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Associations between adult attention-deficit/hyperactivity disorder (ADHD) symptoms and dietary habits have not been well established and the underlying mechanisms remain unclear. We explored these associations using a Swedish population-based twin study with 17,999 individuals aged 20-47 years. We estimated correlations between inattention and hyperactivity/impulsivity with dietary habits and fitted twin models to determine the genetic and environmental contributions. Dietary habits were defined as (a) consumption of food groups, (b) consumption of food items rich in particular macronutrients, and (c) healthy and unhealthy dietary patterns. At the phenotypic level, inattention was positively correlated with seafood, high-fat, high-sugar, high-protein food consumptions, and unhealthy dietary pattern, with correlation coefficients ranging from 0.03 (95%CI: 0.01, 0.05) to 0.13 (95% CI: 0.11, 0.15). Inattention was negatively correlated with fruits, vegetables consumptions and healthy dietary pattern, with correlation coefficients ranging from -0.06 (95%CI: -0.08, -0.04) to -0.07 (95%CI: -0.09, -0.05). Hyperactivity/impulsivity and dietary habits showed similar but weaker patterns compared to inattention. All associations remained stable across age, sex and socioeconomic status. Nonshared environmental effects contributed substantially to the correlations of inattention (56-60%) and hyperactivity/impulsivity (63-80%) with dietary habits. The highest and lowest genetic correlations were between inattention and high-sugar food (r A = .16, 95% CI: 0.07, 0.25), and between hyperactivity/impulsivity and unhealthy dietary pattern (r A = .05, 95% CI: -0.05, 0.14), respectively. We found phenotypic and etiological overlap between ADHD and dietary habits, although these associations were weak. Our findings contribute to a better understanding of common etiological pathways between ADHD symptoms and various dietary habits., (© 2020 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

Background: Predicting which children will go on to develop mental health symptoms as adolescents is critical for early intervention and preventing future, severe negative outcomes. Although many aspects of a child's life, personality, and symptoms have been flagged as indicators, there is currently no model created to screen the general population for the risk of developing mental health problems. Additionally, the advent of machine learning techniques represents an exciting way to potentially improve upon the standard prediction modelling technique, logistic regression. Therefore, we aimed to I.) develop a model that can predict mental health problems in mid-adolescence II.) investigate if machine learning techniques (random forest, support vector machines, neural network, and XGBoost) will outperform logistic regression., Methods: In 7,638 twins from the Child and Adolescent Twin Study in Sweden we used 474 predictors derived from parental report and register data. The outcome, mental health problems, was determined by the Strengths and Difficulties Questionnaire. Model performance was determined by the area under the receiver operating characteristic curve (AUC)., Results: Although model performance varied somewhat, the confidence interval overlapped for each model indicating non-significant superiority for the random forest model (AUC = 0.739, 95% CI 0.708-0.769), followed closely by support vector machines (AUC = 0.735, 95% CI 0.707-0.764)., Conclusion: Ultimately, our top performing model would not be suitable for clinical use, however it lays important groundwork for future models seeking to predict general mental health outcomes. Future studies should make use of parent-rated assessments when possible. Additionally, it may not be necessary for similar studies to forgo logistic regression in favor of other more complex methods., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: H. Larsson has served as a speaker for Evolan Pharmaand Shire and has received research grants from Shire; all outside the submitted work. P. Lichtenstein has served as a speaker for Medice, also outside the submitted work. R. McCabe serves as a data scientist for Spotify outside of the submitted work. All other authors declare that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Autism spectrum disorder (ASD) is diagnosed more often in boys than girls. Here, we compared the degree of autism - and related disorders - symptomatology in boys and girls with a registered diagnosis of ASD. We used parent telephone interview A-TAC (Autism-Tics, ADHD and other Comorbidities) ratings of 30,392 twins aged 9 or 12 (including 308 boys and 122 girls with National Patient Register diagnoses of ASD) participating in the Child and Adolescent Twin Study in Sweden. We used z-scores for ASD-symptoms, standardized separately for boys and girls. Boys with a diagnosis of ASD had a higher raw mean score than girls with a diagnosis on the A-TAC ASD domain. However, utilizing the z-scores, girls with a diagnosis of ASD deviated further away from the female population mean than did the boys with ASD from the male population mean. Girls also had higher standardized mean values for symptoms of Attention-Deficit/Hyperactivity Disorder, Learning Disabilities and Oppositional Defiant Disorder. The findings suggest that girls diagnosed with autism may represent an even more extreme end of the female population autistic features distribution, than diagnosed boys from the male population autistic features distribution. Future studies may benefit from examining the use of sex-specific cut-off scores., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Anxiety disorders in adolescence have been associated with several psychiatric outcomes. We sought to describe the prospective relationship between various levels of adolescent anxiety and psychiatric diagnoses (anxiety-, bipolar/psychotic-, depressive-, and alcohol and drug misuse disorders) and suicidal ideation in early adulthood while adjusting for childhood attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental coordination disorder (DCD). Furthermore, we aimed to estimate the proportion attributable to the various anxiety levels for the outcomes., Methods: We used a nation-wide population-based Swedish twin study comprising 14,106 fifteen-year-old twins born in Sweden between 1994 and 2002 and a replication sample consisting of 9211 Dutch twins, born between 1985 and 1999. Adolescent anxiety was measured with parental and self-report. Psychiatric diagnoses and suicidal ideation were retrieved from the Swedish National Patient Register and via self-report., Results: Adolescent anxiety, of various levels, predicted, in the Swedish National Patient Register, anxiety disorders: hazard ratio (HR) = 4.92 (CI 3.33-7.28); depressive disorders: HR = 4.79 (3.23-7.08), and any psychiatric outcome: HR = 3.40 (2.58-4.48), when adjusting for ADHD, ASD, and DCD. The results were replicated in the Dutch data. The proportion of psychiatric outcome attributable to adolescent anxiety over time (age 15-21) was 29% for any psychiatric outcome, 43-40% for anxiety disorders, and 39-38% for depressive disorders., Conclusion: Anxiety in adolescence constitutes an important risk factor in the development of psychiatric outcomes, revealing unique predictions for the different levels of anxiety, and beyond the risk conferred by childhood ADHD, ASD, and DCD. Developmental trajectories leading into psychiatric outcomes should further empirically investigated.

Dogs were the first domesticated animal and, according to the archaeological evidence, have had a close relationship with humans for at least 15,000 years. Today, dogs are common pets in our society and have been linked to increased well-being and improved health outcomes in their owners. A dog in the family during childhood is associated with ownership in adult life. The underlying factors behind this association could be related to experiences or to genetic influences. We aimed to investigate the heritability of dog ownership in a large twin sample including all twins in the Swedish Twin Registry born between 1926 and 1996 and alive in 2006. Information about dog ownership was available from 2001 to 2016 from national dog registers. The final data set included 85,542 twins from 50,507 twin pairs with known zygosity, where information on both twins were available in 35,035 pairs. Structural equation modeling was performed to estimate additive genetic effects (the heritability), common/shared environmental, and unique/non-shared environmental effects. We found that additive genetic factors largely contributed to dog ownership, with heritability estimated at 57% for females and 51% for males. An effect of shared environmental factors was only observed in early adulthood. In conclusion, we show a strong genetic contribution to dog ownership in adulthood in a large twin study. We see two main implications of this finding: (1) genetic variation may have contributed to our ability to domesticate dogs and other animals and (2) potential pleiotropic effects of genetic variation affecting dog ownership should be considered in studies examining health impacts of dog ownership.

It is unknown whether the association between body mass index (BMI) and chronic kidney disease (CKD) is mediated by genetic confounding or obesity-associated diabetes. We investigated the association between BMI and incident CKD in 29,136 Swedish twins with no history of CKD or diabetes, first using traditional Cox regression in a cohort design, and second controlling for shared genetic factors within twin pairs. Hazard ratios (HR) per unit increase in BMI were calculated and adjusted for age, sex, comorbidities, and lifestyle factors. We contrasted CKD risk between twins with discordant BMI and adjusted for diabetes as a time-varying covariate. During an average follow-up of 12.8 years, 1,113 (3.8%) incident CKD and 2,282 (7.8%) diabetes cases were observed. BMI was associated with CKD risk in the traditional cohort analysis (HR 1.13; 95% CI, 1.11-1.14). Effect sizes were similar in analyses clustered by twin pairs to adjust for factors shared by twins (HR 1.16; 95 CI 1.09-1.22 in same-sex fraternal twins and HR 1.17; 95% CI 1.06-1.29 in identical twins). Heavier twins had higher incidence rates of both CKD and diabetes than their leaner siblings, particularly when BMI differed by >2 kg/m 2 . The proportion of CKD cases attributable to BMI ≥25 kg/m 2 was estimated to be 32%, with approximately 19% of those cases explained by diabetes. We conclude that a higher BMI, irrespective of genetic confounding, is associated with increased CKD risk. A large proportion of CKD cases might be prevented if the population maintained a normal BMI., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

In order to further illuminate the potential role of dominant genetic variation in the "missing heritability" debate, we investigated the additive (narrow-sense heritability, h(2)) and dominant (δ(2)) genetic variance for 18 human complex traits. Within the same study base (10,682 Swedish twins), we calculated and compared the estimates from classic twin-based structural equation model with SNP-based genomic-relatedness-matrix restricted maximum likelihood [GREML(d)] method. Contributions of δ(2) were evident for 14 traits in twin models (average δ(2)twin = 0.25, range 0.14-0.49), two of which also displayed significant δ(2) in the GREMLd analyses (triglycerides δ(2)SNP = 0.28 and waist circumference δ(2)SNP = 0.19). On average, the proportion of h(2)SNP/h(2)twin was 70% for ADE-fitted traits (for which the best-fitting model included additive and dominant genetic and unique environmental components) and 31% for AE-fitted traits (for which the best-fitting model included additive genetic and unique environmental components). Independent evidence for contribution from shared environment, also in ADE-fitted traits, was obtained from self-reported within-pair contact frequency and age at separation. We conclude that despite the fact that additive genetics appear to constitute the bulk of genetic influences for most complex traits, dominant genetic variation might often be masked by shared environment in twin and family studies and might therefore have a more prominent role than what family-based estimates often suggest. The risk of erroneously attributing all inherited genetic influences (additive and dominant) to the h(2) in too-small twin studies might also lead to exaggerated "missing heritability" (the proportion of h(2) that remains unexplained by SNPs)., (Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

The second to fourth digit (2D:4D) ratio is of interest in autism spectrum disorder (ASD). Studies on the relationship of this ratio with other neurodevelopmental disorders (NDDs) are lacking. Investigating the association between the ratio and NDDs in twins can provide insight into genetic and/or environmental factors driving the ratio. Hand images were collected in N = 238 twins with NDDs or typical development from 70 monozygotic and 49 dizygotic pairs to examine ratios and their associations to DSM-5 defined categorical NDDs, autistic traits, zygosity, and sex. There were small associations for males between the ratios and any NDD and ADHD diagnoses. Males had lower ratios than females. Future studies exploring the ratio alongside physical anomalies could provide etiological insight into NDDs.

Background: Emerging research suggests that attention-deficit/hyperactivity disorder (ADHD) increases the risk for cardiovascular (CVDs) and metabolic disorders (i.e., cardiometabolic disorders) in adulthood. Yet, available studies are scarce and have mainly been focused on individuals receiving clinical ADHD diagnoses. We aimed to investigate the prospective associations of ADHD symptoms in young and mid-adulthood with subsequent cardiometabolic disorders and the underlying mechanisms. Methods: We studied 10,394 twins from the Swedish Twin Registry (STR), born between 1958 and 1985 without previous medical history of cardiometabolic disorders. They provided self-assessment of ADHD symptoms (score range 0–36) via a validated, DSM-IV-based scale in a web-based questionnaire/telephone interview within the Study of Twin Adults: Genes and Environment (STAGE), in 2005–2006 (aged 19–47 years), and were followed until the end of 2018 (33–59 years) to identify incident clinical diagnoses/medication prescriptions for cardiometabolic disorders acquired from Swedish national registers. We used Cox regression models to investigate the associations between ADHD symptoms score and cardiometabolic outcomes, with and without adjustment for relevant covariates, and a co-twin control design to study familial confounding. Results: A one-unit increase in the level of ADHD symptoms was associated with a 2% increase in the rate of CVDs (hazard ratio [HR] = 1.02, 95% confidence interval 1.01–1.04) and a 3% increase in the rate of metabolic disorders (HR = 1.03, 1.02–1.05), after adjusting for birth year and sex. The associations were no longer significant after adjusting for educational attainment, lifestyle factors, and comorbid psychiatric disorders. The associations remained significant after adjusting for familial factors shared by dizygotic twin pairs but became nonsignificant after adjusting for factors shared by monozygotic twin pairs. However, the strength of the associations attenuated significantly in monozygotic twins compared to dizygotic twins for CVDs only, suggesting genetic confounding. Conclusions: ADHD symptom score is associated with a higher risk for cardiometabolic disorders, which may be explained by lower educational attainment, adverse lifestyle factors, and psychiatric comorbidities. Moreover, the associations appear to be partly confounded by shared genetic factors, especially for CVDs. Further research is needed to investigate the identified associations at the level of individual cardiometabolic disorders and to follow-up participants until a more advanced older age. [ABSTRACT FROM AUTHOR]

Previous studies on brain connectivity correlates of autism have often focused on selective connections and yielded inconsistent results. By applying global fiber tracking and utilizing a within-twin pair design, we aimed to contribute to a more unbiased picture of white matter connectivity in association with clinical autism and autistic traits. Eighty-seven twin pairs (n = 174; 55% monozygotic; 24 with clinical autism) underwent diffusion tensor imaging. Linear regressions assessed within-twin pair associations between structural brain connectivity of anatomically defined brain regions and both clinical autism and autistic traits. These were explicitly adjusted for IQ, other neurodevelopmental/psychiatric conditions and multiple testing, and implicitly for biological sex, age, and all genetic and environmental factors shared by twins. Both clinical autism and autistic traits were associated with reductions in structural connectivity. Twins fulfilling diagnostic criteria for clinical autism had decreased brainstem-cuneus connectivity compared to their co-twins without clinical autism. Further, twins with higher autistic traits had decreased connectivity of the left hippocampus with the left fusiform and parahippocampal areas. These associations were also significant in dizygotic twins alone. Reduced brainstem-cuneus connectivity might point towards alterations in low-level visual processing in clinical autism while higher autistic traits seemed to be more associated with reduced connectivity in networks involving the hippocampus and the fusiform gyrus, crucial especially for processing of faces and other (higher order) visual processing. The observed associations were likely influenced by both genes and environment. [ABSTRACT FROM AUTHOR]

Background: Twin studies have demonstrated shared genetic and environmental effects between eating disorders and alcohol involvement in adults and middle adolescents. However, fewer studies have focused on late adolescents or investigated a wide range of eating disorder dimensions and alcohol involvement subscales in both sexes. We examined genetic and environmental correlations among three eating disorder dimensions and two alcohol involvement subscale scores in late adolescent twins using bivariate twin models. Methods: Participants were 3568 female and 2526 male same‐sex twins aged 18 years old from the Child and Adolescent Twin Study in Sweden. The Eating Disorder Inventory‐2 (EDI) assessed the drive for thinness, bulimia, and body dissatisfaction. Alcohol involvement was assessed with the Alcohol Use Disorder Identification Test consumption (AUDIT‐C) and problem (AUDIT‐P) subscales. Results: Only phenotypic and twin correlations in female twins met our threshold for twin modeling. The proportion of total variance for each trait accounted for by additive genetic factors ranged from 0.50 to 0.64 in female twins, with the rest explained by nonshared environmental factors and measurement error. Shared environmental factors played a minimal role in the variance of each trait. The strongest genetic correlation (ra) emerged between EDI bulimia and AUDIT‐P (ra = 0.46, 95% confidence interval: 0.37, 0.55), indicating that the proportion of genetic variance of one trait that was shared with the other trait was 0.21. Nonshared environmental correlations between eating disorder dimensions and alcohol involvement ranged from 0.03 to 0.13. Conclusions: We observed distinct patterns of genetic and environmental effects for co‐occurring eating disorder dimensions and alcohol involvement in female vs. male twins, supporting sex‐specific treatment strategies for late adolescents with comorbid eating disorders and alcohol use disorder. Our findings emphasize the importance of assessing family history of multiple eating disorder dimensions while treating late adolescents with problematic alcohol use, and vice versa, to improve detection and treatment. [ABSTRACT FROM AUTHOR]

Identifying metabolic biomarkers of frailty, an age‐related state of physiological decline, is important for understanding its metabolic underpinnings and developing preventive strategies. Here, we systematically examined 168 nuclear magnetic resonance‐based metabolomic biomarkers and 32 clinical biomarkers for their associations with frailty. In up to 90,573 UK Biobank participants, we identified 59 biomarkers robustly and independently associated with the frailty index (FI). Of these, 34 associations were replicated in the Swedish TwinGene study (n = 11,025) and the Finnish Health 2000 Survey (n = 6073). Using two‐sample Mendelian randomization, we showed that the genetically predicted level of glycoprotein acetyls, an inflammatory marker, was statistically significantly associated with an increased FI (β per SD increase = 0.37%, 95% confidence interval: 0.12–0.61). Creatinine and several lipoprotein lipids were also associated with increased FI, yet their effects were mostly driven by kidney and cardiometabolic diseases, respectively. Our findings provide new insights into the causal effects of metabolites on frailty and highlight the role of chronic inflammation underlying frailty development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Frailty is a complex, dynamic geriatric condition, but limited evidence has shown how genes and environment may contribute to its longitudinal changes. We sought to investigate sources of individual differences in the longitudinal trajectories of frailty, considering potential selection bias when including a sample of oldest-old twins. Methods Data were from 2 Swedish twin cohort studies: a younger cohort comprising 1 842 adults aged 29–96 years followed up to 15 waves, and an older cohort comprising 654 adults aged ≥79 years followed up to 5 waves. Frailty was measured using the frailty index (FI). Age-based latent growth curve models were used to examine longitudinal trajectories, and extended to a biometric analysis to decompose variability into genetic and environmental etiologies. Results A bilinear model with an inflection point at age 75 best described the data, indicating a fourfold to fivefold faster FI increase after 75 years. Twins from the older cohort had significantly higher mean FI at baseline but slower rate of increase afterward. FI level at age 75 was moderately heritable in both men (42%) and women (55%). Genetic influences were relatively stable across age for men and increasing for women, although the most salient amplification in FI variability after age 75 was due to individual-specific environmental influences for both men and women; conclusions were largely consistent when excluding the older cohort. Conclusion Increased heterogeneity of frailty in late life is mainly attributable to environmental influences, highlighting the importance of targeting environmental risk factors to mitigate frailty in older adults. [ABSTRACT FROM AUTHOR]

Background: Intellectual disability (ID) aggregates in families, but factors affecting individual risk and heritability estimates remain unknown. Methods: A population‐based family cohort study of 4,165,785 individuals born 1973–2013 in Sweden, including 37,787 ID individuals and their relatives. The relative risks (RR) of ID with 95% confidence intervals (95% CI) were obtained from stratified Cox proportional‐hazards models. Relatives of ID individuals were compared to relatives of unaffected individuals. Structural equation modeling was used to estimate heritability. Results: Relatives of ID individuals were at increased risk of ID compared to individuals with unaffected relatives. The RR of ID among relatives increased proportionally to the degree of genetic relatedness with ID probands; 256.70(95% CI 161.30–408.53) for monozygotic twins, 16.47(13.32–20.38) for parents, 14.88(12.19–18.16) for children, 7.04(4.67–10.61) for dizygotic twins, 8.38(7.97–8.83) for full siblings, 4.56(4.02–5.16) for maternal, 2.90(2.49–3.37) for paternal half‐siblings, 3.03(2.61–3.50) for nephews/nieces, 2.84(2.45–3.29) for uncles/aunts, and 2.04(1.91–2.20) for cousins. Lower RRs were observed for siblings of probands with chromosomal abnormalities (RR 5.53, 4.74–6.46) and more severe ID (mild RR 9.15, 8.55–9.78, moderate RR 8.13, 7.28–9.08, severe RR 6.80, 5.74–8.07, and profound RR 5.88, 4.52–7.65). Male sex of relative and maternal line of relationship with proband was related to higher risk (RR 1.33, 1.25–1.41 for brothers vs. sisters and RR 1.49, 1.34–1.68 for maternal vs. paternal half‐siblings). ID was substantially heritable with 0.95(95% CI 0.93–0.98) of the variance in liability attributed to genetic influences. Conclusions: The risk estimates will benefit researchers, clinicians, families in understanding the risk of ID in the family and the whole population. The higher risk of ID related to male sex and maternal linage will be of value for planning and interpreting etiological studies in ID. [ABSTRACT FROM AUTHOR]

Keeping appropriate interpersonal distance is an evolutionary conserved behavior that can be adapted based on learning. Detailed knowledge on how interpersonal space is represented in the brain and whether such representation is genetically influenced is lacking. We measured brain function using functional magnetic resonance imaging in 294 twins (71 monozygotic, 76 dizygotic pairs) performing a distance task where neural responses to human figures were compared to cylindrical blocks. Proximal viewing distance of human figures was compared to cylinders facilitated responses in the occipital face area (OFA) and the superficial part of the amygdala, which is consistent with these areas playing a role in monitoring interpersonal distance. Using the classic twin method, we observed a genetic influence on interpersonal distance related activation in the OFA, but not in the amygdala. Results suggest that genetic factors may influence interpersonal distance monitoring via the OFA whereas the amygdala may play a role in experience‐dependent adjustments of interpersonal distance. [ABSTRACT FROM AUTHOR]

Objective: Type 1 diabetes and Hashimoto’s thyroiditis frequently cluster in individuals and in families, indicating shared origins. The objective of this study was to investigate familial co-aggregation of these diseases and to quantify shared genetic and environmental factors. Design: This study is a twin cohort study. Methods: National health registers were used to identify cases among 110 814 Swedish twins. Co-aggregation was calculated as risk ratios for type 1 diabetes among co-twins of individuals with Hashimoto’s thyroiditis, and viceversa. Variance explained by genetics (i.e. heritability), and the proportions thereof shared between the diseases, was estimated by contrasting associations in monozygotic and dizygotic twins using structural equation models. Results: Individuals with one disease were at a high risk for the other disease (adjusted risk ratio: 11.4 (95% CI: 8.5– 15.3)). Co-aggregation was more common in monozygotic than in dizygotic pairs, with adjusted risk ratios of 7.0 (95% CI: 3.2–15.1) and 1.7 (95% CI: 0.7–4.1), respectively. Genetic effects shared across diseases accounted for 11% of the variance for type 1 diabetes and 9% of the variance for Hashimoto’s thyroiditis, while environmental factors unique to individual twins, but shared across diseases, accounted for 10% of the variance for type 1 diabetes and 18% of the variance for Hashimoto’s thyroiditis. Conclusions: Both genes and environment unique to individual twins contribute to considerable etiologic overlap between type 1 diabetes and Hashimoto’s thyroiditis. These findings add to the current knowledge on the mechanisms behind autoimmune disease clustering and could guide future research aimed at identifying pathophysiological mechanisms and intervention targets. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis and obesity are diseases with high prevalence, and they share common etiologies. We investigated the sex-specific genetic susceptibility to hip and knee osteoarthritis necessitating total joint replacement (TJR), and how body mass index (BMI) moderated the heritability of these osteoarthritis phenotypes.Methods: We linked 29,893 twin pairs with information on BMI in the Swedish Twin Registry with the Swedish National Patient Register to identify twins who underwent primary TJR of the hip or knee combined with a concomitant diagnosis of primary osteoarthritis of these joints. Structural equation modeling was used to calculate the heritability of hip and knee osteoarthritis treated with TJR, with estimates adjusted for the first available BMI, birth year, and sex. We also investigated how heritability varied with BMI treated as a continuous variable.Results: Similar heritability estimates for hip replacement (0.65 [95% confidence interval (CI), 0.59 to 0.70]) and knee replacement (0.57 [95% CI, 0.50 to 0.64]) were found. Heritability decreased with higher BMI in both sexes for hip replacement and in men for knee replacement. In contrast, heritability for knee replacement increased with higher BMI in women; the estimate was 0.37 (90% likelihood interval [LI], 0.25 to 0.49) for a BMI of 20 kg/m2 and 0.87 (90% LI, 0.68 to 0.94) for a BMI of 35 kg/m2.Conclusions: In our population, heritability explained, on average, about half of the susceptibility to undergo primary TJR of the hip or knee with the indication of primary osteoarthritis, but it varied with BMI and sex. We demonstrated substantial heritability for knee replacement in obese women.Level Of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Aim: To identify whether periodontal traits derived from electronic dental records are biologically informative and heritable. Materials and methods: The study included 11,974 adult twins (aged 30–92 years) in the Swedish Twin Registry. Periodontal records from dental examinations were retrieved from a national register and used to derive continuous measures of periodontal health. A latent class approach was used to derive categorial measures of periodontal status. The correlation patterns in these traits were contrasted in monozygotic and dizygotic twin pairs using quantitative genetic models to estimate the heritability of the traits. Results: For continuous traits, heritability estimates ranged between 41.5% and 48.3% with the highest estimates for number of missing tooth surfaces and rate of change in number of deep periodontal pockets (≥6 mm). For categorial traits, the latent class approach identified three classes (good periodontal health, mild periodontitis signs and severe signs of periodontitis) and there was a clear difference in the hazard for subsequent tooth loss between these three classes. Despite this, the class allocations were only slightly more heritable than a conventional dichotomous disease definition (45.2% vs. 42.6%). Conclusions: Periodontitis is a moderately heritable disease. Quantitative periodontal traits derived from electronic records are an attractive target for future genetic association studies. [ABSTRACT FROM AUTHOR]

Background: Exhaled nitric oxide and blood eosinophils are clinical asthma T‐helper type 2 markers in use. Immunoglobulin E (IgE) is often involved in the inflammation associated with atopic asthma. The effect of both blood eosinophils and allergen‐specific IgE on exhaled nitric oxide levels is not completely understood. Twin‐design studies can improve understanding of the underlying contribution of genetically and/or environmentally driven inflammation markers in asthma. Our aim was to disentangle the covariance between asthma and exhaled nitric oxide into genetic and environmental contributions that can account for inflammation markers in a paediatric population. Methods: This population‐based, cross‐sectional twin study enrolled 612 monozygotic (MZ) and same‐sex dizygotic (DZ) schoolchildren. Multivariate structural equation modelling was utilized to separate the covariance between asthma and exhaled nitric oxide into genetic and/or environmental effects, taking allergen‐specific IgE level and blood eosinophil count into account while controlling for confounding factors. Results: The cross‐twin/cross‐trait correlations had a higher magnitude in the MZ twins than in the DZ twins, indicating that genes affect the association. The likelihood ratio test for model fitting resulted in the AE model (ie additive genetic effects, A, and non‐shared environmental effects, E) as the most parsimonious. A majority, 73%, of the phenotypic correlation between asthma and exhaled nitric oxide, r =.19 (0.05‐0.33), was attributable to genetic effects which mainly was due to the allergen‐specific IgE level. Conclusions: This study indicates that the association between asthma and exhaled nitric oxide in children is to a large extent explained by genetics via allergen‐specific IgE level and not blood eosinophils. This might partly explain the clinical heterogeneity in this group. A next step could be to include allergen‐specific IgE level in multivariate omic studies. [ABSTRACT FROM AUTHOR]

Parents with substance misuse provide their children with a potentially risky rearing environment. According to the evolutionary life history theory, such environments steer individuals towards faster reproductive strategy. However, parents providing their children with hazardous environments may also pass on genes associated with early parenthood. In register data on individuals born in Sweden 1973–1993 (N = 2,176,128), the hazard ratio of entering parenthood by age 25 was 1.70 (95% CI 1.69–1.72) and 1.85 (1.82–1.89) among offspring of fathers and mothers with substance misuse, respectively, compared to others. In analyses using an offspring-of-siblings design in three types of parental sibling pairs (half siblings, full siblings and dizygotic twins, and monozygotic twins) increasingly controlling for genetic confounding, associations between parental substance misuse and offspring's early reproduction gradually attenuated. Our results suggest that the association between parental substance misuse and earlier parenthood in offspring is at least partly genetically confounded. Life history theory should be further tested with genetically informative research designs. [ABSTRACT FROM AUTHOR]

Background: Attention‐deficit/hyperactivity disorder (ADHD) frequently co‐occurs with other psychiatric disorders. Twin studies have established that these co‐occurrences are in part due to shared genetic risks. However, the strength of these genetic overlaps and the potential heterogeneity accounted for by type of psychiatric symptoms, age, and methods of assessment remain unclear. We conducted a systematic review to fill this gap. Methods: We searched PubMed, PsycINFO, Embase, and Web of Science until March 07, 2019. Genetic correlations (rg) were used as effect size measures. Results: A total of 31 independent studies fulfilled the inclusion criteria. The pooled estimates showed that the associations between ADHD and other psychiatric symptoms were partly explained by shared genetic factors, with a pooled genetic correlation of 0.50, 95% confidence interval: 0.46–0.60. The genetic correlations (rg) between ADHD and externalizing (rg =.49 [0.37–0.61]), internalizing (rg =.50 [0.39–0.69]), and neurodevelopmental (rg =.56 [0.47–0.66]) symptoms were similar in magnitude. The genetic correlations in childhood and adulthood were rg =.53 (0.43–0.63) and rg =.51 (0.44–0.56), respectively. For methods of assessment, the genetic correlations were also similar in strength, self‐reports rg =.52 (0.47–0.58), other informants rg =.55 (0.41–0.69), and combined raters rg =.50 (0.33–0.65). Conclusions: These findings indicate that the co‐occurrence of externalizing, internalizing, and neurodevelopmental disorder symptoms in individuals with ADHD symptoms in part is due to a shared genetic risk. [ABSTRACT FROM AUTHOR]

Background: Causes of the comorbidity of substance misuse with anxiety-related and depressive disorders (anxiety/depression) remain poorly known. We estimated associations of substance misuse and anxiety/depression in the general population and tested them while accounting for genetic and shared environmental factors. Methods: We studied individuals born in Sweden 1968–1997 (n = 2 996 398) with follow-up in nationwide register data for 1997–2013. To account for familial effects, stratified analyses were conducted within siblings and twin pairs. Substance misuse was defined as ICD-10 alcohol or drug use disorder or an alcohol/drug-related criminal conviction. Three dimensions of ICD-10 anxiety and depressive disorders and a substance misuse dimension were identified through exploratory factor analysis. Results: Substance misuse was associated with a 4.5-fold (95% CI 4.50–4.58) elevated risk of lifetime generalized anxiety/depression, 4.7-fold (95% CI 4.63–4.82) elevated risk of panic disorder and agora/social phobia, and 2.9-fold elevated risk of phobias/OCD (95% CI 2.82–3.02) as compared to those without substance misuse. The associations were attenuated in within-family analyses but we found elevated risks in monozygotic twin pairs discordant for substance misuse as well as significant non-shared environmental correlations. The association between anxiety/depression and substance misuse was mainly driven by generalized anxiety/depression, whereas other anxiety/depression dimensions had minor or no independent associations with substance misuse. Conclusions: Substance misuse and anxiety/depression are associated at the population level, and these associations are partially explained by familial liabilities. Our findings indicate a common genetic etiology but are also compatible with a potential partially causal relationship between substance misuse and anxiety/depression. [ABSTRACT FROM AUTHOR]

Physical examinations are recommended as part of a comprehensive evaluation for individuals with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and attention–deficit/hyperactivity disorder. These examinations should include assessment for morphological variants. Previous studies have shown an increase in morphological variants in individuals with NDDs, particularly ASD, and that these variants may be present in greater amounts in individuals with genetic alterations. Unfortunately, assessment for morphological variants can be subjective and time‐consuming, and require a high degree of clinical expertise. Therefore, objective, automated methods of morphological assessment are desirable. This study compared the use of Face2Gene, an automated tool to explore facial morphological variants, to clinical consensus assessment, using a cohort of N = 290 twins enriched for NDDs (n = 135 with NDD diagnoses). Agreement between automated and clinical assessments were satisfactory to complete (78.3–100%). In our twin sample, individuals with NDDs did not have greater numbers of facial morphological variants when compared to those with typical development, nor when controlling for shared genetic and environmental factors within twin pairs. Common facial morphological variants in those with and without NDDs were similar and included thick upper lip vermilion, abnormality of the nasal tip, long face, and upslanted palpebral fissure. We conclude that although facial morphological variants can be assessed reliably in NDDs with automated tools like Face2Gene, clinical utility is limited when just exploring the facial region. Therefore, currently, automated assessments may best complement, rather than replace, in‐person clinical assessments. [ABSTRACT FROM AUTHOR]

Objective: Co-aggregation of autoimmune diseases is common, suggesting pa rtly shared etiologies. Genetic factors are believed to be important, but objective measures of environ mental vs heritable influences on co-aggregation are absent. With a novel approach to twin studies, we aimed at esti mating heritability and genetic overlap in seven organspecific autoimmune diseases. Design: Prospective twin cohort study. Methods: We used a cohort of 110 814 twins to examine co-aggregation an d heritability of Hashimoto's thyroiditis, atrophic gastritis, celiac disease, Graves' disease, type 1 dia betes, vitiligo and Addison's disease. Hazard ratios (HR) were calculated for twins developing the same or different disea se as compared to their co-twin. The differences between monozygotic and dizygotic twin pairs were used to estim ate the genetic influence on co-aggregation. Heritability for individual disorders was calculated using stru ctural equational modeling adjusting for censoring and truncation of data. Results: Co-aggregation was more pronounced in monozygotic twins (media n HR: 3.2, range: 2.2-9.2) than in dizygotic twins (median HR: 2.4, range: 1.1-10.0). Heritability was moder ate for atrophic gastritis (0.38, 95% CI: 0.23-0.53) but high for all other diseases, ranging from 0.60 (95% CI: 0.49-0. 71) for Graves' disease to 0.97 (95% CI: 0.91-1.00) for Addison's disease. Conclusions: Overall, co-aggregation was more pronounced in monozygotic tha n in dizygotic twins, suggesting that disease overlap is largely attributable to genetic factors. Co- aggregation was common, and twins faced up to a ten-fold risk of developing diseases not present in their co-twin. Our r esults validate and refine previous heritability estimates based on smaller twin cohorts. [ABSTRACT FROM AUTHOR]

Background: Females with autism spectrum disorder have been reported to exhibit fewer and less severe restricted and repetitive behaviors and interests compared to males. This difference might indicate sex-specific alterations of brain networks involved in autism symptom domains, especially within cortico-striatal and sensory integration networks. This study used a well-controlled twin design to examine sex differences in brain anatomy in relation to repetitive behaviors. Methods: In 75 twin pairs (n = 150, 62 females, 88 males) enriched for autism spectrum disorder (n = 32), and other neurodevelopmental disorders (n = 32), we explored the association of restricted and repetitive behaviors and interests—operationalized by the Autism Diagnostic Interview-Revised (C domain) and the Social Responsiveness Scale-2 (Restricted Interests and Repetitive Behavior subscale)—with cortical volume, surface area and thickness of neocortical, sub-cortical, and cerebellar networks. Results: Co-twin control analyses revealed within-pair associations between RRBI symptoms and increased thickness of the right intraparietal sulcus and reduced volume of the right orbital gyrus in females only, even though the mean number of RRBIs did not differ between the sexes. In a sub-sample of ASD-discordant pairs, increased thickness in association with RRBIs was found exclusively in females in the orbitofrontal regions, superior frontal gyrus, and intraparietal sulcus, while in males RRBIs tended to be associated with increased volume of the bilateral pallidum. Limitations: However, due to a small sample size and the small difference in RRBI symptoms within pairs, the results of this exploratory study need to be interpreted with caution. Conclusions: Our findings suggest that structural alterations of fronto-parietal networks in association with RRBIs are found mostly in females, while striatal networks are more affected in males. These results endorse the importance of investigating sex differences in the neurobiology of autism symptoms, and indicate different etiological pathways underlying restricted and repetitive behaviors and interests in females and males. [ABSTRACT FROM AUTHOR]

Background: Smoking and use of Swedish smokeless tobacco (snus) are associated with increased risk of type 2 diabetes (T2D). Our aim was to estimate the unique and shared genetic components of these traits and to what extent the association is explained by shared genetic factors.Methods: We used twins of the Swedish Twin Registry who responded to a questionnaire between 1998 and 2006 (n = 40 247) and were followed until 2015 in the National Prescription and Patient Registries. We estimated hazard ratios (HRs) and odds ratios (ORs) for the association between smoking/snus use and T2D (n = 2130) and used structural equation models to estimate genetic and environmental variance components and genetic correlations.Results: Current smokers [HR 1.69, 95% confidence interval (CI), 1.49-1.92] and snus users (HR 1.19, 95% CI 1.01-1.41) had an increased risk of T2D. In within-pair analyses of monozygotic twins, corresponding ORs were 1.36, 95% CI 0.75-2.46 (smoking) and 1.54, 95% CI 0.80-2.99 (snus). Heritability was 43% (95% CI 36-51) for ever smoking, 58% (95% CI 44- 70) for ever snus use and 66% (95% CI 59-72) for T2D. The genetic correlation with T2D was 18% (95% CI 1-35) for smoking and -6% (95% CI -24 to 4) for snus use, indicating that only a small fraction of the genetic influence is shared.Conclusions: We could confirm that consumers of snus and cigarettes are at increased risk of T2D. Both snus use and smoking have strong genetic components, which appears to be attributable primarily to genes that are distinct from those promoting T2D. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Understanding the role of premorbid body mass index (BMI) in the emergence of eating disorders may be key to identifying effective prevention strategies. We explore relations between BMI and eating disorders traits in young twins. Method: The effect of BMI at age 9/12 and 15 on eating disorder traits measured using the Eating Disorders Inventory‐2 (EDI) at ages 15 and 18 was examined using bivariate modelling in a longitudinal population sample of Swedish twins. Results: The correlation between BMI and EDI within individuals was stable across all ages and remained significant after adjusting for later BMI. Bivariate analysis indicated significant positive genetic correlations between BMI ages 9/12 and 15 and subsequent EDI scores. The relationship remained significant for BMI age 9/12 and EDI age 15 in the adjusted model, indicating a longitudinal association. Conclusion: Our results have implications for conceptualizing the interrelation of BMI and eating disorders across childhood and adolescence. [ABSTRACT FROM AUTHOR]

Background: Minor physical anomalies (MPAs) are subtle anatomical deviations in one's appearance and may suggest altered embryogenesis. MPAs have been shown to be more common in neurodevelopmental disorders (NDDs) compared with typical development. Still, further studies are needed on MPAs in NDDs, especially using twins to adjust for confounding familial factors. Methods: Clinical assessments were conducted on 116 twins (61 NDD, 55 controls) from 51 monozygotic and 7 dizygotic pairs to examine MPAs and their association with DSM-5 defined NDDs. Additionally, the relationship between the number of MPAs within twins by zygosity was investigated. Results: Within the cohort sample, a specific association was found between MPAs and autism spectrum disorder (ASD) diagnosis (crude odds ratio = 1.29, p = .047; adjusted odds ratios = 1.26-1.33, adjusted p values = .032-.073) and autistic traits (crude ß = 3.02, p = .002; adjusted ß = 2.28, p = .019), but not NDDs in general or ADHD, nor within-pairs. Identified MPAs in ASD included overweight, hypermobility, pes planus, straight eyebrows, vision impairment, arachnodactyly/long toes, long eyelashes, and microtia. The number of MPAs within all monozygotic pairs was highly correlated (r = .88, p < .001). Conclusion: MPAs are more frequent in participants with ASD and may be influenced by genetics. The value of MPAs for (early) detection should be further explored, as they might index individuals at increased risk for ASD in particular. [ABSTRACT FROM AUTHOR]

Background Women with polycystic ovary syndrome (PCOS) are at elevated risk for suffering from depression. Neuroticism is a personality trait that has been associated with an increased risk for developing major depressive disorder (MDD). The aim of the present study was to quantify and decompose the correlation between neuroticism, PCOS, and MDD into shared and unique genetic and environmental etiologies, by using quantitative genetic methods. Methods In a cohort of 12,628 Swedish female twins born from 1959 to 1985, neuroticism, PCOS identified by symptoms of hyperandrogenemia (i.e., hirsutism) and oligo- and/or anovulation, and lifetime MDD status were determined through questionnaire responses. Structural equation modeling was used to study the genetic and environmental sources of the variation within, and covariation between neuroticism, PCOS, and MDD. Results Female twins with PCOS (n = 752) had significantly higher levels of neuroticism than women without PCOS, and a 2-fold increase in odds for a lifetime prevalence of MDD. The phenotypic correlation between PCOS and MDD was 0.19, with 63% of the correlation attributable to common genetic factors between the two traits. When taking into account neuroticism, 41% was attributable to common genetic factors and 9% attributable to common environmental factors shared between all three traits, with the remainder attributable to components unique to PCOS and MDD. Conclusion There are common genetic factors between neuroticism, PCOS, and MDD; however, neuroticism shares approximately half of the genetic and environmental components behind the phenotypic correlation between PCOS and MDD, providing some etiological evidence behind the comorbidity between PCOS and depression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rationale: Associations between fetal growth restriction and lung function impairment could be due to gestational age as well as shared (familial) genetic and environmental factors.Objectives: To study the association between fetal growth and lung function in childhood while taking gestational age and familial factors into account.Methods: First, full-cohort analyses of twins were performed to study the association between birth weight, gestational age, fetal growth, and lung function (FEV1, FVC, and FEV1/FVC) in z-scores before (n = 520) and after (n = 539) bronchodilator treatment. Second, to control for gestational age and familial factors, within-twin-pair analyses were performed.Results: Regarding full-cohort post-bronchodilator treatment, FEV1 was significantly associated with a decrease in birth weight (-0.16 z-score per 500 g; 95% confidence interval [CI], -0.28 to -0.04) and fetal growth (-0.15 z-score per 1 SD decrease; 95% CI, -0.26 to -0.04), and similar and significant associations for FVC with birth weight and fetal growth were also seen. Nonsignificant associations for FEV1 and FVC with gestational age were found. The direction of effect was similar in pre-bronchodilator analyses, although with somewhat less strong and nonsignificant effect estimates for both FEV1 and FVC with fetal growth. No associations were found between any of the exposure variables and FEV1/FVC either pre- or post-bronchodilator. In the within-twin-pair analyses, the direction of effect appeared similar to that of the whole cohort, but the CIs were wider.Conclusions: Our results suggest that there is a significant association between restricted fetal growth and post-bronchodilator FEV1 and FVC, but not FEV1/FVC, in childhood that may be independent of gestational age and shared familial factors. [ABSTRACT FROM AUTHOR]

Background: Twin studies of hoarding symptoms indicate low to moderate heritability during adolescence and considerably higher heritability in older samples, suggesting dynamic developmental etiological effects. The aim of the current study was to estimate the relative contribution of additive genetic and environmental effects to hoarding symptoms during adolescence and young adulthood and to estimate the sources of stability and change of hoarding symptoms during adolescence. Methods: Univariate model-fitting was conducted in three cohorts of twins aged 15 (n = 7,905), 18 (n = 2,495) and 20–28 (n = 6,218). Longitudinal analyses were conducted in a subsample of twins for which data on hoarding symptoms was available at both age 15 and 18 (n = 1,701). Results: Heritability estimates for hoarding symptoms at ages 15, 18 and 20–28 were 41% (95% confidence interval [CI]: 36–45%), 31% (95% CI: 22–39%) and 29% (95% CI: 24–34%) respectively. Quantitative sex-differences emerged in twins aged 15 at which point the heritability in boys was 33% (95% CI: 22–41%) and 17% (95% CI: 0–36%) in girls. Shared environmental effects played a negligible role across all samples with the exception of girls aged 15 where they accounted for a significant proportion of the variance (22%; 95% CI 6–36%). The longitudinal bivariate analyses revealed a significant phenotypic correlation of hoarding symptoms between ages 15 and 18 (0.40; 95% CI: 0.36–0.44) and a strong but imperfect genetic correlation (0.75; 95% CI: 0.57–0.94). The bivariate heritability was estimated to 65% (95% CI: 50–79%). Conclusions: Hoarding symptoms are heritable from adolescence throughout young adulthood, although heritability appears to slightly decrease over time. Shared environmental effects contribute to hoarding symptoms only in girls at age 15. The stability of hoarding symptoms between ages 15 and 18 is largely explained by genetic factors, while non-shared environmental factors primarily have a time-specific effect. The findings indicate that dynamic developmental etiological effects may be operating across the life span. [ABSTRACT FROM AUTHOR]

Objectives: Despite the high prevalence of endometriosis among women of reproductive age, risk factors or markers for developing the condition remain largely unknown. Many of the published studies are based on small selected samples. We therefore investigated the relationships of reproductive and lifestyle factors with endometriosis in a large sample of Swedish female twins. Material and methods: This cross-sectional study included 28,822 women. Among these, endometriosis was reported by 1,228 women and the self-reported diagnosis was confirmed by medical records. Potential risk factors or markers for risk considered were age at menarche, level of education, body mass index (BMI), parity, oral contraceptive (OC) use, infertility, coffee consumption, smoking, and alcohol intake, which were investigated using logistic regression with crude and adjusted analyses. We performed within-pair analysis to examine the sensitivity of the results. Results: Late age at menarche and higher parity showed an inverse association and infertility showed a strong association with endometriosis. We observed positive associations with coffee consumption and smoking and an inverse association with OC use in crude analysis but not in adjusted analysis. There were no significant associations between level of education, BMI, or alcohol intake and endometriosis. Within-pair analysis showed persistent inverse association of parity and association of infertility with endometriosis. Conclusions: Our study suggests that late age at menarche and higher parity are inversely associated and infertility is strongly associated with endometriosis. Future studies are needed to explore the significance of these factors in the diagnosis of endometriosis and understanding of its etiology. [ABSTRACT FROM AUTHOR]

Objective: Attention-deficit/hyperactivity disorder (ADHD) has been linked to immaturity relative to peers in childhood, yet it is unclear how such immaturity is associated with ADHD across development. This longitudinal twin study examined the genetic and environmental contributions to the association between parents' perception of their child's immaturity relative to peers (RI) in childhood and ADHD symptoms across development.Method: 1,302 twin pairs from the Swedish Twin Study of Child and Adolescent Development were followed prospectively from childhood to early adulthood. Parent ratings of RI were collected at 8 to 9 years and parent and self-ratings of ADHD symptoms were collected at 8 to 9, 13 to 14, 16 to 17, and 19 to 20 years using the Child Behavior Checklist Attention Problems scale. In addition, ADHD symptoms corresponding to DSM criteria were used for sensitivity analysis. Analyses were conducted using longitudinal structural equation modeling with multiple raters.Results: RI-related etiologic factors, predominantly influenced by genes, explained 10-14% of the variance in ADHD symptoms from 8 to 9 up to 16 to 17 years. The influence of these RI-related factors on ADHD symptoms attenuated to 4% by 19 to 20 years of age. The remaining variance in ADHD symptoms was primarily explained by genetic factors independent of RI, which remained relatively stable across development, explaining 19% to 30% of the variance in ADHD symptoms from 13 to 14 up to 19 to 20 years.Conclusion: The results show that RI is significantly associated with ADHD symptoms, particularly during childhood and adolescence, and that the association is primarily explained by a shared genetic liability. Nevertheless, the magnitude of associations across development was modest, highlighting that RI is merely one aspect contributing to the complex etiology of ADHD symptoms. [ABSTRACT FROM AUTHOR]

Objective: The authors investigated the relative importance of genetic and environmental influences on perinatal depression, and the genetic overlap between perinatal depression and nonperinatal depression.Method: Analyses were conducted using structural equation modeling for 1) the lifetime version of the Edinburgh Postnatal Depression Scale in 3,427 Swedish female twins and 2) clinical diagnoses of depression separated into perinatal depression and nonperinatal depression in a Swedish population-based cohort of 580,006 sisters.Results: In the twin study, the heritability of perinatal depression was estimated at 54% (95% CI=35%-70%), with the remaining variance attributable to nonshared environment (46%; 95% CI=31%-65%). In the sibling design, the heritability of perinatal depression was estimated at 44% (95% CI=35%-52%) and the heritability of nonperinatal depression at 32% (95% CI=24%-41%). Bivariate analysis showed that 14% of the total variance (or 33% of the genetic variance) in perinatal depression was unique for perinatal depression.Conclusions: The heritability of perinatal depression was estimated at 54% and 44%, respectively, in separate samples, and the heritability of nonperinatal depression at 32%. One-third of the genetic contribution was unique to perinatal depression and not shared with nonperinatal depression, suggesting only partially overlapping genetic etiologies for perinatal depression and nonperinatal depression. The authors suggest that perinatal depression constitutes a subset of depression that could be prioritized for genomic discovery efforts. The study findings have direct translational impact that can assist clinicians in the counseling of their patients regarding risk and prognosis of perinatal depression. [ABSTRACT FROM AUTHOR]

Background Attention-Deficit/Hyperactivity Disorder ( ADHD) frequently co-occurs with externalizing disorders, but a clear understanding of the etiologic underpinnings is hampered by the limited understanding of the codevelopment of the traits from childhood into early adulthood. Methods Using a birth cohort of 2600 twins, the Swedish Twin study of Child and Adolescent Development study, assessed at ages 8-9, 13-14, 16-17, and 19-20, we investigated the codevelopment of ADHD and externalizing behavior from childhood to adulthood. The analyses examined ADHD-like and externalizing traits, as rated by twins and their parents using the Attention Problems scale and Externalizing scale of the Child Behavior Checklist, and estimated cross-lagged effects (one trait at one time-point predicting the other at the next). The covariation between the traits were decomposed into stable (effects carried over from the prior time-points) and innovative (new effects for each time-point) sources; each source was further decomposed into additive genetics, shared and nonshared environment. Results The analysis suggested that externalizing traits in middle childhood (age 8-9) predicted ADHD-like traits in early adolescence (age 13-14), whereas the reverse association was nonsignificant. In contrast, ADHD-like traits in lateadolescence (age 16-17) predicted externalizing traits in early adulthood (age 19-20). The correlation between ADHD-like and externalizing traits increased over time. At all time-points, innovative sources contributed substantially to maintained comorbidity. Genetic effects explained 67% of the covariation at each time-point; importantly, nearly 50% of these effects were innovative. Conclusions This study challenges the belief that ADHD generally precedes externalizing behaviors; rather, change in the etiologic factors across the development is the rule. The effects were due to both new genetic and environmental factors emerging up to young adulthood. Clinicians and researchers needs to consider complex etiologic and developmental models for the comorbidity between ADHD and externalizing behaviors. [ABSTRACT FROM AUTHOR]

Objective: To estimate the relative contribution of genetic influences and prevalence on endometriosis.Design: Analysis of self-reported data from a nationwide population-based twin registry.Setting: Not applicable.Patient(s): A total of 28,370 women, female monozygotic (MZ) or dizygotic (DZ) twins, who participated in either of two surveys (1998-2002 or 2005-2006).Intervention(s): None.Main Outcome Measure(s): Self-reported endometriosis, validated by medical records.Result(s): A history of endometriosis was reported by 1,228 female twins. The probandwise concordance was 0.21 for MZ and 0.10 for DZ twins. Higher within-pair (tetrachoric) correlation was observed among MZ (0.47) compared with DZ (0.20) twins. The best-fitting model revealed a contribution of 47% by additive genetic factors and the remaining 53% attributed to unique environmental effects.Conclusion(s): Our findings suggest both genetic and unique (nonshared) environmental influences on the complex etiology of endometriosis and support the hypothesis that genes have a strong influence on phenotypic manifestations of endometriosis. [ABSTRACT FROM AUTHOR]

Adolescent internalizing problems such as anxiety and depression have been associated with subsequent educational underachievement. However, it has not been investigated if the association is accounted for by neurodevelopmental disorders (NDDs, i.e., attention-deficit/hyperactivity disorder, autism spectrum disorder, developmental coordination disorder, tic disorder, learning disorder). This study is the first to describe the relationship between internalizing problems at age 15 and educational outcomes in later adolescence while controlling for a wide range of NDDs in childhood, and applying a genetically sensitive design. We used the nation-wide population-based Child and Adolescent Twin Study in Sweden, comprising 4997 fifteen-year-old Swedish twins born between 1994 and 1998. Internalizing problems and NDDs were measured with parental report. Educational outcomes were merit rating and upper secondary education eligibility, retrieved from the National School Register. Internalizing problems at age 15 were found to be negatively associated with educational outcomes in later adolescence. Additive genetics accounted for 89% of the covariation between internalizing problems and merit rating, out of which roughly half were unique genetic effects of internalizing problems and the remaining half due to NDDs. In conclusion, internalizing problems form an important risk factor for subsequent educational underachievement, going beyond the risk conferred by childhood NDDs. [ABSTRACT FROM AUTHOR]