Twin Siblings Research Articles

Dependent negative life events and sleep quality: An examination of gene–environment interplay

Objectives Negative life events are associated with sleep disturbances. Further understanding of these associations is beneficial as sleep disturbances are common. We assessed the association between two commonly distinguished types of negative life events (dependent vs. independent) and sleep quality. The extent to which genetic and environmental influences explained the association between dependent negative life events and sleep quality was also assessed. Finally, we examined the presence of gene–environment interaction by assessing whether genetic liability to sleep disturbance varied as a function of dependent negative life events. Methods Structural equation modelling was used to perform the statistical analyses on questionnaire data collected from 1556 twin and non-twin siblings. Results Poor sleep quality was more strongly associated with dependent as compared to independent negative life events ( r = .34 and .15, respectively). There was substantial overlap in the genetic influences on the association between dependent negative life events and poor sleep quality ( rA = .62 [.43–.81]), suggesting gene–environment correlation. Environmental overlap was small ( rE = .16 [.04–.28]). Genetic influences accounted for a large proportion of the association (70% [.47–.92]) with the remaining co-variance due to non-shared environment (30% [.08–.53]). Genetic liability to sleep quality was not moderated by dependent negative life events. Conclusions Genetic and environmental effects on sleep are not necessarily distinct but to some extent work in concert. This should be considered in future studies assessing the genetic and environmental effects on sleep.

Evidence for an Inherited Predisposition to Lumbar Disc Disease

A genetic predisposition for the development of symptomatic lumbar disc disease has been suggested by several twin sibling studies and subsequent genetic marker studies. The purpose of the present study was to define population-based familial clustering among individuals with a diagnosis of, or treated for, lumbar disc herniation or disc degeneration. The Utah Population Database allows analysis of combined health and genealogic data for over one million Utah residents. We used the International Classification of Diseases, Ninth Revision, diagnosis codes entered in patient records to identify patients with a diagnosis of either lumbar disc herniation or lumbar disc degeneration and genealogic data. The hypothesis of excess relatedness (familial clustering) was tested with use of the Genealogical Index of Familiality, which compares the average relatedness of affected individuals with expected population relatedness. Relative risks in relatives were estimated by comparing rates of disease in relatives with expected population rates (estimated from the relatives of matched controls). This methodology has been previously reported for other disease conditions but not for spinal diseases. The Genealogical Index of Familiality test for 1264 patients with lumbar disc disease showed a significant excess relatedness (p < 0.001). Relative risk in relatives was significantly elevated in both first-degree (relative risk, 4.15; p < 0.001) and third-degree relatives (relative risk, 1.46; p = 0.027). Excess relatedness of affected individuals and elevated risks to both near and distant relatives was observed, strongly supporting a heritable contribution to the development of symptomatic lumbar disc disease.

Umbilical Arterial Blood Gas and Perinatal Outcome in the Second Twin according to the Planned Mode of Delivery

To compare umbilical arterial gas parameters in the second twin of twin pregnancies according to the mode of delivery. We retrospectively analyzed the medical records of twin deliveries after 34 weeks of gestation for 3 years. Excluding the cases which underwent emergency cesarean delivery during trial of labor, a total of 79 twin gestations had umbilical arterial blood gas values available and were and divided into cesarean delivery group (N=40) and vaginal delivery group (N=39). The mean differences of umbilical arterial blood parameters and the Apgar score between the first and second twin in each pregnancy were compared according the mode of delivery. The differences of umbilical arterial gas parameters between twin siblings showed no significant difference according to the mode of delivery. With regard to the 1 minute and 5 minute Apgar scores, the differences between twin siblings are significantly increased in vaginal delivery group compared to cesarean delivery group (p=0.048, and p=0.038, respectively). In comparing the 28 cases delivered vaginally with an inter-twin delivery interval < 10 minutes and 40 cases delivered by cesarean section, no significant differences were observed in the umbilical arterial gas parameters and Apgar scores. The inter-twin umbilical arterial blood gas parameters according to the mode of delivery showed no difference. For twin deliveries, it is relatively safe to plan for a vaginal delivery, but an effort should be made to reduce the inter-twin delivery interval time.

Recurrent headache and migraine heritability: Twin study

The aim of the study was to determine recurrent headache (migraine and non-migraine) heritability, among the twin pairs. Headache hritability was investigated among 396 twin pairs (42.4% monozygotic and 57.6% dizygotic) aged 3 to 21 years, on north part territory of Serbia-Vojvodina, during the 20 years period. Within the group of tested twin persons, 30.2% had recurrent headaches, 9.2% migraine headache and 21% other recurrent non-migraine headaches. Heritability quotient of all recurrent headaches was 0.3882. For non- migraine headaches heritability quotient of 0.2286 confirmed that the external factors influence is higher than heritability. Migraine headache heritability quotient 0.8598 clearly proved the heritability of the migraine headache. Both, correlation and determination quotient of the migraine headache of all the twins (r12 0.7498; r21256.12%), monozygotic (r120.8458; r1271.54%) and dizygotic (r120.6342; r21240.22%), show high degree of migraine headache twin siblings dependence, and higher correlation and significance of the difference with monozygotic twins.

Chromatic (Red/Green) and Luminance Contrast Sensitivity in Monozygotic and Dizygotic Twin Infants

Purpose: To determine the extent to which contrast sensitivity (CS) development is governed by genetic mechanisms vs. environment, we compared CS between pairs of twin infants and pairs of unrelated infants. If genetics have a strong influence on CS, Monozygotic (Mz) twin siblings should be more similar (and more strongly correlated) than Dizygotic (Dz) twin siblings, and both Mz and Dz twins should show greater correlations than unrelated infant pairs. By contrast, if genetics have little influence, correlations should be the same for Dz and Mz twins. In this latter scenario, if both Mz and Dz twins show greater correlations than unrelated infant pairs, this suggests a role of shared environment. The current study measured Luminance (light/dark) and Chromatic (red/green) CS to assess sensitivity of the Magnocellular and Parvocellular pathways, respectively. Methods: Ten and 26 pairs of Mz and Dz twin pairs were tested (mean age = 4.5±1.5 mos). Zygosity was assessed using a questionnaire and cheek swab kits. Luminance and Chromatic CS were obtained for sinusoidal gratings using forced-choice preferential looking (∼200 trials per infant; 0.27 cycles/degree; 4.2 Hz). Results: Multiple regression was conducted on 100 runs of random Twin-1/Twin-2 orderings. Results indicated that the CS of one twin predicted 35-40% of the variance (p <0.0001) in the CS of the other twin, while controlling for postnatal age, gestational length, and gender. Simulations with randomly-matched twins suggest these findings are not due to chance. Discussion: Results suggest shared environment and/or genes influence both Luminance and Chromatic CS. With more subjects, we will address whether Luminance vs. Chromatic CS is more or less affected by shared genes/environment. Once we have enough data to compare Mz vs. Dz twins, we can ask which factor, genes or environment, is more influential using structural equation modeling (Neale et al, 2002).

Heritability estimation for speech-sound traits with developmental trajectories.

Numerous studies have examined genetic influences on developmental problems such as speech sound disorders (SSD), language impairment (LI), and reading disability. Disorders such as SSD are often analyzed using their component endophenotypes. Most studies, however, have involved comparisons of twin pairs or siblings of similar age, or have adjusted for age ignoring effects that are peculiar to age-related trajectories for phenotypic change. Such developmental changes in these skills have limited the usefulness of data from parents or siblings who differ substantially in age from the probands. Employing parent-offspring correlation in heritability estimation permits a more precise estimate of the additive component of genetic variance, but different generations have to be measured for the same trait. We report on a smoothing procedure which fits a series of lines that approximate a curve matching the developmental trajectory. This procedure adjusts for changes in measures with age, so that the adjusted values are on a similar scale for children, adolescents, and adults. We apply this method to four measures of phonological memory and articulation in order to estimate their heritability. Repetition of multisyllabic real words (MSW) showed the best heritability estimate of 45% in this sample. We conclude that differences in measurement scales across the age span can be reconciled through non-linear modeling of the developmental process.

Intra-uterine exposure to dual fetal programming sequences among surviving co-twins

Objective. The dynamics of fetal programming following in utero demise of a co-twin are poorly understood.Methods. The authors examined fetal programming using a unique application of the change-point analysis method, and identified two types of fetal programming that occurred when a viable twin sibling died in utero, while the co-twin survived.Results. In one type, the initial twin fetal programming trajectory was maintained while in a subset of surviving co-twins a “switch” from a twin to a singleton fetal program (dual fetal programming exposure) was observed. The results suggest that the timing in utero of conversion from a twin to a singleton programming pattern occurred slightly earlier among opposite-sex than in same-sex surviving co-twins.Conclusion. For the conversion from a twin to a singleton program to happen, the surviving co-twin must have attained a “critical mass” when the twin sibling died. Whereas, for same-sex surviving co-twins the critical mass for conversion was the 80th percentile of gestational-age specific birth weight, opposite-sex surviving co-twins converted at a lower critical mass (70th percentile). These novel findings warrant further study to confirm the new hithertofore unknown phenomenon of dual fetal programming sequence, and to determine the implications in terms of subsequent morbidity or mortality during infancy, childhood and adult life.

Not by Twins Alone: Using the Extended Family Design to Investigate Genetic Influence on Political Beliefs

Variance components estimates of political and social attitudes suggest a substantial level of genetic influence, but the results have been challenged because they rely on data from twins only. In this analysis, we include responses from parents and nontwin full siblings of twins, account for measurement error by using a panel design, and estimate genetic and environmental variance by maximum‐likelihood structural equation modeling. By doing so, we address the central concerns of critics, including that the twin‐only design offers no verification of either the equal environments or random mating assumptions. Moving beyond the twin‐only design leads to the conclusion that for most political and social attitudes, genetic influences account for an even greater proportion of individual differences than reported by studies using more limited data and more elementary estimation techniques. These findings make it increasingly difficult to deny that—however indirectly—genetics plays a role in the formation of political and social attitudes.

Onset of late-onset sepsis in a premature twin: how to manage the co-twin?

<h3>Objective</h3> The diagnosis of sepsis in a twin presents a clinical dilemma regarding optimal management of the apparently well co-twin. The authors present the case of extremely preterm twins who both developed life-threatening coliform sepsis in second postnatal week within a short time period of each other. <h3>Methods</h3> Case report. <h3>Results</h3> Dichorionic diamniotic twins were delivered vaginally at 27 weeks9 gestation following spontaneous onset of labour. Twin 2 presented with overt signs of sepsis on day 10 and required reventilation. At this time, twin 1 was not treated with antibiotics because she was clinically well and C-reactive protein was normal. However, 34 h later she also developed life-threatening <i>Escherichia coli</i> septicaemia, including meningitis. Serious complications ensued, including pulmonary haemorrhage, hypotension, impaired renal function, thrombocytopenia, necrotising enterocolitis with intestinal perforation and digital ischaemic injury. The <i>E coli</i> strain isolated from the blood of twin 2, and both blood and CSF of twin 1 had similar antibiotic susceptibility patterns. Typing confirmed the same strains of <i>E coli</i> in both twins, namely, serotype 031 K1. Perinatal colonisation of the organism was suspected. <h3>Conclusions</h3> This case supports concurrent evaluation and consideration of empirical antibiotic treatment of an apparently well preterm co-twin when a twin sibling presents with late-onset sepsis within the first 2 weeks postnatal. Reliance solely on enhanced clinical surveillance for infection in an asymptomatic twin may be insufficient.

Duration of fertility after fresh and frozen ovary transplantation

To evaluate the function of human ovarian transplants. Follow a series of fresh ovarian transplants for up to 5 years, and compare fresh and frozen ovarian tissue transplantation. Tertiary referral community hospital. Nine women with premature ovarian failure who received an ovary donated from a monozygotic twin sibling, and 16 young cancer patients undergoing ovarian cryopreservation. Two of the transplant recipients were cancer survivors rendered sterile by their therapy. Fresh ovary transplantation between monozygotic twin sisters, as well as transplantation of previously frozen ovarian tissue, and study of cryopreserved tissue in cancer patients. Return of normal menstrual cycling, hormone levels, pregnancy, healthy babies, duration of transplant function, and ovarian tissue evaluation. Normal serum FSH and regular menstrual cycles returned by 5 months after surgery in all cases, both fresh and frozen. Fourteen spontaneous pregnancies were established leading to eight healthy live births and two healthy ongoing conceptions. All three frozen tissue transplants conceived spontaneously, one delivered, and two were ongoing. Oocyte survival with slow freezing was 42% and after vitrification 89%. Ovarian transplantation in humans is a robust procedure, even after cryopreservation, and vitrification might prove to be more effective than slow freezing.

A Bivariate Twin Study of Regional Brain Volumes and Verbal and Nonverbal Intellectual Skills During Childhood and Adolescence

Twin studies indicate that both intelligence and brain structure are moderately to highly heritable. Recent bivariate studies of adult twins also suggest that intelligence and brain morphometry are influenced by shared genetic factors. The current study examines shared genetic and environmental factors between brain morphometry and intelligence in a sample of children and adolescents (twins, twin siblings, and singletons; n = 649, ages 4-19). To extend previous studies, brain morphometric data were parsed into subregions (lobar gray/white matter volumes, caudate nucleus, lateral ventricles) and intelligence into verbal and nonverbal skills (Wechsler Vocabulary and Block Design subtests). Phenotypic relationships between brain volumes and intelligence were small. Verbal skills shared unique environmental effects with gray matter volumes while nonverbal skills shared genetic effects with both global and regional gray and white matter. These results suggest that distinct mechanisms contribute to the small phenotypic relationships between brain volumes and verbal versus nonverbal intelligence.

Dental treatment of twin monozygotic brothers with Fragile X syndrome

Fragile X syndrome (FXS) is the main cause of inherited mental retardation and is the result of transcriptional silencing of the fragile X mental retardation gene FMR1. An absence of the associated protein FMRP leads to the deregulation of many genes, which results in phenotypes of Attention-Deficit Hyperactivity Disorder (ADHD), anxiety, epilepsy and autism. The aim of this article is to report the clinical case of twin siblings affected by FXS and to describe the procedures for dental treatment with intravenous sedation. Information regarding the characteristic manifestations of FXS not only aided in the handling of the patients but also enabled us to develop clinical programs to promote and maintain oral health using individualized and specific dental procedures.

Body Size of Twins Compared with Siblings and the General Population: From Birth to Late Adolescence

We examined whether and when differences in body size disappear over time and whether twins attain normal final height and body mass index (BMI). Height, weight, and BMI data of twins at ages 1, 4, and 18 years were compared with data from their nontwin siblings. Second, twin and sibling data were compared with population standards. In addition to height, weight, and BMI, data on body proportions at age 18 years were analyzed. At the age of 18 years, twins were as tall as their siblings but were significantly leaner. Compared with children from the general population, adolescent twins attained the same height and BMI. Birth weight was shown to have a considerable effect on height in adolescent twins. Twins attained normal final height compared with siblings and children from the general population. No differences in BMI were shown between 18-year-old twins and children from the general population, whereas the siblings of twins had increased BMI values compared with the general population.

Inaccuracies in food and physical activity diaries of obese subjects: complementary evidence from doubly labeled water and co-twin assessments

To study whether eating or physical-activity (PA) habits differ between obese and non-obese monozygotic (MZ) co-twins independent of genetic effects. Rare MZ pairs discordant for obesity (n=14, body mass index difference 5.2+/-1.8 kg m(-2)) and weight-concordant control pairs (n=10, 1.0+/-0.7 kg m(-2)), identified through a population-based registry of 24-28-year-old twins (n=658 MZ pairs), completed 3-day food and PA diaries and eating behavior questionnaires. Each twin was asked to compare his/her own eating and PA patterns with the co-twin's behavior by structured questionnaires. Accuracy of energy intake was validated by doubly labeled water. Non-obese co-twins consistently reported that their obese twin siblings ate more food overall, consumed less healthy foods and exercised less than the non-obese co-twins do. However, no differences in energy intake (9.6+/-1.0 MJ per day vs 9.8+/-1.1 MJ per day, respectively) in the food diaries or in the mean PA level (1.74+/-0.02 vs 1.79+/-0.04, respectively) in the PA diaries were found between obese and non-obese co-twins. A considerable underreporting of energy intake (3.2+/-1.1 MJ per day, P=0.036) and overreporting of PA (1.8+/-0.8 MJ per day, P=0.049) was observed in the obese, but not in the non-obese co-twins. On the basis of rare MZ twin pairs discordant for obesity, the co-twin assessments confirmed substantial differences in eating and PA behavior between obese and non-obese persons. These may be overlooked in population studies using food and PA diaries because of considerable misreporting by the obese.

PO10-TU-61 Asymptomatic subjects with a twin sibling with MS show signs of cognitive decline: a Finnish co-twin study

PO10-TU-61 Asymptomatic subjects with a twin sibling with MS show signs of cognitive decline: a Finnish co-twin study

Twins Eye Study in Tasmania (TEST): Rationale and Methodology to Recruit and Examine Twins

Visual impairment is a leading cause of morbidity and poor quality of life in our community. Unravelling the mechanisms underpinning important blinding diseases could allow preventative or curative steps to be implemented. Twin siblings provide a unique opportunity in biology to discover genes associated with numerous eye diseases and ocular biometry. Twins are particularly useful for quantitative trait analysis through genome-wide association and linkage studies. Although many studies involving twins rely on twin registries, we present our approach to the Twins Eye Study in Tasmania to provide insight into possible recruitment strategies, expected participation rates and potential examination strategies that can be considered by other researchers for similar studies. Five separate avenues for cohort recruitment were adopted: (1) piggy-backing existing studies where twins had been recruited, (2) utilizing the national twin registry, (3) word-of-mouth and local media publicity, (4) directly approaching schools, and finally (5) collaborating with other research groups studying twins.

Variable Expressivity and High Penetrance of CYP1B1 Mutations Associated with Primary Congenital Glaucoma

To investigate penetrance and expressivity of CYP1B1 genotypes associated with primary congenital glaucoma (PCG). Observational case series, systematic review, and comparative analysis of the literature. Forty probands affected with PCG, 16 siblings affected with PCG, and 103 siblings and 75 parents of the probands reported not to be affected by history. The participants were members of 40 unrelated families. Mutations were screened by restriction fragment length polymorphism, allele-specific polymerase chain reaction amplification, and direct sequencing. Ophthalmologic examination included slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, gonioscopy, and high magnification stereoscopic fundus examination, followed by standard achromatic perimetry. Identification of subjects carrying CYP1B1 mutations. Glaucoma diagnosis based on slit-lamp examination, IOP measurement, gonioscopic findings, optic nerve appearance, and perimetry. Fifteen different homozygous or compound heterozygous mutant CYP1B1 genotypes were identified. Most probands and previously diagnosed subjects harbored G61E, R368H, R390H, and R469W mutations. Among the 178 apparently unaffected family members, 20 subjects from 12 families were observed to harbor 2 CYP1B1 mutations, suggesting an average penetrance of 73% for all the mutations. These 20 subjects ranged in age from 14 to 54 years. R390H appeared to have a notably high penetrance. Penetrance was 50% in the subset of families with incomplete penetrance. Ophthalmologic examination on 14 of the 20 apparently nonpenetrant individuals showed that 8 subjects were affected with juvenile open-angle glaucoma (JOAG) or primary open-angle glaucoma (POAG), and that 3 subjects were glaucoma suspect. One of the individuals with a JOAG diagnosis was the identical twin sibling of a proband affected with PCG. At least 57% of the PCG nonpenetrant individuals examined clinically were affected with JOAG or POAG to varying degrees, and overall penetrance of "affected CYP1B1 genotypes" with respect to glaucoma may be more than 90%. These findings suggest that "affected CYP1B1 genotypes" exhibit variable expressivity rather than nonpenetrance. The clinical implication of this observation is that seemingly unaffected relatives of patients with PCG, particularly those known to harbor CYP1B1 mutations, should undergo regular ophthalmologic examination to allow early diagnosis.

Cardiac and neurological implications in beta-thalassaemia with left ventricular hypertrabeculation/non-compaction: reply

We thank Professors Stollberger and Finsterer for their interest in our report and note the questions raised. We confirm that the echocardiographic features of left-ventricular hypertrabeculation/non-compaction (LVHT), as defined by the widely used criteria of Jenni et al. ,1 were only present in the twin siblings. The female sibling also demonstrated mild echocardiographic changes of LVHT, but these did not fulfil the diagnostic criteria. Echocardiographic images of one of the twins and the female sibling from approximately 2 years earlier were available for review, and demonstrate normal left ventricular systolic function in both cases. In the short-axis view, there was a degree of hypertrabeculation apparent in both cases, but more pronounced in the twin. However, the images were not of sufficient quality to make accurate measurements of the thickness …

The correlation in birth timing between singleton and twin gestations in the same mother

Objective. To test the hypothesis that the timing of twin births is correlated to that of their singleton siblings.Methods. Using the Missouri Department of Health's birth certificate database we performed a retrospective population-based cohort study of 2222 women who had at least one singleton and one twin birth (1989–1997). Pearson correlation analysis was conducted to examine the relationship in gestational age between singleton and twin births occuring in the same mother.Results. Among 2222 mothers who had both a singleton and twin pregnancy during the study period, the mean difference in birth timing between singleton and twin siblings was 3.05 weeks (±2.9 weeks). The correlation between singleton and twin birth timing was statistically significant (r = 0.28, p < 0.001), and remained significant even after controlling for potential confounders (β = 0.459, p < 0.001).Conclusions. We identified a significant correlation in the timing of birth between singleton and twin pregnancies in the same mother, which could be due to shared genetic, environmental, medical, social and other influences. This finding could be useful to help predict birth timing in mothers at especially high risk of preterm birth, those with a twin gestation.

Do Genetic Factors Influence Religious Life? Findings from a Behavior Genetic Analysis of Twin Siblings

Social scientific research assumes that religious involvement is primarily, if not exclusively, the product of social‐environmental influences There is growing evidence, however, that genetic or other biological factors also play a role Analyzing twin sibling data from the National Survey of Midlife Development in the United States (MIDUS), this study addresses this issue by showing that individual‐level variation on four different aspects of religious life—organizational involvement, personal religiosity and spirituality, conservative ideologies, and transformations and commitments—is indeed the product of both genetic and environmental influences Specifically, genetic factors explain 19–65 percent of the variation, while environmental influences account for the remaining 35–81 percent depending upon the aspect of religion under investigation Research of this type enhances contemporary social science by providing a new perspective that nicely supplements existing ones, but it also highlights potential implications, including explanatory power deficiencies and potentially bias