due to residual environmental effects as r2 = .450 +/- .207. Although the parameter estimates were comparable, the statistical tests of hypotheses were, relative to other designs, of low statistical power. It appears that environmental indices are necessary for powerful tests of hypotheses.     

Twinning rates in Ghana.

The incidence of twin births in Accra and Kumasi, the two major cities in Ghana, was investigated. In Accra, data were collected from the Korle-Bu Teaching Hospital while data were collected and analyzed from the Komfo Anokye Teaching Hospital in Kumasi. Both hospitals are the leading teaching hospitals in Ghana. The data consisted mainly of single and twin births recorded in the hospitals over a period of 12 years in Accra (1988-1999) and 15 years in Kumasi (1985-1999). The study revealed an incidence of 33.4 twin births per thousand live births for Accra and 26.6 twin births per thousand live births for Kumasi. Though these values are not as high as those reported among the Yoruba tribe of southwest Nigeria, who are reported to have the highest twin birth rates in the world, the present values still rank among the highest recorded twin birth rates.     

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.     

Analysis of twin data using SAS

Summary .  Twin studies are essential for assessing disease inheritance. Data generated from twin studies are traditionally analyzed using specialized computational programs. For many researchers, especially those who are new to twin studies, understanding and using those specialized computational programs can be a daunting task. Given that SAS (Statistical Analysis Software) is the most popular software for statistical analysis, we suggest that the use of SAS procedures for twin data may be a helpful alternative and demonstrate that we can obtain similar results from SAS to those produced by specialized computational programs. This numerical validation is practically useful, because a natural concern with general statistical software is whether it can deal with data that are generated from special study designs such as twin studies and if it can test a particular hypothesis. We concluded through our extensive simulation that SAS procedures can be used easily as a very convenient alternative to specialized programs for twin data analysis.     

The fitness of twin mothers: evidence from rural Gambia

We used a longitudinal database from a natural fertility population in rural Gambia to compare the overall fertility of mothers who had given birth to twins at some point in their reproductive history and mothers who had only ever given birth to singletons. We found that twin mothers had shorter birth intervals, higher age‐specific fertility and more surviving children than singleton mothers. This suggests that, despite the considerably higher mortality of twins found in this population, twin mothers have a fitness advantage over singleton mothers, even in the absence of modern medical care. We ran a simple simulation model to estimate the relative fitness of twin and singleton mothers, and found that the model also estimated higher fitness for twin mothers. Further, girls who went on to become twin mothers were of higher anthropometric status during their teenage years than those who became singleton mothers.     

A model for sibling effects in man.

A model is developed to specify the environmental effect of one sibling on another for a polygenic trait. Such effects are detectable in priniciple and the approach is illustrated with twin data relating to psychoticism. The relationship between the model and those employed in the treatment of kin selection is indicated.     

The inter-ovarian distribution of twin ovulations and embryo survival in the bovine

Data in the literature on twin ovulations and twin pregnancies were used to examine the distribution (unilateral vs bilateral) of twin ovulations and associated effects on embryo survival. Unilateral twin ovulations averaged 52% but there was significant heterogeneity among sources. Twenty-five percent of subjects which became pregnant following twin ovulations had unilateral twin ovulations. This suggests that fertilisation failure or embryo mortality, or both, are greater for unilateral twin ovulations. Using data on pregnant cows, the probability of embryo loss increased by an estimated 0.22 for unilateral twin ovulations compared with bilateral twin ovulations or single ovulations. Using the estimates obtained, the expected litter size was calculated for a range of ovulation rates with varying proportions of unilateral twin ovulations and different levels of embryo mortality. Litter size was not very sensitive to the distribution of twin ovulations.