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Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
The purpose of this study is to present curves of estimated placental growth in twins and to evaluate the relative contribution of gestational age, zygosity, chorionicity, fusion of the placentas, sex of the individual and of the twin pair, site of the umbilical cord insertion, birth order, maternal age, and parity. Perinatal data and placental data were obtained from 6315 live-born twin pairs from the East Flanders Prospective Twin Survey. Of 4318 twin pairs, with no missing values, the placental weights of different gestational ages were analyzed using a nonlinear multivariate Gaussian regression. Two groups were distinguished: (1) twins with two separate placentas, and (2) twins with only one placental mass (one placenta in case of monochorionic twins or two fused placentas in case of dichorionic placentas). Overall, placental weight was influenced by gestational age, fusion of the placentas, and parity. In the case of one placental mass, monozygotic dichorionic twins had the lowest weights. If two separate placentas were present, birth order played a role in favor of the first-born twin. For parity and zygosity, the differences were most pronounced between 27 and 29 weeks, whereas the difference for birth order was most pronounced between 33 and 37 weeks. In conclusion, basic physiological characteristics, routinely examined at birth, influence placental weight. Taking these covariates into account allows a better evaluation of the placental weight given a gestational age, as an indicator of growth.
Alongitudinal study of growth and physical fitness of twins and their parents was designed in 1985. The major aims of this Leuven Longitudinal Twin Study were to quantify the genetic and environmental determination of (1) somatic characteristics, biological maturation and physical performance characteristics during the growth process, (2) the growth and developmental patterns, and (3) the covariation in somatic and performance characteristics.
The assessment of fetal growth is an essential component of good antenatal care, especially for twins. The aims of this study are to develop twin-specific intrauterine 'growth' charts, based on cross-sectional birthweight data, for monochorionic and dichorionic twins according to sex and parity, and to detect twins at risk for neonatal death by comparing the use of twin-specific and singleton charts. The study sample consisted of 76,471 singletons and 8454 twins (4227 pairs) born in East Flanders (Belgium). Birthweights were analyzed using a nonlinear Gaussian regression. After 33 weeks of gestation, the birthweights of twins started to deviate from singletons (difference of 900 grams at 42 weeks). Birthweights of dichorionic twins continued to increase, whereas those of monochorionic twins decreased after week 40 (difference of more than 300 g at 42 weeks). After 31 weeks of gestation, neonatal mortality increased as centile decreased, and was especially high if birthweight was below the twin-specific third centile: .032 (below) versus .007 (above). Using singleton centiles, this was less obvious. In conclusion, twin-specific growth charts, taking chorionicity into account, are more accurate to detect twins at risk for neonatal death. Therefore the presented charts, based on cross-sectional birthweight data, enable an improved assessment of twin growth.
This study explores the use of an individual's genetic (IGFS) and environmental factor score (IEFS), constructed using genetic model fitting of a multivariate strength phenotype. Maximal isometric and dynamic strength measures, one maximal repetition load (1RM) and muscle cross-sectional area (MCSA) were measured in 25 monozygotic and 16 dizygotic twin pairs. The use of IGFS and IEFS in predicting the sensitivity to environmental stress was evaluated by the association of the scores with strength training gains after a 10-week high resistance strength training programme. Results show a high contribution of genetic factors to the covariation between maximal strength and muscle cross-sectional area (84–97%) at pre-training evaluation. Individual factor scores explained the largest part of the variation in 1RM and other strength measures at pre-training and post-training evaluation respectively. Genes that are switched on due to training stress (gene–environment interaction) could explain the decrease in explained variation over time. A negative correlation was found between IGFS and strength training gains (−0.24 to −0.51, P < 0.05); individuals with a high IGFS tend to gain less strength than individuals with low IGFS. Individual environmental factor scores have lower differential power. The predictive value of the IGFS has potential utility in identifying an individual's susceptibility to environmental stress in a variety of multifactorial characteristics, eg diseases and impairments, and for selection of sib pairs for QTL analyses. Twin Research (2000) 3, 99–108.
Previous findings show strong evidence for the role of retinoblastoma (Rb) in myoblast proliferation and differentiation. However, it is not known whether variation in the retinoblastoma gene (RB1) is responsible for normal variation in human muscle strength. Therefore, a linkage analysis for quantitative traits was performed on 329 young male siblings from 146 families with muscle strength, using a polymorphic marker in RB1 (D13S153 on 13q14.2). Trunk strength, a general strength indicator that requires activation of large muscle groups, was measured on a Cybex TEF isokinetic dynamometer. We found evidence for linkage between locus D13S153 at 13q14.2 and several measurements of trunk flexion with LOD scores between 1.62 and 2.78 (.002 < p < .0002). No evidence for linkage was found with trunk extension. This first exploration of the relationship between RB1 and human muscle strength through linkage analysis warrants efforts for further fine mapping of this region.
Unlike-sex twins provide a unique natural experiment to investigate the influence of sex on gestation. Our data showed that length of gestation of unlike-sex pairs is similar to that of female same-sex pairs, and significantly (0.4 wks, p = .02) longer than that of male same-sex pairs. Birthweight of female unlike-sex twins was similar to female same-sex twins, but male unlike-sex twins weighed 78 g more than male same-sex twins ( p = .001). These data show that in unlikesex pairs it is the girl that prolongs gestation for her brother, resulting in a higher birthweight than that of same-sex boys.
Insulin resistance and obesity are underlying causes of type 2 diabetes and therefore much interest is focused on the potential genes involved. A series of anthropometric and metabolic characteristic were measured in 240 MZ and 112 DZ twin pairs recruited from the East Flanders Prospective Twin Survey. Microsatellite markers located close to ABCC8, ADIPOQ, GCK, IGF1, IGFBP1, INSR, LEP, LEPR, PPARγ and the RETN gene were genotyped. Univariate single point variance components linkage analyses were performed using two methods: (1) the standard method, only comprising the phenotypic and genotypic data of the DZ twin pairs and (2) the extended method, also incorporating the phenotypic data of the MZ twin pairs. Suggestive linkages (LOD > 1) were observed between the ABCC8 marker and waist-to-hip ratio and HDL-cholesterol levels. Both markers flanking ADIPOQ showed suggestive linkage with triglycerides levels, the upstream marker also with body mass and HDL-cholesterol levels. The IGFBP1 marker showed suggestive linkage with fat mass, fasting insulin and leptin levels and the LEP marker showed suggestive linkage with birth weight. This study suggests that DNA variants in ABCC8, ADIPOQ, IGFBP1 and LEP gene region may predispose to type 2 diabetes. In addition, the two methods used to perform linkage analyses yielded similar results. This was however not the case for birth weight where chorionicity seems to be an important confounder.
This study investigates the validity of retrospective determination of chorion type by asking the question to the mother about the number of placentas. In the “East Flanders Prospective Twin Survey” (EFPTS), accurate information on the placentation and zygosity of the multiples was collected prospectively. The mothers of 231 monozygotic (95 dichorionic and 136 monochorionic) twins and 255 dizygotic twins were asked to fill in a simple questionnaire regarding 1) the zygosity and 2) the number of placentas of their twins. The accuracy of the response to the question on “the number of placentas” was 60% for monozygotic twins and 37% for dizygotic twins. The accuracy of the response to the question on the zygosity of the twins was 93% for monozygotic and 95% for dizygotic twins. If the questionnaire was used for the determination of chorion type, a total of 31 monozygotic twins (13%) should have been assigned as dichorionic on the fact that there were two separate placentas. Of these, 10 (32%) are monochorionic and 12 (39%) were falsely reported as having two placentas. We conclude from these findings that this simple questionnaire method is unreliable for the retrospective determination of the chorion type.
The East Flanders Prospective Twin Survey (EFPTS) is a prospective, population-based registry of multiple births in the province of East Flanders, Belgium. EFPTS has several unique features: it is population based and prospective, with the possibility of long-term follow-up; the twins (and higher order multiple births) are ascertained at birth; basic perinatal data recorded; chorion type and zygosity established; and since 1969 placental biopsies have been taken and frozen at −20 °C for later determination of genetic markers. The EFPTS is the only large register that includes placental data and allows differentiation of 3 subtypes of monozygotic (MZ) twins based on the time of the initial zygotic division: the dichorionic–diamnionic pairs (early, before the 4th day after fertilization), the monochorionic–diamnionic pairs (intermediate, between the 4th and the 7th day post fertilization), and the monochorionic–monoamnionic pairs (late, after the 8-day post fertilization). This added a new dimension to didymology (the science of twins; didymos is the Greek word for twin): the timing of MZ twinning. Studies can be initiated taking into account primary biases, those originating in utero. Such studies could throw new light on the controversy over the validity of the classic twin method, the consequences of early embryological events (before and just after implantation of the embryo), the origin of congenital malformations, the sex proportion of multiples, the gene–environment interactions as far as intrauterine environment is concerned, to name but a few.
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