Twin Zygosity Research Articles

Adequacy of Using a Three-Item Questionnaire to Determine Zygosity in Chinese Young Twins.

The present study examined the adequacy of a three-item parent questionnaire in determining the zygosity of young Chinese twins and whether there was any association between parent response accuracy and some demographic variables. The sample consisted of 334 pairs of same-sex Chinese twins aged from 3 to 11years. Three scoring methods, namely the summed score, logistic regression, and decision tree, were employed to evaluate parent response accuracy of twin zygosity based on single nucleotide polymorphism (SNP) information. The results showed that all three methods achieved high level of accuracy ranging from 91 to 93% which was comparable to the accuracy rates in previous Chinese twin studies. Correlation results also showed that the higher the parents' education level or the family income was, the more likely parents were able to tell correctly that their twins are identical or fraternal. The present findings confirmed the validity of using a three-item parent questionnaire to determine twin zygosity in a Chinese school-aged twin sample.

Hypertensive disorders during monozygotic and dizygotic twin gestations: A population-based study

ABSTRACTObjective: To determine whether the incidence of hypertensive disorders is different in monozygotic compared to dizygotic twin pregnancies. Methods: A registry-based survey of twin pregnancies delivered during 2003 to 2012. We used the best clinical estimate of zygosity based on the concept that all monochorionic twins are monozygotic and all unlike-sex pairs are dizygotic, thus excluding same-sex dichorionic twin gestations for which zygosity cannot be ascertained on clinical grounds. Study cohorts were twin pregnancies with or without preeclampsia and gestational hypertension. Results: A total of 3419 twin gestations met the inclusion criteria, of which 442 (12.9%) were monochorionic and 1255 (36.7%) were unlike-sex twins, excluding 1722 same-sex dichorionic twin gestations (50.4%). There was no significant difference in the incidence of preeclampsia (OR: 0.9; 95% CI: 0.4–2.0 for monozygotic males and OR: 0.6; 95% CI: 0.3–1.4 for monozygotic females) and gestational hypertension (OR: 0.7; 95% CI: 0.2–2.5 for monozygotic males, and OR: 0.7; 95% CI: 0.2–2.3 for monozygotic females) between monochorionic and unlike-sex pairs. Maternal prepregnancy obesity and nulliparity were the only significant associated factors of preeclampsia (OR: 3.8; 95% CI: 2.0–7.0, and OR: 2.5; 95% CI: 1.4–4.4, respectively). Maternal prepregnancy obesity (OR: 5.5; 95% CI: 2.5–12.2), maternal age ≥36 years (OR: 2.5; 95% CI: 1.1–6.1), and family history of hypertension (OR: 2.6; 95% CI: 1.3–5.1) were significantly associated with gestational hypertension. Conclusion: Based on a large population-based dataset and on the best clinical estimate of twin zygosity, it appears that zygosity is not associated with hypertensive disorders in twin gestations.

Physical activity attenuates genetic effects on BMI: Results from a study of Chinese adult twins.

This study aimed to examine the gene-environment interaction of physical activity and body mass index (BMI) using the Chinese National Twin Registry (CNTR). A total of 19,308 same-sex adult twins from CNTR were included in the analysis. Twin zygosity was determined by self-reported questionnaire. Height and weight were measured using self-reported questionnaire. The vigorous physical activity was defined as greater or equal to five times a week of at least 30 min moderate- or high-intensity physical activity. A twin structural equation model was used to analyze the gene-environment interaction of vigorous exercise with BMI among 13,506 monozygotic twins and 5,802 dizygotic twins. A structural equation model adjusting for age and sex found vigorous exercise significantly moderated the additive genetic effects (P < 0.001) and shared environmental effects (P < 0.001) on BMI. The genetic contributions to BMI were significantly lower for people who adopted a physically active lifestyle [h(2) = 40%, 95% confidence interval (CI): 35%-46%] than those who were relative sedentary (h(2) = 59%, 95% CI: 52%-66%). The observed gene-physical activity interaction was more pronounced in men than women. Our results suggested that adopting a physically active lifestyle may help to reduce the genetic influence on BMI among the Chinese population.

Ecosensitivity and genetic polymorphism of somatic traits in the perinatal development of twins

In view of criticism regarding the usefulness of heritability coefficients, the aim of this study was to analyze separately the information on genetic and environmental variability. Such an approach, based on the normalization of trait's variability for its value, is determined by the coefficients of genetic polymorphism (Pg) and ecosensitivity (De).The studied material included 1263 twin pairs of both sexes (among them 424 pairs of monozygotic twins and 839 pairs of dizygotic twins) born between the 22nd and 41st week of gestation. Variability of six somatic traits was analyzed. The zygosity of same-sex twins was determined based on the polymorphism of DNA from lymphocytes of the umbilical cord blood, obtained at birth. The coefficients of genetic polymorphism and ecosensitivity for analyzed traits of male and female twins born at various months of gestation were calculated.Our study revealed that a contribution of the genetic component predominated over that of the environmental component in determining the phenotypic variability of somatic traits of newborns from twin pregnancies. The genetically determined phenotypic variability in male twins was greater than in the females. The genetic polymorphism and ecosensitivity of somatic traits were relatively stable during the period of fetal ontogeny analyzed in this study. Only in the case of body weight, a slight increase in the genetic contribution of polygenes to the phenotypic variance could be observed with gestational age, along with a slight decrease in the influence of environmental factors.

Oral bony outgrowths: Prevalence and genetic factor influence. Study of twins

ObjectiveThe aim of the study was to verify the influence of a genetic factor on the etiology of oral bony outgrowths and to determine the prevalence and type of oral bony outgrowths (tori and exostoses) among a group of Lithuanian twins. Materials and methodsIn total, 162 twins (81 twin pairs) were analyzed for the presence or absence, type, and size of oral bony outgrowths. Statistical analysis was carried out to find the prevalence of bony protuberances and the relationship between zygosity and occurrence of oral bony enlargements. Zygosity of twins was confirmed by DNA analysis. Results59.9% of the subjects had oral bony outgrowths. Mandibular tori were found in 56.8% and palatal tori in 1.8% of the sample. Palatal exostoses and mandibular exostoses were present in 1.8% and 3.1% of the sample, respectively, whereas maxillary exostoses were not found. A higher percentage of tori and exostoses were found in the group of older subjects (>18 years old, p=0.025). No significant difference was found between men and women in the prevalence of bony outgrowths. High κ and r values (0.91±0.062) showed very good concordance of oral bony outgrowths between monozygotic and moderate concordance (0.58±0.141) between dizygotic co-twins (p<0.001). The calculation of heritability estimate verifies dominant influence of genetic factor on the etiology of oral bony outgrowths (h2=0.658). ConclusionThe most common bony outgrowth was torus mandibularis. Our results show that the genetic factor is dominant in the etiology of oral bony outgrowths.

Heritability and the Equal Environments Assumption: Evidence from Multiple Samples of Misclassified Twins

Classically derived estimates of heritability from twin models have been plagued by the possibility of genetic-environmental covariance. Survey questions that attempt to measure directly the extent to which more genetically similar kin (such as monozygotic twins) also share more similar environmental conditions represent poor attempts to gauge a complex underlying phenomenon of GE-covariance. The present study exploits a natural experiment to address this issue: Self-misperception of twin zygosity in the National Longitudinal Survey of Adolescent Health (Add Health). Such twins were reared under one "environmental regime of similarity" while genetically belonging to another group, reversing the typical GE-covariance and allowing bounded estimates of heritability for a range of outcomes. In addition, we examine twins who were initially misclassified by survey assignment--a stricter standard--in three datasets: Add Health, the Minnesota Twin Family Study and the Child and Adolescent Twin Study in Sweden. Results are similar across approaches and datasets and largely support the validity of the equal environments assumption.

Twin–Singleton Differences in Cognitive Abilities in a Sample of Africans in Nigeria

Recent studies comparing cognitive abilities between contemporary twins and singletons in developed countries have suggested that twin deficits in cognitive abilities no longer exist. We examined cognitive abilities in a sample of twins and singletons born recently in Nigeria to determine whether recent findings can be replicated in developing countries. Our sample consisted of 413 pairs of twins and 280 singletons collected from over 45 public schools in Abuja and its neighboring states in Nigeria. The ages of twins and singletons ranged from 9 to 20 years with a mean (SD) of 14.6 years (2.2 years) for twins and 16.1 years (1.8 years) for singletons. Zygosity of the same-sex twins was determined by analysis of 16 deoxyribonucleic acid markers. We asked participants to complete a questionnaire booklet that included Standard Progressive Matrices-Plus Version (SPM+), Mill-Hill Vocabulary Scale (MHV), Family Assets Questionnaire, and demographic questions. The data were corrected for sex and age and then analyzed using maximum likelihood model-fitting analysis. Although twins and singletons were comparable in family social class indicators, singletons did better than twins across all the tests (d = 0.10 to 0.35). The average of d for SPM+ total [0.32; equivalent to 4.8 Intelligence Quotient (IQ) points] and d for MHV (0.24; equivalent to 3.6 IQ points) was 0.28 (equivalent to 4.2 IQ points), similar to the twin-singleton gap found in old cohorts in developed countries. We speculate that malnutrition, poor health, and educational systems in Nigeria may explain the persistence of twin deficits in cognitive abilities found in our sample.

Noninvasive twin zygosity assessment and aneuploidy detection by maternal plasma DNA sequencing

This study aimed to provide an individualized assessment of fetal trisomy 21 and trisomy 18 status for twin pregnancies by maternal plasma DNA sequencing. Massively parallel sequencing was performed on the plasma/serum DNA libraries of eight twin pregnancies and 11 singleton pregnancies. The apparent fractional fetal DNA concentrations between genomic regions were assessed to determine the zygosities of the twin pregnancies and to calculate the fetal DNA concentrations of each individual member of dizygotic twin pairs. Z-scores were determined for the detection of trisomy 18 and trisomy 21. Circulating DNA sequencing showed elevated chromosome 21 representation in one set of twins and elevated chromosome 18 representation in another pair of twins. Apparent fractional fetal DNA concentration analysis revealed both sets of twins to be dizygotic. The fractional fetal DNA concentrations for each individual fetus of the dizygotic twin pregnancies were determined. Incorporating the information about the fetal DNA fraction, we ascertained that each fetus contributed adequate amounts of DNA into the maternal circulation for the aneuploidy test result to be interpreted with confidence. Noninvasive prenatal assessment of fetal chromosomal aneuploidy for twin pregnancies can be achieved with the use of massively parallel sequencing of cell-free DNA in maternal blood.

Twin-to-Twin Transfusion Syndrome

Twin-to-twin transfusion syndrome (TTTS) is a disease that affects roughly 15% of monochorionic twins. Although TTTS is not extremely prevalent, the rate of mortality and morbidly approaches 100% without early detection and treatment. The following case study is a triplet pregnancy that included a set of monochorionic twins affected by TTTS. Typically, it is assumed that monochorionicity can identify the zygosity of twins, which was disproven in this case. Research indicates that there has been an increased rate of monochorionic twins with in vitro fertilization. There is great debate about the most appropriate treatment modality for TTTS. Perinatal treatment followed by neonatal management is the standard of care for TTTS. Implications for the neonatal nurse practitioner and care for the patients are discussed.

Noninvasive Prenatal Determination of Twin Zygosity by Maternal Plasma DNA Analysis

The current methods for distinguishing the zygosities of twins include ultrasound scanning, which is nondefinitive, and amniocentesis, which is invasive. We explored the use of massively parallel sequencing of maternal plasma DNA for the noninvasive prenatal assessment of the zygosities of twin pregnancies. Plasma DNA was extracted from blood collected from 8 women pregnant with twins. Target enrichment and massively parallel sequencing were performed for each plasma DNA library. Apparent fractional fetal DNA concentrations were calculated for multiple genomic regions by determining the ratio of minor to major alleles among single-nucleotide polymorphism sites. Variations in the apparent fractional fetal DNA concentrations between genomic regions were used to infer whether individual fetuses in a twin pair were genotypically different and hence dizygotic. The extent of the variation in the apparent fractional fetal DNA concentration across chromosomes was 0.82-1.35 SDs for monozygotic twin pregnancies and 2.42-4.80 SDs for dizygotic twin pregnancies. The proportions of apparent fractional fetal DNA concentration values that deviated beyond the range expected for stochastic variation were 0.00%-1.93% for monozygotic twin pregnancies and 36.2%-78.1% for dizygotic twin pregnancies. After identifying a pair of twins as likely dizygotic, the method also allowed determination of the fractional fetal DNA concentrations contributed by the individual fetuses of a dizygotic twin pair. Noninvasive prenatal determination of twin zygosity by maternal plasma DNA sequencing is feasible. It is also possible to determine the relative fractional fetal DNA concentrations for each fetus for dizygotic twin pregnancies.

Curiosity in the genes: the DNA fingerprinting story

Curiosity in the genes: the DNA fingerprinting story

Birth weight, infant mortality, and race: Twin comparisons and genetic/environmental inputs

Genetic and environmental inputs may shape population health disparities in varying ways. In this article, we use unique variation involved in twin births to attempt to untangle how genetic and prenatal environmental variation may make different contributions to infant health among white and black populations in the United States. Using twin fixed effects models and data from the 1995–1997 Matched Multiple Birth Dataset we compare birth weight–mortality associations across twin sex composition, zygosity, and race. Findings reveal suggestive differences between fraternal and imputed identical twin estimates for white and black twin pairs.

Keratoconus in 18 pairs of twins

To describe the concordance of keratoconus in 18 sets of twins. Thirteen monozygotic (MZ) and five dizygotic (DZ) pairs of twins were identified during an investigation of familial keratoconus. We used 16 forensic microsatellite markers to confirm the zygosity of same sex twins. Patients and available relatives were examined for signs of keratoconus using corneal topography. For each pair of twins, the severity of keratoconus in each eye was graded according to the steepest keratometry value and the average difference in score between the MZ and DZ twins compared. All of the MZ twins and four of the five DZ twins were concordant for keratoconus but with differences in age of onset and severity of disease. The subjective age of onset of keratoconus tended to be earlier in the MZ twins (16.4 years, SD 4.66) than in the DZ twins (20.3 years, SD 7.55) (p=0.086). Additional relatives with keratoconus were identified in two (16%) of the families with MZ twins and in three (60%) of the families of DZ twins. The mean difference in severity scores was 1.4 (SD 1.73) for the MZ twins and 3.0 (SD 1.00) for the DZ twins (p=0.035). This data provide evidence that the severity of keratoconus is more concordant in MZ than in DZ twins. The results support the currently accepted hypothesis of an important genetic contribution towards the pathogenesis of keratoconus, but suggest that there is also an environmental effect on the expression of disease.

Validation of a Cost-Efficient Multi-Purpose SNP Panel for Disease Based Research

BackgroundHere we present convergent methodologies using theoretical calculations, empirical assessment on in-house and publicly available datasets as well as in silico simulations, that validate a panel of SNPs for a variety of necessary tasks in human genetics disease research before resources are committed to larger-scale genotyping studies on those samples. While large-scale well-funded human genetic studies routinely have up to a million SNP genotypes, samples in a human genetics laboratory that are not yet part of such studies may be productively utilized in pilot projects or as part of targeted follow-up work though such smaller scale applications require at least some genome-wide genotype data for quality control purposes such as DNA “barcoding” to detect swaps or contamination issues, determining familial relationships between samples and correcting biases due to population effects such as population stratification in pilot studies.Principal FindingsEmpirical performance in classification of relative types for any two given DNA samples (e.g., full siblings, parental, etc) indicated that for outbred populations the panel performs sufficiently to classify relationship in extended families and therefore also for smaller structures such as trios and for twin zygosity testing. Additionally, familial relationships do not significantly diminish the (mean match) probability of sharing SNP genotypes in pedigrees, further indicating the uniqueness of the “barcode.” Simulation using these SNPs for an African American case-control disease association study demonstrated that population stratification, even in complex admixed samples, can be adequately corrected under a range of disease models using the SNP panel.ConclusionThe panel has been validated for use in a variety of human disease genetics research tasks including sample barcoding, relationship verification, population substructure detection and statistical correction. Given the ease of genotyping our specific assay contained herein, this panel represents a useful and economical panel for human geneticists.

Are self-report of disability pension and long-term sickness absence accurate? Comparisons of self-reported interview data with national register data in a Swedish twin cohort

BackgroundSelf-reported disability pension (DP) and sickness absence are commonly used in epidemiological and other studies as a measure of exposure or even as an outcome. The aims were (1) to compare such self-reports with national register information in order to evaluate the validity of self-reported DP and sickness absence, and (2) to estimate the concordance of reporting behaviour in different twin zygosity groups, also by sex.MethodsAll Swedish twins born 1933-1958 who participated in the Screening Across the Lifespan Twin study (SALT) 1998-2003, were included (31,122 individuals). The self-reported DP and long-term sickness absence (LTSA) at the time of interview was compared to the corresponding register information retrieved from the National Social Insurance Agency by calculating the proportions of agreements, kappa, sensitivity, specificity, concordance rates, and chi-square test, to evaluate construct validity.ResultsThe proportions of overall agreement were 96% and specificity 99% for both DP and LTSA, while the sensitivity was 70% for DP and 45% for LTSA. Kappa estimates were 0.76 for DP, and 0.58 for LTSA. The proportions of positive agreement were 64% for DP and 42% for LTSA. No difference in response style was found between zygosity groups among complete twin pairs for DP and LTSA. Results were similar for women and men and across age. Kappa estimates for DP differed somewhat depending on years of education, 0.68 (college/university) vs. 0.77 (less than 13 years in school) but not for LTSA.ConclusionsSelf-reported DP data may be very useful in studies when register information is not available, however, register data is preferred especially for LTSA. The same degree of twin similarity was found for truthful self-report of DP and LTSA in both monozygotic and dizygotic twin pairs. Thus, the response style was not influenced by genetic factors. One consequence of this would be that when estimating the relative importance of genetic and environmental effects from twin models, heritability estimates would not be biased.

Research on animal blood groups and biochemical polymorphisms at Onderstepoort (1956-1990) : historical article

The introduction and wide use of artificial insemination in cattle in the 1950s led to a need for accurate parentage identification. Blood group determination by means of the newly emerging scientific discipline called immunogenetics provided the answer. A blood group laboratory was consequently established at Onderstepoort in 1956, initially concentrating on the production of blood typing reagents. Once established the technology was also applied to studies on a variety of problems in various animals as summarised in this paper. Investigations include zygosity in cattle twins, blood transfusion in domestic animals, breed relationships, genetic polymorphisms and the identification of useful genetic markers for production and disease parameters in breeding programmes.

A Twin Study of Sleep Duration and Body Mass Index

To determine the relative importance of genetic and environmental contributions to the association between sleep duration and body mass index (BMI). Twins from the University of Washington Twin Registry, a community-based sample of U.S. twins, provided self-reported height and weight for BMI calculation and habitual sleep duration. A generalized estimating equation model evaluated the overall and within twin pair effects of sleep duration on BMI with and without stratification by twin zygosity. A structural equation model was used to assess genetic and non-genetic contributions to BMI and sleep duration. The study sample included 1,224 twins comprised of 423 monozygotic, 143 dizygotic, and 46 indeterminate pairs. The mean age was 36.9 years; 69% were female. A multivariate adjusted analysis of all twins revealed an elevated mean BMI (26.0 kg/m2) in short sleeping twins (< 7 h/night) compared to twins sleeping 7-8.9 h/night (BMI 24.8 kg/m2; p < 0.01). The within-twin pair analysis revealed similar results, with the short sleeping twins having a mean BMI of 25.8 kg/ m2 compared to 24.9 kg/m2 for the 7-8.9 h/night sleep duration group (p = 0.02). When restricted to monozygotic twins, the within-twin pair analysis continued to reveal an elevated BMI in the short sleeping twins (25.7 kg/m2) compared to the 7-8.9 h/night reference group (24.7 kg/m2; p = 0.02). No differences in mean BMI were observed between the 7-8.9 h/night reference group twins and longer sleeping twins (> or = 9 h/night) in the analysis of all twins, the overall within-twin pair analysis, or the within-twin pair analysis stratified by zygosity. The heritability of sleep duration was 0.31 (p = 0.08) and BMI 0.76 (p < 0.01). Bivariate genetic analysis revealed little evidence of shared genetics between sleep duration and BMI (p = 0.28). Short sleep was associated with elevated BMI following careful adjustment for genetics and shared environment. These findings point toward an environmental cause of the relationship between sleep duration and BMI.

Difference in nuchal translucency between monozygotic and dizygotic spontaneously conceived twins

To assess nuchal translucency (NT) thickness and differences in inter-twin NT thickness among naturally conceived monozygotic and dizygotic twins. Enrolled women prospectively underwent NT measurement for both twins between 11 and 14 weeks of gestational age. NT thickness and inter-twin NT difference were recorded and compared among dizygotic twins, monozygotic dichorionic twins, and monozygotic monochorionic twins. This study obtained analyzable data for 174 monozygotic twins and 107 dizygotic twins. Of the 174 monozygotic twins, 105 were monochorionic, and 69 were dichorionic. Monozygotic monochorionic twin pregnancies had a significantly higher mean fetal NT thickness (1.48 +/- 0.62 mm) than either dizygotic twin pregnancies (1.34 +/- 0.50 mm) or monozygotic dichorionic twin pregnancies (1.31 +/- 0.48 mm). Mean inter-twin NT difference was significantly lower in monozygotic dichorionic twin pregnancies (0.37 +/- 0.19 mm) than in dizygotic twin pregnancies (0.57 +/- 0.22 mm) or monochorionic twin pregnancies (0.65 +/- 0.43 mm).Irrespective of twin zygosity, NT thickness and inter-twin NT difference were larger in monochorionic twins than in dichorionic twins (1.48 +/- 0.62 mm versus 1.33 +/- 0.49 mm, and 0.65 +/- 0.43 mm versus 0.49 +/- 0.23 mm, respectively). During first-trimester ultrasonographic screening for Down syndrome, monochorionic twin pregnancies have the greatest NT thickness and monozygotic dichorionic twin pregnancies have the lowest inter-twin NT difference.

Quantitative heritability of anti–citrullinated protein antibody–positive and anti–citrullinated protein antibody–negative rheumatoid arthritis

The majority of genetic risk factors for rheumatoid arthritis (RA) are associated with anti-citrullinated protein antibody (ACPA)-positive RA, while far fewer genetic risk factors have been identified for ACPA-negative RA. This study was undertaken to quantify the contribution of genetic risk factors in general, and of the predisposing HLA-DRB1 shared epitope (SE) alleles in particular, to the ACPA-positive and ACPA-negative subsets of RA, by computing their heritability and assessing the contribution of the HLA SE alleles. One hundred forty-eight RA twin pairs, in which at least 1 twin of each pair had RA, were tested for ACPAs and typed for HLA-DRB1 genotypes. Heritability was assessed in a logistic regression model including a bivariate, normally distributed random effect, representing the contribution of unobserved genetic factors to RA susceptibility, with the correlation of the random effects fixed according to twin zygosity. The contribution of the HLA SE alleles to genetic variance was assessed using a similar model, except that estimates were based on genotype-specific population prevalences. The heritability of RA among the twin pairs was 66% (95% confidence interval [95% CI] 44-75%). For ACPA-positive RA, the heritability was 68% (95% CI 55-79%), and for ACPA-negative RA it was 66% (95% CI 21-82%). Presence of the HLA SE alleles explained 18% (95% CI 16-19%) of the genetic variance of ACPA-positive RA but only 2.4% (95% CI 1.6-10%) of the genetic variance of ACPA-negative RA. The heritability of ACPA-positive RA is comparable with that of ACPA-negative RA. These data indicate that genetic predisposition plays an important role in the pathogenesis of ACPA-negative RA, for which most individual genetic risk factors remain to be identified.

Genetic determination of sibship and twin zygosity in a case of an alleged double infant homicide

A 32 year-old woman was hospitalised with severe septic symptoms. The examination of the patient revealed placenta residues in the woman’s uterus as cause of the infection. The police was called and investigated her apartment in search of the missing baby. Finally, the bodies of two newborn babies were found in the freezer. According to the mother, the babies were stillborn twins. The autopsy revealed that the smaller, moderately putrefied child was stillborn, while the larger infant showed typical signs of drowning and only slight putrefaction. The placenta was judged by gynaecologists to be that of a single pregnancy. Thus the prosecution suspected that the woman had had two independent pregnancies and ordered an additional genetic analysis. A genetic analysis clearly revealed that the babies were monozygotic twins, supporting the mother’s statement of a twin pregnancy.