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.     

Genetic and Environmental Influences on the Tracking of Body Size from Birth to Early Adulthood

Objective: This study identified genetic and environmental influences on the tracking of body size from birth to 16 to 18.5 years of age. Research Methods and Procedures: Longitudinal information was collected from a nationally representative sample of Finnish twin adolescents (birth cohorts 1975 to 1979) and their parents through questionnaires mailed when the twins were ages 16 and 18.5 years old. The sample included 702 monozygotic, 724 same‐sex dizygotic, and 762 opposite‐sex dizygotic sets of twins. The measures used were length, weight, ponderal index (kilograms per cubic meters), and gestational age at birth, and height, weight, and body mass index (kilograms per square meters) at 16 to 18.5 years of age. The changes in genetic and environmental influences on body size from birth to early adulthood were analyzed by quantitative genetic modeling. Results: The twins who had a higher weight or ponderal index at birth were taller and heavier in early adulthood, whereas those who were longer at birth were taller, but not heavier, later in life. Adult height was affected more by the birth size than body mass index. In the genetic modeling analyses, the genetic factors accounting for the variation of body size became more apparent with age, and both genetic and environmental influences on stature had a sizable carry‐over effect from birth to late adolescence, whereas for relative weight, the influences were more age‐specific. Discussion: The genetic and environmental architecture of body size changes from birth to adulthood. Even in monozygotic twins who share their genetic background, the initially larger twin tended to remain larger, demonstrating the long‐lasting effects of fetal environment on final body size.     

Glucose and insulin metabolism in twins: influence of zygosity and birth weight.

Several epidemiological and metabolic studies have demonstrated an impact of the intrauterine environment on the development of disease in adult life, including Type 2 diabetes and glucose intolerance. Our finding of lower birth weights among monozygotic diabetic twins compared to their non-diabetic genetically identical co-twins confirms this association and, furthermore, eliminates the possibility that the association could be explained solely by common genes leading to both impaired intrauterine growth and increased risk of Type 2 diabetes. Due to an often shared placenta monozygotic twins may experience a more adverse intrauterine environment compared to dizygotic twins and may therefore be more prone to develop various metabolic abnormalities. Our findings of a higher glucose and insulin profile after oral glucose ingestion, and recently lower insulin-stimulated glucose uptake--indicating glucose intolerance and insulin resistance--among monozygotic compared to dizygotic twins may to some extent question the validity of classical twin studies in diabetes research where equal environmental influences in monozygotic and dizygotic twins is assumed. The potential role of an adverse intrauterine environment in causing Type 2 diabetes in humans, may to some degree alter our conception of the twin model in diabetes research including the interpretation of aetiological conclusions reached in previous classical twin studies of diabetes. However, our present knowledge is far too insufficient to discard the results from classical twin studies concerning the relative role of genes versus environment for the development of diabetes and its metabolic effects.     

Effect of parental anthropometric parameters on neonatal birth weight and birth length

Data on 550 healthy pregnant women, 550 healthy fathers and their healthy term neonates born from singleton pregnancies (37(+0) through 41(+6) week) during a one-year period were reviewed. Maternal mean age was 27.7 +/- 9.37 years, mean pregestational weight 64.0 +/- 9.50 kg, mean gestational weight gain 15.4 +/- 4.33 kg, mean height 169.7 +/- 5.81 cm, and mean gestational age 40.1 +/- 0.95 weeks. Paternal mean age was 31.4 +/- 6.22 years, mean weight 84.6 +/- 10.35 kg, and mean height 182.8 +/- 6.84 cm. Mean birth weight was 3,709.8 +/- 500.48 g and 3,562.5 +/- 443.02 g, and mean birth length 51.5 +/- 1.91 cm and 50.7 +/- 1.62 cm in male and female newborns, respectively, yielding a birth weight greater by 147.3 g and birth length by 0.8 cm in the former. Study variables showed statistically significant correlations: maternal age contributed to the significant correlation between maternal weight and parity, maternal pregestational weight, weight at delivery, gestational weight gain and body height correlated significantly with neonatal birth weight and birth length, gestational age correlated significantly with neonatal weight and length (p = 0.01 all), parity had no major impact (p > 0.05). Paternal height and weight correlated significantly with neonatal birth weight and birth length (p = 0.01). Study results pointed to a significant correlation of maternal pregestational weight, gestational weight gain and body height, and of paternal weight and height with the neonate birth weight and birth length.     

Growth patterns in young adult monozygotic twin pairs discordant and concordant for obesity.

Weight discordance is very rare in monozygotic (MZ) twin pairs; when found, however, such pairs are advantageous in the search for either environmental or epigenetic causes and consequences of obesity. We analyzed the growth patterns of young adult MZ pairs discordant and concordant for obesity. Screening 5 consecutive birth cohorts (1975-1979) of 22- to 27-year-old Finnish twins (the FinnTwin16 study), we found 14 obesity discordant (Body Mass Index [BMI] difference > or = 4 kg/m2) MZ pairs out of 658. Ten pairs participated in clinical studies. Nine concordant pairs (BMI difference < or = 2 kg/m2) were examined as controls. Lifetime measured heights and weights recorded in hospitals and health centers were traced manually. Height development was similar in all the co-twins of both groups. The weight differences between the co-twins of the discordant pairs began to emerge at 18 years leading to an average discordance of 16.4 kg, 5.6 kg/m2 (p for both = .005) at 25.7 years. The heavier co-twin weighed 221 g (p = .066), 1.0 kg/m2 (p = .01) more already at birth than the leaner, but the differences waned by 6 months of age and reappeared only after adolescence. Both the leaner and the heavier co-twins of the discordant pairs weighed more than expected by the singleton reference values (Cole et al., 1998) after 8 years. The concordant co-twins, on the other hand, grew similarly and after 6 months, their mean growth was not distinguishable from the singleton patterns. Young adulthood represents a critical period of gaining weight irrespective of genetic background in this twin sample.     

Twin births to mothers who are twins: a registry based study.

OBJECTIVES: To estimate the risk of having twin infants for mothers who are twins; to investigate the genetic influence on twinning. DESIGN: Retrospective study of multiple births in two nationwide registries. SETTING: Sweden. SUBJECTS: Multiple births among 31,586 deliveries between 1973 and 1991 to women who were twins. MAIN OUTCOME MEASURES: Numbers of monozygotic and dizygotic twin births expected and estimated. RESULTS: Women who are dizygotic twins have a moderately increased risk of having twins (relative risk 1.30, 95% confidence interval 1.14 to 1.49) which seems to be completely the result of dizygotic twinning. When a mother is a monozygotic twin, her risk of having twins of the same sex is significantly increased (1.47; 1.10 to 1.97). This is the result of an excess of monozygotic twins (39 pairs estimated, 18 expected). CONCLUSIONS: Women who are twins have an increased risk of giving birth to twins. Genetic components of monozygotic and dizygotic twinning seem to be independent.     

The association between prolonged fatigue and cardiovascular disease in World War II veteran twins.

Reports of fatigue preceding cardiac events have recently been confirmed by large prospective studies. To assess for genetic confounding, we investigated prolonged fatigue and cardiovascular disease (CVD) in a cohort of World War II veteran twins. We examined data from a questionnaire mailed to members of the National Academy of Sciences-National Research Council (NAS-NRC) World War II Twins Registry in 1998 and 1999 which included questions on demographics, medical conditions and symptoms of fatigue. Data from twins discordant for prolonged fatigue lasting a month or more were analyzed using conditional logistic regression. Among 1955 twin pairs, 157 monozygotic and 174 dizygotic pairs (mean age 74 years) were discordant for prolonged fatigue. An association was found between prolonged fatigue and a history of myocardial infarction or coronary artery surgery adjusting for age, socioeconomic status, smoking, alcohol use and depression (OR [Odds Ratio]: 2.2; 95% CI: 1.3-4.0). When analyses were performed separately by zygosity, the association was slightly larger for monozygotic (OR: 3.3; 95% CI: 1.2-9.1) than dizygotic twins (OR: 1.9; 95% CI: 0.9-4.0). These data corroborate the association of fatigue with CVD and suggest that it is not influenced by a common genetic factor. Further studies are needed to clarify the relationship and to better understand the biologic mechanisms.     

Adult monozygotic twins discordant for intra-uterine growth have indistinguishable genome-wide DNA methylation profiles

Background

Low birth weight is associated with an increased adult metabolic disease risk. It is widely discussed that poor intra-uterine conditions could induce long-lasting epigenetic modifications, leading to systemic changes in regulation of metabolic genes. To address this, we acquire genome-wide DNA methylation profiles from saliva DNA in a unique cohort of 17 monozygotic monochorionic female twins very discordant for birth weight. We examine if adverse prenatal growth conditions experienced by the smaller co-twins lead to long-lasting DNA methylation changes.

Results

Overall, co-twins show very similar genome-wide DNA methylation profiles. Since observed differences are almost exclusively caused by variable cellular composition, an original marker-based adjustment strategy was developed to eliminate such variation at affected CpGs. Among adjusted and unchanged CpGs 3,153 are differentially methylated between the heavy and light co-twins at nominal significance, of which 45 show sensible absolute mean β-value differences. Deep bisulfite sequencing of eight such loci reveals that differences remain in the range of technical variation, arguing against a reproducible biological effect. Analysis of methylation in repetitive elements using methylation-dependent primer extension assays also indicates no significant intra-pair differences.

Conclusions

Severe intra-uterine growth differences observed within these monozygotic twins are not associated with long-lasting DNA methylation differences in cells composing saliva, detectable with up-to-date technologies. Additionally, our results indicate that uneven cell type composition can lead to spurious results and should be addressed in epigenomic studies.     

Size at birth, fasting glucose and insulin levels and insulin resistance in adult twins.

Studies in singletons have found an association between birthweight and Type 2 diabetes in adult life. The aim of this study was to investigate whether this association could also be seen in twins. 59 monozygotic (MZ) and 69 dizygotic (DZ) same-sex twin pairs aged 19-50 years and 89 singleton controls matched for age, gestational age, gender, maternal age and parity were recruited from a local obstetric database. Associations between adult glucose, HbA(1)C and insulin levels and insulin resistance and birthweight were assessed by linear regression with adjustment for confounding variables. Twins were significantly lighter at birth than singleton controls, but there were no significant differences in adult weight, glucose, HbA(1)C and insulin levels or insulin resistance between twins and controls. The relationship between birthweight and fasting glucose and insulin levels, and insulin resistance was not significantly different from zero in either twins or controls, but birthweight was significantly negatively associated with HbA(1)C only in controls. There was no evidence of a difference between MZ and DZ twins in unpaired or within-pair analysis. These results provide little evidence that low birthweight in twins increases the risk of impaired glucose-insulin metabolism in young adults or that genetic factors can account for the association observed in singletons.     

The polymorphism in insulin receptor substrate-1 gene and birth weight in neonates at term

BACKGROUND: The mutation of the IRS-1 gene is one of the genetic risk factors which, it is speculated, is associated with insulin resistance or predisposition to type 2 diabetes. The aim of our study was to evaluate the association between the Gly972Arg polymorphism in the IRS-1 gene and birth weight in newborn children with adequate gestational age. MATERIAL AND METHODS: 100 newborn children with adequate gestational age (38-42 weeks), whose mother had no disorders during pregnancy, were studied. Genomic DNA was extracted from umbilical cord blood leukocytes, and Gly972Arg polymorphism in the IRS-1 gene was genotyped using the PCR-based method. RESULTS: Birth weight was significantly lower in the newborn with the IRS-1 Gly972Arg polymorphism compared with a control group (3161.75 +/- 380.86 g vs. 3427.92 +/- 468.86 g). Body length and head circumference at birth were also lower in the neonates with that polymorphism (54.38 +/- 3.13 cm vs. 52.69 +/- 2.91 cm, and 34.08 +/- 1.47 vs. 33.63 +/- 0.81, respectively). CONCLUSIONS: The results suggest that the Gly972Arg genotype is associated with lower birth weight, body length and head circumference in neonates with adequate gestational age.     

Sex difference in heritability of BMI in South Korean adolescent twins

Twin studies of BMI on the basis of Asian twins are extremely rare. Eight hundred eighty-eight pairs of twins [279 monozygotic (MZ) and 82 dizygotic (DZ) pairs of male twins, 319 MZ and 82 DZ pairs of female twins, and 126 opposite-sex pairs of DZ twins] completed items concerning height and weight through a mail and a telephone survey. A general sex-limitation model was applied to the data. Heritability estimate was greater among women than among men. However, there was little evidence of sex-specific genes. Under the best-fitting model, additive genetic variances were 82% [95% confidence interval (CI): 72% to 95%] for men and 87% (95% CI: 77% to 99%) for women; shared environmental variances were negligible in both men and women. These estimates of genetic and environmental factors in BMI found among South Korean adolescent twins were broadly in the range of those reported in previous studies of BMI based on Western twin samples.     

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.     

Zygosity misclassification of twins at birth in Japan.

Though twinning rates have been rapidly increasing in Japan, the problem of zygosity misclassification at birth has been paid little attention. By analyzing four independent samples, the authors found that at a constant rate about 25-30% of monozygotic twins were misclassified as dizygotic twins at birth. This percentage is in very good accordance with that of monozygotic twins having dizygous placenta. Generally the obstetricians informed twins' parents about their children's zygosity. The number of placentas, as informed by obstetricians, was very strongly associated with zygosity. Concluding, even now many monozygotic twins in Japan may be misclassified as dizygotic at birth by obstetricians based solely on the number of placenta.     

Contribution of genetic and environmental factors in the phenotypic variability of major indices of child development at different stages of postnatal ontogenesis

Main indices of physical development of monozygotic and dizygotic twins were investigated during 13 years period. Using the coefficients of the within-pair correlation of characters studied an attempt was made to estimate the correlative contribution of genetic and environmental determinants to formation of phenotypic variance of height, weight and chest circumference from birth up to 13 years old. The indices of composing components obtained suggest that underlying formation of phenotypic variance of each of the characters analysed are the mechanisms reflecting qualitative, quantitative and time peculiarities of functioning of polygenic systems involved in determination of characters studied and peculiarities of their interaction with environmental factors.     

青少年双生子体型指征相关指标的遗传度研究(英文)

目的:用经典的双生子设计探讨遗传因素对青少年身高、体重、体质指数(BMI)等体型指征的影响程度。方法:从青岛市双生子库中选择自愿参加本研究的362对11-19岁双生子,测量身高、体重。同性别的双生子通过16个多态标记进行卵型鉴定,在此基础上,应用Mx软件构建结构方程模型分析计算遗传度。结果:对362对有效双生子数据进行分析,其中同卵双生子194对,异卵双生子168对,身高的最佳拟合模型ACE模型,体重和BMI的最佳拟合模型为AE模型。调整年龄性别后,身高的遗传度为66%,体重的遗传度为84%,体质指数的遗传度为75%。结论:在青少年体型指征的相关指标中,身高、体重、BMI受遗传因素影响都较大。     

Craniofacial anomalies in twins

Studies of twins provide insight into the relative contribution of genetic and environmental factors in the causality of structural anomalies. Thirty-five affected twin pairs were identified from a group of 1114 patients with congenital craniofacial deformities evaluated from 1972 to 1989. Forty-three of these 70 twins exhibited one or more craniofacial anomalies; these were analyzed for dysmorphic characteristics, zygosity, concordance, and family history. The anomalies were categorized into two groups: malformations and deformations. The malformations (n = 36) included hemifacial microsomia (n = 10), cleft lip and palate (n = 8), cleft palate (n = 4), rare facial cleft (n = 2), craniosynostosis (n = 2), Binder syndrome (n = 2), Treacher Collins syndrome (n = 2), craniopagus (n = 2), CHARGE association (n = 1), frontonasal dysplasia (n = 2), and constricted ears (n = 1). The deformations (n = 7) included plagiocephaly (n = 5), hemifacial hypoplasia (n = 1), and micrognathia (n = 1). Twenty-one monozygotic and 14 dizygotic twin pairs were identified. The concordance rate was 33 percent for monozygotic twins and 7 percent for dizygotic twins.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of final height in monozygotic twins,one with idiopathic and isolated growth hormone deficiency treated with low dose of growth hormone

OBJECTIVE: We report final heights in a pair of monozygotic twins, one unaffected and the other affected with idiopathic and isolated growth hormone (GH) deficiency treated with human GH, and discuss the effect of GH dosage on the attainment of the genetic height potential in GH deficiency. PATIENTS: Male monozygotic twins were born at 35 weeks of gestation; birth weights were 1,876 g in the unaffected and 1,510 g in the affected twin. At 4.9 years of age, the affected twin was studied for short stature (-3.38 SD) and was diagnosed as having idiopathic and isolated GH deficiency, whereas the unaffected twin was normal in height (+/- 0 SD). GH treatment was started at the age of 5.7 years and continued throughout childhood and adolescence. The average dose of GH administered during the treatment period was 0.35 IU (0.12 mg)/kg/week. The affected twin appeared to grow normally without other hormone replacement and achieved a final height of 165.6 cm (-0.86 SD) compared with that of 166.4 cm (-0.71 SD) in the unaffected twin at 17.5 years of age. CONCLUSION: Our results indicate that a relatively low dose of GH treatment started at an early age may preserve genetic height potential in patients with isolated GH deficiency.     

Soft tissue body composition differences in monozygotic twins discordant for spinal cord injury.

To determine the effect of paralysis on body composition, eight pairs of male monozygotic twins, one twin in each pair with paraplegia, were studied by dual-energy X-ray absorptiometry. Significant loss of total body lean tissue mass was found in the paralyzed twins compared with their able-bodied co-twins: 47.5 +/- 6. 7 vs. 60.1 +/- 7.8 (SD) kg (P < 0.005). Regionally, arm lean tissue mass was not different between the twin pairs, whereas trunk and leg lean tissue masses were significantly lower in the paralyzed twins: -3.0 +/- 3.3 kg (P < 0.05) and -10.1 +/- 4.0 kg (P < 0.0005), respectively. Bone mineral content of the total body and legs was significantly related to lean tissue mass in the able-bodied twins (R = 0.88 and 0.98, respectively) but not in the paralyzed twins. However, the intrapair difference scores for bone and lean tissue mass were significantly related (R = 0.80 and 0.81, respectively). The paralyzed twins had significantly more total body fat mass and percent fat per unit body mass index than the able-bodied twins: 4.8 kg (P < 0.05) and 7 +/- 2% (P < 0.01). In the paralyzed twins, total body lean tissue was significantly lost (mostly from the trunk and legs), independent of age, at a rate of 3.9 +/- 0.2 kg per 5-yr period of paralysis (R = 0.87, P < 0.005). Extreme disuse from paralysis appears to contribute to a parallel loss of bone with loss of lean tissue in the legs. The continuous lean tissue loss may represent a form of sarcopenia that is progressive and accelerated compared with that in ambulatory individuals.     

Heritability of eleven metabolic phenotypes in Danish and Chinese twins: A cross‐population comparison

Objectives : A twin‐based comparative study on the genetic influences in metabolic endophenotypes in two populations of substantial ethnic, environmental, and cultural differences was performed. Design and Methods : Data on 11 metabolic phenotypes including anthropometric measures, blood glucose, and lipids levels as well as blood pressure were available from 756 pairs of Danish twins (309 monozygotic and 447 dizygotic twin pairs) with a mean age of 38 years (range: 18‐67) and from 325 pairs of Chinese twins (183 monozygotic and 142 dizygotic twin pairs) with a mean age of 40.5 years (range: 18‐69). Twin modeling was performed on full and nested models with the best fitting models selected. Results : Heritability estimates were compared between Danish and Chinese samples to identify differential genetic influences on each of the phenotypes. Except for hip circumference, all other body measures exhibited similar heritability patterns in the two samples with body weight showing only a slight difference. Higher genetic influences were estimated for fasting blood glucose level in Chinese twins, whereas the Danish twins showed more genetic regulation over most lipids phenotypes. Systolic blood pressure was more genetically controlled in Danish than in Chinese twins. Conclusions : Metabolic endophenotypes show disparity in their genetic determinants in populations under distinct environmental conditions.     

Comparing blood pressure of twins and their singleton siblings: being a twin does not affect adult blood pressure.

The hypothesis was tested that monozygotic (MZ) and dizygotic (DZ) twins, with their lower average birth weight, have higher adult blood pressure than their singleton brothers or sisters. From the Netherlands Twin Registry, 261 twin families were recruited from a young adult and an older adult cohort with mean ages of 26.2 and 50.4 respectively. These families yielded 204 MZ twins with 71 singleton siblings and 271 DZ twins with 103 of their singleton siblings. Anti-hypertensive medication use of these 649 participants was assessed twice with a two-year interval. Resting blood pressure was measured thrice during a standardized laboratory protocol. In spite of a significant difference in birth weight (1036 gram), no differences were found in anti-hypertensive medication use at both time points between twins and singletons nor between their resting laboratory diastolic or systolic blood pressure. These results applied to each gender and to both age cohorts. Limiting the analyses to matched twin-sibling pairs of the same families and taking current weight and height into account did not change the results; no evidence was found for a twin-singleton difference. It was concluded that estimates of genetic and environmental contributions to blood pressure deriving from twin studies do not appear to be biased and may be generalized to singletons. Our results suggest that the lower birth weight in twins does not reflect the intrauterine disadvantage described by the Barker hypothesis.