Female Monozygotic Twin Pairs Research Articles

A core gut microbiome in obese and lean twins

The human distal gut harbors a vast ensemble of microbes (the microbiota) that provide us with important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides1–6. Studies of a small number of unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes6–8, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is utilized and stored3–5. To address the question of how host genotype, environmental exposures, and host adiposity influence the gut microbiome, we have characterized the fecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person’s gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable ‘core microbiome’ at the gene, rather than at the organismal lineage level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity, and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiologic states (obese versus lean).

Developmental‐genetic effects on level and change in childhood fears of twins during adolescence

If the adaptive significance of specific fears changes with age, the genetic contribution to individual differences may be lowest at the age of greatest salience. The roles of genes and environment in the developmental-genetic trajectory of five common childhood fears are explored in 1094 like-sex pairs of male and female monozygotic and dizygotic twins assessed on up to three occasions during adolescence (ages 8-18 years). Dichotomous self-ratings of a cluster of five correlated fears from Ollendick's schedule of fears (FSSC-R) were extracted for subjects at each occasion of assessment. The effects of genes and environment on overall level of fears and rates of adolescent decline were explored by fitting an item-response theory ('IRT') model that allowed for individual genetic and environmental differences in initial fear level ('intercept') and rates of adolescent change ('slope') across the repeated waves of measurement. Different forms of the model were explored using Markov Chain Monte Carlo (MCMC) methods to derive the posterior distribution of subject and item parameters from the raw responses. Additive genetic differences affect the common factor underlying the five fear-items. The same genes also affect rates of change with age, especially in boys. Male adolescents with higher overall genetic predisposition to childhood fears tended to show slower recovery with age than subjects with relatively low initial values. Thus, the genetic variance apparently increases with age. This finding is consistent with a prediction that the regulation of genetic differences will be strongest, and thus the additive genetic variance will be smallest, at the age when the particular stimulus is most salient. Items differed in the extent to which they were sensitive to underlying random differences in the rate of developmental change. Individual differences in rates of change with age were more marked in boys than girls.

The Role of Exercising in a Pair of Female Monozygotic (High-Class Athletes) Twins Discordant for Adolescent Idiopathic Scoliosis

The report of 2 cases and review of the literature. To report the cases of a pair of female monozygotic (high-class athletes) twins discordant for adolescent idiopathic scoliosis. The relation between scoliosis and exercising is rather unclear. The latter has often been considered both as a therapeutic means and a causative factor of the former. The existence of genetic predisposition in the development of adolescent idiopathic scoliosis is commonly accepted. According to the best of our knowledge, this is the first report of a pair of female monozygotic (high-class athletes) twins, discordant for adolescent idiopathic scoliosis. METHODS.: A pair of 13.5-year-old female monozygotic twins, high-class level athletes of synchronized swimming, was clinically examined during a school screening program. Both girls were observed in the standing erect position for asymmetries of the lateral contours of the trunk, shoulders, and scapulas and their limb's length was measured. The "forward bending test" was performed to determine the existence of rib hump asymmetry. One of the sisters was considered to be suspicious of suffering from scoliosis. The radiologic evaluation that followed confirmed the existence of adolescent idiopathic scoliosis (left thoracolumbar curve of 32 degrees as measured by the Cobb angle). The clinical and radiologic evaluation of her sibling failed to reveal the existence of any spinal deformity. Adolescent idiopathic scoliosis seems to be a multifactorial skeletal disorder. The role of exercising and heredity in its development remain controversial.

Smith-Lemli-Opitz syndrome in female, monozygotic twins

A pair of monozygotic female twins with SLO syndrome is presented. We have found only one paper in the literature that referred to twins with this rare syndrome. The multiple congenital defects in these cases, consist of limb and genital abnormalities, retardation of growth, mental deficiency, craniofacial defects and abnormal neurological status.

Differential methylation of the X‐chromosome is a possible source of discordance for bipolar disorder female monozygotic twins

Monozygotic (MZ) twins may be subject to epigenetic modifications that could result in different patterns of gene expression. Several lines of evidence suggest that epigenetic factors may underlie mental disorders such as bipolar disorder (BD) and schizophrenia (SZ). One important epigenetic modification, of relevance to female MZ twins, is X-chromosome inactivation. Some MZ female twin pairs are discordant for monogenic X linked disorders because of differential X inactivation. We postulated that similar mechanisms may also occur in disorders with more complex inheritance including BD and SZ. Examination of X-chromosome inactivation patterns in DNA samples from blood and/or buccal swabs in a series of 63 female MZ twin pairs concordant or discordant for BD or SZ and healthy MZ controls suggests a potential contribution from X-linked loci to discordance within twin pairs for BD but is inconclusive for SZ. Discordant female bipolar twins showed greater differences in the methylation of the maternal and paternal X alleles than concordant twin pairs and suggest that differential skewing of X-chromosome inactivation may contribute to the discordance observed for bipolar disorder in female MZ twin pairs and the potential involvement of X-linked loci in the disorder.

Correlates of cigarette smoking during pregnancy and its genetic and environmental overlap with nicotine dependence

Cigarette smoking during pregnancy (CSDP) is associated with a number of negative outcomes in the offspring. Therefore, clarifying the correlates of CSDP and the extent to which CSDP is associated with nicotine dependence is an important step toward reducing its rate in the general population. Using data from 1,134 adult Australian female monozygotic and dizygotic twin pairs, we explored the associations between CSDP and sociodemographic and psychiatric correlates and between CSDP and patterns of cigarette smoking. Further, we examined the role of heritable and environmental influences on CSDP and investigated whether these latent risk factors are shared with a predisposition to nicotine dependence. Women smoking during an entire pregnancy reported heavier dependence and more unsuccessful quit attempts, compared with the community sample of mothers and with women who smoked during only part of a pregnancy. Educational attainment, weekly church attendance, spousal current smoking, and nicotine dependence also were associated with CSDP. Heritable influences explained 34% of the variation in CSDP, with the remainder related to nonshared environmental factors. A large proportion of the genetic influences on CSDP were shared with DSM-III-R nicotine dependence, with little overlap across the nonshared environmental influences. A lifetime history of difficulty with smoking cessation, in conjunction with social background and psychiatric comorbidity, especially during pregnancy, needs to be considered by treatment providers when counseling expectant mothers about the potential risks of CSDP.

Amygdala Volume Analysis in Female Twins with Major Depression

Previous research examining the amygdala volumes in major depressive disorder (MDD) has found conflicting evidence for association. Furthermore, few of these studies have examined differences in individuals with an onset during childhood or adolescence. This study examined amygdala volume and its potential association with early onset major depression. A community-based sample of 47 right-handed young adult female monozygotic and dizygotic twin pairs was examined. For 29 twin pairs, one twin per pair had a lifetime history of MDD, while 18 age-matched control twin pairs had no lifetime history of MDD or other Axis I disorder. Core, noncore, and total amygdala volumes were estimated based on a combination of manual tracing, automated segmentation, and expert rater regional boundary definitions. No significant differences were found in amygdala volumes between depressed, high-risk, or control subjects. However, analyses comparing control monozygotic twins to randomly created control subject pairs suggest that there are familial, perhaps genetic, influences on core and total amygdala volumes. Findings suggest that although there were no significant differences in amygdala volumes between groups, familial factors influence amygdala volumes. Discrepancies between studies measuring amygdala volume in MDD may be due to differences in amygdala boundary definitions.

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.

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.

Risk of Premature Ovarian Failure in Twins

A series of female monozygotic (MZ) twin-pairs discordant for premature ovarian failure (POF) has been presented for ovarian isotransplantation at one of our centers. These cases were surprising and unexplained because age at menopause is thought to be strongly genetically determined. A study was therefore launched to investigate the prevalence of POF and discordant menopausal age in twins in Australian and British databases

Sports Participation during Adolescence: A Shift from Environmental to Genetic Factors

A twin design was used to assess the relative contribution of genetic and environmental influences on the variation in sports participation of Dutch male and female twins between the ages of 13 and 20 yr. Survey data from 2628 complete twin pairs were available (443 male and 652 female monozygotic twin pairs, 377 male and 434 female dizygotic twin pairs, and 722 opposite-sex twin pairs). Subjects were classified as participating in sports if they engaged in competitive or noncompetitive leisure-time sports activities with a minimal intensity of 4 METs for at least 60 min.wk. An overall main effect of age and sex was found on the sports participation dichotomy. Younger twins participated more in sports than older twins, and for each age group males participated more often than females. Genetic analyses of twin resemblance showed a shift in the factors contributing to sports participation from adolescence to adulthood. Between the ages of 13 and 16 yr, environmental factors shared by children from the same family largely account for individual differences in sports participation (78-84%), whereas genes are of no importance. At the age of 17-18 yr, genetic influences start to appear (36%), and the role of common environment decreases (47%). After the age of 18 yr, genes largely explain individual differences in sports participation (85%), and common environmental factors no longer contribute. Environmental factors shared by family members determine sports participation in young adolescence but cease to be of importance in adulthood when individual differences in sports participation are largely due to genetic variation.

X Inactivation as a Source of Behavioural Differences in Monozygotic Female Twins

Although members of monozygotic twin pairs are identical in genome sequence, they may differ in patterns of gene expression. One early and irreversible process affecting gene expression, which can create differences within pairs of female monozygotic twins, is X inactivation — one twin can express mainly paternally-received genes on the X chromosome while the other twin expresses mainly maternally-received genes. It follows that non-identical X chromosome expression may cause female monozygotic twins to correlate less strongly than male monozygotic twins on complex behavioural traits affected by X-linked loci. We tested this hypothesis using data from around 4000 same-sex twin pairs on 9 social, behavioural and cognitive measures at ages 2, 3 and 4. Consistent with our hypothesis, monozygotic males were generally more similar than monozygotic females. Three of four significant differences were in traits showing higher correlations in males than females, and these traits — prosocial behaviour, peer problems, and verbal ability — have all been proposed previously in the literature as being influenced by genes on the X chromosome. Interestingly, dizygotic twins showed the reverse pattern of correlations for similar variables, which is also consistent with the X inactivation hypothesis; taken together, then, our monozygotic and dizygotic results suggest the presence of quantitative trait loci on the X chromosome.

Monozygotic twin pairs discordant for lifetime anorexia nervosa: An exploratory investigation

Although there is an increasing understanding of the impact of genetic factors on the development of anorexia nervosa (AN), clear identification of environmental risk factors remains unclear. Using monozygotic twins discordant for a disorder can be a useful tool for identifying such environmental risk factors. Differences between nine pairs of female monozygotic twins in the Australian Twin Registry who were discordant for lifetime AN were investigated. Twins were compared on self-report measures, including measures of current and lifetime psychopathology, temperament and coping, and parental bonding. None of the twins currently met the weight criterion for AN, indicating that current psychopathology would be unlikely to affect results. The twin affected by past AN reported a higher birth weight but a lower current body mass index than their co-twin; the affected twin tended to be more anxious than their co-twin. It may be useful for larger studies to further explore differences between twins discordant for AN in the areas of novelty seeking, and ways of coping, especially with respect to seeking social support.

Accounting for depressive symptoms in women: a twin study of associations with interpersonal relationships

Background: This study examined how interpersonal relationships, specifically marital quality and adequacy of social support, are associated with depressive symptoms among women. Methods: A sample of 326 female monozygotic and dizygotic twin pairs and their spouses was drawn from the Swedish Twin Registry. Associations among the three variables were evaluated by comparing similarities among monozygotic and dizygotic female twin pairs. Results: Interpersonal relationships contributed between 18% and 31% of the variance for depressive symptoms in women. Associations among the three variables were accounted for by genetic influences when women's reports were used. Non-shared environmental influences were important for the association between marital quality and depressive symptoms when a combination of husband and wife reports of marital quality were used. Limitations: The data is cross-sectional and the generalizability of these findings to depressive symptoms in men or to individuals with major depression is not clear. Conclusions: These findings indicate important associations among marital quality, social support and depressive symptoms in women, which should be taken into consideration for prevention and intervention strategies targeting depression.

A Bivariate Frailty Model with a Cure Fraction for Modeling Familial Correlations in Diseases

We suggest a cure-mixture model to analyze bivariate time-to-event data, as motivated by the article of Chatterjee and Shih (2001, Biometrics 57, 779-786), but with a simpler estimation procedure and the correlated gamma-frailty model instead of the shared gamma-frailty model. This approach allows us to deal with left-truncated and right-censored lifetime data, and accounts for heterogeneity, as well as for an insusceptible (cure) fraction in the study population. We perform a simulation study to evaluate the properties of the estimates in the proposed model and apply it to breast cancer incidence data for 5857 Swedish female monozygotic and dizygotic twin pairs from the so-called old cohort of the Swedish Twin Registry. This model is used to estimate the size of the susceptible fraction and the correlation between the frailties of the twin partners. Possible extensions, advantages, and limitations of the proposed method are discussed.

The responses of serum and adipose Fatty acids to a one-year weight reduction regimen in female obese monozygotic twins.

We have reported strong intrapair resemblances (IPRs) in serum phosphatidylcholine (PC) fatty acid composition within adult monozygotic twins living apart. This study assessed the contribution of genetic factors to changes in serum and adipose tissue fatty acids resulting from weight loss and followed by a subsequent year of weight maintenance. Eleven pairs of female obese monozygotic twins (age: 38.9 +/- 1.8; BMI: 32.5 +/- 0.9) were recruited for the study. Fasting serum and adipose tissue were obtained after 1 week of inpatient stabilization, after 1 month of inpatient very-low-calorie diet (VLCD), and again after 1 year of outpatient weight maintenance. Fatty acids in serum lipid fractions and adipose tissue were quantitated by gas chromatography. Using multiple regression adjusted for age and initial value, IPRs were determined for the changes induced by VLCD and by the year of weight maintenance. There were few IPRs in nonessential fatty acids. By contrast, there were numerous IPRs for essential fatty acids (EFA), especially in the n-3 family across the VLCD. Following the maintenance year, however, frequent IPRs for nonessential fatty acids were seen, particularly in serum PC, and strong IPRs were seen for 18:3 n-3 and 20:5 n-3 across multiple fractions. These results infer the existence of strong genetic factors determining both the nonessential and EFA compositions of tissue lipids in humans independent of diet. Of particular note were the consistent IPRs for n-3 fatty acids despite dietary stress, indicating that the conservation and distribution of this EFA family are subject to considerable genetic variance in humans.

Assessment of dietary and genetic factors influencing serum and adipose fatty acid composition in obese female identical twins.

Fourteen pairs of obese female monozygotic twins were recruited for a study of genetic influences on serum and adipose fatty acid (FA) composition. Following 1 wk of inpatient stabilization, fasting serum and adipose tissue obtained by surgical excision were analyzed by thin-layer and gas chromatography. Intrapair resemblances (IPR) for individual FA were assessed by Spearman rank correlation and by analysis of variance and were found in serum cholesteryl esters (CF), triglycerides (TG), and adipose TG. With two exceptions (CE linoleate and adipose eicosapentaenoate), these IPR were limited to the nonessential FA. Palmitate had significant IPR in four lipid fractions; in serum CE and adipose TG palmitate was strongly correlated with multiple measures of adiposity. In contrast to other lipid fractions, serum phosphatidylcholine (PC) FA had 12 [PR, of which 6 were essential FA including arachidonate (r = 0.76, P < 0.0005), eicosapentaenoate (r = 0.78, P < 0.0005), and docosahexaenoate (r = 0.86, P< 0.0001). The PC [PR could not be explained by analysis of preadmission 7-d food records. After dividing the pairs into two groups differing and nondiffering according to fat intake of individuals in the pair, there was no evidence of a gene-environment interaction between fat intake and FA composition. The IPR for nonessential FA indicate that there is active genetic control of either food choices or postabsorptive metabolic processing. The high level of IPR in the PC fraction in contrast to the other lipid fractions suggests strong genetic influence over selection of specific FA for this membrane fraction independent of diet.

A comparison of family functioning, temperament, and childhood conditions in monozygotic twin pairs discordant for lifetime bulimia nervosa.

The authors investigated differences between twins in nine pairs of female monozygotic twins in the Australian Twin Registry who were discordant for lifetime bulimia nervosa. The twins affected and unaffected by lifetime bulimia nervosa were compared on self-report measures, including a measure of parental bonding, four measures of temperament, and six early-childhood medical conditions. No twins had current bulimia nervosa, and there was no difference in weight or eating status between the affected and unaffected twins. The affected twins reported significantly lower self-esteem and less warmth but more overprotection by their mothers during childhood. Although limited by the small number of discordant twin pairs and the inability to detect causal relationships, these results suggest that environmental influences that promote low self-esteem may also increase the risk for bulimia nervosa. These temperamental differences may explain the discrepancies in parenting or perceived parenting.

Is the genetic liability in multifactorial disorders higher in concordant than discordant monozygotic twin pairs? A population-based family twin study of migraine without aura.

Migraine without aura (MO) is a multifactorial disorder. Expression of a disorder with multifactorial inheritance depends on the genetic liability and on environmental factors. A high liability is reflected by a high frequency of affected relatives. We have previously shown that monozygotic (MZ) twin pairs have a significant higher concordance of MO than dizygotic twin pairs. The incomplete concordance among MZ twin pairs may be due to a lower genetic liability among discordant than concordant MZ twin pairs. The present study analysed the genetic liability in MZ twin pairs concordant and discordant for MO by the population-relative risk of MO among parents and siblings. The twin pairs were from the population-based Danish Twin Register. First-degree relatives of 29 concordant and 34 discordant MZ twin pairs were blindly telephone interviewed by a physician. The participation rate of the eligible first-degree relatives was 96%. The population-relative risk of MO among parents and siblings was 2.73 (2.39-3.06) in concordant and 2.37 (2.03-2.71) in discordant MZ twin pairs. The relative risk of MO was significantly higher in female first-degree relatives of concordant than of discordant MZ male and female twin pairs. An opposite effect was observed in male first-degree relatives, although this was not significant for male first-degree relatives of female MZ twin pairs. The present study found no statistically significant difference in genetic liability to MO among concordant and discordant MZ twin pairs. However, a difference in genetic liability among MZ and DZ twin pairs is anticipated to be small. Thus, it may be possible to show the effect in a larger study population or by investigating a more frequent trait than MO.

Transsexualism in female monozygotic twins: a case report

Objective: A case report is presented of a gender identity disorder involving a pair of female monozygotic twins who requested sex reassignment. As far as we know, this case is the first in psychiatric literature and supports a genetic aetiology of this disorder.Clinical picture: The patients were two 18-year-old female monozygotic twins who had showed symptoms of transsexualism since early childhood. They had no other physical or psychiatric disorder except borderline mental functioning.Treatment: The patients were referred for sex reassignment.Outcome: They were lost to follow up after initial evaluation.Conclusion: In addition to other possible (yet not confirmed) causes of trans-sexualism, a genetic basis for this disorder is suggested by this case.