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It remains unclear if individuals with Tourette syndrome (TS) or chronic tic disorder (CTD) have an elevated risk of subsequent substance misuse. In this population-based cohort study, we investigated the association between ICD diagnoses of TS/CTD and substance misuse outcomes, accounting for psychiatric comorbidity and familial factors. The cohort included all individuals living in Sweden at any time between January 1, 1973, and December 31, 2013. Substance misuse outcomes were defined as an ICD code of substance use–related disorder or cause of death, or as a substance use–related criminal conviction in the nationwide registers. The cohort included 14,277,199 individuals, of whom 7832 had a TS/CTD diagnosis (76.3% men). TS/CTD was associated with an increased risk of any subsequent substance misuse outcomes (adjusted hazard ratio [aHR], 3.11; 95% confidence interval [CI], 2.94–3.29), including alcohol-related disorder (aHR, 3.45; 95% CI, 3.19–3.72), drug-related disorder (aHR, 6.84; 95% CI, 6.32–7.40), substance-related criminal convictions (aHR, 2.56; 95% CI, 2.36–2.77), and substance-related death (aHR, 2.54; 95% CI, 1.83–3.52). Excluding psychiatric comorbidities had little effect on the magnitude of the associations, with the exception of attention-deficit/hyperactivity disorder, which attenuated the risk of any substance misuse outcomes (aHR, 2.00; 95% CI, 1.82–2.19). The risk of any substance misuse outcomes in individuals with TS/CTD was substantially attenuated but remained significant when compared with their unaffected siblings (aHR, 1.74; 95% CI, 1.53–1.97). TS/CTD were associated with various types of subsequent substance misuse outcomes, independently of psychiatric comorbidity and familial factors shared between siblings. Screening for drug and alcohol use should become part of the standard clinical routines, particularly in patients with comorbid attention-deficit/hyperactivity disorder. [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]

Background: A recent family study of young adult males suggests a shared familial liability between attention-deficit/hyperactivity disorder (ADHD) and high body mass index (BMI), and a genome-wide meta-analysis reported a genetic correlation of 0.26 between ADHD and BMI. To date, it is unclear whether these findings generalize to the relationship between ADHD and clinically diagnosed obesity. Method: By linking the Swedish national registers, we identified 25 38 127 individuals born between 1973 and 2000, together with their siblings and cousins. The risk of clinical obesity in individuals with ADHD was compared with the risk in those without ADHD. The relative contributions of genetic and environmental factors to the association between ADHD and clinical obesity were examined via assessment of the familial co-aggregation of the two conditions and quantitative genetic analysis. Results: Individuals with ADHD were at an increased risk of clinical obesity compared with those without (risk difference 3.73%, 95% confidence interval (CI) 3.55–3.90%; risk ratio 3.05, 95% CI 2.95–3.15). Familial co-aggregation of ADHD and clinical obesity was detected and the strength of the co-aggregation decreased by decreasing genetic relatedness. The correlation between the liabilities to ADHD and clinical obesity can be entirely attributed to their genetic correlation (r g 0.30, 95% CI 0.17–0.44). Conclusion: The association between ADHD and clinical obesity in adolescence and young adulthood can be entirely attributed to genetic underpinnings shared by the two conditions. Children with ADHD should be monitored for weight gain so that preventive measures can be taken for those on a suboptimal trajectory. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate if the association between maternal pre-pregnancy BMI and offspring’s body composition in late adolescence and young adulthood varies by offspring birth order and sex.DesignFamily cohort study, with data from registers, questionnaires and physical examinations. The main outcome under study was offspring body composition (percentage fat mass (%FM), percentage lean mass (%LM)) measured by dual-energy X-ray absorptiometry.SettingUppsala, Sweden.SubjectsTwo hundred and twenty-six siblings (first-born v. second-born; average age 19 and 21 years) and their mothers.ResultsIn multivariable linear regression models, maternal pre-pregnancy BMI was positively associated with daughter’s %FM, with stronger estimates for first-born (β=0·97, 95 % CI 0·14, 1·80) v. second-born daughters (β=0·64, 95 % CI 0·08, 1·20). Mother’s BMI before her first pregnancy was associated with her second-born daughter’s body composition (β=1·05, 95 % CI 0·31, 1·79 (%FM)) Similar results albeit in the opposite direction were observed for %LM. No significant associations were found between pre-pregnancy BMI and %FM (β=0·59, 95 % CI−0·27, 1·44 first-born; β=−0·13, 95 % CI−0·77, 0·52 second-born) or %LM (β=−0·54, 95 % CI−1·37, 0·28 first-born; β=0·11, 95 % CI−0·52, 0·74 second-born) for sons.ConclusionsA higher pre-pregnancy BMI was associated with higher offspring %FM and lower offspring %LM in late adolescence and young adulthood, with stronger associations for first-born daughters. Preventing obesity at the start of women’s reproductive life might reduce the risk of obesity in her offspring, particularly for daughters. [ABSTRACT FROM PUBLISHER]

Aims To investigate the association in males between cognitive ability in late adolescence and subsequent substance misuse-related events, and to study the underlying genetic and environmental correlations. Design A population-based longitudinal study with three different family-based designs. Cox proportional hazards models were conducted to investigate the association at the individual level. Bivariate quantitative genetic modelling in (1) full brothers and maternal half-brothers, (2) full brothers reared together and apart and (3) monozygotic and dizygotic twin brothers was used to estimate genetic and environmental correlations. Setting Register-based study in Sweden. Participants The full sample included 1 402 333 Swedish men born 1958-91 and conscripted at mean age 18.2 [standard deviation (SD) = 0.5] years. A total of 1 361 066 men who had no substance misuse events before cognitive assessment at mandatory military conscription were included in the Cox regression models, with a follow-up time of up to 35.6 years. Measures Cognitive ability was assessed at conscription with the Swedish Enlistment Battery. Substance misuse events included alcohol- and drug-related court convictions, medical treatments and deaths, available from governmental registries. Findings Lower cognitive ability in late adolescence predicted an increased risk for substance misuse events [hazard ratio (HR) for a 1-stanine unit decrease in cognitive ability: 1.29, 95% confidence interval (CI) = 1.29-1.30]. The association was somewhat attenuated within clusters of full brothers (HR = 1.21, 95% CI = 1.20-1.23). Quantitative genetic analyses indicated that the association was due primarily to genetic influences; the genetic correlations ranged between -0.39 (95% CI = -0.45, -0.34) and -0.52 (95% CI -0.55, -0.48) in the three different designs. Conclusions Shared genetic influences appear to underlie the association between low cognitive ability and subsequent risk for substance misuse events among Swedish men. [ABSTRACT FROM AUTHOR]

BackgroundWe aimed to provide unbiased estimates of familial risk and heritability of social anxiety disorder (SAD) and avoidant personality disorder (AVPD).MethodWe identified 18 399 individuals diagnosed with SAD and 2673 with AVPD in the Swedish National Patient Register between 1997 and 2009. Risks (odds ratios; OR) for SAD in all biological and non-biological relatives of probands, compared to relatives of unaffected individuals were calculated. We also estimated the risks for AVPD in relatives of probands with SAD.ResultsThe risk for SAD among relatives of SAD probands increased proportionally to the degree of genetic relatedness. The risks for first-degree relatives [OR 4.74, 95% confidence interval (CI) 4.28–5.25] were significantly higher than for second-degree and third-degree relatives. Second-degree relatives (OR 2.30, 95% CI 2.01–2.63) had significantly higher risk than third-degree relatives (OR 1.72, 95% CI 1.52–1.94). Relatives at similar genetic distances had similar risks for SAD, despite different degrees of shared environment. Heritability was estimated to be approximately 56%. There were no significant sex differences in the familial patterns. The risk of AVPD in relatives of SAD probands was significantly elevated, even after excluding individuals with both diagnoses (first-degree OR 3.54, second-degree OR 2.20, third-degree OR 1.62). Non-biological relatives (spouses/partners) also had elevated risks for both SAD (OR 4.01) and AVPD (OR 3.85).ConclusionsSAD clusters in families primarily due to genetic factors. SAD and AVPD are aetiologically related and may represent different expressions of the same vulnerability. The strong marital concordance observed in SAD/AVPD may indicate assortative mating but the exact mechanisms and implications require further investigation. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is highly heritable, yet how its familial risk and heritability may vary by cognitive ability is not well understood. In this population-based cohort study, we examined the familial risk and heritability of ASD with and without co-occurring intellectual disability (ID). We estimated odds ratios and heritability of ASD with ID (ASD+ID) and ASD without ID (ASD-ID) using register-based diagnosis data of 567,436 index persons born in 1984-2009 in Stockholm County, Sweden, and their parents, siblings, cousins, aunts, and uncles. The familial risk profile exhibited differences between ASD-ID and ASD+ID, most notably for index persons with affected parents. For example, for an index person who had at least one parent with ASD, the child's odds of ASD-ID and ASD+ID (95% confidence interval (CI)) increased by 16.2 (14.2-18.6) and 7.4 (5.5-10.0) folds, respectively. The more closely related a family member with ASD was, the greater the observed risk was of ASD in the index person, especially for ASD-ID. The broad-sense heritability (95% CI) for ASD - ID and ASD+ID were 64.6% (46.0-100.0%) and 33.4% (14.4-58.4%), respectively. Familial risk and heritability of ASD may vary by intellectual ability, which implies that risk factors between these ASD phenotypes may differ. Our findings from the heritability analysis and familial risk analysis suggest that ASD-ID may have a greater genetic basis than ASD+ID, although this should be verified in future studies. LAY SUMMARY: Autism spectrum disorder (ASD) is highly heritable, yet how its familial risk and heritability may vary by cognitive ability is not well-understood. In a population-based cohort study on families of 567,436 index persons using Swedish registers data, we found that the familial risk profile differed between ASD with and without intellectual disability. Our findings from the heritability analysis and familial risk analysis suggest that ASD-ID may have a greater genetic basis than ASD+ID, although this should be verified in future studies., (© 2020 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Background The influence of familial factors on the prognosis of heart failure ( HF ) is unknown. This nationwide follow-up study aimed to determine familial mortality risks of HF among Swedish siblings hospitalized for HF . Methods and Results We linked several Swedish nationwide registers for individuals aged 0 to 80 years. The study population consisted of 373 people hospitalized for HF for the first time between 2000 and 2012 with 1 proband sibling previously hospitalized for HF for the first time between 2000 and 2007. Families with congenital heart disease were excluded. Familial hazard ratios ( HR s) for mortality after first HF hospitalization were determined with Cox regression. The influence of proband survival was categorized as short survival (<5 years) or long survival (≥5 years) and determined continuously for the initial 5 years of proband survival. Adjustments were made for age, sex, time period, and common HF comorbidities. Short proband survival was associated with a HR of 2.02 (95% confidence interval, 1.32-3.09) for overall mortality. This HR was 2.35 (95% confidence interval, 1.18-4.67) in patients without preceding coronary heart disease, whereas patients with ischemic HF had an HR of 1.84 (95% confidence interval, 1.05-3.23). For each year of proband survival, the risk of death decreased, with a HR of 0.86 (95% confidence interval, 0.77-0.98). Conclusions Our results suggest that family history of poor survival in specific relation to HF is an important risk factor for death in HF patients. Additional studies are needed to characterize the molecular underpinnings and detailed phenotypic characteristics of such patients.

Background: Uncertainty remains whether bipolar I disorder (BDI) and bipolar II disorder (BDII) differ etiologically. We used a population-based family sample to examine the etiological boundaries between BDI and BDII by assessing their familial aggregation/coaggregation and by assessing the coaggregation between them and schizophrenia, depression, attention-deficit/hyperactivity disorder, eating disorders, autism spectrum disorder, substance use disorders, anxiety disorders, and personality disorders., Methods: By linking Swedish national registers, we established a population-based cohort (N = 15,685,511) and identified relatives with different biological relationships. Odds ratios (ORs) were used to measure the relative risk of BDI and BDII in relatives of individuals diagnosed with BDI (n = 4309) and BDII (n = 4178). The heritability for BDI and BDII and the genetic correlation across psychiatric disorders were estimated by variance decomposition analysis., Results: Compared with the general population, the OR of BDI was 17.0 (95% confidence interval [CI] 13.1-22.0) in first-degree relatives of BDI patients, higher than that of BDII patients (OR 9.8, 95% CI 7.7-12.5). The ORs of BDII were 13.6 (95% CI 10.2-18.2) in first-degree relatives of BDII patients and 9.8 (95% CI 7.7-12.4) in relatives of BDI patients. The heritabilities for BDI and BDII were estimated at 57% (95% CI 32%-79%) and 46% (95% CI 21%-67%), respectively, with a genetic correlation estimated as 0.78 (95% CI 0.36-1.00). The familial coaggregation of other psychiatric disorders, in particular schizophrenia, showed different patterns for BDI and BDII., Conclusions: Our results suggest a distinction between BDI and BDII in etiology, partly due to genetic differences., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Previous research indicates that attention-deficit/hyperactivity disorder (ADHD) is highly associated with substance use disorders (SUD). However, these studies have failed to clarify the nature of the overlap. The main aim of this study was to explore whether the overlap between ADHD and SUD could be explained by shared genetic and environmental factors or by harmful effects of ADHD medication., Methods: We employed a matched cohort design across different levels of family relatedness recorded from 1973-2009. By linking longitudinal Swedish national registers, 62,015 ADHD probands and first-degree and second-degree relatives were identified and matched 1:10 with control subjects without ADHD and their corresponding relatives. Any record of SUD was defined by discharge diagnoses of the International Classification of Diseases or a purchase of any drug used in the treatment of SUD., Results: First-degree relatives of ADHD probands were at elevated risk for SUD (odds ratios 2.2 and 1.8) compared with relatives of control subjects. The corresponding relative risk in second-degree relatives was substantially lower (odd ratios 1.4 and 1.4). The familial aggregation patterns remained similar for first-degree and second-degree relatives after excluding individuals with coexisting disorders such as schizophrenia, bipolar disorder, depression, and conduct disorder., Conclusions: Our findings suggest that the co-occurrence of ADHD and SUD is due to genetic factors shared between the two disorders, rather than to a general propensity for psychiatric disorders or harmful effects of ADHD medication., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)