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Already at a very early age, infants preferentially attend to social stimuli. Although this is believed to be important for later social cognition and learning, little is known about the aetiology of infant social attention and associations to later abilities. In this thesis, I used eye tracking to study the influence of genes and environment on individual differences in different aspects of social attention, and developmental outcomes across different domains in toddlerhood in relation to both typical and atypical development. In Study I, the influence of genes and environment on the preference for looking at eyes versus mouth (eye-mouth-index) was assessed in 5-month-old twins. The eye-mouth-index was highly heritable, and a stronger tendency to look at the eyes was associated with later language comprehension. In Study II, sustained attention to faces was assessed in the same sample of infants, and found to be moderately heritable. Longer sustained attention was associated with more socio-communicative behaviours in toddlerhood. In Study III, videos of children interacting were shown to 18-month-olds with and without an elevated likelihood of autism. At specific time intervals in the videos, there was a significant difference in gaze allocation between the toddlers who did and did not receive an autism diagnosis later in childhood. The findings of this thesis suggest that both sustained attention to faces and eye versus mouth preference are heritable, meaning that young infants may select their environment based on their genotype, by looking at different aspects of a scene or a face. Being exposed to different types of input might influence later development, and these results indicate that social attention is associated with later social and communicative abilities, as well as later autism. In summary, this thesis contributes to the understanding of early social attention and how different aspects of this phenomenon are related to later development., Att selektivt titta mot ansikten är en grundläggande mänsklig egenskap, som anses vara en viktig del av den sociala utvecklingen hos barn. Genom att titta på andra människor får man information om deras känsloliv, intentioner och kommunikativa signaler. Trots den viktiga funktionen av social uppmärksamhet vet vi väldigt lite om etiologin bakom individuella skillnader i hur man tittar på andra människor, och huruvida sådana skillnader kan kopplas till senare social och kommunikativ utveckling. I den här avhandlingen har jag använt mig av ögonrörelsemätningar för att studera hur barn tittar på sociala stimuli. I Studie I och II bestod deltagarna av fem månader gamla enäggs- och tvåäggstvillingar, vilket gör att man kan undersöka hur ärftligt ett visst beteende är. I Studie I undersökte vi om tendensen att titta på ögon (jämfört med mun) är ärftlig, genom att visa barnen videor av en kvinna som sjunger, pratar och ler mot kameran. Resultaten visade att ärftligheten av att titta på ögon jämfört med mun var hög, och att en tendens att titta mer på ögonen vid fem månaders ålder var associerad med högre språkförståelse vid 14 månaders ålder. I Studie II undersökte vi om benägenheten att upprätthålla uppmärksamhet mot ett ansikte är ärftlig, genom att visa bilder på leende och neutrala ansikten. Tiden det tog, i medeltal, att titta på ett ansikte innan barnet tittade bort visade sig vara ärftligt och associerat med socio-kommunikativa förmågor vid 14 månaders ålder. I Studie III bestod deltagarna av barn som har en nära familjemedlem med autism, och som därför har en större sannolikhet att själva utveckla autism jämfört med den generella befolkningen. Vid 18 månaders ålder fick barnen se videor med två äldre barn, där en pojke ber en flicka om att få en leksak som hon håller i, men där flickan vägrar att ge leksaken. Det visade sig att barnen som senare diagnosticerades med autism tittade betydligt mindre på flickans ansikte efter att pojken bett om leksaken, jämfört med b

Already at a very early age, infants preferentially attend to social stimuli. Although this is believed to be important for later social cognition and learning, little is known about the aetiology of infant social attention and associations to later abilities. In this thesis, I used eye tracking to study the influence of genes and environment on individual differences in different aspects of social attention, and developmental outcomes across different domains in toddlerhood in relation to both typical and atypical development. In Study I, the influence of genes and environment on the preference for looking at eyes versus mouth (eye-mouth-index) was assessed in 5-month-old twins. The eye-mouth-index was highly heritable, and a stronger tendency to look at the eyes was associated with later language comprehension. In Study II, sustained attention to faces was assessed in the same sample of infants, and found to be moderately heritable. Longer sustained attention was associated with more socio-communicative behaviours in toddlerhood. In Study III, videos of children interacting were shown to 18-month-olds with and without an elevated likelihood of autism. At specific time intervals in the videos, there was a significant difference in gaze allocation between the toddlers who did and did not receive an autism diagnosis later in childhood. The findings of this thesis suggest that both sustained attention to faces and eye versus mouth preference are heritable, meaning that young infants may select their environment based on their genotype, by looking at different aspects of a scene or a face. Being exposed to different types of input might influence later development, and these results indicate that social attention is associated with later social and communicative abilities, as well as later autism. In summary, this thesis contributes to the understanding of early social attention and how different aspects of this phenomenon are related to later development., Att selektivt titta mot ansikten är en grundläggande mänsklig egenskap, som anses vara en viktig del av den sociala utvecklingen hos barn. Genom att titta på andra människor får man information om deras känsloliv, intentioner och kommunikativa signaler. Trots den viktiga funktionen av social uppmärksamhet vet vi väldigt lite om etiologin bakom individuella skillnader i hur man tittar på andra människor, och huruvida sådana skillnader kan kopplas till senare social och kommunikativ utveckling. I den här avhandlingen har jag använt mig av ögonrörelsemätningar för att studera hur barn tittar på sociala stimuli. I Studie I och II bestod deltagarna av fem månader gamla enäggs- och tvåäggstvillingar, vilket gör att man kan undersöka hur ärftligt ett visst beteende är. I Studie I undersökte vi om tendensen att titta på ögon (jämfört med mun) är ärftlig, genom att visa barnen videor av en kvinna som sjunger, pratar och ler mot kameran. Resultaten visade att ärftligheten av att titta på ögon jämfört med mun var hög, och att en tendens att titta mer på ögonen vid fem månaders ålder var associerad med högre språkförståelse vid 14 månaders ålder. I Studie II undersökte vi om benägenheten att upprätthålla uppmärksamhet mot ett ansikte är ärftlig, genom att visa bilder på leende och neutrala ansikten. Tiden det tog, i medeltal, att titta på ett ansikte innan barnet tittade bort visade sig vara ärftligt och associerat med socio-kommunikativa förmågor vid 14 månaders ålder. I Studie III bestod deltagarna av barn som har en nära familjemedlem med autism, och som därför har en större sannolikhet att själva utveckla autism jämfört med den generella befolkningen. Vid 18 månaders ålder fick barnen se videor med två äldre barn, där en pojke ber en flicka om att få en leksak som hon håller i, men där flickan vägrar att ge leksaken. Det visade sig att barnen som senare diagnosticerades med autism tittade betydligt mindre på flickans ansikte efter att pojken bett om leksaken, jämfört med b

Introduction: Much of our understanding of infant psychological development relies on an in-person, laboratory-based assessment. This limits research generalizability, scalability, and equity in access. One solution is the development of new, remotely deployed assessment tools that do not require real-time experimenter supervision. Methods: The current nationwide (Sweden) infant twin study assessed participants remotely via their caregiver's tablets (N = 104, ages 3 to 17 months). To anchor our findings in previous research, we used a gaze-following task where experimental and age effects are well established. Results: Closely mimicking results from conventional eye tracking, we found that a full head movement elicited more gaze following than isolated eye movements. Furthermore, predictably, we found that older infants followed gaze more frequently than younger infants. Finally, while we found no indication of genetic contributions to gaze-following accuracy, the latency to disengage from the gaze cue and orient toward a target was significantly more similar in monozygotic twins than in dizygotic twins, an indicative of heritability. Discussion: Together, these results highlight the potential of remote assessment of infants' psychological development, which can improve generalizability, inclusion, and scalability in developmental research.

La dislexia es el trastorno del uso escrito del lenguaje debido a la debilidad visoespacial en la percepción de las formas lingüísticas. En este trabajo, se postula que una posible caracterización funcional de los déficits de la naturaleza lingüística en hablantes pacientes que presentan dislexia cuando no se presupone todavía una total adquisición de la lectura y la escritura va a favorecer tanto el diagnóstico como la propuesta de intervención. Para demostrar esta hipótesis, estudiamos el caso de dos hablantes pacientes gemelos que comparten el diagnóstico de dislexia con el objetivo de comprobar el carácter genético-hereditario de la patología y proponer terapias específicas a partir del análisis funcional lingüístico. Así, presentamos el marco teórico que permite el conocimiento histórico y las definiciones ofrecidas sobre este trastorno, las dificultades que entraña su etiología y los diferentes modelos de intervención que existen actualmente para paliarlo. A continuación, realizamos el estudio de caso de los dos sujetos emparentados, comprobando, a partir de los resultados del estudio, que ambos hermanos sufren un retraso lector moderado con problemas de inversión y rotación y una escritura con problemas de inversión, rotación y disgrafía. El nivel de dislexia, aunque es similar, no es idéntico, lo que sugiere propuestas de intervención diferentes., Dyslexia is a disorder in the written use of language due to visuospatial weakness in the perception of linguistic forms. This paper postulates that a possible functional characterization of the deficits of a linguistic nature in patient speakers who present dyslexia when a full acquisition of reading and writing is not yet assumed will favor both the diagnosis and the intervention proposal. To demonstrate this hypothesis, we study the case of two twin patient-speakers who share the diagnosis of dyslexia, with the aim of checking the genetic-hereditary nature of the pathology and proposing specific therapies based on linguistic functional analysis. We thus present the theoretical framework that allows the historical knowledge and definitions offered on this disorder, the difficulties involved in its etiology, and the different models of intervention that currently exist to alleviate it. Then we then carry out a case study of the two related subjects, verifying, from the results of the study, that both siblings suffer a moderate reading delay with inversion and rotation problems, and a writing with problems also of inversion, rotation and dysgraphia. The level of dyslexia, although similar, is not identical, suggesting different intervention proposals)., A dislexia é uma desordem no uso escrito da língua devido à fraqueza visuoespacial na percepção das formas linguísticas. Este artigo postula que uma possível caracterização funcional de défices de natureza linguística em falantes de pacientes que apresentam dislexia quando a aquisição completa da leitura e da escrita ainda não é assumida favorecerá tanto o diagnóstico como a proposta de intervenção. Para demonstrar essa hipótese, estudamos o caso de dois pacientes falantes gémeos que partilham o diagnóstico de dislexia, com o objectivo de verificar a natureza genética-hereditária da patologia e propor terapias específicas baseadas na análise funcional linguística. Apresentamos o quadro teórico que permite o conhecimento histórico e as definições oferecidas sobre esta patologia, as dificuldades envolvidas na sua etiologia e os diferentes modelos de intervenção actualmente existentes para a aliviar, e realizamos depois um estudo de caso dos dois temas relacionados, verificando, a partir dos resultados do estudo, que ambos os irmãos sofrem de atraso moderado na leitura com problemas de inversão e rotação, e escrita com problemas de inversão, rotação e disgrafia. O nível de dislexia, embora semelhante, não é idêntico, sugerindo propostas de intervenção diferentes).

Already at a very early age, infants preferentially attend to social stimuli. Although this is believed to be important for later social cognition and learning, little is known about the aetiology of infant social attention and associations to later abilities. In this thesis, I used eye tracking to study the influence of genes and environment on individual differences in different aspects of social attention, and developmental outcomes across different domains in toddlerhood in relation to both typical and atypical development. In Study I, the influence of genes and environment on the preference for looking at eyes versus mouth (eye-mouth-index) was assessed in 5-month-old twins. The eye-mouth-index was highly heritable, and a stronger tendency to look at the eyes was associated with later language comprehension. In Study II, sustained attention to faces was assessed in the same sample of infants, and found to be moderately heritable. Longer sustained attention was associated with more socio-communicative behaviours in toddlerhood. In Study III, videos of children interacting were shown to 18-month-olds with and without an elevated likelihood of autism. At specific time intervals in the videos, there was a significant difference in gaze allocation between the toddlers who did and did not receive an autism diagnosis later in childhood. The findings of this thesis suggest that both sustained attention to faces and eye versus mouth preference are heritable, meaning that young infants may select their environment based on their genotype, by looking at different aspects of a scene or a face. Being exposed to different types of input might influence later development, and these results indicate that social attention is associated with later social and communicative abilities, as well as later autism. In summary, this thesis contributes to the understanding of early social attention and how different aspects of this phenomenon are related to later development., Att selektivt titta mot ansikten är en grundläggande mänsklig egenskap, som anses vara en viktig del av den sociala utvecklingen hos barn. Genom att titta på andra människor får man information om deras känsloliv, intentioner och kommunikativa signaler. Trots den viktiga funktionen av social uppmärksamhet vet vi väldigt lite om etiologin bakom individuella skillnader i hur man tittar på andra människor, och huruvida sådana skillnader kan kopplas till senare social och kommunikativ utveckling. I den här avhandlingen har jag använt mig av ögonrörelsemätningar för att studera hur barn tittar på sociala stimuli. I Studie I och II bestod deltagarna av fem månader gamla enäggs- och tvåäggstvillingar, vilket gör att man kan undersöka hur ärftligt ett visst beteende är. I Studie I undersökte vi om tendensen att titta på ögon (jämfört med mun) är ärftlig, genom att visa barnen videor av en kvinna som sjunger, pratar och ler mot kameran. Resultaten visade att ärftligheten av att titta på ögon jämfört med mun var hög, och att en tendens att titta mer på ögonen vid fem månaders ålder var associerad med högre språkförståelse vid 14 månaders ålder. I Studie II undersökte vi om benägenheten att upprätthålla uppmärksamhet mot ett ansikte är ärftlig, genom att visa bilder på leende och neutrala ansikten. Tiden det tog, i medeltal, att titta på ett ansikte innan barnet tittade bort visade sig vara ärftligt och associerat med socio-kommunikativa förmågor vid 14 månaders ålder. I Studie III bestod deltagarna av barn som har en nära familjemedlem med autism, och som därför har en större sannolikhet att själva utveckla autism jämfört med den generella befolkningen. Vid 18 månaders ålder fick barnen se videor med två äldre barn, där en pojke ber en flicka om att få en leksak som hon håller i, men där flickan vägrar att ge leksaken. Det visade sig att barnen som senare diagnosticerades med autism tittade betydligt mindre på flickans ansikte efter att pojken bett om leksaken, jämfört med b

Introduction: Much of our understanding of infant psychological development relies on an in-person, laboratory-based assessment. This limits research generalizability, scalability, and equity in access. One solution is the development of new, remotely deployed assessment tools that do not require real-time experimenter supervision. Methods: The current nationwide (Sweden) infant twin study assessed participants remotely via their caregiver's tablets (N = 104, ages 3 to 17 months). To anchor our findings in previous research, we used a gaze-following task where experimental and age effects are well established. Results: Closely mimicking results from conventional eye tracking, we found that a full head movement elicited more gaze following than isolated eye movements. Furthermore, predictably, we found that older infants followed gaze more frequently than younger infants. Finally, while we found no indication of genetic contributions to gaze-following accuracy, the latency to disengage from the gaze cue and orient toward a target was significantly more similar in monozygotic twins than in dizygotic twins, an indicative of heritability. Discussion: Together, these results highlight the potential of remote assessment of infants' psychological development, which can improve generalizability, inclusion, and scalability in developmental research.

Byzantine consensus protocols are designed to build resilient systems to achieve consensus under Byzantine settings, maintaining safety guarantees under any network synchrony model and providing liveness in partially or fully synchronous networks. However, several Byzantine consensus protocols have been shown to violate liveness properties under certain scenarios. Existing testing methods for checking the liveness of consensus protocols check for time-bounded liveness violations, which generate a large number of false positives. In this thesis, for the first time, we check the liveness of Byzantine consensus protocols by the temperature and lasso detection methods and precisely detail ad-hoc system state abstractions that should be used to test these algorithms. We provide a theoretical analysis of the recently-published safety and liveness attacks and whether the existing test method is able to detect them. To investigate the issues, we focus on the streamlined blockchain consensus, particularly the HotStuff protocol family, which has been recently developed for blockchain consensus. Among these protocols, the HotStuff protocol itself is both safe and live under the partial synchrony assumption, whereas 2-Phase Hotstuff and Sync HotStuff protocols can violate liveness in subtle fault scenarios. We implemented our liveness checking methods on top of the Twins automated unit test generator to test the HotStuff protocol family and explored the scenarios with message delay. Our results indicate that our methods successfully detect all known liveness violations and produce fewer false positives than the bounded liveness checks., Computer Engineering | Distributed Systems

Mollusk shells protect the animals that form and inhabit them. They are composites of minerals and organics, with diverse mesostructures, including nacre, prismatic calcite, crossed-lamellar aragonite, and foliated calcite. Twins, that is, crystals mirror symmetric with respect to their coherent interface, occurring as formation or deformation twins, are observed in all mollusk shell mesostructures but never within calcite prisms. Here, nanotwins and microwins within single calcite prisms are observed in different shells. Using Polarization-dependent Imaging Contrast (PIC) mapping with 20–60 nm resolution, twins are observed to be 0.2–3 µm thick layers of differently oriented and colored crystals with respect to the main prism crystal. Multiple twins are interspersed with the prism crystal, parallel to one another, and similarly oriented. When comparing images of calcite prisms and twins obtained by PIC mapping and by Electron Back-Scattered Diffraction (EBSD), the images correspond precisely. All twins are e-twin types, with 127° angular distance between c-axes. E-twins are the most common deformation twins in geologic calcite, as also observed here in Carrara marble. Location of all twins near the outer surface of all shells and e-twin type both suggest that twins within calcite prisms in mollusk shells result from deformation twinning.

The ability to perceive approximate numerosity is present in many animal species, and emerges early in human infants. Later in life, it is moderately heritable and associated with mathematical abilities, but the etiology of the Approximate Number System (ANS) and its degree of independence from other cognitive abilities in infancy is unknown. Here, we assessed the phenotypic specificity as well as the influence of genetic and environmental factors on the ANS in a sample of 5-month-old twins (N = 514). We found a small-to-moderate but statistically significant effects of genetic factors on ANS acuity (heritability = 0.18, 95% CI: 0.02, 0.33), but only when differences in numerosity were relatively large (1:4 ratio). Non-verbal ability assessed with the Mullen Scales of Early Learning (MSEL) was found to be heritable (0.47; 95% CI: 0.34, 0.57) and the phenotypic association between ANS acuity and non-verbal ability performance was close to zero. Similarly, we found no association between ANS acuity and general attention during the task. An unexpected weak but statistically significant negative association between ANS auity and scores on the receptive language scale of the MSEL was found. These results suggest that early ANS function may be largely independent from other aspects of non-verbal development. Further, variability in ANS in infancy seems to, to some extent, reflect genotypic differences in the population. Assessing 514 infant twins with eye tracking, we found that infant’s sense of approximate numerosity is heritable and not positively associated with concurrent attentional, cognitive or motor abilities. These results have implications for our understanding of development of mathematical ability and the link between cognitive abilities early in postnatal life.

Background: Evidence indicates that the adverse health effects of obesity differ between genetically and environmentally influenced obesity. We examined differences in the association between obesity and cardiovascular disease (CVD) between individuals with a genetically predicted low, medium, or high body mass index (BMI). Methods: We used cohort data from Swedish twins born before 1959 who had BMI measured between the ages of 40–64 years (midlife) or at the age of 65 years or later (late-life), or both, and prospective CVD information from nationwide register linkage through 2016. A polygenic score for BMI (PGSBMI) was used to define genetically predicted BMI. Individuals missing BMI or covariate data, or diagnosed with CVD at first BMI measure, were excluded, leaving an analysis sample of 17,988 individuals. We applied Cox proportional hazard models to examine the association between BMI category and incident CVD, stratified by the PGSBMI. Co-twin control models were applied to adjust for genetic influences not captured by the PGSBMI. Findings: Between 1984 and 2010, the 17,988 participants were enrolled in sub-studies of the Swedish Twin Registry. Midlife obesity was associated with a higher risk of CVD across all PGSBMI categories, but the association was stronger with genetically predicted lower BMI (hazard ratio from 1.55 to 2.08 for those with high and low PGSBMI, respectively). Within monozygotic twin pairs, the association did not differ by genetically predicted BMI, indicating genetic confounding not captured by the PGSBMI. Results were similar when obesity was measured in late-life, but suffered from low power. Interpretation: Obesity was associated with CVD regardless of PGSBMI category, but obesity influenced by genetic predisposition (genetically predicted high BMI) was less harmful than obesity influenced by environmental factors (obesity despite genetically predicted low BMI). However, additional genetic factors, not captured by the PGSBMI, still in, CC BY 4.0© 2023 The Author(s)Corresponding author: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-1177 Stockholm, Sweden.E-mail address: ida.karlsson@ki.se (I.K. Karlsson).This work was supported by the Strategic Research Program in Epidemiology at Karolinska Institutet; Loo and Hans Osterman’s Foundation (2022-01222); Foundation for Geriatric Diseases at Karolinska Institutet (2022-01296); the Swedish Research Council for Health, Working Life and Welfare (2018-01201 and 2022-00672); the Swedish Research Council (2016-03081); and the National Institutes of Health (R01 AG060470). We acknowledge the Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no. 2017-00641. The STR sub-studies were supported by the National Institutes of Health (grants R01 AG10175, R01 AG08724, R01 AG08861, R01 AG028555, and U01 DK066134), the MacArthur Foundation Research Network on Successful Aging, the Axel and Margaret Ax:son Johnsons Foundation, the Swedish Research Council, the Swedish Foundation for Health Care Sciences and Allergy Research, and the Swedish Council for Working Lifeand Social Research (2013-2292).

Background: Evidence indicates that the adverse health effects of obesity differ between genetically and environmentally influenced obesity. We examined differences in the association between obesity and cardiovascular disease (CVD) between individuals with a genetically predicted low, medium, or high body mass index (BMI). Methods: We used cohort data from Swedish twins born before 1959 who had BMI measured between the ages of 40–64 years (midlife) or at the age of 65 years or later (late-life), or both, and prospective CVD information from nationwide register linkage through 2016. A polygenic score for BMI (PGSBMI) was used to define genetically predicted BMI. Individuals missing BMI or covariate data, or diagnosed with CVD at first BMI measure, were excluded, leaving an analysis sample of 17,988 individuals. We applied Cox proportional hazard models to examine the association between BMI category and incident CVD, stratified by the PGSBMI. Co-twin control models were applied to adjust for genetic influences not captured by the PGSBMI. Findings: Between 1984 and 2010, the 17,988 participants were enrolled in sub-studies of the Swedish Twin Registry. Midlife obesity was associated with a higher risk of CVD across all PGSBMI categories, but the association was stronger with genetically predicted lower BMI (hazard ratio from 1.55 to 2.08 for those with high and low PGSBMI, respectively). Within monozygotic twin pairs, the association did not differ by genetically predicted BMI, indicating genetic confounding not captured by the PGSBMI. Results were similar when obesity was measured in late-life, but suffered from low power. Interpretation: Obesity was associated with CVD regardless of PGSBMI category, but obesity influenced by genetic predisposition (genetically predicted high BMI) was less harmful than obesity influenced by environmental factors (obesity despite genetically predicted low BMI). However, additional genetic factors, not captured by the PGSBMI, still in, CC BY 4.0© 2023 The Author(s)Corresponding author: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-1177 Stockholm, Sweden.E-mail address: ida.karlsson@ki.se (I.K. Karlsson).This work was supported by the Strategic Research Program in Epidemiology at Karolinska Institutet; Loo and Hans Osterman’s Foundation (2022-01222); Foundation for Geriatric Diseases at Karolinska Institutet (2022-01296); the Swedish Research Council for Health, Working Life and Welfare (2018-01201 and 2022-00672); the Swedish Research Council (2016-03081); and the National Institutes of Health (R01 AG060470). We acknowledge the Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no. 2017-00641. The STR sub-studies were supported by the National Institutes of Health (grants R01 AG10175, R01 AG08724, R01 AG08861, R01 AG028555, and U01 DK066134), the MacArthur Foundation Research Network on Successful Aging, the Axel and Margaret Ax:son Johnsons Foundation, the Swedish Research Council, the Swedish Foundation for Health Care Sciences and Allergy Research, and the Swedish Council for Working Lifeand Social Research (2013-2292).

The ability to perceive approximate numerosity is present in many animal species, and emerges early in human infants. Later in life, it is moderately heritable and associated with mathematical abilities, but the etiology of the Approximate Number System (ANS) and its degree of independence from other cognitive abilities in infancy is unknown. Here, we assessed the phenotypic specificity as well as the influence of genetic and environmental factors on the ANS in a sample of 5-month-old twins (N = 514). We found a small-to-moderate but statistically significant effects of genetic factors on ANS acuity (heritability = 0.18, 95% CI: 0.02, 0.33), but only when differences in numerosity were relatively large (1:4 ratio). Non-verbal ability assessed with the Mullen Scales of Early Learning (MSEL) was found to be heritable (0.47; 95% CI: 0.34, 0.57) and the phenotypic association between ANS acuity and non-verbal ability performance was close to zero. Similarly, we found no association between ANS acuity and general attention during the task. An unexpected weak but statistically significant negative association between ANS auity and scores on the receptive language scale of the MSEL was found. These results suggest that early ANS function may be largely independent from other aspects of non-verbal development. Further, variability in ANS in infancy seems to, to some extent, reflect genotypic differences in the population. Assessing 514 infant twins with eye tracking, we found that infant’s sense of approximate numerosity is heritable and not positively associated with concurrent attentional, cognitive or motor abilities. These results have implications for our understanding of development of mathematical ability and the link between cognitive abilities early in postnatal life.

Given the common anatomical features and similar short-term weight loss outcomes, Biliopancreatic Diversion with Duodenal Switch (BPD/DS) and Single-Anastomosis Duodenoileal bypass with Sleeve gastrectomy (SADI-S) are considered identical bariatric procedures, apart from technical complexity being lower for SADI-S. In the absence of prospective randomized trials or long-term comparative studies the rationale for choosing between procedures is hampered. Post-bariatric hormonal profiles could contribute to understand the underlying mechanisms and potentially be used as a decision aid when choosing between procedures. The main aim of this study was to compare the outcomes of BPD/DS and SADI-S, in genetically identical individuals exposed to similar environmental factors. Two identical twin (T) female patients, one submitted to BPD/DS (T_BPD/DS) and another to SADIS-S (T_SADI-S) were followed up to one year after surgery. Before surgery and at 3, 6 and 12 months after surgery, both patients underwent mixed meal tolerance tests (MMTT) to evaluate postprandial glucose, glucagon and GLP-1 response. In addition, 3 months after surgery, glucose dynamics were assessed using a Flash Glucose Monitoring (FGM) system for 14 days. The percentage of total weight loss (%TWL) was higher for T_BPD/DS compared to T_SADI-S (34.03 vs 29.03 %). During MMTT, T_BPD/DS presented lower glucose, glucagon, insulin and C-peptide excursions at all timepoints when compared to SADI-S; along with a greater percentage of time within the low glucose range (55.97 vs 39.93 %) and numerically lower glucose variability indexes on FGM (MAG change:0.51 vs 0.63 mmol/l×h−1). In patients with the same genetic background, BPD/DS was shown to result in greater weight loss than SADI-S. The differences in glucose and enteropancreatic hormone profiles observed after BPD/DS and SADI-S suggest that different mechanisms underlie weight loss.

Background Research has yielded evidence for genetic and environmental factors influencing the risk of schizophrenia. Numerous environmental factors have been identified; however, the individual effects are small. The additive and interactive effects of multiple risk factors are not well elucidated. Twin pairs discordant for schizophrenia offer a unique opportunity to identify factors that differ between patients and unaffected co-twins, who are perfectly matched for age, sex and genetic background. Methods Register data were combined with clinical data for 216 twins including monozygotic (MZ) and dizygotic (DZ) proband pairs (one or both twins having a schizophrenia spectrum diagnosis) and MZ/DZ healthy control (HC) pairs. Logistic regression models were applied to predict (1) illness vulnerability (being a proband v. HC pair) and (2) illness status (being the patient v. unaffected co-twin). Risk factors included: A polygenic risk score (PRS) for schizophrenia, birth complications, birth weight, Apgar scores, paternal age, maternal smoking, season of birth, parental socioeconomic status, urbanicity, childhood trauma, estimated premorbid intelligence and cannabis. Results The PRS [odds ratio (OR) 1.6 (1.1-2.3)], childhood trauma [OR 4.5 (2.3-8.8)], and regular cannabis use [OR 8.3 (2.1-32.7)] independently predicted illness vulnerability as did an interaction between childhood trauma and cannabis use [OR 0.17 (0.03-0.9)]. Only regular cannabis use predicted having a schizophrenia spectrum diagnosis between patients and unaffected co-twins [OR 3.3 (1.1-10.4)]. Conclusion The findings suggest that several risk factors contribute to increasing schizophrenia spectrum vulnerability. Moreover, cannabis, a potentially completely avoidable environmental risk factor, seems to play a substantial role in schizophrenia pathology.

Background Males have a lower prevalence of depression than females and testosterone may be a contributing factor. A comparison of opposite-sex and same-sex twins can be used indirectly to establish the role of prenatal testosterone exposure and the risk of depression. We therefore aimed to explore differences in depression risk using opposite-sex and same-sex twins. Methods We included 126 087 opposite-sex and same-sex twins from the Danish Twin Registry followed in nationwide Danish registers. We compared sex-specific incidences of depression diagnosis and prescriptions of antidepressants between opposite-sex and same-sex twins using Cox proportional hazard regression. Results During follow-up, 2664 (2.1%) twins were diagnosed with depression and 19 514 (15.5%) twins had purchased at least one prescription of antidepressants. First, in male twins, we found that the opposite-sex male twins had the same risk of depression compared to the same-sex male twins {hazard ratio (HR) = 1.01 [95% confidence interval (CI) 0.88-1.17)]}. Revealing the risk of use of antidepressants, the opposite-sex male twins had a slightly higher risk of 4% (HR = 1.04 (95% CI 1.00-1.11)) compared with the same-sex male twins. Second, in the female opposite-sex twins, we revealed a slightly higher, however, not statistically significant risk of depression (HR = 1.08 (95% CI 0.97-1.29)) or purchase of antidepressants (HR = 1.01 (95% CI 0.96-1.05)) when compared to the same-sex female twins. Conclusions We found limited support for the hypothesis that prenatal exposure to testosterone was associated with the risk of depression later in life.

Background: Findings of reward disturbances in unaffected relatives of patients with schizophrenia suggest reward disturbances as an endophenotype for schizophrenia. Twin studies, where 1 twin has been diagnosed with a schizophrenia spectrum disorder, can further explore this. Methods: We used Danish registries to identify twin pairs with at least 1 twin having a schizophrenia spectrum disorder diagnosis and control twin pairs matched on age, sex, and zygosity. The analyses included data from 34 unaffected co-twins (16 females), 42 probands with schizophrenia spectrum disorder (17 females), and 83 control twins (42 females). Participants performed a modified incentive delay task during functional magnetic resonance imaging. Whole-brain group differences were analyzed by performing comparisons between co-twins and control twins. Correlations with cognitive flexibility were tested. Results: Compared with control twins, co-twins showed no differences in striatal regions, but increased signal in the dorsolateral prefrontal cortex (DLPFC) during missed target contrast was observed. In co-twins, increased DLPFC signal was associated with lower intra-extra dimensional set-shifting scores indicative of higher cognitive flexibility. Conclusions: Unaffected co-twins did not have decreased striatal activity during anticipation as previously reported for patients with schizophrenia. Instead, they showed increased activity in the DLPFC during evaluation of missed target contrast, which correlated with their level of cognitive flexibility. Unaffected co-twins had no diagnosis at a mean age of 40 years. This could indicate that greater cognitive flexibility and increased activity in the right DLPFC during processing of unexpected negative outcome represents a compensatory resilience mechanism in predisposed twins.

Background: Findings of reward disturbances in unaffected relatives of patients with schizophrenia suggest reward disturbances as an endophenotype for schizophrenia. Twin studies, where 1 twin has been diagnosed with a schizophrenia spectrum disorder, can further explore this. Methods: We used Danish registries to identify twin pairs with at least 1 twin having a schizophrenia spectrum disorder diagnosis and control twin pairs matched on age, sex, and zygosity. The analyses included data from 34 unaffected co-twins (16 females), 42 probands with schizophrenia spectrum disorder (17 females), and 83 control twins (42 females). Participants performed a modified incentive delay task during functional magnetic resonance imaging. Whole-brain group differences were analyzed by performing comparisons between co-twins and control twins. Correlations with cognitive flexibility were tested. Results: Compared with control twins, co-twins showed no differences in striatal regions, but increased signal in the dorsolateral prefrontal cortex (DLPFC) during missed target contrast was observed. In co-twins, increased DLPFC signal was associated with lower intra-extra dimensional set-shifting scores indicative of higher cognitive flexibility. Conclusions: Unaffected co-twins did not have decreased striatal activity during anticipation as previously reported for patients with schizophrenia. Instead, they showed increased activity in the DLPFC during evaluation of missed target contrast, which correlated with their level of cognitive flexibility. Unaffected co-twins had no diagnosis at a mean age of 40 years. This could indicate that greater cognitive flexibility and increased activity in the right DLPFC during processing of unexpected negative outcome represents a compensatory resilience mechanism in predisposed twins.

Background: Globally, the rapid increase of obesity is reaching alarming proportions. A new approach to reduce obesity and its comorbidities involves tackling the built environment. Environmental influences seem to play an important role, but the environmental influences in early life on adult body composition have not been thoroughly investigated. This study seeks to fill the research gap by examining early-life exposure to residential green spaces and traffic exposure in association with body composition among a population of young adult twins. Methods: As part of the East Flanders Prospective Twin Survey (EFPTS) cohort, this study included 332 twins. Residential addresses of the mothers at time of birth of the twins were geocoded to determine residential green spaces and traffic exposure. To capture body composition, body mass index, waist-to-hip ratio (WHR), waist circumference, skinfold thickness, leptin levels, and fat percentage were measured at adult age. Linear mixed modelling analyses were conducted to investigate early-life environmental exposures in association with body composition, while accounting for potential confounders. In addition, moderator effects of zygosity/chorionicity, sex and socio-economic status were tested. Results: Each interquartile range (IQR) increase in distance to highway was found associated with an increase of 1.2% in WHR (95%CI 0.2–2.2%). For landcover of green spaces, each IQR increase was associated with 0.8% increase in WHR (95%CI 0.4–1.3%), 1.4% increase in waist circumference (95%CI 0.5–2.2%), and 2.3% increase in body fat (95%CI 0.2–4.4%). Stratified analyses by zygosity/chorionicity type indicated that in monozygotic monochorionic twins, each IQR increase in land cover of green spaces was associated with 1.3% increase in WHR (95%CI 0.5–2.1%). In monozygotic dichorionic twins, each IQR increase in land cover of green spaces was associated with 1.4% increase in waist-circumference (95%CI 0.6–2.2%). Conclusions: The buil

The ability to perceive approximate numerosity is present in many animal species, and emerges early in human infants. Later in life, it is moderately heritable and associated with mathematical abilities, but the etiology of the Approximate Number System (ANS) and its degree of independence from other cognitive abilities in infancy is unknown. Here, we assessed the phenotypic specificity as well as the influence of genetic and environmental factors on the ANS in a sample of 5-month-old twins (N = 514). We found a small-to-moderate but statistically significant effects of genetic factors on ANS acuity (heritability = 0.18, 95% CI: 0.02, 0.33), but only when differences in numerosity were relatively large (1:4 ratio). Non-verbal ability assessed with the Mullen Scales of Early Learning (MSEL) was found to be heritable (0.47; 95% CI: 0.34, 0.57) and the phenotypic association between ANS acuity and non-verbal ability performance was close to zero. Similarly, we found no association between ANS acuity and general attention during the task. An unexpected weak but statistically significant negative association between ANS auity and scores on the receptive language scale of the MSEL was found. These results suggest that early ANS function may be largely independent from other aspects of non-verbal development. Further, variability in ANS in infancy seems to, to some extent, reflect genotypic differences in the population. Assessing 514 infant twins with eye tracking, we found that infant’s sense of approximate numerosity is heritable and not positively associated with concurrent attentional, cognitive or motor abilities. These results have implications for our understanding of development of mathematical ability and the link between cognitive abilities early in postnatal life.

Background: Evidence indicates that the adverse health effects of obesity differ between genetically and environmentally influenced obesity. We examined differences in the association between obesity and cardiovascular disease (CVD) between individuals with a genetically predicted low, medium, or high body mass index (BMI). Methods: We used cohort data from Swedish twins born before 1959 who had BMI measured between the ages of 40–64 years (midlife) or at the age of 65 years or later (late-life), or both, and prospective CVD information from nationwide register linkage through 2016. A polygenic score for BMI (PGSBMI) was used to define genetically predicted BMI. Individuals missing BMI or covariate data, or diagnosed with CVD at first BMI measure, were excluded, leaving an analysis sample of 17,988 individuals. We applied Cox proportional hazard models to examine the association between BMI category and incident CVD, stratified by the PGSBMI. Co-twin control models were applied to adjust for genetic influences not captured by the PGSBMI. Findings: Between 1984 and 2010, the 17,988 participants were enrolled in sub-studies of the Swedish Twin Registry. Midlife obesity was associated with a higher risk of CVD across all PGSBMI categories, but the association was stronger with genetically predicted lower BMI (hazard ratio from 1.55 to 2.08 for those with high and low PGSBMI, respectively). Within monozygotic twin pairs, the association did not differ by genetically predicted BMI, indicating genetic confounding not captured by the PGSBMI. Results were similar when obesity was measured in late-life, but suffered from low power. Interpretation: Obesity was associated with CVD regardless of PGSBMI category, but obesity influenced by genetic predisposition (genetically predicted high BMI) was less harmful than obesity influenced by environmental factors (obesity despite genetically predicted low BMI). However, additional genetic factors, not captured by the PGSBMI, still in, CC BY 4.0© 2023 The Author(s)Corresponding author: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-1177 Stockholm, Sweden.E-mail address: ida.karlsson@ki.se (I.K. Karlsson).This work was supported by the Strategic Research Program in Epidemiology at Karolinska Institutet; Loo and Hans Osterman’s Foundation (2022-01222); Foundation for Geriatric Diseases at Karolinska Institutet (2022-01296); the Swedish Research Council for Health, Working Life and Welfare (2018-01201 and 2022-00672); the Swedish Research Council (2016-03081); and the National Institutes of Health (R01 AG060470). We acknowledge the Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no. 2017-00641. The STR sub-studies were supported by the National Institutes of Health (grants R01 AG10175, R01 AG08724, R01 AG08861, R01 AG028555, and U01 DK066134), the MacArthur Foundation Research Network on Successful Aging, the Axel and Margaret Ax:son Johnsons Foundation, the Swedish Research Council, the Swedish Foundation for Health Care Sciences and Allergy Research, and the Swedish Council for Working Lifeand Social Research (2013-2292).

In Soleil amer, Lilia Hassaine revisits Algerian immigration in the post-colonial period. We will see in this article that the author chooses to make her characters evolve over three decades, each of which illustrates a stage in the urban planning during that period. The sixties were those of utopia with the birth of social housing, the seventies those of abandonment with the change in social policies, and the eighties those of decadence, condemning these large suburban estates to progressive ghettoisation. We understand that Saïd and Naja's family, dragged down by this same decadence, is also a victim of the consequences of these social policies and of the end of the mirage of integration that the HLM housing estates represented in the 1960s. The writer points to the political responsibility for the exclusion of these suburban areas, but also to the Franco-Algerian wound that is still open today., En Soleil amer, Lilia Hassaine retoma el tema de la inmigración argelina en el periodo poscolonial. Veremos aquí que la autora opta por hacer evolucionar a sus personajes al ritmo de tres décadas, cada una reflejando respectivamente una etapa del urbanismo de entonces. Los años sesenta fueron los de la utopía con el nacimiento de la vivienda de protección oficial, los setenta los del abandono con el cambio de las políticas sociales, y los ochenta los de la decadencia, condenando a estos grandes conjuntos suburbanos a una progresiva guetificación. Entendemos que la familia de Saïd y Naja, arrastrada por esta misma decadencia, es también víctima de las consecuencias de estas políticas sociales y del fin del espejismo de integración que representaban las urbanizaciones HLM en los 60. La escritora apunta a la responsabilidad política de la exclusión de estas zonas suburbanas, pero también a la herida franco-argelina que todavía sigue abierta., Dans Soleil amer, Lilia Hassaine revient sur l’immigration algérienne de la période postcoloniale. Nous verrons dans cet article que l’auteure choisit de faire évoluer ses personnages au rythme de trois décennies qui illustrent, chacune d’elle, une étape de la planification urbaine de l’époque. Les années 60 seront celles de l’utopie avec la naissance des HLM, les années 70 celles de l’abandon avec le changement des politiques sociales et, la décennie des 80 celle de la décadence condamnant ces grands ensembles de banlieues à une ghettoïsation progressive. Nous comprendrons que la famille de Saïd et Naja, entraînée dans ce même déclin, est elle aussi victime des conséquences de ces politiques sociales et de la fin de ce mirage d’insertion que représentèrent les cités HLM dans les années 60. L’écrivaine pointera ainsi du doigt les responsabilités politiques dans l’exclusion de ces zones périurbaines mais aussi, la plaie franco-algérienne encore ouverte de nos jours.

Background: Insomnia with short sleep duration has been postulated as more severe than that accompanied by normal/long sleep length. While the short duration subtype is considered to have greater genetic influence than the other subtype, no studies have addressed this question. This study aimed to compare these subtypes in terms of: (1) the heritability of insomnia symptoms; (2) polygenic scores (PGS) for insomnia symptoms and sleep duration; (3) the associations between insomnia symptoms and a wide variety of traits/disorders. Methods: The sample comprised 4000 pairs of twins aged 16 from the Twins Early Development Study. Twin models were fitted to estimate the heritability of insomnia in both groups. PGS were calculated for self-reported insomnia and sleep duration and compared among participants with short and normal/long sleep duration. Results: Heritability was not significantly different in the short sleep duration group (A = 0.13 [95%CI = 0.01, 0.32]) and the normal/long sleep duration group (A = 0.35 [95%CI = 0.29, 0.40]). Shared environmental factors accounted for a substantial proportion of the variance in the short sleep duration group (C = 0.19 [95%CI = 0.05, 0.32]) but not in the normal/long sleep duration group (C = 0.00 [95%CI = 0.00, 0.04]). PGS did not differ significantly between groups although results were in the direction expected by the theory. Our results also showed that insomnia with short (as compared to normal/long) sleep duration had a stronger association with anxiety and depression (p < .05)—although not once adjusting for multiple testing. Conclusions: We found mixed results in relation to the expected differences between the insomnia subtypes in adolescents. Future research needs to further establish cut-offs for ‘short’ sleep at different developmental stages and employ objective measures of sleep.

Study Objectives: Digital technology use is associated with poor sleep quality in adolescence and young adulthood although research findings have been mixed. No studies have addressed the association between the two using a genetically informative twin design which could extend our understanding of the etiology of this relationship. This study aimed to test: (1) the association between adolescents’ perceived problematic use of digital technology and poor sleep quality, (2) whether the association between problematic use of technology and poor sleep quality remains after controlling for familial factors, and (3) genetic and environmental influences on the association between problematic use of technology and poor sleep quality. Methods: Participants were 2232 study members (18-year-old twins) of the Environmental Risk (E-Risk) Longitudinal Twin Study. The sample was 48.9% male, 90% white, and 55.6% monozygotic. We conducted regression and twin difference analyses and fitted twin models. Results: Twin differences for problematic use of technology were associated with differences for poor sleep quality in the whole sample (p < 0.001; B = 0.15) and also when we limited the analyses to identical twins only (p < 0.001; B = 0.21). We observed a substantial genetic correlation between problematic use of technology and sleep quality (rA = 0.31), whereas the environmental correlation was lower (rE = 0.16). Conclusions: Adolescent reported problematic use of digital technology is associated with poor sleep quality—even after controlling for familial factors including genetic confounds. Our results suggest that the association between adolescents’ sleep and problematic digital technology use is not accounted for by shared genetic liability or familial factors but could reflect a causal association. This robust association needs to be examined in future research designed to test causal associations.

Background: Evidence indicates that the adverse health effects of obesity differ between genetically and environmentally influenced obesity. We examined differences in the association between obesity and cardiovascular disease (CVD) between individuals with a genetically predicted low, medium, or high body mass index (BMI). Methods: We used cohort data from Swedish twins born before 1959 who had BMI measured between the ages of 40–64 years (midlife) or at the age of 65 years or later (late-life), or both, and prospective CVD information from nationwide register linkage through 2016. A polygenic score for BMI (PGSBMI) was used to define genetically predicted BMI. Individuals missing BMI or covariate data, or diagnosed with CVD at first BMI measure, were excluded, leaving an analysis sample of 17,988 individuals. We applied Cox proportional hazard models to examine the association between BMI category and incident CVD, stratified by the PGSBMI. Co-twin control models were applied to adjust for genetic influences not captured by the PGSBMI. Findings: Between 1984 and 2010, the 17,988 participants were enrolled in sub-studies of the Swedish Twin Registry. Midlife obesity was associated with a higher risk of CVD across all PGSBMI categories, but the association was stronger with genetically predicted lower BMI (hazard ratio from 1.55 to 2.08 for those with high and low PGSBMI, respectively). Within monozygotic twin pairs, the association did not differ by genetically predicted BMI, indicating genetic confounding not captured by the PGSBMI. Results were similar when obesity was measured in late-life, but suffered from low power. Interpretation: Obesity was associated with CVD regardless of PGSBMI category, but obesity influenced by genetic predisposition (genetically predicted high BMI) was less harmful than obesity influenced by environmental factors (obesity despite genetically predicted low BMI). However, additional genetic factors, not captured by the PGSBMI, still in, CC BY 4.0© 2023 The Author(s)Corresponding author: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-1177 Stockholm, Sweden.E-mail address: ida.karlsson@ki.se (I.K. Karlsson).This work was supported by the Strategic Research Program in Epidemiology at Karolinska Institutet; Loo and Hans Osterman’s Foundation (2022-01222); Foundation for Geriatric Diseases at Karolinska Institutet (2022-01296); the Swedish Research Council for Health, Working Life and Welfare (2018-01201 and 2022-00672); the Swedish Research Council (2016-03081); and the National Institutes of Health (R01 AG060470). We acknowledge the Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no. 2017-00641. The STR sub-studies were supported by the National Institutes of Health (grants R01 AG10175, R01 AG08724, R01 AG08861, R01 AG028555, and U01 DK066134), the MacArthur Foundation Research Network on Successful Aging, the Axel and Margaret Ax:son Johnsons Foundation, the Swedish Research Council, the Swedish Foundation for Health Care Sciences and Allergy Research, and the Swedish Council for Working Lifeand Social Research (2013-2292).

Background: Evidence indicates that the adverse health effects of obesity differ between genetically and environmentally influenced obesity. We examined differences in the association between obesity and cardiovascular disease (CVD) between individuals with a genetically predicted low, medium, or high body mass index (BMI). Methods: We used cohort data from Swedish twins born before 1959 who had BMI measured between the ages of 40–64 years (midlife) or at the age of 65 years or later (late-life), or both, and prospective CVD information from nationwide register linkage through 2016. A polygenic score for BMI (PGSBMI) was used to define genetically predicted BMI. Individuals missing BMI or covariate data, or diagnosed with CVD at first BMI measure, were excluded, leaving an analysis sample of 17,988 individuals. We applied Cox proportional hazard models to examine the association between BMI category and incident CVD, stratified by the PGSBMI. Co-twin control models were applied to adjust for genetic influences not captured by the PGSBMI. Findings: Between 1984 and 2010, the 17,988 participants were enrolled in sub-studies of the Swedish Twin Registry. Midlife obesity was associated with a higher risk of CVD across all PGSBMI categories, but the association was stronger with genetically predicted lower BMI (hazard ratio from 1.55 to 2.08 for those with high and low PGSBMI, respectively). Within monozygotic twin pairs, the association did not differ by genetically predicted BMI, indicating genetic confounding not captured by the PGSBMI. Results were similar when obesity was measured in late-life, but suffered from low power. Interpretation: Obesity was associated with CVD regardless of PGSBMI category, but obesity influenced by genetic predisposition (genetically predicted high BMI) was less harmful than obesity influenced by environmental factors (obesity despite genetically predicted low BMI). However, additional genetic factors, not captured by the PGSBMI, still in, CC BY 4.0© 2023 The Author(s)Corresponding author: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-1177 Stockholm, Sweden.E-mail address: ida.karlsson@ki.se (I.K. Karlsson).This work was supported by the Strategic Research Program in Epidemiology at Karolinska Institutet; Loo and Hans Osterman’s Foundation (2022-01222); Foundation for Geriatric Diseases at Karolinska Institutet (2022-01296); the Swedish Research Council for Health, Working Life and Welfare (2018-01201 and 2022-00672); the Swedish Research Council (2016-03081); and the National Institutes of Health (R01 AG060470). We acknowledge the Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no. 2017-00641. The STR sub-studies were supported by the National Institutes of Health (grants R01 AG10175, R01 AG08724, R01 AG08861, R01 AG028555, and U01 DK066134), the MacArthur Foundation Research Network on Successful Aging, the Axel and Margaret Ax:son Johnsons Foundation, the Swedish Research Council, the Swedish Foundation for Health Care Sciences and Allergy Research, and the Swedish Council for Working Lifeand Social Research (2013-2292).

During the last decade quantitative and molecular genetic research on sleep has increased considerably. New behavioural genetics techniques have marked a new era for sleep research. This paper provides a summary of the most important findings from the last ten years, on the genetic and environmental influences on sleep and sleep disorders and their associations with health-related variables (including anxiety and depression) in humans. In this review we present a brief summary of the main methods in behaviour genetic research (such as twin and genome-wide association studies). We then discuss key research findings on: genetic and environmental influences on normal sleep and sleep disorders, as well as on the association between sleep and health variables (highlighting a substantial role for genes in individual differences in sleep and their associations with other variables). We end by discussing future lines of enquiry and drawing conclusions, including those focused on problems and misconceptions associated with research of this type. In this last decade our knowledge about genetic and environmental influences on sleep and its disorders has expanded. Both, twin and genome-wide association studies show that sleep and sleep disorders are substantially influenced by genetic factors and for the very first time multiple specific genetic variants have been associated with sleep traits and disorders.

The ability to perceive approximate numerosity is present in many animal species, and emerges early in human infants. Later in life, it is moderately heritable and associated with mathematical abilities, but the etiology of the Approximate Number System (ANS) and its degree of independence from other cognitive abilities in infancy is unknown. Here, we assessed the phenotypic specificity as well as the influence of genetic and environmental factors on the ANS in a sample of 5-month-old twins (N = 514). We found a small-to-moderate but statistically significant effects of genetic factors on ANS acuity (heritability = 0.18, 95% CI: 0.02, 0.33), but only when differences in numerosity were relatively large (1:4 ratio). Non-verbal ability assessed with the Mullen Scales of Early Learning (MSEL) was found to be heritable (0.47; 95% CI: 0.34, 0.57) and the phenotypic association between ANS acuity and non-verbal ability performance was close to zero. Similarly, we found no association between ANS acuity and general attention during the task. An unexpected weak but statistically significant negative association between ANS auity and scores on the receptive language scale of the MSEL was found. These results suggest that early ANS function may be largely independent from other aspects of non-verbal development. Further, variability in ANS in infancy seems to, to some extent, reflect genotypic differences in the population. Assessing 514 infant twins with eye tracking, we found that infant’s sense of approximate numerosity is heritable and not positively associated with concurrent attentional, cognitive or motor abilities. These results have implications for our understanding of development of mathematical ability and the link between cognitive abilities early in postnatal life.

Background: There is some evidence that autism spectrum disorder (ASD) frequently co-occurs with immune-mediated conditions including asthma. We aimed to explore the familial co-aggregation of ASD and asthma using different genetically informed designs. Methods: We first examined familial co-aggregation of asthma and ASD in individuals born in Sweden from 1992 to 2007 (n = 1 569 944), including their full- and half-siblings (n = 1 704 388 and 356 544 pairs) and full cousins (n = 3 921 890 pairs), identified using Swedish register data. We then applied quantitative genetic modeling to siblings (n = 620 994 pairs) and twins who participated in the Child and Adolescent Twin Study in Sweden (n = 15 963 pairs) to estimate the contribution of genetic and environmental factors to the co-aggregation. Finally, we estimated genetic correlations between traits using linkage disequilibrium score regression (LDSC). Results: We observed a within-individual association [adjusted odds ratio (OR) 1.33, 95% confidence interval (CI) 1.28-1.37] and familial co-aggregation between asthma and ASD, and the magnitude of the associations decreased as the degree of relatedness decreased (full-siblings: OR 1.44, 95% CI 1.38-1.50, maternal half-siblings: OR 1.28, 95% CI 1.18-1.39, paternal half-siblings: OR 1.05, 95% CI 0.96-1.15, full cousins: OR 1.06, 95% CI 1.03-1.09), suggesting shared familial liability. Quantitative genetic models estimated statistically significant genetic correlations between ASD traits and asthma. Using the LDSC approach, we did not find statistically significant genetic correlations between asthma and ASD (coefficients between -0.09 and 0.12). Conclusions: Using different genetically informed designs, we found some evidence of familial co-aggregation between asthma and ASD, suggesting the weak association between these disorders was influenced by shared genetics.

Background: Globally, the rapid increase of obesity is reaching alarming proportions. A new approach to reduce obesity and its comorbidities involves tackling the built environment. Environmental influences seem to play an important role, but the environmental influences in early life on adult body composition have not been thoroughly investigated. This study seeks to fill the research gap by examining early-life exposure to residential green spaces and traffic exposure in association with body composition among a population of young adult twins. Methods: As part of the East Flanders Prospective Twin Survey (EFPTS) cohort, this study included 332 twins. Residential addresses of the mothers at time of birth of the twins were geocoded to determine residential green spaces and traffic exposure. To capture body composition, body mass index, waist-to-hip ratio (WHR), waist circumference, skinfold thickness, leptin levels, and fat percentage were measured at adult age. Linear mixed modelling analyses were conducted to investigate early-life environmental exposures in association with body composition, while accounting for potential confounders. In addition, moderator effects of zygosity/chorionicity, sex and socio-economic status were tested. Results: Each interquartile range (IQR) increase in distance to highway was found associated with an increase of 1.2% in WHR (95%CI 0.2–2.2%). For landcover of green spaces, each IQR increase was associated with 0.8% increase in WHR (95%CI 0.4–1.3%), 1.4% increase in waist circumference (95%CI 0.5–2.2%), and 2.3% increase in body fat (95%CI 0.2–4.4%). Stratified analyses by zygosity/chorionicity type indicated that in monozygotic monochorionic twins, each IQR increase in land cover of green spaces was associated with 1.3% increase in WHR (95%CI 0.5–2.1%). In monozygotic dichorionic twins, each IQR increase in land cover of green spaces was associated with 1.4% increase in waist-circumference (95%CI 0.6–2.2%). Conclusions: The buil

The ability to perceive approximate numerosity is present in many animal species, and emerges early in human infants. Later in life, it is moderately heritable and associated with mathematical abilities, but the etiology of the Approximate Number System (ANS) and its degree of independence from other cognitive abilities in infancy is unknown. Here, we assessed the phenotypic specificity as well as the influence of genetic and environmental factors on the ANS in a sample of 5-month-old twins (N = 514). We found a small-to-moderate but statistically significant effects of genetic factors on ANS acuity (heritability = 0.18, 95% CI: 0.02, 0.33), but only when differences in numerosity were relatively large (1:4 ratio). Non-verbal ability assessed with the Mullen Scales of Early Learning (MSEL) was found to be heritable (0.47; 95% CI: 0.34, 0.57) and the phenotypic association between ANS acuity and non-verbal ability performance was close to zero. Similarly, we found no association between ANS acuity and general attention during the task. An unexpected weak but statistically significant negative association between ANS auity and scores on the receptive language scale of the MSEL was found. These results suggest that early ANS function may be largely independent from other aspects of non-verbal development. Further, variability in ANS in infancy seems to, to some extent, reflect genotypic differences in the population. Assessing 514 infant twins with eye tracking, we found that infant’s sense of approximate numerosity is heritable and not positively associated with concurrent attentional, cognitive or motor abilities. These results have implications for our understanding of development of mathematical ability and the link between cognitive abilities early in postnatal life.

Human induced pluripotent stem cells (hiPSCs) enable reproductive diseases to be studied when the reproductive health of the participant is known. In this study, monozygotic (MZ) monoamniotic (MA) twins discordant for primary ovarian insufficiency (POI) consent to research to address the hypothesis that discordant POI is due to a shared primordial germ cell (PGC) progenitor pool. If this is the case, reprogramming the twin's skin cells to hiPSCs is expected to restore equivalent germ cell competency to the twins hiPSCs. Following reprogramming, the infertile MA twin's cells are capable of generating human PGC-like cells (hPGCLCs) and amniotic sac-like structures equivalent to her fertile twin sister. Using these hiPSCs together with genome sequencing, our data suggest that POI in the infertile twin is not due to a genetic barrier to amnion or germ cell formation and support the hypothesis that during gestation, amniotic PGCs are likely disproportionately allocated to the fertile twin with embryo splitting.

We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.

ObjectiveTwins account for approximately 1 in 30 live births in the United States. However, there are limited clinical experience studies published in noninvasive prenatal testing (NIPT) for detecting aneuploidies in twins. This study reports the performance of an SNP-based NIPT in the largest cohort with known outcomes for high-risk aneuploidy results.MethodThis is a retrospective analysis of 18,984 results from commercial single-nucleotide polymorphism (SNP)-based NIPT tests performed in twins between October 2, 2017 and December 31, 2019. Follow-up for all 211 high-risk cases was solicited.ResultsFollow-up outcomes were obtained in 105 cases. Positive predictive values (PPVs) for high-risk results were 88.7% (63/71, 95% Confidence Interval [CI]: 79.0%-95.0%) for trisomy 21% and 72.7% (8/11, 95% CI: 39.0%-94.0%) for trisomy 18. The results were stratified into monozygotic (MZ) and dizygotic (DZ). The PPVs in MZ were 100% for both trisomy 21 (4/4, 95% CI: 40%-100%) and trisomy 18 (1/1, 95% CI: 2.5%-100%). No trisomy 13 cases were detected in the MZ group. The PPVs in DZ were 88.1% (59/67, 95% CI: 77.8%-94.7%), 70.0% (7/10, 95% CI: 34.8%-93.3%), and 66.7% (2/3, 95% CI: 9.4%-99.2%) for trisomy 21, trisomy 18, and trisomy 13, respectively.ConclusionThe performance of SNP-based NIPT in this large twin cohort was comparable to previously reported twin NIPT studies. SNP-based NIPT allows for zygosity-based PPV assessment.

Theories in sociology argue that family background and individual experiences shape cultural tastes and participation. Yet, we do not know the relative importance of each explanation or the extent to which family background operates via shared genes or shared environments. In this article, we use new data on same-sex monozygotic and dizygotic twins from Denmark to estimate the total impact of family background (genetic and environmental) and individual experiences on highbrow and lowbrow tastes and participation and on omnivorousness in music and reading. We find that family background explains more than half of the total variance in cultural tastes and participation and in omnivorousness. Moreover, family background operates mainly via shared genes, with shared environments shaping cultural tastes to some extent, but not cultural participation. Our findings support theories claiming that family background is instrumental in shaping cultural tastes and participation but highlight the relevance of distinguishing genetic and environmental aspects of family background.

Studies in genetically 'identical' individuals indicate that as much as 50% of complex trait variation cannot be traced to genetics or to the environment. The mechanisms that generate this 'unexplained' phenotypic variation (UPV) remain largely unknown. Here, we identify neuronatin (NNAT) as a conserved factor that buffers against UPV. We find that Nnat deficiency in isogenic mice triggers the emergence of a bi-stable polyphenism, where littermates emerge into adulthood either 'normal' or 'overgrown'. Mechanistically, this is mediated by an insulin-dependent overgrowth that arises from histone deacetylase (HDAC)-dependent beta-cell hyperproliferation. A multi-dimensional analysis of monozygotic twin discordance reveals the existence of two patterns of human UPV, one of which (Type B) phenocopies the NNAT-buffered polyphenism identified in mice. Specifically, Type-B monozygotic co-twins exhibit coordinated increases in fat and lean mass across the body; decreased NNAT expression; increased HDAC-responsive gene signatures; and clinical outcomes linked to insulinemia. Critically, the Type-B UPV signature stratifies both childhood and adult cohorts into four metabolic states, including two phenotypically and molecularly distinct types of obesity.Yang et al. show that neuronatin (NNAT) can explain part of the phenotypic variation of complex traits, independently of genetics or the environment. Such NNAT-dependent variations can stratify human cohorts into four metabolic sub-types, including two distinct types of obesity.

BACKGROUND: Emotion dysregulation (ED) is common in attention-deficit/hyperactivity disorder (ADHD) and often results in adverse outcomes. However, ED has been suggested as a transdiagnostic construct, why the specific association between ADHD and ED when adjusting for other mental health conditions needs further investigation. It is also important to determine the aetiological basis of the association between ADHD and ED to inform the theoretical conceptualization of ADHD. METHOD: This study used a co-twin control design, including a sample of dizygotic (DZ) and monozygotic (MZ) twins (N = 389; 45.8% females, age = 8-31 years, MZ twin pairs 57.6%). ED was assessed using the dysregulation profile from the parent-rated Child Behaviour Checklist and its adult version. Regression analyses were used across individuals and within the pairs, while adjusting for diagnoses of autism, intellectual disability, other neurodevelopmental conditions and affective conditions. RESULTS: ADHD was significantly associated with ED, even when adjusting for age, sex, attention problems and other mental health conditions, and was the diagnosis most strongly associated with ED. Within-pair analyses revealed that twins with ADHD had higher levels of ED compared to their co-twin without ADHD. This association remained within DZ twins and was non-significant in the MZ subsample, with non-overlapping confidence intervals between the DZ and MZ estimates. CONCLUSION: ADHD is strongly and in part independently linked to ED, stressing the importance of early detection and treatment of emotional difficulties within this group. The findings from the within-pair analyses indicate a genetic influence on the association between ADHD and ED.

This work studies the role of the twins Claridiano and Rosalvira in the second part of the Espejo de Príncipes y Caballeros, by Pedro de la Sierra (1580), since it is a family bond that is prominent in the cycle. This research postulates that in this work, twins become an emblematic resource that reinforces the continuity between the parts, as they resume the bond of the protagonists of the first part, meet objectives set in it and introduce structural innovation. Three aspects are reviewed: the passage of the twins from the first to the second part, the narrative possibilities of twins of different sex, and the development of the main conflict, which revolves around incest., El presente trabajo estudia la función de los mellizos Claridiano y Rosalvira en la segunda parte del Espejo de Príncipes y Caballeros de Pedro de la Sierra (1580), ya que es un vínculo familiar que abunda en el ciclo. La investigación postula que en esta obra los mellizos se convierten en un recurso emblemático que refuerza la continuidad entre las partes, pues retoman el vínculo de los protagonistas de la primera parte, cumplen objetivos planteados en esta e introducen innovación estructural. Se revisan tres aspectos: el paso de los mellizos de la primera a la segunda parte, las posibilidades narrativas de mellizos de diferente sexo y el desarrollo del conflicto principal, relacionado con el incesto., El presente trabajo estudia la función de los mellizos Claridiano y Rosalvira en la segunda parte del Espejo de Príncipes y Caballeros, de Pedro de la Sierra (1580), ya que es un de vínculo familiar que abunda en el ciclo. La investigación postula que en esta obra los mellizos se convierten en un recurso emblemático que refuerza la continuidad entre las partes, pues retoman el vínculo de los protagonistas de la primera parte, cumplen objetivos planteados en esta e introducen innovación estructural. Se revisan tres aspectos: el paso de los mellizos de la primera a la segunda parte, las posibilidades narrativas de mellizos de diferente sexo y el desarrollo del conflicto principal, relacionado con el incesto.

Theories in sociology argue that family background and individual experiences shape cultural tastes and participation. Yet, we do not know the relative importance of each explanation or the extent to which family background operates via shared genes or shared environments. In this article, we use new data on same-sex monozygotic and dizygotic twins from Denmark to estimate the total impact of family background (genetic and environmental) and individual experiences on highbrow and lowbrow tastes and participation and on omnivorousness in music and reading. We find that family background explains more than half of the total variance in cultural tastes and participation and in omnivorousness. Moreover, family background operates mainly via shared genes, with shared environments shaping cultural tastes to some extent, but not cultural participation. Our findings support theories claiming that family background is instrumental in shaping cultural tastes and participation but highlight the relevance of distinguishing genetic and environmental aspects of family background.

While prior research has demonstrated a relationship between sleep and cognitive performance, how sleep relates to underlying genetic and environmental etiologies contributing to cognitive functioning, regardless of the level of cognitive function, is unclear. The present study assessed whether the importance of genetic and environmental contributions to cognition vary depending on an individual’s aging-related sleep characteristics. The large sample consisted of twins from six studies within the Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium spanning mid- to late-life (Average age [Mage] = 57.6, range = 27–91 years, N = 7052, Female = 43.70%, 1525 complete monozygotic [MZ] pairs, 2001 complete dizygotic [DZ] pairs). Quantitative genetic twin models considered sleep duration as a primary moderator of genetic and environmental contributions to cognitive performance in four cognitive abilities (Semantic Fluency, Spatial-Visual Reasoning, Processing Speed, and Episodic Memory), while accounting for age moderation. Results suggested genetic and both shared and nonshared environmental contributions for Semantic Fluency and genetic and shared environmental contributions for Episodic Memory vary by sleep duration, while no significant moderation was observed for Spatial-Visual Reasoning or Processing Speed. Results for Semantic Fluency and Episodic Memory illustrated patterns of higher genetic influences on cognitive function at shorter sleep durations (i.e. 4 hours) and higher shared environmental contributions to cognitive function at longer sleep durations (i.e. 10 hours). Overall, these findings may align with associations of upregulation of neuroinflammatory processes and ineffective beta-amyloid clearance in short sleep contexts and common reporting of mental fatigue in long sleep contexts, both associated with poorer cognitive functioning., Published:21 June 2022IGEMS is supported by the National Institutes of Health Grants No. R01 AG037985, R56 AG037985, R01 AG059329, R01 AG060470, RF1 AG058068. SATSA was supported by grants R01 AG04563, R01 AG10175, the John D. and Catherine T. MacArthur Foundation Research Network on Successful Aging, the Swedish Council For Working Life and Social Research (FAS) (97:0147:1B, 2009-0795) and Swedish Research Council (825-2007-7460, 825-2009-6141). OCTO-Twin was supported by grant R01 AG08861. The Danish Twin Registry is supported by grants from The National Program for Research Infrastructure 2007 from the Danish Agency for Science and Innovation, the Velux Foundation and the US National Institute of Health (P01 AG08761). The Minnesota Twin Study of Adult Development and Aging was supported by NIA grant R01 AG06886. VETSA was supported by National Institute of Health grants NIA R01 AG018384, R01 AG018386, R01 AG022381, and R01 AG022982, and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. This MIDUS study was supported by the John D. and Catherine T. MacArthur Foundation Research Network on Successful Midlife Development and by National Institute on Aging Grant AG20166.

Genetic and early environmental differences including early health habits associate with future health. To provide insight on the causal nature of these associations, monozygotic (MZ) twin pairs discordant for health habits provide an interesting natural experiment. Twin pairs discordant for leisure-time physical activity (LTPA) in early adult life is thus a powerful study design to investigate the associations between long-term LTPA and indicators of health and wellbeing. We have identified 17 LTPA discordant twin pairs from two Finnish twin cohorts and summarize key findings of these studies in this paper. The carefully characterized rare long-term LTPA discordant MZ twin pairs have participated in multi-dimensional clinical examinations. Key findings highlight that compared with less active twins in such MZ twin pairs, the twins with higher long-term LTPA have higher physical fitness, reduced body fat, reduced visceral fat, reduced liver fat, increased lumen diameters of conduit arteries to the lower limbs, increased bone mineral density in loaded bone areas, and an increased number of large high-density lipoprotein particles. The findings increase our understanding on the possible site-specific and system-level effects of long-term LTPA.

BACKGROUND: Twins and late preterm (LPT) infants are at an increased risk of being breastfed to a lesser extent than term singletons. This study aimed to describe the initiation and duration of any and exclusive breastfeeding at the breast for mothers of LPT twins and term twins during the first 4 months and to explore the breastfeeding experiences of mothers of LPT twins. METHODS: A sequential two-sample quantitative-qualitative explanatory mixed-methods design was used. The quantitative data were derived from a longitudinal cohort study in which 22 mothers of LPT twins and 41 mothers of term twins answered questionnaires at one and four months after birth (2015-2017). The qualitative data were obtained from semi-structured interviews with 14 mothers of LPT twins (2020-2021), based on results from the quantitative study and literature. Analysis included descriptive statistics of quantitative data and deductive content analysis of the qualitative data, followed by condensation and synthesis. RESULTS: All mothers of LPT twins (100%) and most mothers of term twins (96%) initiated breastfeeding. There was no difference in any breastfeeding during the first week at home (98% versus 95%) and at 1 month (88% versus 85%). However, at 4 months, the difference was significant (44% versus 75%). The qualitative data highlighted that mothers of LPT twins experienced breastfeeding as complex and strenuous. Key factors influencing mothers' experiences and decisions were their infants' immature breastfeeding behaviors requiring them to express breast milk alongside breastfeeding, the burden of following task-oriented feeding regimes, and the lack of guidance from healthcare professionals. As a result, mothers started to question the worth of their breastfeeding efforts, leading to changes in breastfeeding management with diverse results. Support from fathers and grandparents positively influenced sustained breastfeeding. CONCLUSIONS: Mothers of LPT twins want to breastfeed, but th

BACKGROUND: Twins and late preterm (LPT) infants are at an increased risk of being breastfed to a lesser extent than term singletons. This study aimed to describe the initiation and duration of any and exclusive breastfeeding at the breast for mothers of LPT twins and term twins during the first 4 months and to explore the breastfeeding experiences of mothers of LPT twins. METHODS: A sequential two-sample quantitative-qualitative explanatory mixed-methods design was used. The quantitative data were derived from a longitudinal cohort study in which 22 mothers of LPT twins and 41 mothers of term twins answered questionnaires at one and four months after birth (2015-2017). The qualitative data were obtained from semi-structured interviews with 14 mothers of LPT twins (2020-2021), based on results from the quantitative study and literature. Analysis included descriptive statistics of quantitative data and deductive content analysis of the qualitative data, followed by condensation and synthesis. RESULTS: All mothers of LPT twins (100%) and most mothers of term twins (96%) initiated breastfeeding. There was no difference in any breastfeeding during the first week at home (98% versus 95%) and at 1 month (88% versus 85%). However, at 4 months, the difference was significant (44% versus 75%). The qualitative data highlighted that mothers of LPT twins experienced breastfeeding as complex and strenuous. Key factors influencing mothers' experiences and decisions were their infants' immature breastfeeding behaviors requiring them to express breast milk alongside breastfeeding, the burden of following task-oriented feeding regimes, and the lack of guidance from healthcare professionals. As a result, mothers started to question the worth of their breastfeeding efforts, leading to changes in breastfeeding management with diverse results. Support from fathers and grandparents positively influenced sustained breastfeeding. CONCLUSIONS: Mothers of LPT twins want to breastfeed, but th

Masterarbeit Universität Innsbruck 2022

This paper focuses on the Indo-European myth of the primordial incest, foremost using evidence from Vedic (Ṛgveda and Atharvaveda) and, more broadly, Indo-Iranian. On the basis of a philological and linguistic analysis of the dialogue hymn RV 10.10 (Yama and Yamī), I argue that Yamī, notorious for her hyper-sexuality, can be considered as the central figure of this common Indo-Iranian myth, being the (potential) sexual partner of the first human, Yama, and yet retaining connection with the world of gods and half-gods (demons) and betraying a number of features of a female half-deity. I will also briefly discuss possible parallels from other Indo-European mythologies, in particular, from Celtic and Germanic (Norse) mythologies, paying special attention to the goddess of sexuality Freyja, comparable in several respects to Yamī.

Studies in genetically 'identical' individuals indicate that as much as 50% of complex trait variation cannot be traced to genetics or to the environment. The mechanisms that generate this 'unexplained' phenotypic variation (UPV) remain largely unknown. Here, we identify neuronatin (NNAT) as a conserved factor that buffers against UPV. We find that Nnat deficiency in isogenic mice triggers the emergence of a bi-stable polyphenism, where littermates emerge into adulthood either 'normal' or 'overgrown'. Mechanistically, this is mediated by an insulin-dependent overgrowth that arises from histone deacetylase (HDAC)-dependent beta-cell hyperproliferation. A multi-dimensional analysis of monozygotic twin discordance reveals the existence of two patterns of human UPV, one of which (Type B) phenocopies the NNAT-buffered polyphenism identified in mice. Specifically, Type-B monozygotic co-twins exhibit coordinated increases in fat and lean mass across the body; decreased NNAT expression; increased HDAC-responsive gene signatures; and clinical outcomes linked to insulinemia. Critically, the Type-B UPV signature stratifies both childhood and adult cohorts into four metabolic states, including two phenotypically and molecularly distinct types of obesity.Yang et al. show that neuronatin (NNAT) can explain part of the phenotypic variation of complex traits, independently of genetics or the environment. Such NNAT-dependent variations can stratify human cohorts into four metabolic sub-types, including two distinct types of obesity.

BACKGROUND: Emotion dysregulation (ED) is common in attention-deficit/hyperactivity disorder (ADHD) and often results in adverse outcomes. However, ED has been suggested as a transdiagnostic construct, why the specific association between ADHD and ED when adjusting for other mental health conditions needs further investigation. It is also important to determine the aetiological basis of the association between ADHD and ED to inform the theoretical conceptualization of ADHD. METHOD: This study used a co-twin control design, including a sample of dizygotic (DZ) and monozygotic (MZ) twins (N = 389; 45.8% females, age = 8-31 years, MZ twin pairs 57.6%). ED was assessed using the dysregulation profile from the parent-rated Child Behaviour Checklist and its adult version. Regression analyses were used across individuals and within the pairs, while adjusting for diagnoses of autism, intellectual disability, other neurodevelopmental conditions and affective conditions. RESULTS: ADHD was significantly associated with ED, even when adjusting for age, sex, attention problems and other mental health conditions, and was the diagnosis most strongly associated with ED. Within-pair analyses revealed that twins with ADHD had higher levels of ED compared to their co-twin without ADHD. This association remained within DZ twins and was non-significant in the MZ subsample, with non-overlapping confidence intervals between the DZ and MZ estimates. CONCLUSION: ADHD is strongly and in part independently linked to ED, stressing the importance of early detection and treatment of emotional difficulties within this group. The findings from the within-pair analyses indicate a genetic influence on the association between ADHD and ED.

BACKGROUND: Emotion dysregulation (ED) is common in attention-deficit/hyperactivity disorder (ADHD) and often results in adverse outcomes. However, ED has been suggested as a transdiagnostic construct, why the specific association between ADHD and ED when adjusting for other mental health conditions needs further investigation. It is also important to determine the aetiological basis of the association between ADHD and ED to inform the theoretical conceptualization of ADHD. METHOD: This study used a co-twin control design, including a sample of dizygotic (DZ) and monozygotic (MZ) twins (N = 389; 45.8% females, age = 8-31 years, MZ twin pairs 57.6%). ED was assessed using the dysregulation profile from the parent-rated Child Behaviour Checklist and its adult version. Regression analyses were used across individuals and within the pairs, while adjusting for diagnoses of autism, intellectual disability, other neurodevelopmental conditions and affective conditions. RESULTS: ADHD was significantly associated with ED, even when adjusting for age, sex, attention problems and other mental health conditions, and was the diagnosis most strongly associated with ED. Within-pair analyses revealed that twins with ADHD had higher levels of ED compared to their co-twin without ADHD. This association remained within DZ twins and was non-significant in the MZ subsample, with non-overlapping confidence intervals between the DZ and MZ estimates. CONCLUSION: ADHD is strongly and in part independently linked to ED, stressing the importance of early detection and treatment of emotional difficulties within this group. The findings from the within-pair analyses indicate a genetic influence on the association between ADHD and ED.

BACKGROUND: Emotion dysregulation (ED) is common in attention-deficit/hyperactivity disorder (ADHD) and often results in adverse outcomes. However, ED has been suggested as a transdiagnostic construct, why the specific association between ADHD and ED when adjusting for other mental health conditions needs further investigation. It is also important to determine the aetiological basis of the association between ADHD and ED to inform the theoretical conceptualization of ADHD. METHOD: This study used a co-twin control design, including a sample of dizygotic (DZ) and monozygotic (MZ) twins (N = 389; 45.8% females, age = 8-31 years, MZ twin pairs 57.6%). ED was assessed using the dysregulation profile from the parent-rated Child Behaviour Checklist and its adult version. Regression analyses were used across individuals and within the pairs, while adjusting for diagnoses of autism, intellectual disability, other neurodevelopmental conditions and affective conditions. RESULTS: ADHD was significantly associated with ED, even when adjusting for age, sex, attention problems and other mental health conditions, and was the diagnosis most strongly associated with ED. Within-pair analyses revealed that twins with ADHD had higher levels of ED compared to their co-twin without ADHD. This association remained within DZ twins and was non-significant in the MZ subsample, with non-overlapping confidence intervals between the DZ and MZ estimates. CONCLUSION: ADHD is strongly and in part independently linked to ED, stressing the importance of early detection and treatment of emotional difficulties within this group. The findings from the within-pair analyses indicate a genetic influence on the association between ADHD and ED.