| 1. |
- 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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| 2. |
- Jelenkovic, A., et al.
(författare)
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Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994
- 2016
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Ingår i: eLIFE. - Cambridge, United Kingdom : eLife Sciences Publications. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.
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| 3. |
- Jami, E. S., et al.
(författare)
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Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms
- 2022
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 61:7, s. 934-945
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n(effective) = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (vertical bar r(g)vertical bar > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range vertical bar r(g)vertical bar = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
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| 4. |
- Silventoinen, K., et al.
(författare)
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Differences in genetic and environmental variation in adult BMI by sex, age, time period, and region : An individual-based pooled analysis of 40 twin cohorts
- 2017
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Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 106:2, s. 457-466
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m2)], but factors modifying these variance components are poorly understood.Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity.Design: We used genetic structural equation modeling to analyze BMI in twins ≥20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs).Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20-29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI.Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population.
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| 5. |
- Silventoinen, K., et al.
(författare)
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The CODATwins Project : The current status and recent findings of COllaborative Project of Development of Anthropometrical Measures in Twins
- 2019
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 22:6, s. 800-808
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Tidskriftsartikel (refereegranskat)abstract
- The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
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| 6. |
- Bartels, M., et al.
(författare)
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Childhood aggression and the co-occurrence of behavioural and emotional problems: results across ages 3-16years from multiple raters in six cohorts in the EU-ACTION project
- 2018
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Ingår i: European Child & Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 27:9, s. 1105-1121
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Tidskriftsartikel (refereegranskat)abstract
- Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopathology. We focus on the co-occurrence of aggression and other childhood behavioural and emotional problems, including other externalising problems, attention problems and anxiety-depression. The data were brought together within the EU-ACTION (Aggression in Children: unravelling gene-environment interplay to inform Treatment and InterventiON strategies) project. We analysed the co-occurrence of aggression and other childhood behavioural and emotional problems as a function of the child's age (ages 3 through 16years), gender, the person rating the behaviour (father, mother or self) and assessment instrument. The data came from six large population-based European cohort studies from the Netherlands (2x), the UK, Finland and Sweden (2x). Multiple assessment instruments, including the Child Behaviour Checklist (CBCL), the Strengths and Difficulties Questionnaire (SDQ) and Multidimensional Peer Nomination Inventory (MPNI), were used. There was a good representation of boys and girls in each age category, with data for 30,523 3- to 4-year-olds (49.5% boys), 20,958 5- to 6-year-olds (49.6% boys), 18,291 7- to 8-year-olds (49.0% boys), 27,218 9- to 10-year-olds (49.4% boys), 18,543 12- to 13-year-olds (48.9% boys) and 10,088 15- to 16-year-olds (46.6% boys). We replicated the well-established gender differences in average aggression scores at most ages for parental ratings. The gender differences decreased with age and were not present for self-reports. Aggression co-occurred with the majority of other behavioural and social problems, from both externalising and internalising domains. At each age, the co-occurrence was particularly prevalent for aggression and oppositional and ADHD-related problems, with correlations of around 0.5 in general. Aggression also showed substantial associations with anxiety-depression and other internalizing symptoms (correlations around 0.4). Co-occurrence for self-reported problems was somewhat higher than for parental reports, but we found neither rater differences, nor differences across assessment instruments in co-occurrence patterns. There were large similarities in co-occurrence patterns across the different European countries. Finally, co-occurrence was generally stable across age and sex, and if any change was observed, it indicated stronger correlations when children grew older. We present an online tool to visualise these associations as a function of rater, gender, instrument and cohort. In addition, we present a description of the full EU-ACTION projects, its first results and the future perspectives.
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| 7. |
- Beck, J. J., et al.
(författare)
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Genetic meta-analysis of twin birth weight shows high genetic correlation with singleton birth weight
- 2021
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 30:19, s. 1894-1905
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Tidskriftsartikel (refereegranskat)abstract
- Birth weight (BW) is an important predictor of newborn survival and health and has associations with many adult health outcomes, including cardiometabolic disorders, autoimmune diseases and mental health. On average, twins have a lower BW than singletons as a result of a different pattern of fetal growth and shorter gestational duration. Therefore, investigations into the genetics of BW often exclude data from twins, leading to a reduction in sample size and remaining ambiguities concerning the genetic contribution to BW in twins. In this study, we carried out a genome-wide association meta-analysis of BW in 42 212 twin individuals and found a positive correlation of beta values (Pearson's r = 0.66, 95% confidence interval [CI]: 0.47-0.77) with 150 previously reported genome-wide significant variants for singleton BW. We identified strong positive genetic correlations between BW in twins and numerous anthropometric traits, most notably with BW in singletons (genetic correlation [r(g)]= 0.92, 95% CI: 0.66-1.18). Genetic correlations of BW in twins with a series of health-related traits closely resembled those previously observed for BW in singletons. Polygenic scores constructed from a genome-wide association study on BW in the UK Biobank demonstrated strong predictive power in a target sample of Dutch twins and singletons. Together, our results indicate that a similar genetic architecture underlies BW in twins and singletons and that future genome-wide studies might benefit from including data from large twin registers.
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| 8. |
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| 9. |
- Neumann, A, et al.
(författare)
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A genome-wide association study of total child psychiatric problems scores
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:8, s. e0273116-
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Tidskriftsartikel (refereegranskat)abstract
- Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.
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| 10. |
- Silventoinen, K., et al.
(författare)
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Educational attainment of same-sex and opposite-sex dizygotic twins : An individual-level pooled study of 19 twin cohorts
- 2021
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Ingår i: Hormones and Behavior. - : Elsevier. - 0018-506X .- 1095-6867. ; 136
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Tidskriftsartikel (refereegranskat)abstract
- Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (β = −0.05 educational years, 95% CI −0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (β = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers.
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| 11. |
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| 12. |
- Taal, H. Rob, et al.
(författare)
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Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
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| 13. |
- Vogelezang, Suzanne, et al.
(författare)
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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
- 2020
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
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Tidskriftsartikel (refereegranskat)abstract
- The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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| 14. |
- 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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| 15. |
- Slob, E. M. A., et al.
(författare)
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Early-life antibiotic use and risk of attention-deficit hyperactivity disorder and autism spectrum disorder: results of a discordant twin study
- 2021
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Ingår i: International journal of epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 50:2, s. 475-484
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 16. |
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| 17. |
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| 18. |
- Abdellaoui, A, et al.
(författare)
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CNV Concordance in 1,097 MZ Twin Pairs
- 2015
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Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 18:1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Monozygotic (MZ) twins are genetically identical at conception, making them informative subjects for studies on somatic mutations. Copy number variants (CNVs) are responsible for a substantial part of genetic variation, have relatively high mutation rates, and are likely to be involved in phenotypic variation. We conducted a genome-wide survey for post-twinning de novo CNVs in 1,097 MZ twin pairs. Comparisons between MZ twins were made by CNVs measured in DNA from blood or buccal epithelium with the Affymetrix 6.0 microarray and two calling algorithms. In addition, CNV concordance rates were compared between the different sources of DNA, and gene-enrichment association analyses were conducted for thought problems (TP) and attention problems (AP) using CNVs concordant within MZ pairs. We found a total of 153 putative post-twinning de novo CNVs >100 kb, of which the majority resided in 15q11.2. Based on the discordance of raw intensity signals a selection was made of 20 de novo CNVs for a qPCR validation experiments. Two out of 20 post-twinning de novo CNVs were validated with qPCR in the same twin pair. The 13-year-old MZ twin pair that showed two discordances in CN in 15q11.2 in their buccal DNA did not show large phenotypic differences. From the remaining 18 putative de novo CNVs, 17 were deletions or duplications that were concordant within MZ twin pairs. Concordance rates within twin pairs of CNV calls with CN ≠ 2 were ~80%. Buccal epithelium-derived DNA showed a slightly but significantly higher concordance rate, and blood-derived DNA showed significantly more concordant CNVs per twin pair. The gene-enrichment analyses on concordant CNVs showed no significant associations between CNVs overlapping with genes involved in neuronal processes and TP or AP after accounting for the source of DNA.
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| 19. |
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| 20. |
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| 21. |
- Akingbuwa, W. A., et al.
(författare)
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Genetic Associations between Childhood Psychopathology and Adult Depression and Associated Traits in 42998 Individuals: A Meta-Analysis
- 2020
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Ingår i: JAMA Psychiatry. - : American Medical Association (AMA). - 2168-622X .- 2168-6238. ; 77:7, s. 715-728
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Adult mood disorders are often preceded by behavioral and emotional problems in childhood. It is yet unclear what explains the associations between childhood psychopathology and adult traits. Objective: To investigate whether genetic risk for adult mood disorders and associated traits is associated with childhood disorders. Design, Setting, and Participants: This meta-analysis examined data from 7 ongoing longitudinal birth and childhood cohorts from the UK, the Netherlands, Sweden, Norway, and Finland. Starting points of data collection ranged from July 1985 to April 2002. Participants were repeatedly assessed for childhood psychopathology from ages 6 to 17 years. Data analysis occurred from September 2017 to May 2019. Exposures: Individual polygenic scores (PGS) were constructed in children based on genome-wide association studies of adult major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI). Main Outcomes and Measures: Regression meta-analyses were used to test associations between PGS and attention-deficit/hyperactivity disorder (ADHD) symptoms and internalizing and social problems measured repeatedly across childhood and adolescence and whether these associations depended on childhood phenotype, age, and rater. Results: The sample included 42998 participants aged 6 to 17 years. Male participants varied from 43.0% (1040 of 2417 participants) to 53.1% (2434 of 4583 participants) by age and across all cohorts. The PGS of adult major depression, neuroticism, BMI, and insomnia were positively associated with childhood psychopathology (β estimate range, 0.023-0.042 [95% CI, 0.017-0.049]), while associations with PGS of subjective well-being and educational attainment were negative (β, -0.026 to -0.046 [95% CI, -0.020 to -0.057]). There was no moderation of age, type of childhood phenotype, or rater with the associations. The exceptions were stronger associations between educational attainment PGS and ADHD compared with internalizing problems (Δβ, 0.0561 [Δ95% CI, 0.0318-0.0804]; ΔSE, 0.0124) and social problems (Δβ, 0.0528 [Δ95% CI, 0.0282-0.0775]; ΔSE, 0.0126), and between BMI PGS and ADHD and social problems (Δβ, -0.0001 [Δ95% CI, -0.0102 to 0.0100]; ΔSE, 0.0052), compared with internalizing problems (Δβ, -0.0310 [Δ95% CI, -0.0456 to -0.0164]; ΔSE, 0.0074). Furthermore, the association between educational attainment PGS and ADHD increased with age (Δβ, -0.0032 [Δ 95% CI, -0.0048 to -0.0017]; ΔSE, 0.0008). Conclusions and Relevance: Results from this study suggest the existence of a set of genetic factors influencing a range of traits across the life span with stable associations present throughout childhood. Knowledge of underlying mechanisms may affect treatment and long-term outcomes of individuals with psychopathology.. © 2020 Lippincott Williams and Wilkins. All rights reserved.
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| 22. |
- Jelenkovic, A, et al.
(författare)
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Genetic and environmental influences on height from infancy to early adulthood: An individual-based pooled analysis of 45 twin cohorts
- 2016
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Ingår i: Scientific reports. - London, United Kingdom : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 28496-
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Tidskriftsartikel (refereegranskat)abstract
- Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1–19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Slob, EMA, et al.
(författare)
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Early-life antibiotic use and risk of asthma and eczema: results of a discordant twin study
- 2020
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:4
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Tidskriftsartikel (refereegranskat)abstract
- Early-life antibiotic use has been associated with the development of atopic diseases, but the aetiology remains unclear. To elucidate the aetiology, we used a discordant twin design to control for genetic and environmental confounding.MethodsWe conducted a retrospective cohort study in twins aged 3–10 years from the Netherlands Twin Register (NTR, n=35 365) and a replication study in twins aged 9 years from the Childhood and Adolescent Twin Study in Sweden (CATSS, n=7916). Antibiotic use was recorded at age 0–2 years. Doctor-diagnosed asthma and eczema were reported by parents when children were aged 3–12 years in both cohorts. Individuals were included in unmatched analyses and in co-twin control analyses with disease discordant twin pairs.ResultsEarly-life antibiotic use was associated with increased risk of asthma (NTR OR 1.34, 95% CI 1.28–1.41; CATSS OR 1.45, 95% CI 1.34–1.56) and eczema (NTR OR 1.08, 95% CI 1.03–1.13; CATSS OR 1.07, 95% CI 1.01–1.14) in unmatched analyses. Co-twin analyses in monozygotic and dizygotic twin pairs showed similar results for asthma (NTR OR 1.54, 95% CI 1.20–1.98; CATSS OR 2.00, 95% CI 1.28–3.13), but opposing results for eczema in the NTR (OR 0.99, 95% CI 0.80–1.25) and the CATSS (OR 1.67, 95% CI 1.12–2.49). The risk of asthma increased for antibiotics prescribed for respiratory infections (CATSS OR 1.45, 95% CI 1.34–1.56), but not for antibiotics commonly used for urinary tract/skin infections (CATSS OR 1.02, 95% CI 0.88–1.17).ConclusionChildren exposed to early-life antibiotic use, particularly prescribed for respiratory infections, may be at higher risk of asthma. This risk can still be observed when correcting for genetic and environmental factors. Our results could not elucidate whether the relationship between early-life antibiotic use and eczema is confounded by familial and genetic factors.
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| 27. |
- Vuoksimaa, E, et al.
(författare)
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Aggression and academic performance
- 2017
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Ingår i: BEHAVIOR GENETICS. - 0001-8244. ; 47:6, s. 656-656
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 28. |
- Vuoksimaa, E., et al.
(författare)
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Higher aggression is related to poorer academic performance in compulsory education
- 2021
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Ingår i: Journal of Child Psychology and Psychiatry. - : Wiley. - 0021-9630 .- 1469-7610. ; 62:3, s. 327-338
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Tidskriftsartikel (refereegranskat)abstract
- Background To conduct a comprehensive assessment of the association between aggression and academic performance in compulsory education. Method We studied aggression and academic performance in over 27,000 individuals from four European twin cohorts participating in the ACTION consortium (Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies). Individual level data on aggression at ages 7-16 were assessed by three instruments (Achenbach System of Empirically Based Assessment, Multidimensional Peer Nomination Inventory, Strengths and Difficulties Questionnaire) including parental, teacher and self-reports. Academic performance was measured with teacher-rated grade point averages (ages 12-14) or standardized test scores (ages 12-16). Random effect meta-analytical correlations with academic performance were estimated for parental ratings (in all four cohorts) and self-ratings (in three cohorts). Results All between-family analyses indicated significant negative aggression-academic performance associations with correlations ranging from -.06 to -.33. Results were similar across different ages, instruments and raters and either with teacher-rated grade point averages or standardized test scores as measures of academic performance. Meta-analytical r's were -.20 and -.23 for parental and self-ratings, respectively. In within-family analyses of all twin pairs, the negative aggression-academic performance associations were statistically significant in 14 out of 17 analyses (r = -.17 for parental- and r = -.16 for self-ratings). Separate analyses in monozygotic (r = -.07 for parental and self-ratings), same-sex dizygotic (r's = -.16 and -.17 for parental and self-ratings) and opposite-sex dizygotic (r's = -.21 and -.19 for parental and self-ratings) twin pairs suggested partial confounding by genetic effects. Conclusions There is a robust negative association between aggression and academic performance in compulsory education. Part of these associations were explained by shared genetic effects, but some evidence of a negative association between aggression and academic performance remained even in within-family analyses of monozygotic twin pairs.
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