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Ralf Kuja-Halkola,1 Benjamin Lebwohl,1,2 Jonas Halfvarson,3 Louise Emilsson,4–6 Patrik K Magnusson,1 Jonas F Ludvigsson1,2,7,8 1Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; 2Department of Medicine, Celiac Disease Center, Columbia University Medical Center, Columbia University, New York, NY, USA; 3Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 4Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Oslo, Norway; 5Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; 6Centre for Clinical Research, Vårdcentralen Värmlands Nysäter, County Council of Värmland, Värmland, 7Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; 8Division of Epidemiology and Public Health, School of Medicine, City Hospital, University of Nottingham, Nottingham, UK Objective: Earlier research suggests that birth weight may be associated with celiac disease (CD), but the direction of association has been unclear potentially due to confounding effect from genetic and intrafamilial factors. Through within-twin analyses, we aimed to minimize confounding effects such as twins that share genetic and early environmental exposures.Materials and methods: Using the Swedish Twin Registry, we examined the birth weight of 146,830 twins according to the CD status. CD was defined as having villous atrophy according to a small intestinal biopsy reports.Results: The prevalence of diagnosed CD was 0.5% (n=669), and we included 407 discordant pairs of CD–non-CD twins. Comparing the 669 CD patients with non-CD twins, the association between birth weight and future CD was not statistically significant (odds ratio [OR] per 1000 g increase in birth weight: 1.16; 95% confidence interval [CI]=0.97–1.38). In males, the association was positive and statistically significant (OR=1.50; 95% CI=1.11–2.02). However, the association was not significant in within-pair analyses for both dizygotic and monozygotic twins and for both sexes.Conclusion: This population-based study found that in male twins, higher birth weight was associated with higher risk of CD. However, when comparing discordant twin pairs in within-twin pair analyses, there was no statistically significant association between birth weight, intrauterine growth, and future risk of CD. Keywords: autoimmune, gestational age, gluten, registries, risk factors, twins

Alterations in social cognition (SC) are hypothesized to underlie social communication and interaction challenges in autism spectrum disorder (ASD). The aetiological underpinnings driving this association remain unclear. We examined SC in 196 twins with ASD, other neurodevelopmental disorders or typical development using the naturalistic Movie for the Assessment of Social Cognition. Autism and its severity were assessed with the Autism Diagnostic Observation Schedule-2, and autistic traits with the Social Responsiveness Scale-2. Using within twin-pair regression models, controlling for age, sex, IQ, and unmeasured familial confounders such as genetic background and shared-environment, SC correlated with ASD diagnosis, autism severity, and autistic traits. Our findings highlight the importance of SC alterations in autism and suggest a non-shared environmental impact on the association.

Importance: Substance misuse and anxiety-related and depressive disorders (ADs) are among the most common psychiatric conditions and often co-occur. Despite adversities associated with the comorbidity, its causes remain unclear. Objective: We used Swedish nationwide register data aiming to (1) estimate associations of substance misuse and ADs in the population, (2) investigate gender differences in comorbidity, and (3) test the associations while accounting for genetic and shared environmental factors in stratified analyses within twin pairs and siblings. Design, Setting, and Participants: Individuals born in Sweden between January 1968 and December 1997 (n=2,996,403) were followed-up with register-based data for 1997-2013. Main Outcomes and Measures Substance misuse was defined using ICD-10 diagnoses of substance use disorders (F10-F16, F18-F19) and drug-related criminal convictions. ADs included anxiety (F40-F43) and depressive disorders (F32-F34, F38-F39). Confounding by sex, birth year, personality disorders (F60.0-F60.9), socioeconomic covariates, and parental history of psychopathology was adjusted for. Results: Risk of ADs was substantially increased in individuals with substance misuse (Risk Ratios (RR): 2.5-4.5). Of the AD diagnosis clusters derived from exploratory factor analysis, generalized anxiety/depression had the strongest association with substance misuse (RR=4.46, 95% CI 4.42- 4.50). Similarly, those with substance misuse had a 4.6-fold (95% CI: 4.52-4.60) risk of generalized anxiety/depression and a 4.7-fold (95% CI: 4.65-4.84) risk of panic disorder/social phobia as compared to those without substance misuse. The associations were stronger in women than in men, and were attenuated in within-family analyses. However, elevated risks were found even among MZ twins suggesting the comorbidity was not fully explained by familial factors. Conclusions and Relevance: Risk of ADs is elevated in individuals with substance misuse, and vice versa, and these associations are partially confounded by familial liabilities. However, the results are also compatible with a partially causal relationship between substance misuse and ADs.

Previous studies report that dental caries is partially heritable, but there is uncertainty in the magnitude of genetic effects and little understanding of how genetic factors might influence caries progression or caries subtypes. This study aimed to estimate the relative importance of genetic and environmental factors in the etiology of different caries outcomes using a twin-based design. Analysis included up to 41,678 twins in the Swedish Twin Register aged 7 to 97 y, and dental data were obtained from preexisting dental records. The outcome measures were 1) summary indices of caries experience, 2) parameters representing trajectory in caries progression derived from longitudinal modeling, and 3) caries scores in groups of biologically similar tooth surfaces derived from hierarchical clustering of tooth surfaces (termed caries clusters). Additive genetic factors explained between 49.1% and 62.7% of variation in caries scores and between 50.0% and 60.5% of variation in caries trajectories. Seven caries clusters were identified, which had estimates of heritability lying between 41.9% and 54.3%. Shared environmental factors were important for only some of these clusters and explained 16% of variation in fissure caries in molar teeth but little variation in other clusters of caries presentation. The genetic factors influencing these clusters were only partially overlapping, suggesting that different biological processes are important in different groups of tooth surfaces and that innate liability to some patterns of caries presentation may partially explain why groups of tooth surfaces form clusters within the mouth. These results provide 1) improved quantification of genetic factors in the etiology of caries and 2) new data about the role of genetics in terms of longitudinal changes in caries status and specific patterns of disease presentation, and they may help lay the foundations for personalized interventions in the future. [ABSTRACT FROM AUTHOR]

Objective The risk of certain psychiatric disorders is elevated among immigrants. To date, no population studies on immigrant health have addressed eating disorders. We examined whether risk of eating disorders in first- and second-generation immigrants differs from native-born Danes and Swedes. Method All individuals born 1984-2002 (Danish cohort) and 1989-1999 (Swedish cohort) and residing in the respective country on their 10th birthday were included. They were followed up for the development of eating disorders based on out-patient and in-patient data. Results The risks of all eating disorder types were lower among first-generation immigrants compared to the native populations: Incidence-rate ratio (95% confidence interval) was 0.39 (0.29, 0.51) for anorexia nervosa, 0.60 (0.42, 0.83) for bulimia nervosa, and 0.62 (0.47, 0.79) for other eating disorders in Denmark and 0.27 (0.21, 0.34) for anorexia nervosa, 0.30 (0.18, 0.51) for bulimia nervosa, and 0.39 (0.32, 0.47) for other eating disorders in Sweden. Likewise, second-generation immigrants by both parents were at lower risk, whereas those with only one foreign-born parent were not. Conclusion The decreased risk of eating disorders among immigrants is opposite to what has been observed for other psychiatric disorders, particularly schizophrenia. Possible explanations include buffering sociocultural factors and underdetection in health care. [ABSTRACT FROM AUTHOR]

BackgroundAdvancing paternal age has been linked to psychiatric disorders. These associations might be caused by the increased number of de novo mutations transmitted to offspring of older men. It has also been suggested that the associations are confounded by a genetic liability for psychiatric disorders in parents. The aim of this study was to indirectly test the confounding hypotheses by examining if there is a genetic component to advancing paternal age and if men with a genetic liability for psychiatric disorders have children at older ages.MethodWe examined the genetic component to advancing paternal age by utilizing the twin model in a cohort of male twins (N = 14 679). We also studied ages at childbirth in men with or without schizophrenia, bipolar disorder and/or autism spectrum disorder. Ages were examined in: (1) healthy men, (2) affected men, (3) healthy men with an affected sibling, (4) men with healthy spouses, (5) men with affected spouses, and (6) men with healthy spouses with an affected sibling.ResultsThe twin analyses showed that late fatherhood is under genetic influence (heritability = 0.33). However, affected men or men with affected spouses did not have children at older ages. The same was found for healthy individuals with affected siblings. Instead, these men were generally having children at younger ages.ConclusionAlthough there is a genetic component influencing late fatherhood, our data suggest that the associations are not explained by psychiatric disorders or a genetic liability for psychiatric disorders in the parent. [ABSTRACT FROM PUBLISHER]

BackgroundChildhood maltreatment (CM) has been associated with increased risk of attention deficit hyperactivity disorder (ADHD) in children and adults. It is, however, unclear whether this association is causal or due to familial confounding.MethodData from 18 168 adult twins, aged 20–46 years, were drawn from the population-based Swedish twin registry. Retrospective self-ratings of CM (emotional and physical neglect, physical and sexual abuse and witnessing family violence), and self-ratings for DSM-IV ADHD symptoms in adulthood were analysed. Possible familial confounding was investigated using a within twin-pair design based on monozygotic (MZ) and dizygotic (DZ) twins.ResultsCM was significantly associated with increased levels of ADHD symptom scores in adults [regression coefficient: 0.40 standard deviations, 95% confidence interval (CI) 0.37–0.43]. Within twin-pair analyses showed attenuated but significant estimates within DZ (0.29, 95% CI 0.21–0.36) and MZ (0.18, 95% CI 0.10–0.25) twin pairs. Similar results emerged for hyperactive/impulsive and inattentive ADHD symptom scores separately in association with CM. We conducted sensitivity analyses for early maltreatment, before age 7, and for abuse and neglect separately, and found similarly reduced estimates in DZ and MZ pairs. Re-traumatization after age 7 did not significantly influence results.ConclusionsCM was significantly associated with increased ADHD symptoms in adults. Associations were partly due to familial confounding, but also consistent with a causal interpretation. Our findings support cognitive neuroscience studies investigating neural pathways through which exposure to CM may influence ADHD. Clinicians treating adults with ADHD should be aware of the association with maltreatment. [ABSTRACT FROM PUBLISHER]