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While reports of twin pairs concordant for insanity began to appear in the 19th century, the first modern psychiatric twin study that fulfilled Galton’s 1875 promise of the value of the twin method was published by the German Psychiatrist and Geneticist Hans Luxenburger in 1928. Luxenburger introduced four major methodological advances: the use of representative sampling, proband-wise concordance, rigorous zygosity diagnoses, and age correction. He used a narrow Kraepelinian diagnostic approach diagnosis and ascertained twins hospitalized, on a specific day, in all large Bavarian asylums. We include a brief biography of Luxenburger, summarize the findings of his paper and provide a full English translation in the appendix. Luxenburger presents evidence that the frequency of twinning in those with severe mental illness were as expected and reports proband-wise concordance for probable and definite dementia praecox (MZ—76%, DZ—0%) and manic-depressive insanity (MZ—75%, DZ—0%). He also examined eccentricity and hyperthymic or hypothymic personality in the dementia praecox and manic-depressive pairs, respectively. Luxenburger’s substantial contributions to the history of psychiatric genetics should be considered in the context of his intimate but ambivalent relationship with the racial-hygiene policy of the German National Socialists.

Background: It is unknown if genetics contribute to the etiology of acute Achilles tendon rupture (ATR). The aims of the present study were, 1) To calculate the concordance rate for monozygotic (MZ) twins and same-sex dizygotic (SSDZ) twins and 2) to estimate the heritability of ATR. Methods: The study was performed as a registry study using the Danish Twin Registry and the Danish National Patient Registry. Results: The study sample consisted of 85,534 twins born from 1895 to 1995. Of these, 572 (0.67%) were registered with ATR in the period from 1994 to 2014. The concordance rate was 8.1% (95% CI 1.4–14.7%) for MZ twins and 4.3% (95% CI 0.7–7.9%) for SSDZ twins. The heritability of ATR was 47% (95% CI 31–62%). Conclusion: This study found that genetics contribute substantially to the etiology of ATR with an estimated heritability of the liability to ATR of approximately 50%. The finding generates the hypothesis that genetics play a role in the pathological changes that occur in the Achilles tendon before a rupture. The risk of ATR for a twin within a 20 year period, if the co-twin has had an ATR, was 8% for MZ twins and 4% for SSDZ twins.

One of the hallmarks of twin pregnancies is the slower rate of fetal growth when compared with singleton pregnancies during the third trimester. The mechanisms underlying this phenomenon and whether it represents pathology or benign physiological adaptation are currently unclear. One important implication of these questions relates to the type growth charts that should be used by care providers to monitor growth of twin fetuses. If the slower growth represents pathology (ie, intrauterine growth restriction caused uteroplacental insufficiency), it would be preferable to use a singleton growth chart to identify a small twin fetus that is at risk for perinatal mortality and morbidity. If, however, the relative smallness of twins is the result of benign adaptive mechanisms, it is likely preferable to use a twin-based charts to avoid overdiagnosis of intrauterine growth restriction in twin pregnancies. In the current review, we addressed this question by describing the differences in fetal growth between twin and singleton pregnancies, reviewing the current knowledge regarding the mechanisms responsible for slower fetal growth in twins, summarizing available empirical evidence on the diagnostic accuracy of the 2 types of charts for intrauterine growth restriction in twin pregnancies, and addressing the question of whether uncomplicated dichorionic twins are at an increased risk for fetal death when compared with singleton fetuses. We identified a growing body of evidence that shows that the use of twin charts can reduce the proportion of twin fetuses identified with suspected intrauterine growth restriction by up to 8-fold and can lead to a diagnosis of intrauterine growth restriction that is more strongly associated with adverse perinatal outcomes and hypertensive disorders than a diagnosis of intrauterine growth restriction based on a singleton-based chart without compromising the detection of twin fetuses at risk for adverse outcomes caused by uteroplacental insufficiency. We further found that small for gestational age twins are less likely to experience adverse perinatal outcomes or to have evidence of uteroplacental insufficiency than small for gestational age singletons and that recent data question the longstanding view that uncomplicated dichorionic twins are at an increased risk for fetal death caused by placental insufficiency. Overall, it seems that, based on existing evidence, the of use twin charts is reasonable and may be preferred over the use of singleton charts when monitoring the growth of twin fetuses. Still, it is important to note that the available data have considerable limitations and are primarily derived from observational studies. Therefore, adequately-powered trials are likely needed to confirm the benefit of twin charts before their use is adopted by professional societies.

The relationship between pitch-naming ability and childhood onset of music training is well established and thought to reflect both genetic predisposition and music training during a critical period. However, the importance of the amount of practice during this period has not been investigated. In a population sample of twins (N = 1447, 39% male, 367 complete twin pairs) and a sample of 290 professional musicians (51% male), we investigated the role of genes, age of onset of playing music and accumulated childhood practice on pitch-naming ability. A significant correlation between pitch-naming scores for monozygotic (r = .27, p < .001) but not dizygotic twin pairs (r = −.04, p = .63) supported the role of genetic factors. In professional musicians, the amount of practice accumulated between ages 6 and 11 predicted pitch-naming accuracy (p = .025). In twins, age of onset was no longer a significant predictor once practice was considered. Combined, these findings are in line with the notion that pitch-naming ability is associated with both genetic factors and amount of early practice, rather than just age of onset per se. This may reflect a dose–response relation between practice and pitch-naming ability in genetically predisposed individuals. Alternatively, children who excel at pitch-naming may have an increased tendency to practice.

In this essay, the bioethical implications of the recent genetic manipulation in human embryos with CRISPR-Cas9 to eliminate the CCR5 gene and the birth of a pair of discordant twin girls are analyzed. The experiment was disseminated via social media. The main bioethical flaws identified include the justification of the model, the informed consent process and the lack of disclosure of evident conflicts of interest. The consequences of the experiment on the life of the twins that were born were not properly evaluated, such as the impact on their autonomy, the alleged benefits to be received and the future risks of harm during their lifetime. Having manipulated the germ cell line, the effects on their future offspring were not considered. This type of actions negatively affects the way society conceives science. Genetic engineering should be reserved to the basic experimental context or as clinical research for the correction of known serious diseases of genetic origin under strict regulatory and bioethical supervision and using a gradualist approach in accordance with the advances of gene editing techniques.En este ensayo se analizan las implicaciones bioéticas de la reciente manipulación genética en embriones humanos con CRISPR-Cas9 para eliminar el gen CCR5 y el nacimiento de dos gemelas discordantes. El experimento se divulgó en medios sociales. Los principales problemas bioéticos identificados son la justificación del modelo, el proceso de consentimiento informado y la falta de declaración de evidentes conflictos de interés. No se evaluaron apropiadamente las consecuencias del experimento sobre la vida de las gemelas nacidas como la afectación a su autonomía, los supuestos beneficios por recibir y los riesgos futuros de daño durante su vida. Habiendo manipulado la línea celular germinal, no se consideraron los efectos sobre su descendencia futura. Este tipo de acciones tiene un impacto negativo en la forma como la sociedad concibe la ciencia. La ingeniería genética debe reservarse al contexto experimental básico o bien como investigación cínica para la corrección de enfermedades conocidas graves de origen genético, bajo estricta supervisión regulatoria y bioética y de manera gradualista de acuerdo con el progreso de las técnicas de edición genética.

Congenital heart defects have been associated with adverse neurodevelopmental outcomes due to factors that result in a hypoxic-ischemic cerebral cumulative effect. We present a pair of fraternal twins: the first twin was healthy, and the second was born with a complex congenital heart defect (CCHD). They were followed for growth and neurodevelopmental outcomes to determine the comparative effect of exposure to a CCHD. Results show that exposure to a CCHD could be related to a persistent motor deficiency with hypotonia and concurrent height for age delay. CCHD requires a comprehensive neurodevelopmental approach; the pathophysiology and the surrounding stimuli are influential.

Keeping appropriate interpersonal distance is an evolutionary conserved behavior that can be adapted based on learning. Detailed knowledge on how interpersonal space is represented in the brain and whether such representation is genetically influenced is lacking. We measured brain function using functional magnetic resonance imaging in 294 twins (71 monozygotic, 76 dizygotic pairs) performing a distance task where neural responses to human figures were compared to cylindrical blocks. Proximal viewing distance of human figures was compared to cylinders facilitated responses in the occipital face area (OFA) and the superficial part of the amygdala, which is consistent with these areas playing a role in monitoring interpersonal distance. Using the classic twin method, we observed a genetic influence on interpersonal distance related activation in the OFA, but not in the amygdala. Results suggest that genetic factors may influence interpersonal distance monitoring via the OFA whereas the amygdala may play a role in experience-dependent adjustments of interpersonal distance.

To develop a nomogram of the thickness of the umbilical cord (UC) and its components in monochorionic diamniotic (MCDA) twin pregnancies.This prospective longitudinal study involved 47 MCDA twin pregnancies (94 fetuses) between 18 and 33 weeks of gestation. Ultrasound assessments of UC cross-sections and measurements of the umbilical cord area (UCA), the umbilical vein area (UVA), the umbilical artery area (UAA), and the Wharton jelly area (WJA) were made. The UC measurements were correlated with gestational ages. Reference values for the gestational ages of MCDA pregnancies were determined and compared with those of dichorionic twins and singletons. The cases which developed selective intrauterine growth restriction were contrasted with normal cases.A positive correlation was found between all UC components and gestational age and fetal weight. The UCA of MCDA fetuses was significantly larger than that of DC fetuses (p 0.001) at the expense of a larger WJA (p 0.001) and similar to that of singleton pregnancies. The MCDA fetuses with an estimated fetal weight below the 10th percentile had a smaller UCA than fetuses with a normal estimated weight (p 0.001).The MCDA twins exhibited a thicker UC than that of dichorionic twins.

It is widely recognized that dizygotic twinning (DZT) runs in families, but estimates of heritability from twin and family data are remarkably scarce and vary considerably. Here, we traced seven large, sometimes historical, multigeneration pedigrees from West Africans, fin de siècle French Jews, Canadians (two pedigrees), and the French royal family, in which twin births were recorded. We estimated heritability of twinning (of all types) as zygosity information was not available, diluting the true DZT heritability by a third or so. The estimates in the range 8−20% are remarkably consistent across time (8−19 generations) and ethnicities and also consistent with twin and family estimates.

We report on the functional connectivity (FC), its intraclass correlation (ICC), and heritability among 70 areas of the human cerebral cortex. FC was estimated as the Pearson correlation between averaged prewhitened Blood Oxygenation Level-Dependent time series of cortical areas in 988 young adult participants in the Human Connectome Project. Pairs of areas were assigned to three groups, namely homotopic (same area in the two hemispheres), ipsilateral (both areas in the same hemisphere), and heterotopic (nonhomotopic areas in different hemispheres). ICC for each pair of areas was computed for six genetic groups, namely monozygotic (MZ) twins, dizygotic (DZ) twins, singleton siblings of MZ twins (MZsb), singleton siblings of DZ twins (DZsb), non-twin siblings (SB), and unrelated individuals (UNR). With respect to FC, we found the following. (a) Homotopic FC was stronger than ipsilateral and heterotopic FC; (b) average FCs of left and right cortical areas were highly and positively correlated; and (c) FC varied in a systematic fashion along the anterior-posterior and inferior-superior dimensions, such that it increased from anterior to posterior and from inferior to superior. With respect to ICC, we found the following. (a) Homotopic ICC was significantly higher than ipsilateral and heterotopic ICC, but the latter two did not differ significantly from each other; (b) ICC was highest for MZ twins; (c) ICC of DZ twins was significantly lower than that of the MZ twins and higher than that of the three sibling groups (MZsb, DZsb, SB); and (d) ICC was close to zero for UNR. Finally, with respect to heritability, it was highest for homotopic areas, followed by ipsilateral, and heterotopic; however, it did not differ statistically significantly from each other.

Although polygenic risk scores (PRS) predict psychiatric problems, these associations might be attributable to indirect pathways including population stratification, assortative mating, or dynastic effects (mediation via parental environments). The goal of this study was to examine whether PRS-psychiatric symptom associations were attributable to indirect versus direct pathways.The sample consisted of 3,907 dizygotic (DZ) twin pairs. In childhood, their parents rated them on 98 symptoms. In adolescence (n = 2,393 DZ pairs), both the parents and the twins rated themselves on 20 symptoms. We extracted one general and seven specific factors from the childhood data, and one general and three specific factors from the adolescent data. We then regressed each general factor model onto ten psychiatric PRS simultaneously. We first conducted the regressions between individuals (β) and then within DZ twin pairs (βIn childhood, the PRS for ADHD predicted general psychopathology (β = 0.09, 95% CI: [0.06, 0.12]; βThis implies that PRS-psychiatric symptom associations did not appear attributable to indirect pathways such as population stratification, assortative mating, or mediation via parental environments. Rather, genetics appeared to directly influence symptomatology.

It is challenging to evaluate the genetic impacts on a biologic feature and separate them from environmental impacts. This is usually achieved through twin studies by assessing the collective genetic impact defined by the differential correlation in monozygotic twins vs dizygotic twins. Since the underlying order in a twin, determined by latent genetic factors, is unknown, the observed twin data are unordered. Conventional methods for correlation are not appropriate. To handle the missing order, we model twin data by a mixture bivariate distribution and estimate under two likelihood functions: the likelihood over the monozygotic and dizygotic twins separately, and the likelihood over the two twin types combined. Both likelihood estimators are consistent. More importantly, the combined likelihood overcomes the drawback of mixture distribution estimation, namely, the slow convergence. It yields correlation coefficient estimator of root-n consistency and allows effective statistical inference on the collective genetic impact. The method is demonstrated by a twin study on immune traits.

Gilles de la Tourette Syndrome (GTS) is a multifactorial neurodevelopmental disorder characterized by tics and multiple comorbidities. The pathophysiology is not yet fully understood, but both environmental and genetic risk factors seem to be involved. Twin studies provide important knowledge on genetic factors. We assessed the concordance of GTS and chronic tic disorders (CTD) in monozygotic (MZ) twins, and examined tic severity, symptoms of obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder and autism spectrum disorder. Twin pairs, where at least one twin was diagnosed with any tic disorder, were identified through Danish Twin Registry, Psychiatric Central Registry, Danish National Patient Registry and National Tourette Clinic, Copenhagen University Hospital, Herlev. Zygosity was tested with single-nucleotide polymorphism (SNP) genotyping and clinical assessment was done with validated tools. 14 MZ twin pairs were included: five were discordant. Seven twin pairs were concordant for GTS, and for two pairs one twin had GTS and the other CTD. Among the twins with CTD or GTS, 50% had at least one comorbidity, which is higher than in background populations. The GTS + OCD-phenotype was significantly more frequent among GTS-concordant than among discordant twins. No statistically significant differences were found between the GTS-concordant and discordant twin pairs regarding tic severity or comorbidities. Thorough clinical assessment and SNP-based genotyping are important when conducting clinical twin studies. We found high concordance of GTS and CTD, which supports the notion that both disorders have common genetic risk factors. Further studies with larger cohorts including dizygotic twins are warranted for more conclusive results.

Data from the Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium were used to examine predictions of different models of gene by environment interaction to understand how genetic variance in self-rated health (SRH) varies at different levels of financial strain. A total of 11,359 individuals from 10 twin studies in Australia, Sweden and the United States contributed relevant data, including 2074 monozygotic and 2623 dizygotic twin pairs. Age ranged from 22-98 years, with a mean age of 61.05 (sd = 13.24). A factor model was used to create a harmonized measure of financial strain across studies and items. Twin analysis of genetic and environmental variance for SRH incorporating age, age(2), sex, and financial strain moderators indicated significant financial strain moderation of genetic influences on self-rated health. Moderation results did not differ across sex or country. Genetic variance for SRH increased as financial strain increased, matching the predictions of the diathesis-stress and social comparison models for components of variance. Under these models, environmental improvements would be expected to reduce genetically based health disparities.

BACKGROUND: Educational attainment is connected to many important life outcomes, and the previous research has already focused on identifying its genetic and environmental components. However, most of these studies used twin data only and did not incorporate information from other family members. Twin studies typically decompose the phenotypic variance into genetic, shared, and unique environment components. In this study design, the shared environment component encompasses the influence of parents and the shared environments of twins and siblings independent of parents (e.g., teachers, schools, and peers). The classical twin design (CTD) conflates these influences as part of the shared environment. This shortcoming can be overcome using the nuclear twin family design (NTFD), which enables separation of the parental and shared twin/sibling environmental components.; AIMS: The aim of this study was to broaden the understanding of the aetiology of educational attainment using the nuclear twin family design to provide a detailed account of the genetic and environmental effects on the type of school leaving certificate.; SAMPLE: The data of 1,048 monozygotic and 916 dizygotic same-sex twins, their biological parents, and non-twin full biological siblings of the German project TwinLife were used in the nuclear twin family design.; METHODS: Structural equationmodelling (SEM) techniques were used to analyse the variance-covariance patterns of the ordinal outcome variable.; RESULTS: Genetic influences were found to make up around 60% of variance, whilst environmental influences shared by all siblings, educational influences shared by the twins only, and non-shared environmental influences explained the remaining variance in equal amounts. Environmental transmission from parent to offspring was found to be negligible.; CONCLUSION: Through its advanced design, our study extends the previous work enabling more detailed and robust estimations of sources of variance and contributes to a better understanding of the complex aetiology of educational attainment. © 2021 The Authors. British Journal of Educational Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

Although twins often participate in medical research, few clinical trials are conducted entirely in twin populations. The purpose of this review is to demonstrate the substantial benefits and address the key challenges of conducting clinical trials in twin populations, or ‘twin-only trials’. We consider the unique design, analysis, recruitment and ethical issues that arise in such trials. In particular, we describe the different approaches available for randomizing twin pairs, highlight the similarity or correlation that exists between outcomes of twins, and discuss the impact of this correlation on sample size calculations and statistical analysis methods for estimating treatment effects. We also consider the role of both monozygotic and dizygotic twins for studying variation in outcomes, the factors that may affect recruitment of twins, and the ethics of conducting trials entirely in twin populations. The advantages and disadvantages of conducting twin-only trials are also discussed. Finally, we recommend that twin-only trials should be considered more often.

1. Nicola Natsis, MD*,†,‡ 2. Fred Soeprono, MD, JD†,‡ 3. Aislyn Nelson, MD, PhD†,‡ 4. Victoria R. Barrio, MD†,‡ 5. Wynnis L. Tom, MD†,‡ 1. *School of Medicine, University of California, San Diego, San Diego, CA 2. †Division of Pediatric and Adolescent Dermatology, Rady Children’s Hospital, San Diego, CA 3. ‡Department of Dermatology, University of California, San Diego, San Diego, CA A boy is born at 27 weeks’ gestation with generalized erosions of the skin, facial bruising, respiratory distress, hypotension, and poor tone. His fraternal twin brother is without any skin abnormalities. Their 20-year-old Gravida 2 Para 1 mother had no complications during pregnancy and no history of sexually transmitted infections. Prenatal testing from an outside hospital was negative for syphilis, chlamydia, hepatitis B, and hepatitis C. She presented in preterm labor and was treated with steroids, magnesium, and terbutaline. Cesarean delivery was performed prior to rupture of membranes, reportedly because the infants were each in the frank breech position and this twin was having decelerations on the fetal heart tracing. The newborn’s Apgar scores are 3, 5, and 7 at 1, 5, and 10 minutes. Due to his skin erosions and prematurity, he is treated with ampicillin and cefotaxime. On day 3, he is transferred to our facility for a higher level of care. His examination reveals dry, diffuse superficial erosions on the neck, trunk, and extremities (Figs 1 and 2). Many lesions are geometric, with some more linear and angulated on the arms and legs. The back has scattered adherent hemorrhagic crusts. He also has thrombocytopenia at 52,000 platelets/mcL, hyperbilirubinemia (total/direct bilirubin 5.2/2.9 mg/dL), elevated C-reactive protein to 5.9 mg/L, and hypertriglyceridemia to 133 mg/dL. His white blood cell count and differential is normal. Additional testing confirmed the diagnosis. Figure 1. A 3-day-old boy with diffuse erosions with superficial crusting, many geometric or linear. Figure 2. Left leg with diffuse erosions with superficial crusting, many geometric or linear. The differential diagnosis for this rash includes infections such as congenital candidiasis, Staphylococcus aureus , Streptococcus pyogenes , varicella zoster virus (VZV), syphilis, and herpes simplex virus (HSV) infection. Noninfectious etiologies include …

Electroencephalography (EEG) signals measured under fixed conditions have been exploited as biometric identifiers. However, what contributes to the uniqueness of one's brain signals remains unclear. In the present research, we conducted a multi-task and multi-week EEG study with ten pairs of monozygotic (MZ) twins to examine the nature and components of person-identifiable brain signals. Through machine-learning analyses, we uncovered a person-identifying EEG component that served as "base signals" shared across tasks and weeks. Such task invariance and temporal stability suggest that these person-identifying EEG characteristics are more of structural brainprints than functional mindprints. Moreover, while these base signals were more similar within than between MZ twins, it was still possible to distinguish twin siblings, particularly using EEG signals coming primarily from late rather than early developed areas in the brain. Besides theoretical clarifications, the discovery of the EEG base signals has practical implications for privacy protection and the application of brain-computer interfaces.

Introduction: White matter hyperintensities (WMH) indicate white matter brain lesions in magnetic resonance imaging (MRI), which can be used as a marker for brain aging and cerebrovascular and neurodegenerative disorders. Twin studies revealed substantial but not uniform WMH heritability in elderly twins. The objective of our study was to investigate the genetic and environmental components of WMH, as well as their importance in a healthy twin population, utilizing 3T MRI scanners in a middle-aged twin population. Methods: Brain MRI was performed on 120 healthy adult twins from the Hungarian Twin Registry on a 3T scanner (86 monozygotic, MZ and 34 dizygotic, DZ twins; median age 50 ± 26.5 years, 72.5% female and 27.5% male). The count of WMH on FLAIR images was calculated using an automated volumetry pipeline (volBrain) and human processing. The age- and sex-adjusted MZ and DZ intra-pair correlations were determined and the total variance was decomposed into genetic, shared and unique environmental components using structural equation modeling. Results: Age and sex-adjusted MZ intrapair correlations were higher than DZ correlations, indicating moderate genetic influence in each lesion (rMZ = 0.466, rDZ = −0.025 for total count; rMZ = 0.482, rDZ = 0.093 for deep white matter count; rMZ = 0.739, rDZ = 0.39 for infratentorial count; rMZ = 0.573, rDZ = 0.372 for cerebellar count and rMZ = 0.473, rDZ = 0.19 for periventricular count), indicating a moderate heritability (A = 40.3%, A = 45%, A = 72.7% and A = 55.5%and 47.2%, respectively). The rest of the variance was influenced by unique environmental effects (E between 27.3% and 59.7%, respectively). Conclusions: The number of WMH lesions is moderately influenced by genetic effects, particularly in the infratentorial region in middle-aged twins. These results suggest that the distribution of WMH in various brain regions is heterogeneous.

Every reared-apart monozygotic (MZ) twin pair offers a fresh perspective on human developmental questions. This is true regardless of whether the co-twins were raised in the same country or across the globe. The members of two pairs of separated MZ female twins have recently come to attention. In one case the twins were raised by different families in Argentina; in the other case the twins were raised by different families in Sweden and Vietnam. The perceptions and perspectives of these twins are insightful. The twin research section that follows begins with a tribute to our late esteemed colleague, Dr Isaac Blickstein (1953−2020). Research concerning the infanticide and sacrifice of Archaic-aged twins and triplets and prehistoric twin burials is reviewed next. Highlights from a conference focused on the 2018 film Three Identical Strangers are also included in this portion. The final section of this article includes media reports of an atypical twin father, an actor’s twin brother, a twin link to the 1921 Tulsa, Oklahoma massacre, the birth of superfetated twins, twin comedians and script writers and Indian twins’ tragic loss to COVID-19.

OBJECTIVE Prior research has found a positive association between the quality or adjustment of an individual's intimate relationship, such as marriage, and their physical health. However, it is possible that this association may be due, at least in part, to confounding variables (i.e., variables that are causally associated both with relationship adjustment and health and could account for their covariation), including genetically influenced confounds. This study was conducted using a genetically informative sample of twins to examine the association between intimate relationship adjustment and self-rated health, accounting for unmeasured genetic and environmental confounds. METHOD A Swedish sample of 539 monozygotic and dizygotic twins (321 male twin pairs and 218 female twin pairs) and their spouse or long-term partner completed self-report measures of relationship adjustment and health. RESULTS Relationship adjustment was positively associated with self-rated health in male and female twins. For male twins, nonshared environmental influences largely accounted for the association between relationship adjustment and health; for female twins, this association was generally explained by shared and nonshared environmental influences. For male twins, results obtained from partners' reports of relationship adjustment were largely consistent with those obtained from twins' reports. CONCLUSIONS Results suggest that the association between relationship adjustment and self-rated health remains after accounting for shared genetic influences, and that nonshared environmental influences, such as partners' characteristics, account for the association between relationship adjustment and self-rated health in men. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Data on the etiological factors underlying the co-occurrence of common adolescent pain with anxiety and depression symptoms are very limited. Opioid prescriptions for adolescent pain problems are on the rise in North America and constitute a risk factor for diversion, misuse, and substance use. In this study, we aimed to investigate the phenotypic and etiological association among pain, depression, and anxiety and to test their link to substance use in adolescents. By taking advantage of the Italian National Twin Registry and of the relatively low incidence of opioid prescriptions in Italy, we applied multivariate modelling analyses to 748 Italian adolescent twins (374 pairs, mean age 16 ± 1.24 years). Twins' responses to the Achenbach Youth Self-Report questionnaire were used to build a composite adolescent pain index and to measure anxiety, depression, and substance use. All monozygotic within-pair correlations were higher than the dizygotic correlations, indicating genetic influences for adolescent pain, anxiety, and depressive problems. A common latent liability factor influenced by genetic and environmental elements shared among pain, depression, and anxiety provided the best fit to explain the co-occurrence of adolescent pain, anxiety, and depression problems. A common phenotypic factor capturing all 3 phenotypes was positively associated (β = 0.19, P < 0.001, confidence interval: 0.10-0.27) with substance use. These findings indicate that several intertwined mechanisms, including genetic factors, can explain a shared liability to common adolescent pain, anxiety, and depression problems. Their association with substance use remains traceable even in societies with relatively low prevalence of opioid prescriptions.

OBJECTIVE: To determine the ratio of dichorionic (DC) to monochorionic (MC) twins by maternal age. METHODS: We reviewed all twin pregnancies undergoing first trimester screening (FTS) with nuchal translucency from April 2009 to December 2012 with sonographic determination of chorionicity. Cases were linked to newborn screening (NBS) results and zygosity estimated based on rates of fetal sex discordance. The ratio of DC to MC placentation by maternal age was calculated. RESULTS: We identified 11,351 twin pregnancies with FTS and documented chorionicity. Among these, 7,861 (64.2%) had linked data on FTS and NBS to allow estimation of zygosity based on neonatal sex. Of these, 1,464 (18.6%) were MC and 6,406 (81.4%) DC. The MC twin rate remained constant while the DC twin rate increased with maternal age until 40y. At < 20y, 55% of twin pregnancies were monozygotic (MZ), as compared to 29% at ≥ 40y. Of MZ twins, 38% were DC at < 20y, while 53% were DC at ≥ 40y. CONCLUSIONS: Our data suggest a relationship of both zygosity and chorionicity with maternal age. DZ twinning increased with maternal age, while among MZ twins, the proportion that were DC also increased with maternal age.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with high heritability, however, understanding the complexity of the underlying genetic basis has proven to be a challenging task. We hypothesized that dissecting the aberrations in alternative splicing (AS) and their effects on expression networks might provide insight. Therefore, we performed AS and co-expression analyses of total RNA isolated from Peripheral Blood Mononuclear Cells (PBMCs) of two pairs of dizygotic (DZ) twins with non-syndromic autism and their parents. We identified 183 differential AS events in 146 genes, seven of them being Simons Foundation Autism Research Initiative (SFARI) Category 1-3 genes, three of which had previously been reported to be alternatively spliced in ASD post-mortem brains. Gene co-expression analysis identified 7 modules with 513 genes, 5 of which were SFARI Category 1 or Category 2 genes. Among differentially AS genes within the modules, ZNF322 and NR4A1 could be potentially interesting targets for further investigations.

To investigate the influence of hypertensive disorders of pregnancy (HDP) on the perinatal outcomes in twin pregnancies.This was a retrospective single-center study in which, 2160 twin pregnancies delivered between January 2016 and December 2019 were analyzed, 1661 of which were dichorionic (DC) and 499 monochorionic (MC). The perinatal outcomes were compared in 404 twin pregnancies with HDP, including 157 gestational hypertension (GH), 107 mild pre-eclampsia (MPE), 140 severe pre-eclampsia (SPE), and 1756 twins without hypertensive disorders of pregnancy (no-HDP). Multiple linear regression was performed to analyze the association between perinatal outcome and HDP. Stratified sampling by twin chorionicity (DC and MC) was also conducted.There were 330 (19.9%) DC cases complicated with HDP and 74 (14.8%) MC with HDP, and the difference between the two groups was statistically significant (The perinatal outcomes of different chorionic twins with HDP are different. HDP has a greater impact on the perinatal outcomes of DC twins. The risk of adverse perinatal outcomes in DC twin pregnancy will increase accordingly with each increase in the grade of HDP, but HDP has little or no relevance on the perinatal outcomes of MC twins.

INTRODUCTION Our study compared the prospective risks of intrauterine fetal death (IUFD), neonatal death (NND), perinatal death (PND), and neonatal morbidities in monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies. METHODS This retrospective cohort study included twin pregnancies who had antenatal care and delivery in a public hospital from 2011 to 2018. Exclusion criteria included monoamnionicity, one/both twin miscarriage, twin-twin transfusion syndrome, or lethal congenital abnormalities. All twins were managed in multiple pregnancy clinic with standardized protocols. Gestational age-specific IUFD, NND, PND, and neonatal morbidity rates were compared according to chorionicity. RESULTS Three hundred seventy-eight MCDA and 1282 DCDA twins were included. MCDA twins had higher risks of PND (1.9% vs. 0.7% in DCDA twins, p = 0.05), composite neonatal morbidity (p = 0.01), preterm delivery (p

Twin studies have long been used to infer heritability. Within the ‘omics era, twin cohorts have even greater research potential. This study describes the formation of the UK IBD Twin Registry and analysis of concordance and environmental factors. Twin pairs with IBD were recruited by advertising via IBD charities and social media, re-tracing a dormant IBD database and clinician referral. Details of zygosity, concordance, disease history and environmental factors were assessed. Pair concordance was calculated, and environmental factors were analysed with logistic regression models adjusted for zygosity and concordance. Ninety-one twin pairs were included in the analysis; forty-two with CD and forty-nine with UC. More MZ twin pairs with CD were concordant compared with DZ pairs, thus inferring heritability (Chi-sq. 15.6. P

Twins regularly score nearly a standard deviation below the population mean on standardized measures of cognitive development in infancy, but recover to the population mean by early childhood, making rapid gains through the toddler years. To date only polynomial growth models have been fit to model cognitive recovery across childhood, limiting the applicability of the growth parameters to later developmental periods. We fit a nonlinear asymptotic Gompertz growth model to prospective cognitive scores from 1,153 individual twins from 578 families (47.9% male, 91.5% White, 61.6% monozygotic) measured at 16 time points between 3 months and 15 years. Twins displayed a lower asymptote of 86.47 (0.90 SD below the population mean) and gained on average 17.01 points, achieving an upper asymptote of 103.48. Growth was observed to be most rapid at 3.26 years, highlighting the importance of the toddler years in cognitive development. Biometric analyses revealed that shared environmental factors accounted for the majority of the variance in initial cognitive ability as well as asymptotic growth in cognitive ability. Gestational age and family socioeconomic status (SES) were robust predictors of cognitive growth. Results from the present study provide insight into the growth processes underlying the recovery of cognitive ability to the population mean for children evincing slight delays in their initial cognitive ability. In particular, findings highlight prenatal factors and family economic resources as important aspects of the environment in the recovery of cognitive ability.

Epidemiological studies have suggested the role of multiple genetic and environmental factors in the development of non-neoplastic gastrointestinal (GI) diseases; however, little information is available on these factors in the Korean population. Therefore, this cross-sectional study explored the effect of these factors by analyzing the concordance of several benign GI disorders in 525 monozygotic twins compared to that in 122 dizygotic twins aged >20 years from the Healthy Twin Study data of the Korean Genome and Epidemiology Study (2005–2014). Chi-square test, Wilcoxon rank-sum, and binomial and multinomial logistic regression models were used for statistical analysis. There was lack of concordance of gastric/duodenal ulcers and cholelithiasis/cholangitis between monozygotic twins compared to that in dizygotic twins, suggesting that environmental factors may mediate those concordant disease expressions in monozygotic twins. The concordance of intestinal polyps in monozygotic twins was 32% lower than that in dizygotic twins (p = 0.028), indicating that the effect of genetic factors on the risk for intestinal polyp development may be low. In conclusion, the lack or low concordance of several benign GI diseases between monozygotic and dizygotic twin groups suggests the relative importance of environmental factors, indicating that these are preventable diseases.

We explored the genetic and environmental inter-relationships among osteoporosis, fracture, arthritis, and bone mineral density concordance in monozygotic twins compared to those in dizygotic twins. This cross-sectional research assessed data of 1032 monozygotic and 242 dizygotic twin pairs aged >20 years included in the Healthy Twin Study data of the Korean Genome and Epidemiology Study between 2005 and 2014. Outcomes of interest included illness concordance and absolute differences in dual-energy X-ray absorptiometry (DEXA) T-scores. We found comparable concordances of osteoporosis, fractures, osteoarthritis, and rheumatoid arthritis between monozygotic and dizygotic twins. Medical histories of osteoporosis, fractures caused by accident or falling, osteoarthritis, and rheumatoid arthritis were not distinct between monozygotic and dizygotic twins. Accidental fracture occurrence in both monozygotic twins showed significantly lower odds than that in dizygotic twins. Genetic influence on liability to fracture risk might thus be maintained. DEXA T-scores for bone mineral density indicated more comparable tendencies within monozygotic twin pairs than within dizygotic ones, suggesting the relative importance of genetic contribution to bone mineral density. The relative importance of genetic factors in bone mineral density is sustained between monozygotic twins; overt disease expression of osteoporosis, fractures, or arthritis may be affected by environmental factors.

IMPORTANCE: Although infancy is the most rapid period of postnatal growth and development, factors associated with variation in infant traits are not well understood. OBJECTIVE: To synthesize the large twin study literature partitioning phenotypic variance in psychological traits and developmental milestones in infancy into estimates of heritability and shared and nonshared environment. DATA SOURCES: PubMed, PsycINFO, and references of included publications were searched up to February 11, 2021. STUDY SELECTION: Peer-reviewed publications using the classical twin design to study psychological traits and developmental milestones from birth to 2 years old were included. DATA EXTRACTION AND SYNTHESIS: Data were extracted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and categorized using the International Classification of Functioning, Disability and Health: Children and Youth Version. Data were pooled in 3-level random effects models, incorporating within-cohort variance in outcome measurement and between-cohort variance. Data were analyzed from March 2021 through September 2021. MAIN OUTCOMES AND MEASURES: The primary outcomes were monozygotic and dizygotic twin correlations. These were used to calculate genetic and shared and nonshared environment estimates. RESULTS: Among 139 publications that were systematically retrieved, data were available on 79 044 twin pairs (31 053 monozygotic and 47 991 dizygotic pairs), 52 independent samples, and 21 countries. Meta-analyses were conducted on psychological traits and developmental milestones from 106 publications organized into 10 categories of functioning, disability, and health. Moderate to high genetic estimates for 8 categories were found, the highest of which was psychomotor functions (pooled h2, 0.59; 95% CI, 0.25-0.79; P

In this study, we analyzed the estimated frequency of monozygotic (MZ) and dizygotic (DZ) spontaneous twins in Lombardy during the period 2007−2017. This is a population-based study using the regional healthcare utilization databases of the Lombardy Region. The total number of spontaneous twin deliveries, in separate strata of like and unlike sex, was obtained. Moreover, estimates of DZ and MZ twin births were calculated using Weinberg’s method. The standardized rates (SRs), adjusted for maternal age, of DZ and MZ twin births were computed according to calendar period. The twinning rates were calculated among strata of parity and maternal age. Finally, DZ:MZ ratio was calculated. Among the 734,278 spontaneous deliveries, 9176 (12.5 out of 1000 births) couples of twins were identified. In the three periods considered (i.e. 2007−2010, 2011−2014 and 2015−2017), no trend in the SRs of MZ twins was observed, respectively 0.41 (95% CI [0.40, 0.43]), 0.43 (95% CI [0.42, 0.45]) and 0.43 (95% CI[0.42, 0.45]). Differently, a slightly decreasing trend was observed in DZ twins SRs, respectively 0.87 (95% CI [0.84, 0.89]), 0.81 (95% CI [0.79, 0.83]), and 0.78 (95% CI [0.76, 0.80]). As concerns parity and maternal age, the rate of DZ twin births was consistently higher in nulliparae women aged 35 years or more. In our cohort, despite the increase of maternal age, a decline of spontaneous twin births emerged, especially due to the downward trend of DZ twins.

Niemann-Pick disease type C (NP-C) (OMIM#257220) is a rare lysosomal storage disorder caused by pathogenic variants in either the NPC1 or NPC2 genes. It manifests with a wide spectrum of clinical symptoms and variable age of onset. We studied the impact of the frequent polymorphic variant c.2793 C > T (p.Asn931 = ), located in the donor splice site (SS) of NPC1 exon 18 on the penetrance of the rare synonymous variant c.2727 C > T (p.Cys909 = ), identified in two 55 y.o. twins with an adult onset form of NP-C. The patients’ diagnosis was supported by biochemical analysis and positive filipin test. Analysis of the patients’ cDNA showed that the c.2727 C > T variant leads to cryptic donor SS activation and frameshift deletion in the NPC1 exon 18. However, the minigene assay demonstrated that this exon shortening takes place only in the presence of the frequent polymorphic variant c.2793 C > T. Results of the transcript specific qPCR showed that only the presence in the NPC1 exon 18 of both variants leads to significant decrease of wild type (WT) transcript isoform.

To evaluate the degree of genetic influence on macular choroidal volume.A cross-sectional twin and family study.In total, 353 Korean adults with healthy eyes from 78 households with 2 or more family members were included in the study. Macular choroidal volume was measured using spectral-domain optical coherence tomography with enhanced depth imaging at 9 macular subfields defined by the ETDRS. Demographics and clinical characteristics were investigated, including age, sex, axial length, hypertension, diabetes, drinking habits, and smoking status. The associations of these factors with macular choroidal volume were assessed using univariate and subsequent multivariate regression analyses while accounting for family structure. The heritability estimates of macular choroidal volume in total and at each of the 9 macular subfields were calculated after adjusting the covariates.Patients who were younger, male, and had a shorter axial length showed associations with greater choroidal volume (P.001 for all 3 independent variables). The covariates-adjusted heritability (±standard error) of the total macular choroidal volume was 0.76 ± 0.06, and the heritabilities of choroidal volume at each subfield ranged from 0.55 ± 0.09 (inner temporal subfield) to 0.77 ± 0.08 (inner superior subfield).The macular choroidal volume is highly heritable.

Monozygotic (MZ) twins ("identical twins") are essentially unique to human beings. Why and how they arise is not known. This article reviews the possible different types of MZ twinning recognized in the previous article on twins and arthrogryposis. There appear to be at least three subgroups of MZ twinning: spontaneous, familial, and those related to artificial reproductive technologies. Each is likely to have different etiologies and different secondary findings. Spontaneous MZ twinning may relate to "overripe ova." Amyoplasia, a specific nongenetic form of arthrogryposis, appears to occur in spontaneous MZ twinning and may be related to twin-twin transfusion.

Amyoplasia is a very specific, nongenetic clinically recognizable form of arthrogryposis, representing about one-third of individuals with arthrogryposis surviving the newborn period. There is a markedly increased number of individuals with Amyoplasia who are one of monozygotic (MZ) twins, with the other twin being normal. Thus, it would appear that Amyoplasia is definitely associated with and may be caused by an MZ twinning event. The twin-twin transfusion seen in MZ twins could play an etiologic role in producing Amyoplasia. In this article, Amyoplasia twinning is compared to twinning in other forms of arthrogryposis. The accompanying paper examines various types of MZ twinning (Hall, 2021). Amyoplasia is primarily associated with spontaneous MZ twinning.

Twin studies of physical exercise for Asian twins are sparse. This study aimed to examine genetic and environmental influences on frequency of vigorous exercise (FVE) in South Korean twins, with a special emphasis on sex effects. Telephone interviews on FVE were administered to 1757 twins (mean age = 19.05 years, SD = 3.01 years). Tetrachoric correlations were significantly different between monozygotic (MZ) and dizygotic (DZ) twins in males (.40 vs. .12), but they were similar in females (.44 vs. .45), suggesting the importance of genetic factors in FVE in males and that of common environmental factors in females. A scalar sex-limitation model incorporating age as a modifier was applied to data. The results revealed that genetic, common and individual environmental influences did not vary significantly with age, but differed across two sexes, confirming twin correlational analyses. In the best-fitting model, additive genetic and individual environmental influences on FVE were, respectively, .35 (95% CI [.26, .39]) and .65 (95% CI [.61, .74]) in males, and common and individual environmental influences were, respectively, .45 (95% CI [.35, .53]) and .55 (95% CI [.47, .65]) in females. These results contrasted starkly with recent findings from a large sample of Chinese adult twins (age >18 years), in which most variance (≥95%) of vigorous physical activity was attributable to common environmental influences in both sexes. Replications in other Asian samples are clearly needed.

Introduction Electronic cigarettes are now the most commonly used form of tobacco product among youth in the United States. Current evidence suggests that although e-cigarettes are perceived as less harmful and preferred over combustible cigarettes by adolescents, adolescents who try e-cigarettes are at greater risk of transitioning to combustible cigarettes. The genetic and environmental contributions to liability for e-cigarette use have not yet been examined using a behavioral genetic design. Methods Behavioral genetic models of lifetime and current e-cigarette use and friends who use e-cigarettes were examined among female monozygotic and dizygotic twins. Results A total of 41 female twin pairs (65.9% monozygotic twins; age = 19.7, SD = 1.6) with complete data on the study variables were included in the present analyses. The majority of the sample (68.1%) had at least some friends who use e-cigarettes. Additive genetic effects on e-cigarette use were not present, but the shared environment explained 98.7% of the variance in lifetime e-cigarette use, 96.6% in current e-cigarette use, and 94.9% in affiliation with friends who use e-cigarettes. Conclusion This first study on the behavioral genetics of e-cigarette use among adolescents and young adults suggest that environmental factors shared by twins within a family seem to play a predominant role in the initial stages of e-cigarette use, a finding that is consistent with what has been found for tobacco. The findings emphasize the importance of continuing population-based tobacco control interventions to reduce the burden of e-cigarette use among adolescents. Implications The shared environment significantly influences the initiation and regular use of electronic cigarettes and affiliation with friends who use electronic cigarettes among adolescent and young adult females. These findings underscore the importance of formulating preventive interventions that mitigate the social effects of familial influences on e-cigarette use through social skills training, education on harms of e-cigarettes for young people, or altering social norms regarding initiation of novel tobacco products.

The present study aimed to determine the genetic and environmental etiology of the association between childhood negative emotionality (NE) and hyperactivity/inattention problems (HIP) using South Korean elementary school twins (mean age = 10.19 years, SD = 1.79 years). Telephone interviews were given to mothers of 919 twins (229 monozygotic males: 112 pairs and 5 individuals; 148 dizygotic males: 73 pairs and 2 individuals; 180 monozygotic females: 87 pairs and 6 individuals; 103 dizygotic females: 50 pairs and 3 individuals; 259 opposite-sex dizygotic twins: 127 pairs and 5 individuals) to assess their children’s NE and HIP. Consistent with prior studies, the phenotypic correlation between NE and the HIP was moderate (r = .29; 95% CI = .24, .34). Model-fitting analysis revealed that additive genetic and nonshared environmental influences on NE were .45 (95% CI [.34, .54]) and .55 (95% CI [.46, .66]), respectively, and that additive and nonadditive genetic, and nonshared environmental influences on HIP were .08 (95% CI [.03, .26]), .41 (95% CI [.21, .51]) and .51 (95% CI = .42, .61), respectively. In addition, the additive genetic correlation between NE and HIP was 1.0 (95% CI [.52, 1.00]), indicating that additive genetic factors are entirely shared between the two phenotypes. Nonadditive genetic influences were unique to HIP and not responsible for the NE-HIP association. Nonshared environmental correlation was significant but modest (re = .18, 95% CI [.06, .30]).

The objective of this study is to investigate the effect of type of pregnancy (singleton, dizygotic, and monozygotic) on infant neurodevelopment and to explore how laterality operates in this relationship.We constructed a prospective cohort of low-risk women with singleton, monozygotic, and dizygotic pregnancies. Laterality was evaluated using the Edinburgh's scale of laterality, while neurodevelopment was assessed using the AgesStages Questionnaire (ASQ). The confounding, modifying, and mediating effect of laterality on the relationship between multiple pregnancy and neurodevelopment was explored by linear regression.We included 207 singletons, 77 dizygotic, and 75 monozygotic pregnancies. The mean age (SD) at assessment of neurodevelopment was 48.5 (7.5) months. There was a significant trend to poorer neurodevelopment across singleton, dizygotic and monozygotic pregnancies in communication (52.2, 47.6 and 42.3;The association of multiple pregnancy to poorer neurodevelopment was independent of children laterality.

In recent years, many studies have described the composition and function of the human microbiome at different body sites and suggested a role for the microbiome in various diseases and health conditions. Some studies, using longitudinal samples, have also suggested how the microbiome changes over time due to disease, diet, development, travel, and other environmental factors. However, to date, no study has demonstrated whether the microorganisms established at birth or in early childhood, either transmitted from parents or obtained from the environment, can stay in the human body until adult or senior age. To directly answer this question is difficult, because microbiome samples at childhood and at later adulthood for the same individual will need to be compared and the field is not old enough to have allowed for that type of sample collection. Here, using a metagenomic approach, we analyzed 1004 gut microbiome samples from senior adults (65 ± 7.8 years) from the TwinsUK cohort. Our data indicate that many species in the human gut acquired in early childhood can stay for a lifetime until senior ages. We identified the rare genomic variants (single nucleotide variation and indels) for 27 prevalent species with enough sequencing coverage for confident genomic variant identification. We found that for some species, twin pairs, including both monozygotic (MZ) and dizygotic (DZ) twins, share significantly more rare variants than unrelated subject pairs. But no significant difference is found between MZ and DZ twin pairs. These observations strongly suggest that these species acquired in early childhood remained in these persons until senior adulthood. Supplementary Information The online version contains supplementary material available at 10.1007/s00248-020-01636-0.

Objective: The aim of the current study was to identify the optimal cutoff that should define discordance in dichorionic twin gestations through correlation with abnormal placental pathology as a specific measure of fetal growth restriction of the smaller twin. Methods: We performed a retrospective cohort study of all women with dichorionic twin pregnancies who gave birth in a single center between 2002 and 2015. We investigated the association between the level of growth discordance and maternal vascular malperfusion (MVM) pathology in the placenta of the smaller twin, with and without adjustment for whether the smaller twin is small for gestational age (SGA). Results: A total of 1,198 women with dichorionic twin gestation met the study criteria. The rate of MVM pathology in the placenta of the smaller twin increased with the level of discordance and was most obvious for discordance ≥25% (rate of MVM 12.0% compared with 2.8% in cases with discordance Conclusion: Our findings suggest that discordant growth in dichorionic twins should raise the concern of fetal growth restriction of the smaller twin, irrespective of whether the smaller twin is SGA, only when the discordance s ≥25%. The association of lower levels of discordance with abnormal placental pathology is mainly driven by the confounding effect of SGA of the smaller twin.

Objectives: Our study aimed to examine a subset of electively reduced twins and compare their outcomes with those of expectantly managed twins, along with a cohort of singleton pregnancies. The secondary aim was to ascertain the procedure-related miscarriage risks. Methods: A retrospective cohort analysis was performed at Apollo Centre for Fetal Medicine, New Delhi, comparing pregnancy outcomes in dichorionic diamniotic twin pregnancies which were reduced to singletons (group 1) with that of women with dichorionic twins managed expectantly (group 0) and women with a singleton pregnancy (group 2). Comparison of continuous and categorical variables was conducted using standard statistical tests. Results: We analysed 35 twins which were reduced to singletons, 421 expectantly managed dichorionic twins and 1915 women with a singleton pregnancy. In the reduction group, the rate of procedure related pregnancy lossp = 1.000). The median gestational age at delivery was significantly higher in reduced twins compared to expectantly managed twin pregnancies (38.0 vs. 35.4 weeks respectively, p < 0.001) with a higher mean birth weight at delivery, both of which were comparable to that among the singleton pregnancies (38.3 weeks). The rates of preterm birth Conclusions: The obstetric and perinatal outcomes after reduction of a dichorionic twin are better than an expectantly managed twin without an associated increase in pregnancy loss rates. Fetal reduction of dichorionic twin to a singleton appears to be a safe procedure in expert hands.

Objective Diagnosis-related groups (DRGs) are used to summarize hospital morbidity and mortality. Each DRG has a weight which is important in calculating the case mix index (CMI), a numeric summary of disease complexity in a population of patients. We utilized DRG weight and resultant CMI to compare postnatal outcomes among singletons versus monochorionic and monoamniotic, monochorionic diamniotic, and dichorionic diamniotic twins. Study Design This single-center and retrospective cohort study evaluated DRGs assigned by the investigators, birth weight, gestational age, length of stay (LOS), NICU admission rate, and mortality in twin births between 2014 and 2016. Twins were analyzed depending on chorionicity and amnionicity. Overall, 3 months of singleton births served as the control. The CMI derived from DRG weights were compared across groups. Results Twins (n = 288) had lower gestational ages and birth weights and higher mortality, LOS, NICU admission rates and DRG weights/CMI compared with singletons (n = 327; p Conclusion DRG weight and CMI values summarize in-hospital complexity and can be a useful tool to evaluate differences in care complexity among groups of patients. Key Points

BACKGROUND: DNA methylation may play a role in progression from normative to problematic drinking and underlie adverse health outcomes associated with alcohol misuse. In the current study, we examined the association between alcohol consumption and DNA methylation patterns using three approaches: a conventional epigenome-wide association study (EWAS); a co-twin comparison design, which controls for genetic and environmental influences that twins share; and a regression of age acceleration, defined as a discrepancy between chronological age and DNA methylation age, on alcohol consumption. METHODS: Participants came from the Finnish Twin Cohorts (FinnTwin12/FinnTwin16; N = 1004; 55% female; average age = 23 years). Individuals reported the number of alcoholic beverages consumed in the past week, and epigenome-wide DNA methylation was assessed in whole-blood using the Infinium HumanMethylation450 BeadChip. RESULTS: In the EWAS, alcohol consumption was significantly related to methylation at 24 CpG sites. When evaluating whether differences between twin siblings (185 monozygotic pairs) in alcohol consumption predicted differences in DNA methylation, co-twin comparisons replicated four CpG sites from the EWAS and identified 23 additional sites. However, when we examined qualitative differences in drinking patterns between twins (heavy drinker versus light drinker/abstainer or moderate drinker versus abstainer; 44 pairs), methylation patterns did not significantly differ within twin pairs. Finally, individuals who reported higher alcohol consumption also exhibited greater age acceleration, though results were no longer significant after controlling for genetic and environmental influences shared by co-twins. CONCLUSIONS: Our analyses offer insight into the associations between epigenetic variation and levels of alcohol consumption in young adulthood.

Heteropaternal superfecundation is an extremely rare phenomenon that occurs when a second ova released during the same menstrual cycle is additionally fertilized by the sperm cells of a different man in separate sexual intercourse. In August, 2018, the Grupo de Genética de Poblaciones e Identificación at Universidad Nacional de Colombia received a request to establish the paternity of a pair of male twins with genetic markers. The following analyses were performed: amelogenin gene, autosomal short tandem repeat (STR), and Y-STR analyses by means of human identification commercial kits, paternity index, and the probability of paternity calculation and interpretation. A paternity index of 2.5134E+7 and a probability of paternity of 99.9999% for twin 2 were obtained while 14 out of 17 Y-chromosome markers and 14 out of 21 autosomal short tandem repeats were excluded for twin 1. The results indicated that the twins have different biological fathers. Although heteropaternal superfecundation is rarely observed among humans given its low frequency, in paternity disputes for dizygotic twins it is mandatory to demand the presence of the two twins in the testing to avoid wrong conclusions.La superfecundación heteropaternal es un fenómeno extremadamente raro que se produce cuando un segundo óvulo, liberado durante el mismo ciclo menstrual, es fertilizado por un espermatozoide de un hombre diferente en relaciones sexuales separadas. En agosto de 2018, el Grupo de Genética de Poblaciones e Identificación de la Universidad Nacional de Colombia recibió una solicitud para establecer la paternidad mediante marcadores genéticos de un par de mellizos varones, en quienes se hizo el análisis del gen de amelogenina, el análisis de repeticiones cortas en tándem (Short Tandem Repeats, STR) autosómicas y del cromosoma Y (Y-STR) mediante kits comerciales de identificación humana y cálculos e interpretación del índice de paternidad y probabilidad de paternidad. Se obtuvo un índice de paternidad de 2,5134E+7 y una probabilidad de paternidad de 99,9999 % para el gemelo 2, en tanto que en el gemelo 1 se excluyeron 14 de los 17 marcadores del cromosoma Y y 14 de los 21 sistemas STR autosómicos evaluados. Los resultados indicaron que los gemelos tienen diferentes padres biológicos. A pesar de que la superfecundación heteropaternal rara vez se observa en humanos debido a su baja frecuencia, en las disputas de paternidad para los gemelos dicigóticos, es obligatorio exigir en la prueba la presencia de los dos gemelos para evitar conclusiones incorrectas.

Susceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n = 3261) completing the C-19 COVID-19 symptom tracker app allowed classical twin studies of COVID-19 symptoms, including predicted COVID-19, a symptom-based algorithm to predict true infection, derived from app users tested for SARS-CoV-2. We found heritability of 49% (32−64%) for delirium; 34% (20−47%) for diarrhea; 31% (8−52%) for fatigue; 19% (0−38%) for anosmia; 46% (31−60%) for skipped meals and 31% (11−48%) for predicted COVID-19. Heritability estimates were not affected by cohabiting or by social deprivation. The results suggest the importance of host genetics in the risk of clinical manifestations of COVID-19 and provide grounds for planning genome-wide association studies to establish specific genes involved in viral infectivity and the host immune response.