Mortality among twins after age 6: fetal origins hypothesis versus twin method.

OBJECTIVE--To test the validity of the fetal origins hypothesis and the classic twin method. DESIGN--Follow up study of pairs of same sex twins in which both twins survived to age 6. SETTING--Denmark. SUBJECTS--8495 twin individuals born 1870-1900, followed through to 31 December 1991. MAIN OUTCOME MEASURES--Mortality calculated on a cohort basis. RESULTS--Mortality among twins and the general population was not significantly different except among females aged 60-89, in whom mortality among twins was 1.14 times (SE 0.03) higher than in the general population. Mortality among female dizygotic twins was 1.77 times (0.18) higher than among monozygotic twins at age 30-59. Otherwise, mortality for monozygotic and dizygotic twins did not consistently differ after age 6. CONCLUSION--According to the fetal origins hypothesis the risk of adult morbidity and mortality is heightened by retardation in intrauterine growth. Twins, and in particular monozygotic twins, experience growth retardation in utero. The findings in the present study suggest that the fetal origins hypothesis is not true for the retardation in intrauterine growth experienced by twins. Furthermore, the data are inconsistent with the underlying assumption of a recent claim that the classic twin method is invalid for studies of adult diseases. The present study is, however, based on the one third of all pairs of twins in which both twins survived to age 6. The possible impact of this selection can be evaluated in future studies of cohorts of younger twins with lower perinatal and infant mortality.     

Monozygous female twins discordant for a pattern of X chromosome inactivation as a model for study on X-linked intellectual traits

Ring the last decades, numerous genes for general cognitive ability were identified on human X-chromosome. They were discovered primarily because of X-linked mutations causing nonspecific mental retardation in males. Evidence for imprinted loci on the X chromosome affecting neurodevelopment was found in studies on 45,X females. Investigation of transmission of X-linked traits in normal individuals might further contribute to problem of shaping human being's mind ability. We suggest monozygous female twins discordant for a parent-of-origin of the X chromosome inactivation to be a proper subject for such explorations.     

X chromosome inactivation patterns correlate with fetal-placental anatomy in monozygotic twin pairs: implications for immune relatedness and concordance for autoimmunity.

BACKGROUND: Monozygotic (MZ) twinning is a poorly understood phenomenon that may result in subtle biologic differences between twins, despite their identical inheritance. These differences may in part account for discordant expression of disease in MZ twin pairs. Due to their stochastic nature, differences in X chromosome inactivation patterns are one source of such variation in female MZ twins. MATERIALS AND METHODS: We investigated X chromosome inactivation patterns in the blood of 41 MZ twin pairs based on methylation of the androgen receptor gene using a Hpa II-PCR assay. Twenty-six female MZ twin pairs with autoimmune disease (rheumatoid arthritis or multiple sclerosis) were studied. In addition, we studied 15 newborn female MZ twin pairs who were characterized at birth with respect to the anatomy of chorionic membranes (dichorionic versus monochorionic). RESULTS: We found a strong correlation between dichorionic fetal anatomy and differences in X chromosome inactivation patterns between members of an MZ twin pair. In contrast, all monochorionic twin pairs had closely correlated patterns of X chromosome inactivation. X chromosome inactivation patterns did not distinguish between MZ twin pairs who were concordant or discordant for autoimmune disease. CONCLUSIONS: The highly similar patterns of X chromosome inactivation among monochorionic twin pairs may result from their shared placental blood supply during intrauterine life. Alternatively, these patterns may indicate that X chromosome inactivation occurs before the twinning event in this anatomic subgroup of MZ twins. The data further suggest that these factors do not make a major contribution to the high discordance rates for autoimmune disease in MZ twin pairs.     

指纹遗传的双生子研究——Ⅱ.指纹纹型的研究

采用双生子法对26对MZ及24对DZ的指纹纹型进行研究,发现在各类指纹纹型中,斗形最多,桡箕最少。男女间纹型频率差异不大。纹型的左右手对称性为77.20％。作者提出了指纹系数的计算公式,即[(斗形纹数)+(斗形纹数+箕形纹数)]×100％。认为以此来反映10指纹型的构成和复杂程度,以及分析指纹较为合适。 纹型和三辐线在MZ与DZ对间一致率的比较,以及指纹系数、花样强度和生物学指纹价在MZ与DZ对间的相关系数的比较,发现MZ对间的一致率及相关系数明显高于DZ对间的一致率及相关系数,其遗传度为56—92％。本文发现指纹系数在MZ对间并非完全一致,即MZ对间纹型不一致,且指纹系数呈一连续常态分布。纹型的分析表明,指纹纹型以多基因遗传的可能性较大,但不能排除异质性遗传的可能。     

Otitis media: genetic factors and sex differences.

Although genetic factors are recognised as major contributors to otitis media, the presence of sex differences in heritability needs clarification. The aim of this study was to estimate the relative contribution of genetic and environmental effects in otitis media liability with particular focus on sex differences. Data from a cohort of Norwegian twins born between 1967 and 1979 with repeated measures on recurrent childhood otitis media were analysed. Altogether the sample included 4247 twin pairs. The tetrachoric correlations for monozygotic twins were .71 and .65 for males and females respectively. In dizygotic twins the correlations were .35 and .25 for males and females, respectively, and was.34 in opposite sexed pairs. The contribution of genetic and environmental effects was analyzed using structural equation modeling. The best fitting model showed that additive genetic effects explained 72% and 61% of the variance in males and females, respectively. The remaining variance was attributed to individual environmental effects. A model specifying equal heritability estimates for males and females yielded an almost equivalent fit. We found substantial genetic effects for liability to otitis media. There is no evidence that different sets of genes influence liability in males and females, but there may be sex differences in the relative importance of genetic effects.     

Evidence for higher heritability of somatotype compared to body mass index in female twins

The influence of genetics on human physique and obesity has been addressed by the literature. Evidence for heritability of anthropometric characteristics has been previously described, mainly for the body mass index (BMI). However, few studies have investigated the influence of genetics on the Heath-Carter somatotype. The aim of the present study was to assess the heritability of BMI and somatotype (endomorphy, mesomorphy, and ectomorphy) in a group of female monozygotic and dizygotic twins from childhood to early adulthood. A total of 28 females aged from 7 to 19 years old were studied. The group included 5 monozygotic and 9 dizygotic pairs of twins. The heritability was assessed by the twin method (h(2)). The anthropometric measures and somatotype were assessed using standard validated procedures. Significant differences between monozygotic and dizygotic pairs of twins were found for height, endomorphy, ectomorphy, and mesomorphy, and the heritability for these measures was high (h(2) between 0.88 and 0.97). No significant differences were found between monozygotic and dizygotic twins for weight, and the BMI and the heritability indexes were lower for these measures (respectively 0.42 and 0.52). The results of the present study have indicated that the somatotype may be more sensible to genetic influences than the BMI in females.     

Differences and similarities in the intra-uterine behaviour of monozygotic and dizygotic twins.

Diagnostic advances have made it possible to use ultrasonograph to assess placentation and therefore zygosity in utero in the case of monochorionic-monozygotic twins. Foetal behaviour of 15 monozygotic and 15 unlike-sexed dizygotic twin pairs was studied serially with ultrasounds from 10 to 22 weeks gestational age. Each twin, regardless of its zygosity, showed individualised behavioural styles. One twin was found to be 'dominant' in the sense of being more active, but less reactive, possibly due to the fewer stimuli being generated by its co-twin. Monozygotic twins, as opposed to dizygotic twins, showed greater similarities in activity and reactivity levels, but were never behaviourally identical and decreased in likeness with increasing age. Our data suggest that so-called identical twins are very similar, but not behaviourally identical, from very early in pregnancy. The unequally shared intrauterine environment contributes to putting each monozygotic twin on a progressively distinct behavioural path.     

A twin study of genetic and environmental influences on psychological traits of eating disorders in a Japanese female sample.

The purpose of the present study was to clarify genetic and environmental origins of psychological traits of eating disorders using a Japanese female twin sample. Participants were 162 pairs of female twins consisting of 116 pairs of monozygotic (MZ) twins and 46 pairs of dizygotic (DZ) twins in their adolescence. Psychological traits of eating disorders were assessed with five subscales of the Eating Disorder Inventory (EDI). As a result of using univariate twin analyses, among five subscales of EDI (maturity fears, ineffectiveness, interpersonal distrust, interoceptive awareness, and perfectionism), perfectionism showed significant additive genetic contributions and individual specific environmental effects. On the other hand, maturity fears, ineffectiveness, interoceptive awareness, and interpersonal distrust indicated significant shared environment contributions and individual specific environment effects. The results suggest the importance of both genetic and shared environmental influences on psychological traits of eating disorders in the present study.     

Quantitative trait loci for bone lengths on chromosome 5 using dual energy X-Ray absorptiometry imaging in the Twins UK cohort

Human height is a highly heritable and complex trait but finding important genes has proven more difficult than expected. One reason might be the composite measure of height which may add heterogeneity and noise. The aim of this study was to conduct a genome-wide linkage scan to identify quantitative trait loci (QTL) for lengths of spine, femur, tibia, humerus and radius. These were investigated as alternative measures for height in a large, population-based twin sample with the potential to find genes underlying bone size and bone diseases. 3,782 normal Caucasian females, 18-80 years old, with whole body dual energy X-ray absorptiometry (DXA) images were used. A novel and reproducible method, linear pixel count (LPC) was used to measure skeletal sizes on DXA images. Intraclass correlations and heritability estimates were calculated for lengths of spine, femur, tibia, humerus and radius on monozygotic (MZ; n = 1,157) and dizygotic (DZ; n = 2,594) twins. A genome-wide linkage scan was performed on 2000 DZ twin subjects. All skeletal sites excluding spine were highly correlated. Intraclass correlations showed results for MZ twins to be significantly higher than DZ twins for all traits. Heritability results were as follows: spine, 66%; femur, 73%; tibia, 65%; humerus, 57%; radius, 68%. Results showed reliable evidence of highly suggestive linkage on chromosome 5 for spine (LOD score = 3.0) and suggestive linkage for femur (LOD score = 2.19) in the regions of 105cM and 155cM respectively. We have shown strong heritability of all skeletal sizes measured in this study and provide preliminary evidence that spine length is linked to the chromosomal region 5q15-5q23.1. Bone size phenotype appears to be more useful than traditional height measures to uncover novel genes. Replication and further fine mapping of this region is ongoing to determine potential genes influencing bone size and diseases affecting bone.     

Genetic basis of human female pelvic morphology: a twin study

To examine the relative role of genetic and environmental factors on pelvic morphology, data on 60 pairs of female twins (30 monozygotic (MZ) and 30 dizygotic (DZ)) were analyzed. Fourteen pelvic measurements were normally distributed, and two were not. Association of twin type with the mean value of a trait was found in only 1 out of 8 traits. Heterogeneity of variance between zygosities was observed in 4 pelvic traits (50%), invalidating within-pair estimates of genetic variance for these traits. Evidence of stronger environmental covariance for MZ than DZ twins was observed for only one trait (sitting height iliocristale). A significant genetic component of variation was observed for age at menarche and in the pelvic area. In instances where inequality of variances between zygosities was demonstrated, total among-pair and within-pair mean squares were larger for dizygotic than for monozygotic twins. This is interpreted as evidence of greater environmental influence between zygosities. Environmental modification was not of the same magnitude in various pelvic traits. Bitrochanteric breadth had the highest magnitude of cultural heritability, indicating that cultural factors played an important role in determining hip breadth.     

Quantitative genetic analysis of internalising and externalising problems in a large sample of 3-year-old twins.

For a quantitative genetic study of pre-school problem behaviours, we have collected data with the Child Behavior Checklist for 2 and 3-year-old children (CBCL 2/3). Questionnaires were completed by mothers of 3620 twin pairs: 633 monozygotic males, 581 dizygotic males, 695 monozygotic females, 519 dizygotic females and 1192 dizygotic opposite sex twin pairs. The genetic and environmental influences on the Externalising and Internalising Problem scales were estimated, simultaneously with sex differences and sibling interaction effects. Genetic factors explained most of the observed variance for both Externalising and Internalising Problems. Cooperative sibling interactions were found for Externalising Problems, indicating that twins reinforce each other's behaviour. Sex differences in genetic architecture were found for Externalising Problems. Genetic factors explained 75% of the variance in girls and 50% in boys. Shared environmental influences were only of importance in boys. For both problem scales, non-shared environmental factors accounted for 25 to 32% of the variance. The observed variances of Internalising Problems could be adequately explained by genetic and nonshared environmental factors, with genetic factors accounting for 68% of the variance.     

A family study of anthropometric traits in a Punjabi community: I. Introduction and familial correlations

Data on 40 anthropometric measurements from 144 nuclear families in Chandigarh, India, are presented. Most families contain a pair of monozygotic or dizygotic twins, one or more singleton siblings, and their parents. Familial correlations for age-sex standardized, normalized measurements are estimated by maximum likelihood for marital, parent-child, sibling, and twin pairs. Heterogeneity tests for sex-specific subtype correlations male-male, male-female, female-female) indicate that the sex of the relative plays no significant role in the magnitude of the familial correlations except for maternal effects and differences among male and female twin pairs for a few of the variables. Marital correlations are high for body measurements, but not for head or face variables. Twin correlations seem to indicate a higher level of heritability than correlations from other family members.     

Population based study of prevalence of islet cell autoantibodies in monozygotic and dizygotic Danish twin pairs with insulin dependent diabetes mellitus.

OBJECTIVE: To study the comparative importance of environment and genes in the development of islet cell autoimmunity associated with insulin dependent diabetes mellitus. DESIGN: Population based study of diabetic twins. SETTING: Danish population. SUBJECTS: 18 monozygotic and 36 dizygotic twin pairs with one or both partners having insulin dependent diabetes. MAIN OUTCOME MEASURES: Presence of islet cell antibodies, insulin autoantibodies, and autoantibodies to glutamic acid decarboxylase (GAD65) in serum samples from twin pairs 10 years (range 0-30 years) and 9.5 years (2-30 years) after onset of disease. RESULTS: In those with diabetes the prevalence of islet cell antibodies, insulin autoantibodies, and autoantibodies to glutamic acid decarboxylase in the 26 monozygotic twins was 38%, 85%, and 92%, respectively, and in the dizygotic twins was 57%, 70%, and 57%, respectively. In those without diabetes the proportions were 20%, 50%, and 40% in the 10 monozygotic twins and 26%, 49%, and 40% in the 35 dizygotic twins. CONCLUSION: There is no difference between the prevalence of islet cell autoantibodies in dizygotic and monozygotic twins without diabetes, suggesting that islet cell autoimmunity is environmentally rather than genetically determined. Furthermore, the prevalence of islet cell antibodies was higher in the non-diabetic twins than in other first degree relatives of patients with insulin dependent diabetes. This implies that the prenatal or early postnatal period during which twins are exposed to the same environment, in contrast with that experienced by first degree relatives, is of aetiological importance.     

Quantitative and genetic features of epidermal ridge minutiae on the palm of twins

The total minutia count (TMC) and fork index (FI), i.e., the proportion of forks in total minutiae, were examined in palm prints of 20 pairs each of monozygotic and dizygotic Japanese twins. No bilateral difference was found in either trait. The mean of the TMC was higher in males than in females, but the FI showed no sex difference. Both traits presented relatively high intraclass correlation coefficients between monozygotic twins, and genetic control of these traits is suggested. However, no correlation was observed between these two traits. A slight correlation was observed between the TMC and the total palmar interdigital ridge count. Some methodological problems concerned with classification criteria were discussed.     

Pericentric X inversion in dizygotic twins who differ in X chromosome inactivation and menstrual cycle function

Summary A 21-year-old female dizygotic twin was referred for cytogenetic evaluation because of mild mental retardation. Significant history, clinical, and physical findings included irregular menses, mildly coarse facies, and microcornea. Chromosome analysis revealed a pericentric inversion of the X chromosome, 46,X,inv(X)(p11;q22). Her twin who is phenotypically normal was also found to carry the same inversion. The twins differ significantly in X chromosome inactivation and menstrual cycle function.     

The influence of sex, age and heritability on human skeletal muscle carnosine content

The dipeptide carnosine is found in high concentrations in human skeletal muscle and shows large inter-individual differences. Sex and age are determining factors, however, systematic studies investigating the sex effects on muscle carnosine content throughout the human lifespan are lacking. Despite the large inter-individual variation, the intra-individual variation is limited. The question may be asked whether the carnosine content is a muscle characteristic which may be largely genetically determined. A total of 263 healthy male and female subjects of 9-83 years were divided into five different age groups: prepubertal children (PC), adolescents (A), young adults (YA), middle adults (MA) and elderly (E). We included 25 monozygotic and 22 dizygotic twin pairs among the entire study population to study the heritability. The carnosine content was measured non-invasively in the gastrocnemius medialis and soleus by proton magnetic resonance spectroscopy (1H-MRS). In boys, carnosine content was significantly higher (gastrocnemius 22.9%; soleus 44.6%) in A compared to PC, while it did not differ in girls. A decrease (~16%) was observed both in males and females from YA to MA. However, elderly did not have lower carnosine levels in comparison with MA. Higher correlations were found in monozygotic (r=0.86) compared to dizygotic (r=0.51) twins, in soleus muscle, but not in gastrocnemius. In conclusion, this study found an effect of puberty on muscle carnosine content in males, but not in females. Muscle carnosine decreased mainly during early adulthood and hardly from adulthood to elderly. High intra-twin correlations were observed, but muscle-dependent differences preclude clear conclusions toward heritability.