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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.
The ‘thrifty phenotype’ hypothesis proposed that fetal undernutrition increases risk of diabetes in later life. Undernourished low birthweight Indian babies are paradoxically more adipose compared to well-nourished European babies, and are at higher risk of diabetes in later life. Twin pregnancies are an example of in utero growth restrictive environment due to shared maternal nutrition. There are few studies of body composition in twins. We performed secondary analysis of anthropometric body composition of twins and singletons in Guinea-Bissau, an economically deprived African country.
Anthropometric data were available on 7–34 year-old twins (n = 209, 97 males) and singletons (n = 182, 86 males) in the Guinea-Bissau Twin Registry at the Bandim Health Project. Twins had lower birthweight (2420 vs 3100 g, p < 0.001); and at follow-up, lower height (HAZ mean Z-score difference, −0.21, p = 0.055), weight (WAZ −0.73, p = 0.024) and BMI (BAZ −0.22, p = 0.079) compared to singletons but higher adiposity (skinfolds: +0.33 SD, p = 0.001). Twins also had higher fasting (+0.38 SD, p < 0.001) and 2-hour OGTT glucose concentrations (+0.29 SD, p < 0.05). Linear mixed-effect model accounting for intrapair correlations and interactions confirmed that twins were thinner but fatter across the age range. Data on maternal morbidity and prematurity were not available in this cohort.
African populations are known to have a muscular (less adipose) body composition. Demonstration of a thin-fat phenotype in twins in a low socio-economic African country supports the thesis that it could be a manifestation of early life undernutrition and not exclusive to Indians. This phenotype could increase risk of diabetes and related conditions.
Multifetal pregnancies are at risk of adverse maternal, neonatal and long-term health outcomes, and gestational weight gain (GWG) is a potentially modifiable risk factor for several of these. However, studies assessing the associations of GWG with long-term health in twins are rare, and studies which do assess these associations in twins often do not account for gestational age. Since longer gestations are likely to lead to larger GWG and lower risk of adverse outcomes, adjusting for gestational age is necessary to better understand the association of GWG with twin health outcomes. We aimed to explore long-term associations of GWG-for-gestational-age with twin anthropometric measures. The Peri/Postnatal Epigenetic Twins Study (PETS) is a prospective cohort study, which recruited women pregnant with twins from 2007 to 2009. Twins were followed-up at 18 months and 6 years of age. GWG-for-gestational-age z-scores were calculated from pre-pregnancy weight and weight at delivery. We fitted regression models to assess associations of GWG with twin weight, height and BMI at birth, 18 months, and 6 years. Of the 250 women in the PETS, 172 had GWG measured throughout pregnancy. Overall, higher GWG-for-gestational-age z-scores were associated with higher birthweight (β: 0.32 z-scores, 95% Confidence Interval (95% CI): 0.19, 0.45), BMI (β: 0.29 z-scores, 95% CI: 0.14, 0.43) and length (β: 0.27 z-scores, 95% CI: 0.09, 0.45). However, these associations were not observed at 18 months or 6 years of age. GWG was associated with twin length, weight and BMI at birth but not during childhood. Further research is needed to determine the long-term effects of GWG on twin health outcomes.
This article describes the Australian Twins Economic Preferences Survey (ATEPS). The data set comprises a wide variety of preference and behavioral measures (risk aversion, impatience, ambiguity aversion, trust, confidence) elicited using incentivized decision tasks. One-thousand one-hundred twenty Australian adult twins (560 pairs) completed the survey, making it one of the largest data sets containing incentivized preference measures of twins. As the survey was conducted during the COVID-19 pandemic, we also collected information on experiences related to the pandemic, along with a variety of questions on political attitudes and mental wellbeing. We hope that ATEPS can make a valuable contribution to social science and genetics research.
Although twins often participate in medical research, few clinical trials are conducted entirely in twin populations. The purpose of this review is to demonstrate the substantial benefits and address the key challenges of conducting clinical trials in twin populations, or ‘twin-only trials’. We consider the unique design, analysis, recruitment and ethical issues that arise in such trials. In particular, we describe the different approaches available for randomizing twin pairs, highlight the similarity or correlation that exists between outcomes of twins, and discuss the impact of this correlation on sample size calculations and statistical analysis methods for estimating treatment effects. We also consider the role of both monozygotic and dizygotic twins for studying variation in outcomes, the factors that may affect recruitment of twins, and the ethics of conducting trials entirely in twin populations. The advantages and disadvantages of conducting twin-only trials are also discussed. Finally, we recommend that twin-only trials should be considered more often.
Turkish-speaking dyzygotic twins (n = 21) and singletons (n = 23) were tested through a standard articulation test to observe whether their consonant articulations were related to their vocabulary sizes, recorded through CDI forms, at age 3;0. Twins were observed to lag behind their singleton peers and performed below the norm level in their production. Vocabulary size failed to predict twins’ articulation scores although it predicted the scores of the singleton group. The results suggested that articulation was not related to vocabulary size in twins. Exposure to sibling language was discussed as an alternative risk factor.
Birthweight has been consistently related to risk of cardiometabolic disorders in later life. Twins are at higher risk of low birthweight than singletons, so understanding the links between birthweight and cardiometabolic health may be particularly important for twins. However, evidence for the association of birthweight with childhood markers of cardiometabolic health in twins is currently lacking. Previous studies have often failed to appropriately adjust for gestational age or fully implement twin regression models. Therefore, we aimed to evaluate the association of birthweight-for-gestational-age z-scores with childhood cardiometabolic health in twins, using within-between regression models. The Peri/Postnatal Epigenetic Twins Study is a Melbourne-based prospective cohort study of 250 twin pairs. Birthweight was recorded at delivery, and childhood anthropometric measures were taken at 18-month and 6-year follow-up visits. Associations of birthweight with markers of cardiometabolic health were assessed at the individual, between- and within-pair level using linear regression with generalised estimating equations. Birthweight-for-gestational-age z-scores were associated with height, weight and BMI at 18 months and 6 years, but not with blood pressure (twins-as-individual SBP: β = 0.15, 95% CI: −0.81, 1.11; twins-as-individual DBP: β = 0.22, 95% CI: −0.34, 0.77). We found little evidence to indicate that the within-between models improved on the twins-as-individuals models. Birthweight was associated with childhood anthropometric measures, but not blood pressure, after appropriately adjusting for gestational age. These associations were consistent across the within-between and twins-as-individuals models. After adjusting for gestational age, results from the twins-as-individuals models are consistent with singleton studies, so these results can be applied to the general population.
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.
Although mental wellbeing has been linked with positive health outcomes, including longevity and improved emotional and cognitive functioning, studies examining the underlying neural mechanisms of both subjective and psychological wellbeing have been sparse. We assessed whether both forms of wellbeing are associated with neural activity engaged during positive and negative emotion processing and the extent to which this association is driven by genetics or environment.
Methods
We assessed mental wellbeing in 230 healthy adult monozygotic and dizygotic twins using a previously validated questionnaire (COMPAS-W) and undertook functional magnetic resonance imaging during a facial emotion viewing task. We used linear mixed models to analyse the association between COMPAS-W scores and emotion-elicited neural activation. Univariate twin modelling was used to evaluate heritability of each brain region. Multivariate twin modelling was used to compare twin pairs to assess the contributions of genetic and environmental factors to this association.
Results
Higher levels of wellbeing were associated with greater neural activity in the dorsolateral prefrontal cortex, localised in the right inferior frontal gyrus (IFG), in response to positive emotional expressions of happiness. Univariate twin modelling showed activity in the IFG to have 20% heritability. Multivariate twin modelling suggested that the association between wellbeing and positive emotion-elicited neural activity was driven by common variance from unique environment (r = 0.208) rather than shared genetics.
Conclusions
Higher mental wellbeing may have a basis in greater engagement of prefrontal neural regions in response to positive emotion, and this association may be modifiable by unique life experiences.
Atomic force microscopy (AFM) measurements of dihedral angles are conducted for the first time to characterize the ratio of the twin-boundary energy (γΤ) to the surface free energy (γS). In plane, twin morphology is measured with AFM, verified by scanning electron microscopy, optical microscopy, and found to be consistent. The chemical composition and homogeneity of annealed Cu10 wt%Zn sample are confirmed by energy-dispersive spectroscopy. AFM data indicate that the average depth and height of the grooves and peaks are 118 ± 45 and 158 ± 45 nm, respectively. Surface roughness parameters, Sq and Sa, are measured by a factor of two to four less than the depth and height of the twin boundaries. Both surface roughness parameters are less with no planar defects present compared with selected areas containing twin boundaries. The average dihedral angle is found to be 167 ± 5° for the grooves and 193 ± 4° for the peaks. The twin to surface interfacial free energy ratio, γT/γS, is 0.0018. The comparison of AFM-based results to the other method-based results obtained on pure metals is discussed.
A dominant feature of anxiety disorders is familial aggregation. However, the underlying mechanisms of between- and within-generational anxiety resemblance remain poorly understood. By disentangling the genetic v. environmental sources of familial resemblance in anxiety, we can help prevent within-family transmission of anxiety disorders. Therefore, data from both parents and twins are needed to obtain unbiased and detailed estimations of genetic and environmental sources of similarity between family members.
Methods
We examined data from 991 families with same-sex twins. Trait anxiety in twins was assessed via self-report and parent report, while parental trait anxiety was assessed via self-report. We established a nuclear twin family model and estimated genetic and environmental variances using two survey waves.
Results
The results suggested that additive genetic (A), dominant genetic (D), and non-shared environmental (E) influences significantly contributed to trait anxiety, whereas familial environmental influences (F) and passive gene–environment correlations (rGE) did not. Sibling environmental influences (S) were only found in self-report data, and increased when genetic influences decreased from Wave 1 to Wave 2.
Conclusions
Our study highlights the important role of broad heritability in intrafamilial trait anxiety similarity. Parent–child resemblance occurred primarily due to shared genetic makeup rather than direct environmental transmission. Sibling-specific environments, as the only source of shared environments, need further investigation. These findings have both theoretical and practical significance for anxiety disorders. Future research can expand our understanding by examining the gene–environment interplay and sex differences.
Children's early vocabulary shows sex differences – with boys having smaller vocabularies than age-comparable girls – a pattern that becomes evident in both singletons and twins. Twins also use fewer words than their singleton peers. However, we know relatively less about sex differences in early gesturing in singletons or twins, and also how singletons and twins might differ in their early gesture use. We examine the patterns of speech and gesture production of singleton and twin children, ages 0;10-to-3;4, during structured parent-child play. Boys and girls – singleton or twin – were similar in speech and gesture production, but singletons used a greater amount and diversity of speech and gestures than twins. There was no effect of twin dyad type (boy-boy, girl-girl, boy-girl) on either speech or gesture production. These results confirm earlier research showing close integration between gesture and speech in singletons in early language development, and further extend these patterns to twin children.
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.
Benjamin B. Lahey was born in 1945 in the United States. He is the Irving B. Harris Professor of Psychiatry at the University of Chicago and was President of the International Society for Research in Child and Adolescent Psychopathology. He received the U.S. National Academy of Neuropsychology research prize for his work on attention-deficit/hyperactivity disorder. He first conducted research on the effectiveness of behavior therapy with school children. He then created a reliable and valid assessment of psychological problems for large samples of children. He directed the American Psychiatric Association field trials on disruptive behavior disorders in children. With Rolf Loeber, he also created a longitudinal study of clinic-referred prepubertal boys with problems of hyperactivity and serious conduct problems: The Developmental Trends Study. He also created a large cohort of twins to study the genetic and environmental contributions to conduct disorder. Results led him and his colleagues to propose a hierarchical causal model of psychological problems in which he hypothesized a general factor of psychopathology that plays a central role. The key idea is that the causes and mechanisms of each dimension of psychological problems cannot be studied and understood separately; they are far too intertwined.
The ‘16Up’ study conducted at the QIMR Berghofer Medical Research Institute from January 2014 to December 2018 aimed to examine the physical and mental health of young Australian twins aged 16−18 years (N = 876; 371 twin pairs and 18 triplet sets). Measurements included online questionnaires covering physical and mental health as well as information and communication technology (ICT) use, actigraphy, sleep diaries and hair samples to determine cortisol concentrations. Study participants generally rated themselves as being in good physical (79%) and mental (73%) health and reported lower rates of psychological distress and exposure to alcohol, tobacco products or other substances than previously reported for this age group in the Australian population. Daily or near-daily online activity was almost universal among study participants, with no differences noted between males and females in terms of frequency or duration of internet access. Patterns of ICT use in this sample indicated that the respondents were more likely to use online information sources for researching physical health issues than for mental health or substance use issues, and that they generally reported partial levels of satisfaction with the mental health information they found online. This suggests that internet-based mental health resources can be readily accessed by adolescent Australians, and their computer literacy augurs well for future access to online health resources. In combination with other data collected as part of the ongoing Brisbane Longitudinal Twin Study, the 16Up project provides a valuable resource for the longitudinal investigation of genetic and environmental contributions to phenotypic variation in a variety of human traits.
There is a commonly observed association between chronic disease and psychological distress, but many potential factors could confound this association. This study investigated the association using a powerful twin study design that can control for unmeasured confounders that are shared between twins, including genetic and environmental factors. We used twin-paired cross-sectional data from the Adult Health and Lifestyle Questionnaire collected by Twins Research Australia from 2014 to 2017. Linear regression models fitted using maximum likelihood estimations (MLE) were used to test the association between self-reported chronic disease status and psychological distress, measured by the Kessler Psychological Distress Scale (K6). When comparing between twin pairs, having any chronic disease was associated with a 1.29 increase in K6 (95% CI: 0.91, 1.66; p < .001). When comparing twins within a pair, having any chronic disease was associated with a 0.36 increase in K6 (95% CI: 0.002, 0.71; p = .049). This within-pair estimate is of most interest as comparing twins within a pair naturally controls for shared factors such as genes, age and shared lived experiences. Whereas the between-pair estimate does not. The weaker effect found within pairs tells us that genetic and environmental factors shared between twins confounds the relationship between chronic disease and psychological distress. This suggests that associations found in unrelated samples may show exaggerated estimates.
Susceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n = 3261) completing the C-19 COVID-19 symptom tracker app allowed classical twin studies of COVID-19 symptoms, including predicted COVID-19, a symptom-based algorithm to predict true infection, derived from app users tested for SARS-CoV-2. We found heritability of 49% (32−64%) for delirium; 34% (20−47%) for diarrhea; 31% (8−52%) for fatigue; 19% (0−38%) for anosmia; 46% (31−60%) for skipped meals and 31% (11−48%) for predicted COVID-19. Heritability estimates were not affected by cohabiting or by social deprivation. The results suggest the importance of host genetics in the risk of clinical manifestations of COVID-19 and provide grounds for planning genome-wide association studies to establish specific genes involved in viral infectivity and the host immune response.
The genome encodes the information needed to make us human, but genes do not directly cause growth and development. Gene expression is regulated and mediated by several biological systems, especially the neurological and endocrine (neuroendocrine) systems. Hormones regulate and coordinate critical developmental processes, integrating across several systems, including the central nervous system, the reproductive system, and the digestive system. Hormones are influenced by nutritional status and infections. Therefore, hormones provide a mechanism by which “real-time” information about a body’s health is communicated to the brain and processed by its regulatory centers in the hypothalamus and pituitary, through which growth is affected accordingly.
Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism's heterogeneity.