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In singletons, asthma may be associated with shorter height and delayed growth during adolescence. Yet, these studies do not account for heritability of asthma, puberty/menarche, and height. We aimed to study the association between asthma and puberty in boys and menarche in girls, and height, in a cohort of twins and subsequently in same-sex twin pairs discordant for asthma. From a Swedish twin cohort, parent- and self-reported data on asthma, puberty/menarche, and height were collected. Pubertal staging was established via the Petersen index. Logistic and linear regression was used to estimate associations between asthma and puberty/menarche and height, respectively. For within-pair analyses in twins discordant for asthma, conditional logistic and linear regression were used. Data on 2,658 (49.1% boys) twins were included. Among boys, asthma prevalence was 8.2% at 8–9 years and 10.2% at 13–14 years. Corresponding numbers for girls were 4.2% and 4.9%, respectively. In the entire cohort, no statistically significant associations were found between current asthma and puberty/menarche. Boys with asthma were shorter than boys without asthma at 8–9 years (on average, 1.86 [0.17–3.56] cm,p= .03) and at 13–14 years (on average, 2.94 [0.98–4.91] cm,p= .003) but not at 19–20 years. No such associations were found for girls. Within same-sex twin pairs discordant for asthma, no statistically significant associations were found for either sex. Twin boys, but not girls, with asthma were shorter than those without asthma. Non-statistically significant estimates from within-pair analyses suggest the association is partly confounded by genetic or familial environmental factors.

Background:The link between asthma and exhaled nitric oxide (FENO) is not completely understood. The aim of this study was to estimate the association between FENO and asthma, taking genetics, sensitization, and inhaled corticosteroids (ICS) into account.Methods:A total of 681 twins (53% monozygotic [MZ] and 47% dizygotic [DZ]) from the population-based STOPPA study (mean age 12.6 years) were recruited and information on FENO (parts per billion), parental report of current asthma, sensitization to airborne allergens (Phadiatop; IgE ≥0.35 kUA/l), and ICS-treatment was collected. We estimated the association between FENO and asthma, sensitization, and ICS in all twins and within pairs (DZ and MZ) to address shared genetic and environmental factors. Linear regression of log-transformed FENO was used and results presented as exponentiated regression coefficients (exp[β]), with 95% confidence interval (CI).Results:We found an association between asthma and FENO in all twins, exp(β) 1.31 [1.11, 1.54]. In within-pairs analysis, the association was stronger within DZ pairs discordant for FENO, exp(β) 1.50 [1.19, 1.89], compared to MZ pairs, exp(β) 1.07 [0.84, 1.37],p= .049. There was no difference in FENO in non-sensitized children with asthma, compared to children with neither asthma nor sensitization, exp(β) 0.89 [0.77, 1.03]. However, increased FENO was associated with sensitization, exp(β) 1.48 [1.30, 1.69], and with sensitization together with asthma, exp(β) 1.98 [1.57, 2.51], in all twins and within DZ pairs discordant for FENO, but not in MZ pairs. The FENO asthma association remained in DZ pairs without regular ICS-treatment.Conclusions:The association between FENO and asthma is explained by genetics and sensitization.

Asthma is a common childhood disease and several risk factors have been identified; however, the impact of genes and environment is not fully understood. The aim of the Swedish Twin study On Prediction and Prevention of Asthma (STOPPA) is to identify environmental (birth characteristics and early life) and genetic (including epigenetic) factors as determinants for asthmatic disease. Based on the Child and Adolescent Twin Study in Sweden (CATSS) (parental interview at 9 or 12 years, N ~23,900) and an asthma and/or wheezing algorithm, we identified a sample of monozygotic (MZ) and dizygotic (DZ) same-sexed twin pairs. The twin pairs were classified as asthma concordant (ACC), asthma discordant (ADC) and healthy concordant (HCC). A sample of 9- to 14-year-old twins and their parents were invited to participate in a clinical examination. Background characteristics were collected in questionnaires and obtained from the National Health Registers. A clinical examination was performed to test lung function and capacity (spirometry with reversibility test and exhaled nitric oxide) and collect blood (serology and DNA), urine (metabolites), feces (microbiota), and saliva (cortisol). In total, 376 twin pairs (752 individual twins) completed the study, response rate 52%. All participating twins answered the questionnaire and >90% participated in lung function testing, blood-, and saliva sampling. This article describes the design, recruitment, data collection, measures, and background characteristics, as well as ongoing and planned analyses in STOPPA. Potential gains of the study include the identification of biomarkers, the emergence of candidates for drug development, and new leads for prevention of asthma and allergic disease.

Background: An association between childhood asthma and IgE sensitization has been established, but our understanding of the genetic and environmental contribution to it is incomplete. Our aim was to estimate the associations and dose-response relationship between asthma and sensitization to airborne allergens in Swedish 9- to 14-year-old twins. Additionally, we aimed to explore the importance of familial confounding from shared genes and environment using co-twin controls.Methods: In the STOPPA cohort, 752 same-sex twin children were screened with Phadiatop® (Thermo Fisher Scientific; Pharmacia, Uppsala, Sweden); if positive further analysis of IgE antibodies to airborne allergens of pets (cat, horse, dog), pollens (birch, timothy, mugwort), mites, and mold were performed. The associations between asthma and airborne allergens were assessed with generalized estimating equations. The co-twin control analysis was performed by conditional logistic regression.Results: Children with positive Phadiatop® had more than doubled odds of asthma (OR 2.53, 95% CI [1.74, 3.70]). Sensitization to pet allergens was associated with increased odds of asthma; for example, cat OR 4.15 (95% CI [2.67, 6.45]), with similar estimates for pollens; for example, birch OR 3.22 (95% CI [2.12, 4.91]). Associations persisted with sensitization as a categorical variable and for trend, indicating a dose-response relationship. Results remained in the co-twin analyses; for example, cat OR 4.75 (95% CI [1.62, 14.0]) and birch OR 5.00 (95% CI [1.45, 17.3]).Conclusion: The association between childhood asthma and sensitization to airborne allergens remains in co-twin analyses, indicating they are not due to confounding from shared environmental or genetic factors.

Introduction:Non-random selection into a study population due to differences between consenters and non-consenters may introduce participation bias. Past investigations of factors predicting consent to collection of medical health records for research imply that age, sex, health status, and education are of importance for participation, but disagree on the direction of effects. Very little is known about influences on consent from adolescents.Methods:Two cohorts of Swedish 15-year-old twins (totaln= 4,611) previously invited to the Child and Adolescent Twin Study in Sweden (CATSS) responded to a questionnaire with information on sex, individual's health, height, weight, and parental factors. The questionnaire included a question for consent to collection of medical health records. Predictors for consent were analyzed using logistic regression. Additionally, regional differences in the collection of health records of consenters were evaluated.Results:Males were significantly less likely to consent compared to females (OR 0.74, 95% CI 0.64–0.85). The twin siblings' decision to consent was strongly associated with consent (OR 10.9, 95% CI 8.76–13.5), and individuals whose parents had responded to the original CATSS study were more likely to consent to record collection at age 15 (OR 2.2, 95% CI 1.81–2.75). Results of the subsequent collection of consenters' medical health records varied between geographical regions of Sweden.Conclusion:We identified several predictors for adolescents' consent to collection of their medical health records. Further selection was introduced through the subsequent record collection. Whether this will induce participation bias in future studies depends on the research questions' relationship to the identified predictors.

Background: Recent studies have reported associations between air pollution exposure and neurodevelopmental disorders in children, but the role of pre- and postnatal exposure has not been elucidated. Aim: We aimed to explore the risk for autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) among children in relation to pre- and postnatal exposure to air pollution from road traffic. Methods: Parents of 3,426 twins born in Stockholm during 1992–2000 were interviewed, when their children were 9 or 12 years old, for symptoms of neurodevelopmental disorders. Residence time-weighted concentrations of particulate matter with a diameter <10 μm (PM10) and nitrogen oxides (NOx) from road traffic were estimated at participants' addresses during pregnancy, the first year, and the ninth year of life using dispersion modeling, controlling for seasonal variation. Multivariate regression models were used to examine the association between air pollution exposure and neurodevelopmental outcomes, adjusting for potential confounding factors. Results: No clear or consistent associations were found between air pollution exposure during any of the three time windows and any of the neurodevelopmental outcomes. For example, a 5–95% difference in exposure to NOx during pregnancy was associated with odds ratios (ORs) of 0.92 (95% confidence interval (CI): 0.44–1.96) and 0.90 (95% CI: 0.58–1.40) for ASD and ADHD respectively. A corresponding range in exposure to PM10 during pregnancy was related to ORs of 1.01 (95% CI: 0.52–1.96) and 1.00 (95% CI: 0.68–1.47) for ASD and ADHD. Conclusions: Our data do not provide support for an association between pre- or postnatal exposure to air pollution from road traffic and neurodevelopmental disorders in children.

Background - Cross‐sectional studies suggested that allergy prevalence in childhood is higher in boys compared to girls, but it remains unclear whether this inequality changes after puberty. We examined the sex‐specific prevalence of asthma and rhinitis as single and as multimorbid diseases before and after puberty onset in longitudinal cohort data. Methods - In six European population‐based birth cohorts of MeDALL, we assessed the outcomes: current rhinitis, current asthma, current allergic multimorbidity (ie, concurrent asthma and rhinitis), puberty status and allergic sensitization by specific serum antibodies (immunoglobulin E) against aero‐allergens. With generalized estimating equations, we analysed the effects of sex, age, puberty (yes/no) and possible confounders on the prevalence of asthma and rhinitis, and allergic multimorbidity in each cohort separately and performed individual participant data meta‐analysis. Findings - We included data from 19 013 participants from birth to age 14‐20 years. Current rhinitis only affected girls less often than boys before and after puberty onset: adjusted odds ratio for females vs males 0.79 (95%‐confidence interval 0.73‐0.86) and 0.86 (0.79‐0.94), respectively (sex‐puberty interaction P = .089). Similarly, for current asthma only, females were less often affected than boys both before and after puberty onset: 0.71, 0.63‐0.81 and 0.81, 0.64‐1.02, respectively (sex‐puberty interaction P = .327). The prevalence of allergic multimorbidity showed the strongest sex effect before puberty onset (female‐male‐OR 0.55, 0.46‐0.64) and a considerable shift towards a sex‐balanced prevalence after puberty onset (0.89, 0.74‐1.04); sex‐puberty interaction: P < .001. Interpretation - The male predominance in prevalence before puberty and the "sex‐shift" towards females after puberty onset were strongest in multimorbid patients who had asthma and rhinitis concurrently. ; European Union under the Health Cooperation Work Programme of the 7th Framework Programme. Grant Number: 261357

The Swedish Twin Registry (STR) today contains more than 194,000 twins and more than 75,000 pairs have zygosity determined by an intra-pair similarity algorithm, DNA, or by being of opposite sex. Of these, approximately 20,000, 25,000, and 30,000 pairs are monozygotic, same-sex dizygotic, and opposite-sex dizygotic pairs, respectively. Since its establishment in the late 1950s, the STR has been an important epidemiological resource for the study of genetic and environmental influences on a multitude of traits, behaviors, and diseases. Following large investments in the collection of biological specimens in the past 10 years we have now established a Swedish twin biobank with DNA from 45,000 twins and blood serum from 15,000 twins, which effectively has also transformed the registry into a powerful resource for molecular studies. We here describe the main projects within which the new collections of both biological samples as well as phenotypic measures have been collected. Coverage by year of birth, zygosity determination, ethnic heterogeneity, and influences of in vitro fertilization are also described.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.