Twin study dissects CXCR3+ memory B cells as non-heritable feature in multiple sclerosis.

BACKGROUND: In multiple sclerosis (MS), B cells are considered main triggers of the disease, likely as the result of complex interaction between genetic and environmental risk factors. Studies on monozygotic twins discordant for MS offer a unique way to reduce this complexity and reveal discrepant subsets. METHODS: In this study, we analyzed B cell subsets in blood samples of monozygotic twins with and without MS using publicly available data. We verified functional characteristics by exploring the role of therapy and performed separate analyses in unrelated individuals. FINDINGS: The frequencies of CXCR3+ memory B cells were reduced in the blood of genetically identical twins with MS compared to their unaffected twin siblings. Natalizumab (anti-VLA-4 antibody) was the only treatment regimen under which these frequencies were reversed. The CNS-homing features of CXCR3+ memory B cells were supported by elevated CXCL10 levels in MS cerebrospinal fluid and their in vitro propensity to develop into antibody-secreting cells. CONCLUSIONS: Circulating CXCR3+ memory B cells are affected by non-heritable cues in people who develop MS. This underlines the requirement of environmental risk factors such as Epstein-Barr virus in triggering these B cells. We propose that after CXCL10-mediated entry into the CNS, CXCR3+ memory B cells mature into antibody-secreting cells to drive MS. FUNDING: This work was supported by Nationaal MS Fonds (OZ2021-016), Stichting MS Research (19-1057 MS, 20-490f MS, and 21-1142 MS), the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program grant agreement no. 882424, and the Swiss National Science Foundation (733 310030_170320, 310030_188450, and CRSII5_183478).

Rigorous evaluation of genetic and epigenetic effects on clinical laboratory measurements using Japanese monozygotic twins.

The investigation of environmental effects on clinical measurements using individual samples is challenging because their genetic and environmental factors are different. However, using monozygotic twins (MZ) makes it possible to investigate the influence of environmental factors as they have the same genetic factors within pairs because the difference in the clinical traits within the MZ mostly reflect the influence of environmental factors. We hypothesized that the within-pair differences in the traits that are strongly affected by genetic factors become larger after genetic risk score (GRS) correction. Using 278 Japanese MZ pairs, we compared the change in within-pair differences in each of the 45 normalized clinical measurements before and after GRS correction, and we also attempted to correct for the effects of genetic factors to identify Cytosine-phosphodiester-Guanine (CpG) sites in DNA sequences with epigenetic effects that are regulated by genetic factors. Five traits were classified into the high heritability group, which was strongly affected by genetic factors. CpG sites could be classified into three groups: regulated only by environmental factors, regulated by environmental factors masked by genetic factors, and regulated only by genetic factors. Our method has the potential to identify trait-related methylation sites that have not yet been discovered.

Oral Health Knowledge and Habits of Hungarian Monozygotic and Dizygotic Twins: A Pilot Study.

OBJECTIVE: The aim of this research was to collate and analyse the data on the oral health knowledge and the related habits of a Hungarian cohort of monozygotic (MZ) and dizygotic (DZ) twins using the newly developed World Health Organisation Oral Health Questionnaire for Adults (Annex 7). METHOD: A total of 15 sets of MZ twins and 14 sets of DZ twins (58 individuals) aged between 18 and 71 years were enrolled in the study. Each participant had to fill out a web-based questionnaire which comprised 23 questions (Google Forms). The data were collated and the oral health/hygiene habits of MZ and DZ twins were compared. RESULTS: No significant differences were detected between MZ and DZ twins with regards to their daily tooth-cleaning habits or the tooth-cleaning products used by the 2 groups. For instance, when asked how often they clean their teeth, 80% of MZ twins and 71% of DZ twins responded similarly. Further, both groups provided similar responses when questioned about the use of fluoride toothpaste, frequency of dental visits, and dental counselling received as well as a number of other parameters such as snacking of sweets and fear of visiting dentists. CONCLUSIONS: Our pilot analysis of the questionnaire responses from MZ and DZ twins in Hungary did not indicate any significant differences in their oral care habits in general. Further studies with a large cohort are required to confirm or refute our findings.

Pregnancy and neonatal outcomes of monozygotic twins resulting from assisted reproductive technology: a 10-year retrospective study.

BACKGROUND: Monozygotic twins (MZTs) are associated with high risks of maternal and fetal complications. Even with the widely used elective single embryo transfer (SET), the risk of MZTs following assisted reproductive technology (ART) treatments remains. However, most studies of MZTs focused on the relevant etiology, with few studies describing pregnancy and neonatal outcomes. METHODS: This retrospective cohort study included 19,081 SET cycles resulting from in-vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), preimplantation genetic testing (PGT) and testicular sperm aspiration (TESA) performed between January 2010 and July 2020 in a single university-based center. A total of 187 MZTs were included in this investigation. The main outcome measures were the incidence, pregnancy and neonatal outcomes of MZTs. Multivariate logistic regression analysis was performed to figure out the risk factors for pregnancy loss. RESULTS: The overall rate of MZTs from ART treatment in SET cycles was 0.98%. No significant difference was found in the incidence of MZTs among the four groups (p = 0.259). The live birth rate of MZTs in the ICSI group (88.5%) was significantly more favorable than in the IVF, PGT and TESA groups (60.5%, 77.2% and 80%, respectively). IVF resulted in a significantly increased risk of pregnancy loss (39.4%) and early miscarriage (29.5%) in MZT pregnancies compared to ICSI (11.4%, 8.5%), PGT (22.7%, 16.6%) and TESA (20%, 13.3%). The total rate of twin-to-twin transfusion syndrome (TTTS) in MZTs was 2.7% (5/187); however, the TESA group had the highest rate at 20% and was significantly higher than the PGT group (p = 0.005). The four ART groups had no significant effect on the occurrence of congenital abnormalities or other neonatal outcomes in newborns from MZT pregnancies. Multivariate logistic regression analysis revealed that infertility duration, cause of infertility, the total dose of Gn used, history of miscarriages, and the number of miscarriages were not related to the risk of pregnancy loss (p > 0.05). CONCLUSIONS: The rate of MZTs was similar among the four ART groups. The pregnancy loss and the early miscarriage rate of MZTs was increased in IVF patients. Neither the cause of infertility nor the history of miscarriage was correlated with the risk of pregnancy loss. MZTs in the TESA group had a higher risk of TTTS, placental effects influenced by sperm and paternally expressed genes may play a role. However, due to the small total number, studies with larger sample sizes are still needed to validate these result. Pregnancy and neonatal outcomes of MZTs after PGT treatment seem to be reassuring but the duration of the study was short, and long-term follow-up of the children is needed.

Perinatal Outcomes In Monozygotic Pregnancies Resulting From Assisted Reproductive Technology Procedures: A Single-Center 6-Year Experience Based On A Large Cohort Of Pregnancies.

OBJECTIVE: Monozygotic twin (MZT) pregnancies increase the risk of maternal and infant mortality and include many complications. The present study describes our assisted reproductive technology (ART) procedures from the viewpoint of perinatal outcomes in MZT pregnancies. METHODS: In this retrospective clinical cross-sectional study, 1159 in vitro fertilization (IVF) cycles performed between October 2014 and December 2019 were reviewed and perinatal outcomes and general clinical conditions analyzed. RESULTS: Sixteen MZT pregnancies were observed, resulting in an incidence of 1.38%. The MZT pregnancy incidence for patients aged ≤35 and >35 years were 0.2% and 1.1%, respectively. Eight MZT pregnancies resulted in live births, while five ended in miscarriage. A significant positive correlation was found between the number of attempts and the age of female (r:0.674; p=0.004) and male (r:0.657; p=0.006) partners. Cumulus-Oocytes Complexes (COC) (r:0.635; p=0.008), Metaphase II Oocyte (MIIO) (r:0.627; p=0.009), Pronucleus Oocyte (PO) (r:0.585; p=0.017) were correlated with serum AMH levels. The number of MZT was positively correlated with male partner age (r:0.527; p=0.036) and negatively correlated with embryo transfer day (ETd) (r:-0.548; p=0.028). CONCLUSIONS: The incidence of MZT pregnancies observed in this study was similar to the incidence reported in the literature, although risk was more pronounced among women aged >35 years. Due to potential risks for mothers and fetuses, MZT pregnancies may become a problem as the number of individuals seeking IVF continues to increase.

Differences in Parenting Behavior are Systematic Sources of the Non-shared Environment for Internalizing and Externalizing Problem Behavior.

Although there is evidence for non-shared environmental links between parenting and problem behavior, so far, age-, informant-, and parent-specific patterns for both internalizing and externalizing problem behaviors have not been examined within one study yet. Using the twin differences design, the present study aimed to test how maternal and paternal parenting systematically act as a source of non-shared environment for problem behavior across different age groups and informants. We examined 1327 monozygotic twin pairs and their parents drawn from three birth cohorts of the German TwinLife study. Our results revealed that particularly child-reported less positive and more negative parenting by both parents contribute significantly to the unique environmental variance of problem behavior, although we did not find a clear pattern across age groups. Our study underlines the necessity of controlling for genetic confounding to uncover the truly environmentally mediated (and thus environmentally influenceable) pathways between parenting and problem behavior. A practical implication could be that it may be useful to primarily consider the child's perspective and focus on maternal as well as paternal parenting in interventions that address parenting to reduce problem behavior.

Thoraco-Omphalopagus Conjoined Twins: A Case Report.

A conjoined twin is an uncommon congenital condition that has a very high morbidity and mortality prevalence. Identical twins united in utero are known as conjoined twins. It's an uncommon occurrence that poses a special difficulty for paediatric surgeons and obstetricians. Conjoined twins are a complicated by-product of monozygotic twinning, which raises the risk of death in the womb. One of the more prevalent varieties of conjoined twins is the thoraco-omphalopagus type, in which the heart is involved in an anterior, chest-based fusion. This case involves a 26-year-old woman who was diagnosed at 19 weeks with conjoined thoraco-omphalopagus twins using ultrasonography.

Twin Study: Genetic and Epigenetic Factors Affecting Circulating Adiponectin Levels.

CONTEXT: Clarification of the association among phenotypes, genetic, and environmental factors with clinical laboratory traits can reveal the cause of diseases and assist in developing methods for the prediction and prevention of diseases. It is difficult to investigate the environmental effect on phenotypes using individual samples because their genetic and environmental factors differ, but we can easily investigate the influence of environmental factors using monozygotic (MZ) twins because they have the same genetic factors. OBJECTIVE: We aimed to examine the methylation level of CpG sites as an environmental factor affecting adiponectin levels on the basis of the same genetic background using MZ twins and to identify the epigenetic factors related to adiponectin levels and the genetic factors associated with sensitivity to acquired changes in adiponectin. METHODS: Using 2 groups built from each twin of 232 MZ twin pairs, we performed a replicated epigenome-wide association study to clarify the epigenetic factors affecting adiponectin levels adjusted by genetic risk score. Moreover, we divided twin pairs into concordant and discordant for adiponectin levels. We conducted a genome-wide association study to identify a genetic background specific for discordance. RESULTS: Methylation levels at 38 CpG sites were reproducibly associated with adjusted adiponectin levels, and some of these CpG sites were in genes related to adiponectin, including CDH13. Some genes related to adiponectin or insulin resistance were found to be genetic factors specific for discordance. CONCLUSION: We clarified specific epigenetic factors affecting adiponectin levels and genetic factors associated with sensitivity to acquired changes in adiponectin.

Phenotypic analysis of discordant monozygotic twins for pain-related temporomandibular joint disorder. Case report / Análise fenotípica de gêmeas monozigóticas discordantes para disfunção temporomandibular dolorosa. Relato de caso

ABSTRACT BACKGROUND AND OBJECTIVES: The design of research with monozygotic twins discordant for the disease has emerged as a powerful tool for the detection of phenotypic risk factors. The aim of this study is to report a clinical case of monozygotic twins discordant for pain-related temporomandibular joint disorder (TMD) from a cognitive-behavioral-emotional phenotypic analysis, from the comparison of clinical variables of pain, history of exposure to painful procedures in early childhood, and coping with pain. CASE REPORT: TMD-Twin presented a diagnosis of painful (myofascial pain with referral) and joint (disk displacement with reduction) TMD according to the criteria of the DC/TMD. Control-Twin did not show TMD, however she presented other chronic pains. TMD-Twin showed reduced pressure pain threshold, hyperalgesia in trigeminal and extra-trigeminal regions compared to the Control-Twin. TMD-Twin was more exposed to painful procedures and emotional events due to congenital heart problems. Both had central sensitization based on the Central Sensitization Inventory, although TMD-Twin had more catastrophic thoughts about pain. TMD-Twin presented an internal locus of control. CONCLUSION: Both monozygotic twins presented a chronic pain phenotype, although they were discordant with the TMD-related pain. The main differences were the lower pressure pain threshold and higher hyperalgesia locally presented by TMD-Twin. The internal locus of control indicates greater pain sensitivity, with better coping of the painful experience for the TMD-Twin. One possible explanation for this clinical condition can be that painful experiences in early childhood have shaped a phenotype of greater sensitivity with better coping and resilience to the painful condition.

RESUMO JUSTIFICATIVA E OBJETIVOS: O desenho da pesquisa com gêmeos monozigóticos discordantes para a doença surgiu como uma ferramenta poderosa para a detecção de fatores de risco fenotípicos. O objetivo deste estudo foi relatar um caso clínico de gêmeas monozigóticas discordantes para disfunção temporomandibular (DTM) dolorosa a partir de análise fenotípica cognitivo-comportamental-emocional entre elas, por meio de comparação de variáveis clínicas de dor, histórico de exposição a procedimentos dolorosos na primeira infância e enfrentamento de dor (autoeficácia e lócus de controle). RELATO DO CASO: A gêmea-DTM apresentou diagnóstico de DTM dolorosa (dor miofascial com referência) e articular (deslocamento do disco com redução) segundo os critérios do Critérios de Diagnóstico para Distúrbios Temporomandibulares. A gêmea--controle não apresentou DTM, contudo apresentou manifestação clínica de outras dores crônicas. A gêmea-DTM apresentou limiar de dor à pressão reduzido, hiperalgesia em regiões trigeminais/extra-trigeminais quando comparados à gêmea-controle, que na primeira infância foi mais exposta a procedimentos dolorosos devido a problemas cardíacos congênitos. Ambas apresentaram sensibilização central de acordo com o Inventário de Sensibilização Central, embora a gêmea-DTM apresentou mais pensamentos catastróficos sobre a dor. A gêmea-DTM apresentou lócus de controle interno. CONCLUSÃO: Ambas as gêmeas apresentaram fenótipo de dor crônica, apesar do fato de serem discordantes para a DTM. Dentre as avaliações, as que mais diferiram entre o par foram o baixo limiar de dor à pressão e hiperalgesia local presentes na gêmea com DTM. O lócus de controle interno associado à maior sensibilidade indicou melhor enfrentamento da experiência dolorosa para a gêmea-DTM. Uma possível explicação para esta manifestação clínica está pautada na hipótese de que experiências dolorosas na primeira infância vivenciadas por ela tenham moldado um fenótipo de maior sensibilidade com melhor enfrentamento e resiliência frente à condição dolorosa.

Developmental dysregulation of excitatory-to-inhibitory GABA-polarity switch may underlie schizophrenia pathology: A monozygotic-twin discordant case analysis in human iPS cell-derived neurons.

Schizophrenia is a major psychiatric disorder, but the molecular mechanisms leading to its initiation or progression remain unclear. To elucidate the pathophysiology of schizophrenia, we used an in vitro neuronal cell culture model involving human induced pluripotent stem cells (hiPSCs) derived from a monozygotic-twin discordant schizophrenia pair. The cultured neurons differentiated from hiPSCs were composed of a mixture of glutamatergic excitatory neurons and gamma aminobutyric acid (GABA)ergic inhibitory neurons. In the electrophysiological analysis, a different pattern of spontaneous neuronal activity was observed under the condition without any stimulants. The frequency of spontaneous excitatory post-synaptic currents (sEPSCs) was significantly higher in the hiPSC-derived neurons of the patient with schizophrenia than in the control sibling at day-in-vitro 30. However, the synaptic formation was not different between the patient with schizophrenia and the control sibling during the same culture period. To explain underlying mechanisms of higher excitability of presynaptic cells, we focused on the potassium-chloride co-transporter KCC2, which contributes to excitatory-to-inhibitory GABA polarity switch in developing neurons. We also revealed the altered expression pattern of KCC2 in hiPSC-derived neurons from the patient with schizophrenia, which could contribute to understanding the pathology of schizophrenia in the developing nervous system.

Severity of Idiopathic Scoliosis Is Associated with Differential Methylation: An Epigenome-Wide Association Study of Monozygotic Twins with Idiopathic Scoliosis.

Epigenetic mechanisms may contribute to idiopathic scoliosis (IS). We identified 8 monozygotic twin pairs with IS, 6 discordant (Cobb angle difference > 10°) and 2 concordant (Cobb angle difference ≤ 2°). Genome-wide methylation in blood was measured with the Infinium HumanMethylation EPIC Beadchip. We tested for differences in methylation and methylation variability between discordant twins and tested the association between methylation and curve severity in all twins. Differentially methylated region (DMR) analyses identified gene promoter regions. Methylation at cg12959265 (chr. 7 DPY19L1) was less variable in cases (false discovery rate (FDR) = 0.0791). We identified four probes (false discovery rate, FDR < 0.10); cg02477677 (chr. 17, RARA gene), cg12922161 (chr. 2 LOC150622 gene), cg08826461 (chr. 2), and cg16382077 (chr. 7) associated with curve severity. We identified 57 DMRs where hyper- or hypo-methylation was consistent across the region and 28 DMRs with a consistent association with curve severity. Among DMRs, 21 were correlated with bone methylation. Prioritization of regions based on methylation concordance in bone identified promoter regions for WNT10A (WNT signaling), NPY (regulator of bone and energy homeostasis), and others predicted to be relevant for bone formation/remodeling. These regions may aid in understanding the complex interplay between genetics, environment, and IS.

Associations Between Parental Psychopathic Traits, Parenting, and Adolescent Callous-Unemotional Traits.

Callous-unemotional (CU) traits (i.e., callousness, low empathy, shallow affect) have been conceptualized as a downward extension of the interpersonal and affective components of adult psychopathy and are associated with stable and severe antisocial behavior. Research suggests that CU traits are moderately heritable, but also influenced by environmental factors, particularly parenting. We examined associations among mother and father psychopathic traits, parenting practices, and offspring CU traits in a community sample of 550 adolescent twins (Mean age = 13.99 years; SD 2.37; 56.4% male), incorporating multiple informants (mothers, fathers, child). Parental interpersonal-affective psychopathic traits were associated with adolescent CU traits and negative parenting (increased harshness, reduced warmth). Moreover, increased parental harshness and reduced warmth partially explained associations between parental interpersonal-affective traits and adolescent CU traits. There was also a significant direct effect specifically between mother interpersonal-affective traits and adolescent CU traits. Finally, using a twin difference design, we confirmed that adolescent CU traits were significantly impacted by non-shared environmental parenting influences (increased harshness, reduced warmth). These results suggest that mother and father interpersonal-affective traits appear to impact parenting practices and serve as risk factors for adolescent CU traits. However, many of the findings did not replicate when using cross-informant reports and were only present within single informant models, highlighting a role for shared informant variance as well. The results suggest the importance of accounting for parent personality in the development of effective parenting interventions for CU traits.

Equivalent DNA methylation variation between monozygotic co-twins and unrelated individuals reveals universal epigenetic inter-individual dissimilarity.

BACKGROUND: Although the genomes of monozygotic twins are practically identical, their methylomes may evolve divergently throughout their lifetime as a consequence of factors such as the environment or aging. Particularly for young and healthy monozygotic twins, DNA methylation divergence, if any, may be restricted to stochastic processes occurring post-twinning during embryonic development and early life. However, to what extent such stochastic mechanisms can systematically provide a stable source of inter-individual epigenetic variation remains uncertain until now. RESULTS: We enriched for inter-individual stochastic variation by using an equivalence testing-based statistical approach on whole blood methylation microarray data from healthy adolescent monozygotic twins. As a result, we identified 333 CpGs displaying similarly large methylation variation between monozygotic co-twins and unrelated individuals. Although their methylation variation surpasses measurement error and is stable in a short timescale, susceptibility to aging is apparent in the long term. Additionally, 46% of these CpGs were replicated in adipose tissue. The identified sites are significantly enriched at the clustered protocadherin loci, known for stochastic methylation in developing neurons. We also confirmed an enrichment in monozygotic twin DNA methylation discordance at these loci in whole genome bisulfite sequencing data from blood and adipose tissue. CONCLUSIONS: We have isolated a component of stochastic methylation variation, distinct from genetic influence, measurement error, and epigenetic drift. Biomarkers enriched in this component may serve in the future as the basis for universal epigenetic fingerprinting, relevant for instance in the discrimination of monozygotic twin individuals in forensic applications, currently impossible with standard DNA profiling.

The Role of Remembered Parenting on Adult Self-Esteem: A Monozygotic Twin Difference Study.

Self-esteem is an attitude about the self that predicts psychopathology and general well-being. Parenting practices have been shown to be related to self-esteem, but these estimates are confounded because parents and children share genes. The aim of the present study was to use the monozygotic (MZ) twin difference design to isolate the non-shared environmental impact of remembered parenting on self-esteem. In a sample of 1328 adults (345 MZ twin pairs, 319 DZ twin pairs), retrospective reports of maternal and paternal affection were related to self-esteem, all of which were significantly heritable. Using MZ difference scores, paternal affection differences, but not maternal affection differences, were significantly related to self-esteem differences. These results suggest that parenting provided by the father directly impacts self-esteem through non-shared environmental mechanisms. Maternal affection, on the other hand, impacts self-esteem through shared genes (not shared environment, as shared environment was not a significant aspect of self-esteem). This has implications for parenting intervention programs.

Unraveling the Genetics of Congenital Diaphragmatic Hernia: An Ongoing Challenge.

Congenital diaphragmatic hernia (CDH) is a congenital structural anomaly in which the diaphragm has not developed properly. It may occur either as an isolated anomaly or with additional anomalies. It is thought to be a multifactorial disease in which genetic factors could either substantially contribute to or directly result in the developmental defect. Patients with aneuploidies, pathogenic variants or de novo Copy Number Variations (CNVs) impacting specific genes and loci develop CDH typically in the form of a monogenetic syndrome. These patients often have other associated anatomical malformations. In patients without a known monogenetic syndrome, an increased genetic burden of de novo coding variants contributes to disease development. In early years, genetic evaluation was based on karyotyping and SNP-array. Today, genomes are commonly analyzed with next generation sequencing (NGS) based approaches. While more potential pathogenic variants are being detected, analysis of the data presents a bottleneck-largely due to the lack of full appreciation of the functional consequence and/or relevance of the detected variant. The exact heritability of CDH is still unknown. Damaging de novo alterations are associated with the more severe and complex phenotypes and worse clinical outcome. Phenotypic, genetic-and likely mechanistic-variability hampers individual patient diagnosis, short and long-term morbidity prediction and subsequent care strategies. Detailed phenotyping, clinical follow-up at regular intervals and detailed registries are needed to find associations between long-term morbidity, genetic alterations, and clinical parameters. Since CDH is a relatively rare disorder with only a few recurrent changes large cohorts of patients are needed to identify genetic associations. Retrospective whole genome sequencing of historical patient cohorts using will yield valuable data from which today's patients and parents will profit Trio whole genome sequencing has an excellent potential for future re-analysis and data-sharing increasing the chance to provide a genetic diagnosis and predict clinical prognosis. In this review, we explore the pitfalls and challenges in the analysis and interpretation of genetic information, present what is currently known and what still needs further study, and propose strategies to reap the benefits of genetic screening.

Monozygotic dichorionic-diamniotic twin pregnancy after single embryo transfer at blastocyst stage: a case report.

Single embryo transfer is highly encouraged on in vitro fertilization due to its lower rates of multiple pregnancy. Nevertheless, the likelihood of multiple pregnancy is higher when using assisted reproductive technology, probably because of embryo handling. Timing is crucial in the post-fertilization division of a single embryo to establish the amniocity and chorionicity of the gestation. In the case reported a 38 year-old woman, nulligravid, had a single blastocyst implanted, which resulted in monozygotic dichorionic-diamniotic twins. Despite being rare, there are reports of similar cases questioning the current knowledge on time of embryo division and the impact of assisted reproduction.

Associations of sleep with psychological problems and well-being in adolescence: causality or common genetic predispositions?

BACKGROUND: Whereas short and problematic sleep are associated with psychological problems in adolescence, causality remains to be elucidated. This study therefore utilized the discordant monozygotic cotwin design and cross-lagged models to investigate how short and problematic sleep affect psychological functioning. METHODS: Adolescent twins (N = 12,803, 13-20 years, 42% male) completed questionnaires on sleep and psychological functioning repeatedly over a two-year interval. Monozygotic twin pairs were classified as concordant or discordant for sleep duration and trouble sleeping. Resulting subgroups were compared regarding internalizing problems, externalizing problems, and subjective well-being. RESULTS: Cross-sectional analyses indicated associations of worse psychological functioning with both short sleep and problematic sleep, and cross-lagged models indicate bidirectional associations. Longitudinal analyses showed that an increase in sleep problems experienced selectively by one individual of an identical twin pair was accompanied by an increase of 52% in internalizing problem scores and 25% in externalizing problem scores. These changes were significantly different from the within-subject changes in cotwins with unchanged sleep quality (respectively, 3% increase and 5% decrease). Psychological functioning did, however, not worsen with decreasing sleep duration. CONCLUSIONS: The findings suggest that sleep quality, rather than sleep duration, should be the primary target for prevention and intervention, with possible effect on psychological functioning in adolescents.

Decreased analgesic requirement in recipient of liver transplantation from monozygotic twin - A case report.

BACKGROUND: There have been many reports about decreased analgesic requirements in liver transplant recipients compared with patients undergoing other abdominal surgery. CASE: Herein we describe a case in which a 42-year-old man underwent living donor liver transplantation from his monozygotic twin. Because innate pain thresholds may be similar in monozygotic twins, we could effectively investigate postoperative pain in the donor and the recipient. Concordant with previous reports, the recipient used less analgesic than the donor in the present study. CONCLUSIONS: Physicians caring for patients who have received liver transplantation should consider their comparatively low requirement for analgesic, to prevent delayed recovery due to excessive use of analgesic.

Application of intraoral scanner to identify monozygotic twins.

BACKGROUND: DNA base identification is a proper and high specificity method. However, identification could be challenged in a situation where there is no database or the DNA sequence is almost identical, as in the case of monozygotic (MZ) twins. The aim of this study was to introduce a novel forensic method for distinguishing between almost identical MZ twins by means of an intraoral scanner using the 3D digital pattern of the human palate. METHODS: The palatal area of 64 MZ twins and 33 same-sex dizygotic (DZ) twins (DZSS) and seven opposite-sex dizygotic twins (DZOS) were scanned three times with an intraoral scanner. From the scanned data, an STL file was created and exported into the GOM Inspect® inspection software. All scans within a twin pair were superimposed on each other. The average deviation between scans of the same subject (intra-subject deviation, ISD) and between scans of the two siblings within a twin pair (intra-twin deviation, ITD) was measured. One-sided tolerance interval covering 99% of the population with 99% confidence was calculated for the ISD (upper limit) and the ITD (lower limit). RESULTS: The mean ISD of the palatal scan was 35.3 µm ± 0.78 µm. The calculated upper tolerance limit was 95 µm. The mean ITD of MZ twins (406 µm ± 15 µm) was significantly (p < 0.001) higher than the ISD, and it was significantly lower than the ITD of DZSS twins (594 µm ± 53 µm, p < 0.01) and the ITD of DZOS twins (853 µm ± 202 µm, p < 0.05). CONCLUSION: The reproducibility of palatal intraoral scans proved to be excellent. The morphology of the palate shows differences between members of MZ twins despite their almost identical DNA, indicating that this method could be useful in forensic odontology.

Phenotypic variance in monozygotic twins with SCA3.

BACKGROUND: Spinocerebellar ataxia type 3 (SCA3) is a hereditary neurodegenerative disorder with high clinical heterogeneity. Twin study is valuable to estimate the contributions of gene and/or environment to phenotypic variance. However, SCA3 twins were extremely sparse and rarely reported. METHODS: A pair of monozygotic twins with SCA3 was assessed using well-acknowledged scales. Genetic modifiers and methylation levels were determined by Sanger sequencing and pyrosequencing. RESULTS: Sharing identical CAG repeat lengths, the twins presented with similar symptoms, whereas, the younger sister had an earlier age at onset of two years. The occurrence time and severity of constipation, blepharospasm and fasciculation were markedly different between the twins. Notable methylation level differences of several CpG sites existed between the twins. CONCLUSIONS: It is the first time to report SCA3 monozygotic twin worldwide. The role of epigenetic factors in the phenotype variance deserved more attention. The DNA methylation may influence the phenotypic variance by altering the occurrence time and severity of symptoms, indicating its potential in alleviating the disease.