Genetic and Environmental Architecture of Five Factor Model and Super-Factors: An Italian Twin Study

No previous research explored the genetic and environmental structure of Big Five dimensions of personality and higher-order factors in a single twin study, except, in part, for just one study. We used the twin design to estimate the effects of genes and environment on both Five Factor model and related second- and third-order factors (i.e., Alpha [stability], Beta [plasticity], and GFP [general factor of personality]). We analyzed data from 314 adult twins (157 pairs: 83 monozygotic, 74 dizygotic; mean age: 52 years) enrolled in the Italian Twin Register. Participants underwent clinical and instrumental evaluations, and completed a 25-adjective list drawn from the Short Adjectives Checklist to Measure Big Five (SACBIF). We applied quantitative genetic models to unravel the sources of variation and covariation for the Big Five and higher-order factors. We found a similar etiological architecture across the different levels of analysis, with moderate to substantial non-additive genetic and unique environmental influences on all the personality traits, and no shared environmental contribution for any of them. We also detected significant genetic correlations for the Big Five dimensions and the Alpha and Beta super-factors. With some limitations, our results suggest that the etiological architecture of personality may be invariant to the factor level of analysis.

Are Genetic and Environmental Contributions to Verbal Fluency and Episodic Memory Solely Moderated by Sleep?

Decreases in sleep duration and cognitive functioning often occur and co-occur in aging although these patterns are not universal. Underlying etiologies, i.e., genetic and environmental factors, contribute to why people differ on cognitive functioning at shorter versus longer sleep durations. The current study tested whether sleep duration alters the genetic and environmental contributions to why middle-aged and older adults vary on cognitive functioning. Using 4 twin studies from the Interplay of Genes and Environment Across Multiple Studies (IGEMS) consortium (Mage=56.5, range=35.0-91.2, N=5,210, 1,083 complete MZ pairs, 1,522 complete DZ pairs) we tested quantitative genetic twin models considering sleep, depressive symptoms, and age as moderators of verbal fluency (i.e., Animal Naming) and episodic memory (i.e., Word List). For verbal fluency, sleep duration and depressive symptoms were significant when dropped together from the model (χ2(6)=15.22, p=0.02) but not individually (χ2sleep(3)=7.17, p=0.07; χ2dep(3)=5.81, p=0.12), indicating that both moderators may affect differences in verbal fluency performance. For episodic memory, sleep duration moderation was only significant via the shared environmental factor (χ2(1)=5.26, p=0.02), indicating that sleep may affect differences in episodic memory performance via environmental influences that make siblings more similar to one another. Overall, results illustrate patterns of higher genetic influences on cognitive function at short sleep (4 hours) and higher shared environmental influences on cognitive function at long sleep (10 hours). These findings may align with associations of upregulation of neuroinflammatory processes at short sleep and common reporting of mental fatigue at long sleep, both of which are associated with poorer cognitive functioning.

Heritability of Sleep and Its Disorders in Childhood and Adolescence

Purpose of Review This review summarizes recent literature on the heritability of sleep and sleep disorders in childhood and adolescence. We also identify gaps in the literature and priorities for future research. Recent Findings Findings indicate that age, measurement method, reporter, and timing of sleep measurements can influence heritability estimates. Recent genome-wide association studies (GWAS) have identified differences in the heritability of sleep problems when ancestral differences are considered, but sample sizes are small compared to adult GWAS. Most studies focus on sleep variables in the full range rather than on disorder. Studies using objective measures of sleep typically comprised small samples. Summary Current evidence demonstrates a wide range of heritability estimates across sleep phenotypes in childhood and adolescence, but research in larger samples, particularly using objective sleep measures and GWAS, is needed. Further understanding of environmental mechanisms and the interaction between genes and environment is key for future research.

Reduced Brain Connectivity in Clinical and Dimensional Autism Phenotypes Beyond Familial Confounding – A Twin Study

BackgroundPrevious studies on brain connectivity in clinical and dimensional autism have largely focused on selective connections and yielded inconsistent results. This study aimed to overcome these limitations. Global fiber tracking allowed a more unbiased assessment of white matter connectivity and utilizing a within-twin pair design introduced implicit control for genetic and environmental factors shared by twins and allowed conclusions regarding their impact. MethodsThe study examined the within-twin pair associations between structural brain connectivity of anatomically defined brain regions and both clinical autism spectrum diagnoses and dimensional autistic traits in 85 twin pairs (n=170; 56% monozygotic; 25 individuals with autism spectrum diagnosis). Structural connectivity was estimated using diffusion tensor imaging and linear regression models were fit, adjusted for IQ, other neurodevelopmental and psychiatric conditions and multiple testing. ResultsOverall, both clinical and dimensional autism phenotypes were associated with localized reductions in structural connectivity, despite comprehensively controlling for possible confounders, including all factors shared by twins. Twins fulfilling autism spectrum diagnostic criteria showed decreased brainstem-cuneus connectivity compared to their co-twins without the diagnosis. Further, twins with higher autistic traits showed decreased connectivity of the left hippocampus with the left fusiform and parahippocampal areas. These associations pointed into the same direction in mono- and dizygotic sub-cohorts, but were only significant in dizygotic twins.LimitationsThe recruitment approach of selecting primarily twin pairs discordant for autistic traits prevented a quantitative estimation of genetic and environmental contributions to brain correlates of clinical and dimensional autism. Further, assessing twins and excluding individuals with an IQ below 75 limited the generalizability of the findings. The statistical power allowed detecting medium-size or larger effects of dimensional autism. Finally, due the relatively small number of twin pairs discordant for a clinical autism, the results for clinical autism need to be interpreted with caution.ConclusionsReduced brainstem-cuneus connectivity might point towards alterations in low-level visual processing in clinical autism while reduced connectivity in networks crucial for visual and especially face processing seem to be more associated with dimensional aspects of autism. The results further suggest that the observed associations were potentially influenced by both genes and environment.

Epigenetics and DOHaD: how translation to predictive testing will require a better public understanding

Epigenetics is likely to play a role in the mediation of the effects of genes and environment in risk for many non-communicable diseases (NCDs). The Developmental Origins of Health and Disease (DOHaD) theory presents unique opportunities regarding the possibility of early life interventions to alter the epigenetic makeup of an individual, thereby modifying their risk for a variety of NCDs. While it is important to determine how we can lower the risk of these NCDs, it is equally important to understand how the public’s knowledge and opinion of DOHaD and epigenetic concepts may influence their willingness to undertake such interventions for themselves and their children. In this review, we provide an overview of epigenetics, DOHaD, NCDs, and the links between them. We explore the issues surrounding using epigenetics to identify those at increased risk of NCDs, including the concept of predictive testing of children. We also outline what is currently understood about the public’s understanding and opinion of epigenetics, DOHaD, and their relation to NCDs. In doing so, we demonstrate that it is essential that future research explores the public’s awareness and understanding of epigenetics and epigenetic concepts. This will provide much-needed information which will prepare health professionals for the introduction of epigenetic testing into future healthcare.

Developmental noise is an overlooked contributor to innate variation in psychological traits

Stochastic developmental variation is an additional important source of variance – beyond genes and environment – that should be included in considering how our innate psychological predispositions may interact with environment and experience, in a culture-dependent manner, to ultimately shape patterns of human behaviour.

Awareness of maternal stress, consequences for the offspring and the need for early interventions to increase stress resilience

Experimental and clinical studies suggest that prenatal experiences may influence health trajectories up to adulthood and high age. According to the hypothesis of developmental origins of health and disease exposure of pregnant women to stress, nutritional challenges, infection, violence, or war may “program” risks for diseases in later life. Stress and anxieties can exist or be provoked in parents after fertility treatment, after information or diagnosis of fetal abnormalities and demand simultaneous caring concepts to support the parents. In vulnerable groups, it is therefore important to increase the stress resilience to avoid harmful consequences for the growing child. “Enriched environment” defines a key paradigm to decipher how interactions between genes and environment change the structure and function of the brain. The regulation of the fetal hippocampal neurogenesis and morphology during pregnancy is one example of this complex interaction. Animal experiments have demonstrated that an enriched environment can revert consequences of stress in the offspring during critical periods of brain plasticity. Epigenetic markers of stress or wellbeing during pregnancy might even be diagnosed by fragments of placental DNA in the maternal circulation that show characteristic methylation patterns. The development of fetal senses further illustrates how external stimulation may impact individual preferences. Here, we therefore not only discuss how maternal stress influences cognitive development and resilience, but also design possibilities of non-invasive interventions for both mothers and children summarized and evaluated in the light of their potential to improve the health of future generations.

Patient-Reported Symptom Severity in a Nationwide Myasthenia Gravis Cohort: Cross-sectional Analysis of the Swedish GEMG Study

Objectives:To describe Myasthenia Gravis-Activities of Daily Living (MG-ADL) in relation to clinical characteristics in a large Swedish nationwide cohort.Methods:In a cross-sectional prevalent cohort study, the Genes and Environment in Myasthenia Gravis study (GEMG), performed November 2018 - August 2019, Myasthenia gravis (MG) patients were invited to submit an extensive 106-item life environment questionnaire, including the MG-ADL score. Patients were classified into early onset MG (EOMG, <50 years), late onset MG (LOMG, ≥50 years) or thymoma-associated MG (TAMG). Comparisons of disease-specific characteristics were made between subgroups, sex and different MG-ADL scores.Results:A total of 1077 patients were included, yielding a 74% response rate: 505 (47%) were classified as EOMG, 520 (48%) LOMG and 45 (4%) TAMG. Mean age at inclusion was 64.3 years (SD 15.7) and mean disease duration was 14.6 years (SD 14.0). Complete MG-ADL scores (n=1035) ranged from 0-18p, where 26% reported a score of 0p. Higher MG-ADL scores were associated with female sex, obesity and diagnostic delay (OR=1.62, 1.72 and 1.69, Padj=0.017, 0.013 and 0.008) and inversely correlated with high educational attainment (OR=0.59, Padj=0.02), but not with age at inclusion, disease subtype nor disease duration. Almost half the population (47%) reported MG-ADL ≥3p, corresponding to an unsatisfactory symptom state.Conclusions:In this nationwide study, comprising more than 40% of the prevalent MG population in Sweden, we observe that almost half of patients report current disease symptoms associated to an unsatisfactory symptom state, indicating the need for improved treatment options.

The Babytwins Study Sweden (BATSS): A Multi-Method Infant Twin Study of Genetic and Environmental Factors Influencing Infant Brain and Behavioral Development

Twin studies can help us understand the relative contributions of genes and environment to phenotypic trait variation, including attentional and brain activation measures. In terms of applying methodologies such as electroencephalography (EEG) and eye tracking, which are key methods in developmental neuroscience, infant twin studies are almost nonexistent. Here, we describe the Babytwins Study Sweden (BATSS), a multi-method longitudinal twin study of 177 MZ and 134 DZ twin pairs (i.e., 622 individual infants) covering the 5−36 month time period. The study includes EEG, eye tracking and genetics, together with more traditional measures based on in-person testing, direct observation and questionnaires. The results show that interest in participation in research among twin parents is high, despite the comprehensive protocol. DNA analysis from saliva samples was possible in virtually all participants, allowing for both zygosity confirmation and polygenic score analyses. Combining a longitudinal twin design with advanced technologies in developmental cognitive neuroscience and genomics, BATSS represents a new approach in infancy research, which we hope to have impact across multiple disciplines in the coming years.