Female Monozygotic Twins Research Articles

The Role of Gene–Environment Interaction in Determining Bone Mineral Density in a Twin Population

AbstractThe possibility that specific environmental factors such as smoking and estrogen use modify the genetic influences (gene–environment interaction) on bone mineral density (BMD) has not been explored in genetic epidemiological studies such as twin studies. The aim of this study was to look for evidence of gene–environment interaction in BMD determination by analyzing data collected on a large number of healthy female twins. BMD of the hip, distal forearm and lumbar spine were measured by dual-energy X-ray absorptiometry on 287 identical and 265 nonidentical volunteer female twin pairs. The environmental factors examined were hormone replacement therapy (HRT) and smoking. In genetic modeling analysis using path analysis, there was evidence of ‘HRT-specific’ genetic component of BMD variance at the forearm (50% of total variance) but not at the hip. At the lumbar spine the magnitude of the genetic component of variance in HRT users (> 60-month HRT use) was less than the genetic component of variance for little or no exposure to HRT (48% vs. 84%). There was no evidence of gene–environment interaction for smoking. The main evidence for gene–environment interaction was the finding that forearm BMD variance was influenced by a significant HRT-specific genetic component. There was also evidence that in HRT users, the genetic component of total variance for lumbar BMD was lower.

Transient red cell aplasia in siblings: a common environmental or a common hereditary factor?

During the years 1987-89, transient erythroblastopenia of childhood was diagnosed in 52 previously healthy Swedish children aged less than 4 y. Among these children there were four pairs of siblings, including one pair of identical female twins. This is a much higher familial occurrence than expected. The probability of finding 4 pairs of siblings with this disease in 50 families was estimated to be considerably less than 10–6. In the retrospectively analysed material, no environmental factor was implicated and no association with human leucocyte antigen could be proven. The twins demonstrated the disease simultaneously. Their anaemia was transient and did not recur, but showed certain features usually seen in congenital hypoplastic anaemia. The other pairs of siblings fulfilled the criteria for transient erythroblastopenia of childhood and several years elapsed between the development of the disease in siblings. Two of the fathers were reported to have had transient anaemia during their childhood. Our findings indicate that transient erythroblastopenia of childhood may involve hereditary factors, eventually demonstrating an autosomal dominant inheritance.

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.

Developmental and genetic determinants of leadership role occupancy among women.

The genetic and developmental influences on leadership role occupancy were investigated using a sample of 178 fraternal and 214 identical female twins. Two general developmental factors were identified, one involving formal work experiences and the other a family experiences factor hypothesized to influence whether women move into positions of leadership in organizations. Results indicated that 32% of the variance in leadership role occupancy was associated with heritability. The 2 developmental factors also showed significant correlations with leadership role occupancy. However, after genetic factors were partialed out, only the work experience factor was significantly related to leadership role occupancy. Results are discussed in terms of prior life events and experiences that may trigger leadership development and the limitations of this study.

A correlated frailty model with long‐term survivors for estimating the heritability of breast cancer

The aim of this study is to investigate the role of genetics and environment in susceptibility to breast cancer (frailty). An interdisciplinary approach was adopted, combining a correlated frailty-mixture model with genetic equations, allowing for decomposition of the frailty variance into genetic and environmental components. In addition, the possibility that a fraction of the population under study is 'immune' to the disease is evaluated, and changes in heritability estimates introducing a fraction of non-susceptible individuals are determined. The methodology is applied to breast cancer data from the Swedish Twin Registry, including information about all female monozygotic and dizygotic twin pairs born in Sweden between 1886 and 1967. The inferential problem is solved in a Bayesian framework and the numerical work is carried out using Markov chain Monte Carlo (MCMC) methods.

Adult onset familial normal pressure hydrocephalus? Neuropsychological profile of monozygotic twins

Background There are few cases of adult onset familial normal pressure hydrocephalus (NPH) reported in the literature but the rarity of the disease makes coincidence unlikely. Female monozygotic twins presenting with the NPH triad of symptoms were assessed on a neuropsychological test battery. The aims were to determine whether the neuropsychological evidence could support the differential diagnosis of adult onset NPH whilst contributing to a further understanding of the neuropsychological profile of adult NPH.

Lower body negative pressure treadmill exercise as a countermeasure for bed rest-induced bone loss in female identical twins

Supine weight-bearing exercise within lower body negative pressure (LBNP) alleviates some of the skeletal deconditioning induced by simulated weightlessness in men. We examined this potential beneficial effect in women. Because dietary acid load affected the degree of bone resorption in men during bed rest, we also investigated this variable in women. Subjects were 7 pairs of female identical twins assigned at random to 2 groups, sedentary bed rest (control) or bed rest with supine treadmill exercise within LBNP. Dietary intake was controlled and monitored. Urinary calcium and markers of bone resorption were measured before bed rest and on bed rest days 5/6, 12/13, 19/20, and 26/27. Bone mineral content was assessed by dual-energy X-ray absorptiometry before and after bed rest. Data were analyzed by repeated-measures two-way analysis of variance. Pearson correlation coefficients were used to define the relationships between diet and markers of bone metabolism and to estimate heritability of markers. During bed rest, all markers of bone resorption and urinary calcium and phosphorus increased ( P < 0.001); parathyroid hormone ( P = 0.06), bone-specific alkaline phosphatase ( P = 0.06), and 1,25-dihydroxyvitamin D ( P = 0.09) tended to decrease. LBNP exercise tended to mitigate bone density loss. The ratio of dietary animal protein to potassium was positively correlated with urinary calcium excretion for all weeks of bed rest in the control group, but only during weeks 1 and 3 in the exercise group. Pre-bed rest data suggested that many markers of bone metabolism have strong genetic determinants. Treadmill exercise within LBNP had less of a protective effect on bone resorption during bed rest in women than previously published results had shown for its effect in men, but the same trends were observed for both sexes. Dietary acid load of these female subjects was significantly correlated with calcium excretion but not with other bone resorption markers.

Scoliosis development in identical twins after intercostal thoracotomy for pulmonary artery sling correction

We present a report on two monozygotic female twins who underwent a left-sided intercostal thoracotomy in the second month of life for pulmonary artery sling correction. Twenty-four years later, in adulthood, the identical twins had both developed right-sided thoracic scoliosis. No previous accounts of scoliosis development after intercostal thoracotomy for pulmonary artery sling correction have been reported.

Idiopathic retinal holes in monozygotic twins

It remains controversial whether there is a significant genetic contribution to the pathogenesis of idiopathic giant retinal tears or retinal dialysis. In contrast, the underlying molecular genetic basis of several inherited vitreoretinal dystrophies is now well established, with also an increasing recognition of genetic factors in the development of myopia. We describe asymptomatic female monozygotic twins who were identified as having identical retinal holes. These cases represent the first evidence to our knowledge of a potential role of inherited factors in the causation of idiopathic peripheral retinal holes. This observation raises the need to examine the twin of any patient presenting with a retinal break(s).

Annular pancreas in identical twin newborns

Annular pancreas is a rare congenital anomaly occurring in 1 of every 12,000 to 15,000 live births [Nerwich N, Shi E. Neonatal duodenal obstruction: a review of 30 consecutive cases. Pediatr Surg Int 1994;9:47-50]. It may remain asymptomatic throughout life, present in adulthood, or present in infancy as a high intestinal obstruction. Review of the literature demonstrates only 8 cases of familial annular pancreas and no case of twins exhibiting the disease. We will describe a case of identical (monochorionic diamniotic) female twins with neonatal presentation of duodenal obstruction and annular pancreas, and discuss data supportive of a genetic etiology.

Concordant bilateral Duane’s Retraction Syndrome (type 1) in female monozygotic twins

We report a single case study of concordant bilateral Duane's Retraction Syndrome (DRS) (type 1) in female monozygotic (MZ) twins aged 47 years. The twin pair were recruited through the Australian Twin Registry as part of a twin study on myopia. This twin pair were full term and had a similar birth weight: 2.27 kg and 1.81 kg in twin 1 and twin 2, respectively. There was no report of any other childhood medical conditions in either twin. Both twins had an equal amount of restriction in right and left abduction. Narrowing of the palpebral fissures and globe retraction in right and left adduction was also observed in both twins. To our knowledge this is the first case to report concordant bilateral DRS (type 1) in female MZ twins. The concordance for the presence of DRS and associated clinical signs observed in this MZ twin pair supports a genetic origin to DRS.

Mental Representations of Attachment in Identical Female Twins with and without Conduct Problems

Insecure mental representations of attachment, a nearly invariant feature of cluster B personality disorders, have never previously been studied in twins. We conducted the Adult Attachment Interview (AAI) on 33 pairs of monozygotic (MZ) female twins reared together as an initial exploration of causal influences on mental representations of attachment. As predicted by attachment theory, we observed substantial twin-twin concordance for attachment security (odds ratio 13.8; P = 0.001), a similar level of concordance between twins and their non-twin siblings, and an inverse relationship between attachment security and current level of aggression (P = 0.01). These data indicate that there are minimal effects of non-shared environmental influences (or measurement error) on attachment classifications derived from the AAI. In this sample of twins with and without histories of Conduct Disorder, mental representations of attachment appear to be highly familial, i.e., strongly influenced by either shared environmental factors, genetic factors, or both.

Does Increasing Women's Schooling Raise the Schooling of the Next Generation?

New data on identical female and male twins are used to estimate the impact of increasing parental schooling on child schooling that incorporates the existence of unmeasured heritable traits and marital sorting. These data yield cross sectional estimates that are consistent with previous studies of the impact of parental schooling on child schooling attainment. However, when twinning is exploited to estimate intergenerational schooling effects, the results are strikingly different. Controlling for women's earnings and childrearing endowments and husband's endowments and schooling leads to a marginally negative rather than a significantly positive coefficient for mother's schooling in the determination of child schooling.

Two Monozygotic Twin Pairs Discordant for Female-to-Male Transsexualism

Two monozygotic female twin pairs discordant for transsexualism are described. These reports double the number of such case studies in the current scientific literature. Interviews with the twins and their families indicated that unusual medical and life history factors did not play causal roles. However, inspection of medical records for one transsexual twin suggested that some early life experiences may have exacerbated tendencies toward male gender identification. In both pairs, the twins' gender identity differences emerged early, consistent with, but not proof of, co-twin differences in prenatal hormonal influences. The identification of additional discordant MZ female twin pairs can advance biological and psychological understanding of transsexualism. Suggestions for future research, based upon findings from these two twin pairs and from studies of female-to-male transsexuals, are provided.

Maternal alcohol use disorder and offspring ADHD: disentangling genetic and environmental effects using a children-of-twins design

Children of alcoholics are significantly more likely to experience high-risk environmental exposures, including prenatal substance exposure, and are more likely to exhibit externalizing problems [e.g. attention deficit hyperactivity disorder (ADHD)]. While there is evidence that genetic influences and prenatal nicotine and/or alcohol exposure play separate roles in determining risk of ADHD, little has been done on determining the joint roles that genetic risk associated with maternal alcohol use disorder (AUD) and prenatal risk factors play in determining risk of ADHD. Using a children-of-twins design, diagnostic telephone interview data from high-risk families (female monozygotic and dizygotic twins concordant or discordant for AUD as parents) and control families targeted from a large Australian twin cohort were analyzed using logistic regression models. Offspring of twins with a history of AUD, as well as offspring of non-AUD monozygotic twins whose co-twin had AUD, were significantly more likely to exhibit ADHD than offspring of controls. This pattern is consistent with a genetic explanation for the association between maternal AUD and increased offspring risk of ADHD. Adjustment for prenatal smoking, which remained significantly predictive, did not remove the significant genetic association between maternal AUD and offspring ADHD. While maternal smoking during pregnancy probably contributes to the association between maternal AUD and offspring ADHD risk, the evidence for a significant genetic correlation suggests: (i) pleiotropic genetic effects, with some genes that influence risk of AUD also influencing vulnerability to ADHD; or (ii) ADHD is a direct risk-factor for AUD.

Female Monozygotic Twins with Selective Mutism-A Case Report

Selective mutism is a rare social anxiety disorder characterized by a total lack of speech in certain specific situations despite the ability to speak in others. Both genetic and psychosocial factors are thought to be involved in its presentation, persistence, and response to treatment. This case report describes a case of young female monozygotic twins who presented with selective mutism and their treatment spanning a 2-year period. It highlights the strong genetic association along with environmental factors such as social isolation and consequences of maternal social phobia, all contributing to treatment resistance, despite an intensive multimodal biopsychosocial approach. General issues related to the difficulties in treating monozygotic twins are also addressed.

Marked discordance for myopia in female monozygotic twins

Female monozygotic twins aged 54 years discordant for myopia are reported. One twin presented with bilateral high myopia (right eye = -6.00/+0.50 x 5 degrees , left eye = -6.00/+0.50 x 45 degrees ) and her identical twin had no significant refractive error (right eye = -0.50/plano, left eye = -0.50/+0.75 x 40 degrees ). An explanation for the striking refractive discordance seen in this case report is yet to be determined.

Role of Genes and Environments for Explaining Alzheimer Disease

Twin studies using selected samples have shown high heritability for Alzheimer disease (AD). To evaluate genetic and environmental influences on AD in a fully ascertained population of older twins, including like- and unlike-sex pairs. Five-group quantitative genetic model: male monozygotic twins, female monozygotic twins, male dizygotic twins, female dizygotic twins, and unlike-sex twins. All twins in the Swedish Twin Registry aged 65 years and older. The study included 11,884 twin pairs, among whom were 392 pairs in which 1 or both members had AD. All individuals were screened for cognitive dysfunction. Suspected cases of dementia and their co-twins received complete clinical diagnostic evaluations for AD. Estimates of heritability, shared environmental influences, and nonshared environmental influences, adjusting for age, were derived from the twin data. Heritability for AD was estimated to be 58% in the full model and 79% in the best-fitting model, with the balance of variation explained by nonshared environmental influences. There were no significant differences between men and women in prevalence or heritability after controlling for age. Within pairs concordant for AD, intrapair difference in age at onset was significantly greater in dizygotic than in monozygotic pairs, suggesting genetic influences on timing of the disease. In the largest twin study to date, we confirmed that heritability for AD is high and that the same genetic factors are influential for both men and women. However, nongenetic risk factors also play an important role and might be the focus for interventions to reduce disease risk or delay disease onset.

Complement Factor H–Associated Atypical Hemolytic Uremic Syndrome in Monozygotic Twins: Concordant Presentation, Discordant Response to Treatment

Hemolytic uremic syndrome not associated with diarrhea (diarrhea negative, atypical) is less common than the diarrhea-positive typical form, but frequently results in end-stage renal failure. Although there are anecdotal cases of successful treatment with fresh frozen plasma alone, the value of this treatment compared with plasma exchange (PE) is difficult to assess. We describe monozygotic female twins who presented at 5 years of age with factor H-related (c.3572 > T; Ser1191Leu) atypical hemolytic uremic syndrome within months of each other. In the first twin to present, 10 sessions of PE with fresh frozen plasma replacement (40 mL/kg) resulted in resolution of hemolysis and improvement in plasma creatinine level (1.9 to 1.5 mg/dL [166 to 137 micromol/L]). Subsequently, 17 infusions of fresh frozen plasma were administered during a 4-month period for recurrent thrombocytopenia. However, within 4 months, plasma creatinine level increased to 5.1 mg/dL (450 micromol/L), necessitating peritoneal dialysis. When the second twin presented with the same disease, an extended PE regimen was instituted. After 10 daily sessions, PE was continued once every 2 weeks. Two recurrences were treated successfully with daily PE for 7 days. After 44 months of follow-up, kidney function is normal (plasma creatinine, 0.6 mg/dL [53 micromol/L]; creatinine clearance, 119 mL/min/1.73 m2 [1.98 mL/s/1.73 m2]) on maintenance PE therapy. In conclusion, the response to treatment of these monozygotic twins suggests that long-term PE may have benefits over plasma infusion alone.

Monozygotic twins discordant for Goldenhar syndrome

To report on a pair of monozygotic female twins discordant for Goldenhar syndrome. The affected twin was a girl, who was delivered by caesarean section at 35 weeks' gestation. Her birth weight was 2,170 g, length 42.5 cm, head circumference 30 cm and her Apgar scores were 3/7. After birth the child developed severe respiratory distress and had to be moved to the neonatal intensive care unit (ICU). The other twin was a girl, born weighing 3,200 g with a length of 49 cm, head circumference of 34 cm and Apgar scores of 8/10. She was transferred to the mother-baby unit soon after birth and was discharged two days later. There was no consanguinity between the twins' parents, who were young and healthy at the time of their conception. The affected child's dysmorphic features included left hemifacial microsomia, severe micrognathia, abnormal ears, bilateral preauricular tags and epibulbar dermoid in the right eye. She developed obstructive apnea due to micrognathia and required tracheostomy. Abdominal and cranial ultrasound findings were normal, as was an ophthalmological assessment. Spine x-ray showed hemivertebra at T9 and T10. An echocardiogram showed Tetralogy of Fallot. GTG-banded karyotyping was performed on peripheral blood cells and revealed 46,XX. Zygosity testing established the pair of twins to be monozygotic with a probability greater than 99:1. Goldenhar syndrome was diagnosed in one of the twins described here. There are several reports of twins discordant for this disorder and therefore non-genetic factors may also play an important role, for instance vascular disruption during morphogenesis.