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| 2. |
- Ip, H. F., et al.
(författare)
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Genetic association study of childhood aggression across raters, instruments, and age
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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| 3. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 4. |
- Derks, I. P. M., et al.
(författare)
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Testing Bidirectional Associations Between Childhood Aggression and BMI: Results from Three Cohorts
- 2019
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 27:5, s. 822-829
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study examined the prospective, potentially bidirectional association of aggressive behavior with BMI and body composition across childhood in three population-based cohorts. Methods Repeated measures of aggression and BMI were available from the Generation R Study between ages 6 and 10 years (N = 3,974), the Netherlands Twin Register (NTR) between ages 7 and 10 years (N = 10,328), and the Swedish Twin Study of Child and Adolescent Development (TCHAD) between ages 9 and 14 years (N = 1,462). In all samples, aggression was assessed with the Child Behavior Checklist. Fat mass and fat-free mass were available in the Generation R Study. Associations were examined with cross-lagged modeling. Results Aggressive behavior at baseline was associated with higher BMI at follow-up in the Generation R Study (beta = 0.02, 95% CI: 0.00 to 0.04), in NTR (beta = 0.04, 95% CI: 0.02 to 0.06), and in TCHAD (beta = 0.03, 95% CI: -0.02 to 0.07). Aggressive behavior was prospectively associated with higher fat mass (beta = 0.03, 95% CI: 0.01 to 0.05) but not fat-free mass. There was no evidence that BMI or body composition preceded aggressive behavior. Conclusions More aggressive behavior was prospectively associated with higher BMI and fat mass. This suggests that aggression contributes to the obesity problem, and future research should study whether these behavioral pathways to childhood obesity are modifiable.
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| 5. |
- Borg, J., et al.
(författare)
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Contribution of non-genetic factors to dopamine and serotonin receptor availability in the adult human brain
- 2016
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Ingår i: Molecular Psychiatry. - London, United Kingdom : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 51, s. 879-879
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Tidskriftsartikel (refereegranskat)abstract
- The dopamine (DA) and serotonin (5-HT) neurotransmission systems are of fundamental importance for normal brain function and serve as targets for treatment of major neuropsychiatric disorders. Despite central interest for these neurotransmission systems in psychiatry research, little is known about the regulation of receptor and transporter density levels. This lack of knowledge obscures interpretation of differences in protein availability reported in psychiatric patients. In this study, we used positron emission tomography (PET) in a twin design to estimate the relative contribution of genetic and environmental factors, respectively, on dopaminergic and serotonergic markers in the living human brain. Eleven monozygotic and 10 dizygotic healthy male twin pairs were examined with PET and [(11)C]raclopride binding to the D2- and D3-dopamine receptor and [(11)C]WAY100635 binding to the serotonin 5-HT1A receptor. Heritability, shared environmental effects and individual-specific non-shared effects were estimated for regional D2/3 and 5-HT1A receptor availability in projection areas. We found a major contribution of genetic factors (0.67) on individual variability in striatal D2/3 receptor binding and a major contribution of environmental factors (pairwise shared and unique individual; 0.70-0.75) on neocortical 5-HT1A receptor binding. Our findings indicate that individual variation in neuroreceptor availability in the adult brain is the end point of a nature-nurture interplay, and call for increased efforts to identify not only the genetic but also the environmental factors that influence neurotransmission in health and disease.
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| 6. |
- Cederlof, M., et al.
(författare)
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Intellectual disability and cognitive ability in Darier disease: Swedish nation-wide study
- 2015
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Ingår i: British Journal of Dermatology. - Hoboken, USA : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 173:1, s. 155-158
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Tidskriftsartikel (refereegranskat)abstract
- Background Darier disease is an autosomal dominant skin disorder caused by mutations in the ATP2A2 gene. Anecdotal reports suggest a relationship between Darier disease and intellectual disabilities, but these reports are based on small clinical samples and limited by absence of control populations. Objectives To examine the risk of intellectual disability and subclinical impairments in cognitive ability in Darier disease. Methods We conducted a matched cohort study based on Swedish Population-, Patient-and Conscript Registers. The risk of being diagnosed with intellectual disability was estimated in 770 individuals with Darier disease, compared with matched comparison individuals without Darier disease. Associations were examined with risk ratios from conditional logistic regressions. In addition, we analysed test-based cognitive ability data (i.e. IQ data) from the Swedish conscript examination, for a subset of patients without diagnosed intellectual disability. Results Individuals with Darier disease had a sixfold increased risk of being diagnosed with intellectual disability (risk ratio 6.2, 95% confidence interval 3.1-12.4). For conscripted individuals with Darier disease but no diagnosed intellectual disability, mean cognitive ability scores were about half a standard deviation lower than for comparison subjects. Conclusions Darier disease is associated with intellectual disability and subclinical impairments in cognitive ability. The Darier-causing mutations merit further attention in molecular genetic research on intellectual disability and cognitive ability.
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| 7. |
- Chen, C., et al.
(författare)
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Associations between general and specific mental health conditions in young adulthood and cardiometabolic complications in middle adulthood : A 40-year longitudinal familial coaggregation study of 672 823 Swedish individuals
- 2023
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Ingår i: European psychiatry. - : Cambridge University Press. - 0924-9338 .- 1778-3585. ; 66:Suppl. 1, s. S67-S68
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Most mental disorders, when examined individually, are associated with an increased risk of cardiometabolic complications. However, these associations might be attributed to a general liability toward psychopathology or confounded by unmeasured familial factors.Objectives: To examine whether the associations between psychiatric diagnoses and increased risk of cardiometabolic complications are attributable to a general liability toward psychopathology, or confounded by unmeasured familial factors.Methods: We conducted a cohort study in Sweden and identified all individuals and their siblings born in Sweden 1955-1962 with follow-up through 2013. After excluding individuals who died or emigrated before 1987, the final sample consisted 672 823 individuals. We extracted ICD-coded diagnoses (recorded 1973-1987) for ten psychiatric conditions and criminal convictions when participants were aged 18-25 years, and ICD-coded diagnoses (recorded 1987-2013) for five cardiometabolic complications (obesity, hypertensive diseases, hyperlipidemia, type 2 diabetes mellitus, and cardiovascular diseases) when the participants were 51-58 years old. Logistic regression models were used to estimate the bivariate associations between psychiatric conditions or criminal convictions and cardiometabolic complications in individuals. A general factor model was used to identify general, internalizing, externalizing, and psychotic factors based on the psychiatric conditions and criminal convictions. We then regressed the cardiometabolic complications on the latent general factor and three uncorrelated specific factors within a structural equation modeling framework in individuals and across sibling pairs.Results: Each psychiatric conditions significantly increased the risk of cardiometabolic complications; however, most of these associations were attributable to the general factor of psychopathology, rather than to specific psychiatric conditions. There were no or only small associations between individuals’ general psychopathology and their siblings’ cardiometabolic complications, suggesting that the associations were not attributable to genetic or environmental confounding factors shared within families. The same pattern was evident for the specific internalizing and psychotic factors.Conclusions: Individuals with mental disorders in early life had an increased long term risk of cardiometabolic complications, which appeared attributable to a general liability toward psychopathology. Sibling analyses suggested that the elevated risk could not beattributed to confounds shared within families. This highlights the importance of transdiagnostic and lifestyle based interventions to reduce the risk of cardiometabolic complications, particularly in patients with several mental disorders.
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| 8. |
- Ghirardi, L., et al.
(författare)
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The familial co-aggregation of ASD and ADHD : a register-based cohort study
- 2018
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Ingår i: Molecular Psychiatry. - London, United Kingdom : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 23:2, s. 257-262
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. The presence of a genetic link between ASD and ADHD symptoms is supported by twin studies, but the genetic overlap between clinically ascertained ASD and ADHD remains largely unclear. We therefore investigated how ASD and ADHD co-aggregate in individuals and in families to test for the presence of a shared genetic liability and examined potential differences between low- and high-functioning ASD in the link with ADHD. We studied 1 899 654 individuals born in Sweden between 1987 and 2006. Logistic regression was used to estimate the association between clinically ascertained ASD and ADHD in individuals and in families. Stratified estimates were obtained for ASD with (low-functioning) and without (high-functioning) intellectual disability. Individuals with ASD were at higher risk of having ADHD compared with individuals who did not have ASD (odds ratio (OR)=22.33, 95% confidence interval (CI): 21.77-22.92). The association was stronger for high-functioning than for low-functioning ASD. Relatives of individuals with ASD were at higher risk of ADHD compared with relatives of individuals without ASD. The association was stronger in monozygotic twins (OR=17.77, 95% CI: 9.80-32.22) than in dizygotic twins (OR=4.33, 95% CI: 3.21-5.85) and full siblings (OR=4.59, 95% CI: 4.39-4.80). Individuals with ASD and their relatives are at increased risk of ADHD. The pattern of association across different types of relatives supports the existence of genetic overlap between clinically ascertained ASD and ADHD, suggesting that genomic studies might have underestimated this overlap.
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| 9. |
- Larsson, Henrik, 1975-, et al.
(författare)
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Genetic and environmental influences on adult attention deficit hyperactivity disorder symptoms : a large Swedish population-based study of twins
- 2013
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 43:1, s. 197-207
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Attention deficit hyperactivity disorder (ADHD) frequently persists into adulthood. Family and twin studies delineate a disorder with strong genetic influences among children and adolescents based on parent- and teacher-reported data but little is known about the genetic and environmental contribution to DSM-IV ADHD symptoms in adulthood. We therefore aimed to investigate the impact of genetic and environmental influences on the inattentive and hyperactive-impulsive symptoms of ADHD in adults.METHOD: Twin methods were applied to self-reported assessments of ADHD symptoms from a large population-based Swedish twin study that included data from 15 198 Swedish male and female twins aged 20 to 46 years.RESULTS: The broad heritability [i.e., A + D, where A is an additive genetic factor and D (dominance) a non-additive genetic factor] was 37% (A = 11%, D = 26%) for inattention and 38% (A = 18%, D = 20%) for hyperactivity-impulsivity. The results also indicate that 52% of the phenotypic correlation between inattention and hyperactivity-impulsivity (r = 0.43) was explained by genetic influences whereas the remaining part of the covariance was explained by non-shared environmental influences. These results were replicated across age strata.CONCLUSIONS: Our findings of moderate broad heritability estimates are consistent with previous literature on self-rated ADHD symptoms in older children, adolescents and adults and retrospective reports of self-rated childhood ADHD by adults but differ from studies of younger children with informant ratings. Future research needs to clarify whether our data indicate a true decrease in the heritability of ADHD in adults compared to children, or whether this relates to the use of self-ratings in contrast to informant data.
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| 10. |
- O'Reilly, L. M., et al.
(författare)
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A Co-Twin Control Study of the Association Between Bullying Victimization and Self-Harm and Suicide Attempt in Adolescence
- 2021
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Ingår i: Journal of Adolescent Health. - : Elsevier BV. - 1054-139X .- 1879-1972. ; 69:2, s. 272-279
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of the study was to investigate the magnitude of an independent association between bullying victimization and self-harm and suicide attempt in adolescence after adjusting for unmeasured and measured confounding factors. Methods: Using the Child and Adolescent Twin Study in Sweden, we examined twins born between 1994 and 1999 (n = 13,852). Twins self-reported bullying victimization at age 15 years and self-harm and suicide attempt at age 18 years. We created a factor score of 13 bullying items, on which self-harm and suicide attempt items were regressed in three models: (1) among unrelated individuals; (2) among co-twins, in which a twin exposed to more bullying was compared with his/her co-twin who was exposed to less; and (3) among co-twins while adjusting for indicators of childhood psychopathology. Results: Among unrelated individuals, a one standard deviation increase in bullying victimization was associated with increased odds for self-harm (odds ratio [OR], 1.29 [95% confidence interval, 1.23–1.36]) and suicide attempt (OR, 1.68 [1.53–1.85]). Among co-twins, the odds attenuated for self-harm (OR, 1.19 [1.09–1.30]) and suicide attempt (OR, 1.39 [1.17–1.66]). Finally, when accounting for childhood psychopathology, there was a 14% (1.04–1.25) and 25% (1.03–1.52) relative increase in odds of self-harm and suicide attempt, respectively. Conclusions: The results suggest that bullying victimization was uniquely associated with self-harm and suicide attempt over and above the confounding because of unmeasured and measured factors (i.e., familial vulnerability and pre-existing psychopathy). However, magnitudes were small, suggesting that additional interventions and screenings are needed to address suicidality apart from bullying interventions. © 2020 Society for Adolescent Health and Medicine
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