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Objectives: The aims of the study are to investigate trajectories of labor market marginalization (IMM) and to examine the associations between family-related life events and LMM trajectories while accounting for familial factors. Methods: This is a prospective cohOIt study of 37.867 Swedish twins. Data were mialyzed by group-based trajectory modeling. Associations of thmily-related life events with trajectory groups were estimated by multinomial logistic regression. Results: Most participants had no or low levels of LMM. Individuals who stayed niarried over time or changed from single without children to married with children had a decreased risk of LM M. The risk of LMM over time was higher among individuals who changed from married to being single. Conclusions: Being or getting married as well as having children decreases the risk of LMM while divorce is a risk factor for LIV[M. [ABSTRACT FROM AUTHOR]

Background Residential regions may impact the possibilities to achieve a sustainable working life (SWL, i.e. not having interruptions due to sickness absence, disability pension or unemployment) due to disparities in social security and labour market. We aimed to investigate concurrent trajectories of regions and SWL among Swedish twins. Methods National register data were used for the degree of SWL in each year, old-age pension, emigration, death and residential regions classified in three categories (cities; towns and suburbs; or rural areas) of Swedish twins in 1998–2016 (n  = 80 398). Group-based multi-trajectory modelling and multinomial regression for relative risks with 95% confidence intervals were calculated. Results The six-group solution had the best fit to data with trajectories: stable living in towns and suburbs with SWL (33.8%); stable living in cities with SWL (22.1%); stable living in towns and suburbs with increasing SWL (13.9%); stable living in towns and suburbs with lack of SWL (13.2%); stable living towns and suburbs with decreasing SWL (8.8%); and stable living towns and suburbs with decreasing and ultimately lack of SWL (8.3%). Age and being woman increased and being married and higher education decreased the likelihood of belonging to groups 2–6 (vs. 1). Conclusions The simultaneous assessment of trajectories of three residential regions and SWL indicated that most people in Sweden seem to live continuously over time in towns and suburbs, but the degree of SWL may vary. More fine-grained assessment of residential regions would be needed to clarify the associations with SWL. [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]

Psychosocial working conditions and sickness absence (SA) lacked consistent associations. However, pain seemed to play a role, either due to the underlying condition, or the psychosocial working conditions. For workplaces and occupational health care this might indicate need to detect pain and psychosocial stressors at work for prevention of SA. Objective: To investigate pain and/or common mental disorders (CMDs) in the associations between psychosocial working conditions and sickness absence (SA) while controlling familial confounding. Methods: Prospective Prospective twin cohort study included survey data for pain and CMD, register data for SA and psychosocial working conditions. The follow-up from 2005 to 2016 of 28,916 twin individuals for first incident SA spell measured as the main International Classification of Diseases version 10 (ICD-10) diagnosis groups (F00-F99, I00-I99, and M00-M99), or the duration. We used regression models to obtain odds ratio (OR), incidence rate ratio (IRR), or relative risk ratio (RRR) with 95% confidence intervals (CI). Results: The covariate adjusted models of 9156 SA spells indicated almost no statistically significant associations between psychosocial working conditions and SA. Conclusions: Psychosocial working conditions were not associated with SA while familial confounding could not be ruled out. [ABSTRACT FROM AUTHOR]

We examined the association between early-life participation in collision sports and later-life cognitive health over a 28-year period in a population-based sample drawn from the longitudinal Swedish Adoption/Twin Study of Aging (1987–2014). Cognitive measures included the Mini-Mental State Examination and performance across multiple cognitive domains (e.g. global cognition, verbal ability, spatial ability, memory, processing speed). Among a sample of 660 adults (mean age at baseline, 62.8 years (range: 50–88); 58.2% female), who contributed 10,944 person-years of follow-up, there were 450 cases of cognitive impairment (crude rate = 41.1/1,000 person-years). Early-life participation in collision sports was not significantly associated with cognitive impairment at baseline or with its onset over a 28-year period in a time-to-event analysis, which accounted for the semi-competing risk of death. Furthermore, growth curve models revealed no association between early-life participation in collision sports and the level of or change in trajectories of cognition across multiple domains overall or in sex-stratified models. We discuss the long-term implications of adolescent participation in collision sports on cognitive health. [ABSTRACT FROM AUTHOR]

The prevalence of type 2 diabetes (T2D) is increasing worldwide, but current treatments have limitations. miRNAs may play a key role in the development of T2D and can be targets for novel therapies. Here, we examined whether T2D is associated with altered expression and DNA methylation of miRNAs using adipose tissue from 14 monozygotic twin pairs discordant for T2D. Four members each of the miR-30 and let-7-families were downregulated in adipose tissue of subjects with T2D versus control subjects, which was confirmed in an independent T2D case-control cohort. Further, DNA methylation of five CpG sites annotated to gene promoters of differentially expressed miRNAs, including miR-30a and let-7a-3, was increased in T2D versus control subjects. Luciferase experiments showed that increased DNA methylation of the miR-30a promoter reduced its transcription in vitro. Silencing of miR-30 in adipocytes resulted in reduced glucose uptake and TBC1D4 phosphorylation; downregulation of genes involved in demethylation and carbohydrate/lipid/amino acid metabolism; and upregulation of immune system genes. In conclusion, T2D is associated with differential DNA methylation and expression of miRNAs in adipose tissue. Downregulation of the miR-30 family may lead to reduced glucose uptake and altered expression of key genes associated with T2D. [ABSTRACT FROM AUTHOR]

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

Background: Development of the gut-brain axis in early life may be disturbed by antibiotic use. It has been hypothesized that this disturbance may contribute to development of neurodevelopmental disorders, including autism spectrum disorder and attention-deficit hyperactivity disorder. We aimed to assess the association between antibiotic use in early life and the risk of developing attention-deficit hyperactivity disorder or autism spectrum disorder, while controlling for shared genetic and environmental factors in a discordant twin design.Methods: We conducted a cohort study in twins (7-12 years; 25 781 twins) from the Netherlands Twin Register (NTR) and a replication study in the Childhood and Adolescent Twin Study in Sweden (CATSS; 7946 9-year-old twins). Antibiotic use was recorded before age 2 years. Attention-deficit hyperactivity disorder and autism spectrum disorder were parent-reported in the Netherlands Twin Register and register-based in the Childhood and Adolescent Twin Study in Sweden.Results: Early-life antibiotic use was associated with increased risk of attention-deficit hyperactivity disorder development [pooled odds ratio (OR) 1.10, 95% confidence interval (CI) 1.02-1.17] and autism spectrum disorder (pooled OR 1.15, 95% CI 1.06-1.25) in a case-control design. When restricting to monozygotic twin pairs discordant for the outcome, associations disappeared for both disorders in both cohorts (attention-deficit hyperactivity disorder OR 0.90, 95% CI 0.48-1.69 and OR 0.80, 95% CI 0.37-1.76, and autism spectrum disorder OR 0.66, 95% CI 0.38-1.16 and OR 0.29, 95% CI 0.02-4.50, respectively).Conclusions: Our findings suggest that the association between early-life antibiotic use and risk of attention-deficit hyperactivity and autism spectrum disorder may be confounded by shared familial environment and genetics. [ABSTRACT FROM AUTHOR]

Whether genetic and familial factors influence the association between cardiorespiratory fitness (CRF) and cardiovascular disease (CVD) is unknown. Two cohorts were formed based on data from 1,212,295 men aged 18 years who were conscripted for military service in Sweden during 1972–1996. The first comprised 4,260 twin pairs in which the twins in each pair had different CRF (≥1 watt). The second comprised 90,331 nonsibling pairs with different CRF and matched on birth year and year of conscription. Incident CVD and all-cause mortality were identified using national registers. During follow-up (median 32 years), there was no difference in CVD and mortality between fitter twins and less fit twins (246 vs. 251 events; hazard ratio (HR) = 1.00, 95% confidence interval (CI): 0.83, 1.20). The risks were similar in twin pairs with ≥60-watt difference in CRF (HR = 0.96, 95% CI: 0.57, 1.64). In contrast, in the nonsibling cohort, fitter men had a lower risk of the outcomes than less fit men (4,444 vs. 5,298 events; HR = 0.83, 95% CI: 0.79, 0.86). The association was stronger in pairs with ≥60-watt difference in CRF (HR = 0.65, 95% CI: 0.59, 0.71). These findings indicate that genetic and familial factors influence the association of CRF with CVD and mortality. [ABSTRACT FROM AUTHOR]

Study Question: Are obstetric and perinatal outcomes in pregnancies after fresh blastocyst transfer (BT) comparable with those born after fresh cleavage stage transfer (CT) and spontaneous conception (SC)?Summary Answer: Fresh BT is associated with a higher risk of placental and perinatal complications.What Is Known Already: BT optimizes the selection of top-quality embryos and increases pregnancy and live birth rates per transfer compared to CT. However, concerns have been raised as extended culture duration may increase obstetric complications and impair perinatal outcomes. Previous studies have shown a higher risk of preterm birth (PTB) among infants born after BT compared with CT. Pregnancies after BT are also prone to a higher risk of same-sex twins after single embryo transfer (SET).Study Design, Size, Duration: A retrospective register-based cohort study used data from Denmark, Norway and Sweden including three cohorts: 56 557 singletons and 16 315 twins born after fresh IVF/ICSI cycles and 2 808 323 SC singletons in Denmark (birth years 1997-2014), Norway (2010-2015) and Sweden (2002-2015). Of the fresh IVF/ICSI singletons, 4601 were born after BT and 51 956 after CT. The twin cohort consisted of 884 fresh IVF/ICSI children born after BT and 15 431 fresh IVF/ICSI children born after CT.Participants/materials, Setting, Methods: Data were obtained from a large Nordic cohort of children born after ART and SC initiated by the Committee of Nordic ART and Safety (CoNARTaS). The CoNARTaS cohort was established by cross-linking National ART-, Medical Birth-, and National Patients Registers using the unique personal identification number, allocated to every citizen in the Nordic countries. Obstetric and perinatal outcomes after BT, CT and SC were compared using logistic regression analysis. For perinatal outcomes, we calculated gestational age based on the date of oocyte pick-up (OPU) and in sensitivity analyses on data from Denmark and Norway, we also calculated gestational age based on the second-trimester ultrasonography (US) scan. Risk of pregnancies with same-sex twins after SET was used as a proxy for risk of monozygotic twins. Adjustments were made for child's sex, birth year, parity (0 or >1), maternal age, body mass index, smoking, educational level, fertilization method (IVF/ICSI), the number of aspirated oocytes, SET and country. Information on educational level and the number of aspirated oocytes was not available for Norway. Children born after frozen embryo transfer were not included. The birth cohorts were restricted according to the year in which BT was introduced in the different countries.Main Results and the Role Of Chance: A higher risk of placenta previa was found in singleton pregnancies after BT compared with CT (adjusted odds ratio [aOR] 2.11 [95% CI 1.76; 2.52]). Singletons born after BT had a higher risk of PTB (aOR 1.14 [95% CI 1.01; 1.29]) compared with CT singletons, when estimated based on OPU. Furthermore, an altered male/female ratio (aOR 1.13 [95% CI 1.06; 1.21]) with more males following BT compared with CT was seen. Risk of same-sex twins after SET was higher after single BT compared with single CT (aOR 1.94 [95% CI 1.42; 2.60]).Limitations, Reasons For Caution: Residual confounding cannot be excluded, in particular related to duration and cause of infertility that we could not adjust for due to lack of reliable data.Wider Implications Of the Findings: Extended embryo culture to the blastocyst stage has the potential to compromise obstetric and perinatal outcomes in fresh cycles. These results are important since an increasing number of IVF/ICSI treatments are performed as BT.Study Funding/competing Interest(s): NORDFORSK (project no: 71450). The Research Fund of Rigshospitalet, Copenhagen University Hospital. ReproUnion Collaborative study, co-financed by the European Union, Interreg V ÖKS. Grants from Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (LUA/ALF 70940), Hjalmar Svensson Research Foundation. The Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. None of the authors has any conflicts of interests to declare regarding this study.Trial Registration Number: ISRCTN11780826. [ABSTRACT FROM AUTHOR]

Background Little is known about adolescent mental health problems, including social phobia, as risk factors for future work incapacity. The aim of this study was to investigate the association between social phobia in adolescence and unemployment and sickness absence (SA) in early adulthood, also evaluating the role of familial factors (genetics and shared environment). Methods A sample of 2845 Swedish twins born in 1985–86 in Sweden was followed longitudinally in the population-based and prospective Twin study of CHild and Adolescent Development. Information on twins' social phobia was collected at ages 13–4, 16–7 and 19–20 years. Logistic regression providing odds ratios (OR) with 95% confidence intervals (95% CI) was used to analyze the associations between social phobia, unemployment and SA during the follow-up 2006–12. The influence of familial factors was evaluated by conditional logistic regression. Results Presence of social phobia during adolescence was associated with increased odds for unemployment and SA in young adulthood. For unemployment, the highest OR was at the age of 13–4 years (1.58 [95% CI: 1.22–2.06]), and the associations became null after adjusting for familial factors. For SA, the highest OR was at the age of 19–20 years (1.73 [95% CI: 1.13–2.65]), and the estimates changed slightly after adjusting for familial factors. Conclusions : Results suggest that social phobia experienced in adolescence contribute to early adulthood unemployment and SA. Familial factors seemed to explain the association between social phobia and unemployment. [ABSTRACT FROM AUTHOR]

Importance: Psychiatric traits associated with categorically defined psychiatric disorders are heritable and present to varying degrees in the general population. It is commonly assumed that diagnoses represent the extreme end of continuously distributed traits in the population, but this assumption has yet to be robustly tested for many psychiatric phenotypes.Objective: To assess whether genetic risk factors associated with psychiatric disorders are also associated with continuous variation in milder population traits.Design, Setting, and Participants: This study combined a novel twin analytic approach with polygenic risk score (PRS) analyses in a large population-based twin sample. Phenotypic and genetic data were available from the Child and Adolescent Twin Study in Sweden. Inpatient data were available for January 1, 1987, to December 31, 2014, and outpatient data for January 1, 2001, to December 31, 2013. The last day of follow-up was December 31, 2014. Data analysis was performed from January 1, 2017, to September 30, 2017.Main Outcomes and Measures: Questionnaires that assessed traits of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), learning difficulties, tic disorders (TDs), obsessive-compulsive disorder (OCD), anxiety, major depressive disorder (MDD), mania, and psychotic experiences were administered to a large Swedish twin sample. Individuals with clinical psychiatric diagnoses were identified using the Swedish National Patient Register. Joint categorical/continuous twin modeling was used to estimate genetic correlations between psychiatric diagnoses and continuous traits. The PRSs for psychiatric disorders were calculated based on independent discovery genetic data. The association between PRSs for each disorder and associated continuous traits was tested.Results: Phenotype data were available for 13 923 twin pairs (35.1% opposite sex and 31.7% same-sex females) at 9 years of age, 5165 pairs (36.9% opposite sex and 34.0% same-sex females) at 15 years of age, and 4273 pairs (36.5% opposite sex and 34.4% same-sex females) at 18 years of age. Genetic data were available for 13 412 individuals (50.2% females). Twin genetic correlations between numerous psychiatric diagnoses and corresponding traits ranged from 0.31 to 0.69. Disorder PRSs were associated with related population traits for ASD (β [SE] = 0.04 [0.01] at 9 years of age), ADHD (β [SE] = 0.27 [0.03] at 9 years of age), TDs (β [SE] = 0.02 [0.004] at 9 years of age), OCD (β [SE] = 0.13 [0.05] at 18 years of age), anxiety (β [SE] = 0.18 [0.08] at 9 years of age; β [SE] = 0.07 [0.02] at 15 years of age; and β [SE] = 0.40 [0.17] at 18 years of age), MDD (β [SE] = 0.10 [0.03] at 9 years of age; β [SE] = 0.11 [0.02] at 15 years of age; and β [SE] = 0.41 [0.10] at 18 years of age), and schizophrenia (β [SE] = 0.02 [0.01] at 18 years of age). Polygenic risk scores for depressive symptoms were associated with MDD diagnoses (odds ratio, 1.16; 95% CI, 1.02-1.32).Conclusions and Relevance: These results suggest that genetic factors associated with psychiatric disorders are also associated with milder variation in characteristic traits throughout the general population for many psychiatric phenotypes. This study suggests that many psychiatric disorders are likely to be continuous phenotypes rather than the categorical entities currently defined in diagnostic manuals, which has strong implications for genetic research in particular. [ABSTRACT FROM AUTHOR]

Objective We examined changes in participation in cognitive, social, and physical leisure activities across middle and older adulthood and tested moderation of trajectories of change in participation by gender. Method In all, 1,398 participants in the Swedish Adoption/Twin Study of Aging (SATSA) completed a 7-item leisure activity questionnaire up to 4 times over 17 years. Mean baseline age was 64.9 years (range = 36–91); 59% were women. Factor analysis identified physical, social, and cognitive/sedentary leisure activity participation factors. Age-based latent growth curve models adjusted for marital status, gender, education, depressive symptoms, and physical health were used. Results Overall, results indicated stability in social activities, increase in cognitive/sedentary activities, and decrease in physical activities, as well as accelerated decline in all three types of activities after about the age of 70 years. Social activity remained mostly stable for women and declined for men. Women reported higher levels of cognitive/sedentary leisure activity across the study. Both men and women declined in physical leisure activity. Variance in leisure activities increased with age; men demonstrated more variance in social activities and women in physical activities. Conclusions Understanding change in leisure activities with age and by gender can have important implications for interventions and for use of leisure activity data in epidemiological research. [ABSTRACT FROM AUTHOR]

Importance: Low academic achievement (AA) in childhood and adolescence is associated with increased substance use. Empirical evidence, using longitudinal epidemiologic data, may provide support for interventions to improve AA as a means to reduce risk of drug abuse (DA).Objective: To clarify the nature of the association between adolescent AA and risk of DA by using instrumental variable and co-relative analysis designs.Design, Setting, and Participants: This study, assessing nationwide data from individuals born in Sweden between 1971 and 1982, used instrumental variable and co-relative analyses of the association between AA and DA. The instrument was month of birth. Co-relative analyses were conducted in pairs of cousins (263 222 pairs), full siblings (154 295), and monozygotic twins (1623) discordant for AA, with raw results fitted to a genetic model. The AA-DA association was modeled using Cox regression. Data analysis was conducted from October 2017 to January 2018.Exposures: Academic achievement assessed at 16 years of age (for instrumental variable analyses), and estimated discordance in AA in pairs of monozygotic twins (for co-relative analyses).Main Outcomes and Measures: Drug abuse registration in national medical, criminal, or pharmacy registries.Results: This instrumental variable analysis included 934 462 participants (478 341 males and 456 121 females) with a mean (SD) age of 34.7 (4.3) years at a mean follow-up of 19 years. Earlier month of birth was associated with a linear effect on AA, with the regression coefficient per month equaling -0.0225 SDs (95% CI, -0.0231 to -0.0219). Controlling for AA, month of birth had no association with risk of DA (hazard ratio [HR], 1.000; 95% CI, 0.997-1.004). Lower AA had a significant association with risk of subsequent DA registration (HR per SD, 2.33; 95% CI, 2.30-2.35). Instrumental variable analysis produced a substantial but modestly attenuated association (HR, 2.04; 95% CI, 1.75-2.33). Controlling for modest associations between month of birth and parental educational status and DA risk reduced the association to a HR of 1.92 (95% CI, 1.67-2.22). The genetic model applied to the results of co-relative analyses fitted the observed data well and estimated the AA-DA association in monozygotic twins discordant for AA to equal a HR of 1.79 (95% CI, 1.64-1.92).Conclusions and Relevance: Two different methodological approaches with divergent assumptions both produced results consistent with the hypothesis that the significant association observed between AA at 16 years of age and risk of DA into middle adulthood may be causal. These results provide empirical support for efforts to improve AA as a means to reduce risk of DA. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD), Attention‐deficit/Hyperactivity disorder (ADHD), and other related neurodevelopmental disorders (NDDs) have, in some previous studies, been shown to increase the risk of being sexually victimized. However, no studies have examined whether the association is driven by a general NDD phenotype versus specific diagnoses, nor the etiology of the association. Method: Using a genetically informative, prospective design, we examined the association between ASD and ADHD in childhood and coercive sexual victimization up to age 18. A total of 4,500 children participating in the Child and Adolescent Twin Study in Sweden (CATSS) were rated by their parents on NDDs at age 9 or 12 years, and self‐reported at age 18 on lifetime experiences of coercive sexual touching and/or coercive sex. First, we regressed sexual victimization on the NDDs. Second, we regressed sexual victimization on general and specific NDD symptoms identified via a bifactor model. Third, we decomposed the observed associations into genetic and environmental parts. Results: In females, ASD was associated with an almost threefolded increased risk of coercive sexual victimization, and ADHD with a doubled risk. In males, the risk associated with ASD and ADHD was of the same magnitude but not significant. When controlling for overall NDD symptom load ASD or ADHD, no longer uniquely predicted coercive sexual victimization. The association between the NDD general factor and coercive sexual victimization was due to shared genetics. Conclusions: General NDD symptom load, rather than specific ASD or ADHD symptoms, seems to be a moderate vulnerability factor for coercive sexual victimization. We speculate that an evocative gene–environment correlation might account for this observation, such that sexual perpetrators actively target NDD individuals. [ABSTRACT FROM AUTHOR]

Background: Several retrospective studies using informant report have shown that individuals with dementia demonstrate considerable personality change. Two prospective studies, also using informant report, have shown that individuals who develop dementia show some personality changes prior to diagnosis. The current study is the first to assess personality trait change prior to dementia diagnosis using self-report measures from longitudinal data. Method: This study used data from the Swedish OCTO-Twin Study, a longitudinal panel of 702 twins aged 80 and older. Analysis was restricted to 86 individuals who completed the Eysenck Personality Inventory and received a dementia diagnosis during follow-up occasions. Latent growth curve analyses were used to examine trajectories of extraversion and neuroticism preceding dementia diagnosis. Results: Controlling for sex, age, education, depressive symptoms, and the interaction between age and education, growth curve analyses revealed a linear increase in neuroticism and stability in extraversion. Individuals who were eventually diagnosed with dementia showed a significant increase in neuroticism preceding diagnosis of dementia. Discussion: Personality change, specifically an increase in neuroticism, may be an early indicator of dementia. Identification of early indicators of dementia may facilitate development of screening assessments and aid in early care strategies and planning. [ABSTRACT FROM AUTHOR]

Objective: The authors sought to determine whether pregnancy is an intrinsic motivator for cessation of drug abuse.Method: The authors conducted prospective cohort, co-relative, co-spouse, and within-person analyses of registration for drug abuse during pregnancy among Swedish women born between 1980 and 1990 who gave birth between ages 20 and 35 (N=149,512). Drug abuse was assessed from medical, criminal, and pharmacy registries.Results: In the population, rates of drug abuse were lower during pregnancy (unadjusted odds ratio=0.67, 95% CI=0.60, 0.74). Compared with population results, the negative association between pregnancy and drug abuse was moderately stronger in cousins (odds ratio=0.49, 95% CI=0.39, 0.62) and substantially stronger in siblings (odds ratio=0.35, 95% CI=0.24, 0.51) discordant for pregnancy. The estimated odds ratio for drug abuse in pregnancy-discordant monozygotic twins was even stronger, at 0.17 (95% CI=0.10, 0.31). Within individuals, the odds ratio for drug abuse while pregnant compared with an equivalent prepregnancy interval was similar to that seen in pregnancy-discordant monozygotic twins, at 0.22 (95% CI=0.19, 0.26). Compared with cohabiting fathers, mothers had a greater reduction in risk for drug abuse during pregnancy (odds ratio=0.40, 95% CI=0.34, 0.47). Pregnancy was more protective in women with low parental education and without a cohabiting, actively drug-abusing father. Compared with prepregnancy baseline, within-individual analyses indicate that risk for drug abuse is also substantially reduced in the postpartum period, for example, the odds ratio for postpartum days 0-242 was 0.13 (95% CI=0.11, 0.16).Conclusions: Risk for drug abuse in women is substantially reduced during pregnancy. Multiple analyses suggest that this association is largely causal, suggesting that pregnancy is indeed a strong intrinsic motivator for drug abuse cessation. Similar strong protective effects may be present in the immediate postpartum period. Our results have implications for our etiologic models of drug abuse and especially for contingency management programs seeking to reduce drug abuse risk. [ABSTRACT FROM AUTHOR]

Background: There is limited information regarding the association between youth mental health problems and work incapacity in adulthood. We investigated whether internalizing (depressive, anxious, somatic complaints) and externalizing (aggressive, rule-breaking) behavior problems in childhood and adolescence were associated with sickness absence (SA) and disability pension (DP) in young adulthood.Methods: Data were used from the population-based and prospective Twin Study of Child and Adolescent Development (TCHAD) which includes all Swedish twins born in 1985-1986 (N = 2570). Internalizing and externalizing behavior problems were assessed with the Child Behavior Checklist at ages of 8-9, 13-14, 16-17, and 19-20 years. Individuals participating in TCHAD were followed regarding SA and DP during 2001-2013 using nationwide registers. Cox regression models were applied to assess hazard ratios (HR) with 95% confidence intervals (CI).Results: Each one-unit increase of rule-breaking behavior implied a significant higher risk for SA in early adulthood, despite of age at assessment, with the highest HR of 1.12 (95% CI 1.05-1.19) at age of 8-9 years. Higher levels of anxious and depressive symptoms in childhood and adolescence were associated with DP in early adulthood despite age at assessment, with the highest risk at age 19-20 years [HR 1.31 (95% CI 1.12-1.53)]. The associations attenuated slightly when familial factors were taken into account.Conclusions: Internalizing and externalizing behavior problems identified at an early age (8-9 years) increased risk for SA and DP in young adulthood. These findings indicate that early prevention and intervention efforts to reduce behavior problems may promote a successful start in working life. [ABSTRACT FROM AUTHOR]

Background: This study investigated the associations between night work, sleep and disability pension (DP) due to musculoskeletal disorders (MSD), while controlling for several confounding factors including both genetic factors and shared family background. Methods: The study sample consisted of 27 165 Swedish twin individuals born in 1935-58 with comprehensive survey data on sociodemographic, health and lifestyle factors. Night work was assessed as years of working hours at night at least every now and then, and categorized into 'not at all, 1-10 years and over 10 years'. Data on DP with MSD (ICD-diagnoses M00-M99) were obtained from the National Social Insurance Agency. Follow-up was from the time of the interview in 1998-2003 until 2013. Information on the length and quality of sleep was available for a sub-sample of twins (n = 1684). Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI). Results: During the follow-up, 1338 (5%) participants were granted DP due to MSD. Both 1-10 years (HR 1.33, 95% CI 1.17-1.53) and over 10 years of night work (HR 1.3995% CI 1.18-1.64) increased the risk of future DP. The associations were not affected by health, lifestyle or sleep factors. In the discordant twin pair analysis, the associations between night work and DP due to MSD attenuated. Conclusions: Night work was associated with increased risk of DP due to MSD independently from health and lifestyle factors. Familial confounding could not be ruled out. [ABSTRACT FROM AUTHOR]

Objective: Most studies suggest that poor cognitive functioning in adolescence increases risk of alcohol use disorders (AUDs). We seek to clarify the causes of this association.Method: In Swedish individuals born from 1972 to 1990 in whom cognitive functioning was assessed by school achievement at age 16 years (males and females, N = 1,796,048) and by IQ at ages 18-20 (males, N = 554,644), we examined the hazard ratio (HR) for AUD ascertained from public registries. We examined and modeled risk of AUD in cousins, full siblings, and monozygotic twin pairs discordant for school achievement and IQ scores.Results: In males and females, HRs for AUD per standard deviation of increasing school achievement equaled 0.47 (95% CI [0.46, 0.47]) and 0.52 (95% CI [0.51, 0.53]), respectively. In males, the HR for AUD per standard deviation of increasing IQ was 0.54 (95% CI [0.53, 0.55]). Excluding onsets of AUD within 5 years of the cognitive evaluation did not weaken the association, nor did controlling for alcohol intake and problems at IQ assessment. The HRs for AUD in relative pairs were higher than those observed in the population but significantly less than unity. We predicted the following HRs for AUD in discordant monozygotic twins for school achievement in males and females and for IQ in males: 0.66 (95% CI [0.62, 0.70]), 0.67 (95% CI [0.62, 0.73]), and 0.72 (95% CI [0.65, 0.79]), respectively.Conclusions: Cognitive ability in adolescence, assessed by two different measures, strongly predicts risk of AUD. This association cannot be explained by early symptoms of AUD impairing performance. Co-relative analyses suggest that this association arises partly from familial confounding and partly from a causal impact of low cognitive ability on AUD risk. [ABSTRACT FROM AUTHOR]

The attributable fraction is a widely used measure to quantify the public health impact of an exposure on an outcome. It was originally proposed for binary outcomes, but attributable fraction estimators have also been proposed for time-to-event outcomes. In this note, we consider an estimator which was proposed by Benichou (Stats Methods Med Res, 2001) and is supposed to estimate the cohort attributable fraction, i.e. the number of events that would have been prevented in the cohort during follow-up, if the exposure would hypothetically have been eliminated. We show that this estimator is only valid under certain assumptions, which are often likely to be violated in practice. We further argue that the cohort attributable fraction may not be of substantial scientific interest in the first place. We propose a potentially more relevant measure of attributable fraction in cohort studies; the baseline attributable fraction. We show how the baseline attributable fraction can be conveniently estimated in Cox proportional hazards models. [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: Cognitive performance shows a marked deterioration in close proximity to death, as postulated by the terminal decline hypothesis. The effect of education on the rate of terminal decline in the oldest people (i.e. persons 85+ years) has been controversial and not entirely understood. In the current study, we investigated the rate of decline prior to death with a special focus on the role of education and socioeconomic position, in two European longitudinal studies of ageing: the Origins of Variance in the Old-Old: Octogenarian Twins (OCTO-Twin) and the Newcastle 85+ study.Methods: A process-based approach was used in which individuals' cognitive scores were aligned according to distance to death. In a coordinated analysis, multilevel models were employed to examine associations between different markers of cognitive reserve (education and socioeconomic position) and terminal decline using the mini-mental state examination (MMSE), controlling for age at baseline, sex, dementia incidence and time to death from the study entry to the time of death within each cohort.Results: The current findings suggest that education was positively associated with higher MMSE scores prior to death in the OCTO-Twin, but not in the Newcastle 85+ study, independent of socioeconomic position and other factors such as baseline age, sex and time to death from the study entry. However, education was not associated with the rate of terminal decline in both of these studies.Conclusions: Our results offer only partial support to the cognitive reserve hypothesis and cognitive performance prior to death. [ABSTRACT FROM AUTHOR]

Background: Pregnancy, delivery, and the postpartum period may imply morbidity leading to work incapacity; however, this is seldom studied. This study aimed to compare twin sisters giving or not giving birth regarding occurrence of sickness absence (SA) and disability pension (DP). Methods: This population-based cohort study included all 6323 female twins born in Sweden 1959–1990, using register data for 1994–2010 about SA and DP. Average number of SA/DP days/year was calculated in relation to the year of the first delivery, or, if not giving birth, the year when the twin sister gave birth. Twin pairs discordant for delivery were used to investigate the importance of genetic and environmental factors for occurrence of SA and DP. Results: In all, 52% had a first delivery during 1994–2010. Except for the year of delivery, the average number of SA days/year was similar when comparing women who gave birth to those who did not, while number of DP days was significantly higher in women who did not give birth. Differences between the groups seem attributable to genetic factors. Women who delivered once had higher levels of SA and DP than those who had several deliveries. DP with mental diagnoses was more common among women who had not delivered whereas DP with musculoskeletal diagnoses occurred more often among women who delivered. Conclusions: Levels of SA were similar among women who gave birth and who did not. Women not giving birth had significantly higher levels of DP, indicating health selections into childbirth. [ABSTRACT FROM AUTHOR]

Clinically significant anxiety symptoms are prevalent among the elderly, yet knowledge about the longitudinal course of anxiety symptoms in later life remains scarce. The goals of this study were to (a) characterize age trajectories of state anxiety symptoms in the second half of life, and (b) estimate genetic and environmental contributions to individual differences in the age trajectory of state anxiety. This study was based on data from 1,482 participants in the Swedish Adoption/Twin Study of Aging who were aged 50 and older at their first occasion (512 complete twin pairs, 458 singletons) and had up to 6 measurement occasions spanning 11 years. Consistent with life span developmental theories of age-related emotional change, anxiety symptom levels declined during the transition from midlife to the mid-60s, followed by a mild increase that gradually plateaued in the 80s. There were substantial individual differences in the age trajectory of anxiety. After accounting for effects of sex, cohort, mode of testing, and proximity to death, this longitudinal variation was partitioned into biometric sources. Nonshared environmental variance was highest in the late 60s and declined thereafter, whereas genetic variance increased at an accelerated pace from approximately age 60 onward. There was no evidence for effects of rearing or other shared environment on anxiety symptoms in later life. These findings highlight how the etiology of anxiety symptoms changes from midlife to old age. [ABSTRACT FROM AUTHOR]

Background.Certain personality traits predispose to criminal behavior (CB). We further clarify this relationship in a Swedish national sample.Method.Psychological strength (PS) was assessed on a nine-point scale at personal interview in 1 653 721 Swedish men aged 18–20 years. We examined the association between PS and total, violent and recurrent CB over the lifetime (logistic regression), prospectively (Cox regression) and by bivariate Cholesky decomposition in 2507 monozygotic and 2244 dizygotic twin pairs (OpenMx).Results.Examining linear effects by logistic regression, PS was robustly associated with lifetime risk of total CB (per point, odds ratio = 0.74) and even more strongly associated with risk for violent (0.69) and recurrent CB (0.52). Prospective predictions of these three forms of CB by PS were similar, with hazard ratios of 0.80, 0.73 and 0.54, respectively. Twin modeling demonstrated that, for all three CB types, the association with PS arose almost entirely from familial effects. Common shared environment accounted for 72, 56 and 43% of the phenotypic correlation between PS and, respectively, total, violent and recurrent CB. Parallel figures for common genetic effects were for 24, 37 and 54%, respectively.Conclusions.PS is strongly related to risk for total CB, and even more strongly for violent and, especially, recurrent CB. This association is probably not causal but rather results from shared familial risk factors that make an impact both on PS and risk for CB. PS has a stronger overall correlation with more severe criminal outcomes and a higher proportion of that correlation results from common genetic factors. [ABSTRACT FROM PUBLISHER]

To date, several studies have investigated the intergenerational effect of preterm and small-for-gestational-age (SGA) births. However, most studies excluded both twin mothers and twin offspring from the analyses. Thus, the objective of this study was to investigate the intergenerational effect of preterm birth and SGA births among twins and singletons. A prospective population-based register study of mother–firstborn offspring pairs recorded in the Swedish Medical Birth Register was performed. The study included 4,073 twins and 264,794 singletons born from 1973–1983 and their firstborns born from 1986–2009. Preterm birth was defined as birth at <37 weeks of gestation, and SGA as birth weight <2 standard deviations of the Swedish standard. Logistic regressions were performed to estimate the intergenerational effect of each birth characteristic. Adjustments were made for maternal grandmothers’ and mothers’ socio-demographic factors, in addition to maternal birth characteristics. Among mothers born as singletons, being born preterm was associated with an increased risk of delivering a preterm child (adjusted odds ratio (OR) 1.39, 95% Confidence Interval (CI) = 1.29–1.50), while being born SGA increased the likelihood of having an SGA child (adjusted OR 3.04, 95% CI = 2.80–3.30) as well as a preterm child (adjusted OR 1.30, 95% CI = 1.20–1.40). In twin mothers, the corresponding ORs tended to be lower, and the only statistically significant association was between an SGA mother and an SGA child (adjusted OR 2.15, 95% CI = 1.40–3.31). A statistically significant interaction between twinning and mother's size for gestational age was identified in a multivariate linear regression analysis, indicating that singleton mothers born SGA were associated with a lower birth weight compared with mothers not born SGA. Preterm birth and SGA appear to be transferred from one generation to the next, although not always reaching statistical significance. These effects seem to be less evident in mothers born as twins compared with those born as singletons. [ABSTRACT FROM PUBLISHER]

ABSTRACT Objective This study explored the cross-sectional and predictive effect of drive for thinness and/or negative affect scores on the development of self-reported anorexia nervosa (AN) and bulimia nervosa (BN). Method K-means were used to cluster the Eating Disorder Inventory-Drive for Thinness (DT) and Child Behavior Checklist Anxious/Depressed (A/D) scores from 615 unrelated female twins at age 16-17. Logistic regressions were used to assess the effect of these clusters on self-reported eating disorder diagnosis at ages 16-17 ( n = 565) and 19-20 ( n = 451). Results DT and A/D scores were grouped into four clusters: Mild (scores lower than 90th percentile on both scales), DT (higher scores only on DT), A/D (higher scores only on A/D), and DT-A/D (higher scores on both the DT and A/D scales). DT and DT-A/D clusters at age 16-17 were associated cross-sectionally with AN and both cross-sectionally and longitudinally with BN. The DT-A/D cluster had the highest prevalence of AN at follow-up compared with all other clusters. Similarly, an interaction was observed between DT and A/D that predicted risk for AN. Discussion Having elevated DT and A/D scores may increase risk for eating disorder symptomatology above and beyond a high score on either alone. Findings suggest that cluster modeling based on DT and A/D may be useful to inform novel and useful intervention strategies for AN and BN in adolescents. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:692-699) [ABSTRACT FROM AUTHOR]

Background Evidence from twin and molecular genetic studies is accumulating that Autism Spectrum Disorder ( ASD) shares substantial etiological factors with other disorders. This is mirrored in clinical practice where ASD without coexisting disorders is rare. The present study aims to examine the range of coexisting disorders in ASD in a genetically informative cohort. Methods Parents of all Swedish 9-year-old twins born between 1992 and 2001 ( n = 19,130) underwent a telephone interview designed to screen for child psychiatric disorders, including ASD. To ensure full coverage of child psychiatric disorders, data were also retrieved from population-based health registers. We investigated the coexistence of eight psychiatric disorders known to coexist with ASDs in probands and their co-twins. Results Half of the individuals with ASDs (50.3%) had four or more coexisting disorders and only 4% did not have any concomitant disorder. The 'healthy co-twin' in ASD discordant monozygotic twin pairs was very often (79% of boys and 50% of girls) affected by at least one non- ASD disorder. The corresponding figures for ASD discordant dizygotic twin pairs were significantly lower (46% of males and 30% of females). Conclusions Detailed phenotypic descriptions including symptoms of problems associated with a wide range of child psychiatric disorders may aid in unraveling the genetic architecture of ASD and should guide the development of intervention strategies addressing each problem type specifically. [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]

The longitudinal relationship between attention deficit hyperactivity disorder (ADHD) and violent criminality has been extensively documented, while long-term effects of autism spectrum disorders (ASDs), tic disorders (TDs), and obsessive compulsive disorder (OCD) on criminality have been scarcely studied. Using population-based registers of all child and adolescent mental health services in Stockholm, we identified 3,391 children, born 1984-1994, with neurodevelopmental disorders, and compared their risk for subsequent violent criminality with matched controls. Individuals with ADHD or TDs were at elevated risk of committing violent crimes, no such association could be seen for ASDs or OCD. ADHD and TDs are risk factors for subsequent violent criminality, while ASDs and OCD are not associated with violent criminality. [ABSTRACT FROM AUTHOR]