Project description:BackgroundAggression in children has genetic and environmental causes. Studies of aggression can pool existing datasets to include more complex models of social effects. Such analyses require large datasets with harmonized outcome measures. Here, we made use of a reference panel for phenotype data to harmonize multiple aggression measures in school-aged children to jointly analyze data from five large twin cohorts.MethodsIndividual level aggression data on 86,559 children (42,468 twin pairs) were available in five European twin cohorts measured by different instruments. A phenotypic reference panel was collected which enabled a model-based phenotype harmonization approach. A bi-factor integration model in the integrative data analysis framework was developed to model aggression across studies while adjusting for rater, age, and sex. Finally, harmonized aggression scores were analyzed to estimate contributions of genes, environment, and social interaction to aggression. The large sample size allowed adequate power to test for sibling interaction effects, with unique dynamics permitted for opposite-sex twins.ResultsThe best-fitting model found a high level of overall heritability of aggression (~60%). Different heritability rates of aggression across sex were marginally significant, with heritability estimates in boys of ~64% and ~58% in girls. Sibling interaction effects were only significant in the opposite-sex twin pairs: the interaction effect of males on their female co-twin differed from the effect of females on their male co-twin. An aggressive female had a positive effect on male co-twin aggression, whereas more aggression in males had a negative influence on a female co-twin.ConclusionsOpposite-sex twins displayed unique social dynamics of aggressive behaviors in a joint analysis of a large, multinational dataset. The integrative data analysis framework, applied in combination with a reference panel, has the potential to elucidate broad, generalizable results in the investigation of common psychological traits in children.

Project description:ImportanceChildhood intrafamilial aggression, a series of aggressive behaviors inflicted by family members, and adulthood mental health are associated with childhood peer bullying (eg, in the neighborhood or in school). However, few studies have been able to identify the contribution of childhood peer bullying to the association between childhood intrafamilial aggression and adult depression.ObjectiveTo examine the mediating role of childhood peer bullying in the association between childhood intrafamilial aggression and depression in adulthood.Design, setting, and participantsThis population-based cross-sectional study used data from the China Health and Retirement Longitudinal Study (CHARLS). Middle-aged and older adults (≥45 years) participated in a CHARLS wave from July 1 to September 30, 2015, and the CHARLS life history survey from June 1 to December 31, 2014, with complete data. A 4-step mediation model with logistic regression was run to test the mediating role of peer bullying. Data analysis was performed from October 1 to 30, 2019.ExposuresChildhood intrafamilial aggression, including parental physical maltreatment and sibling aggression, and peer bullying.Main outcomes and measuresDepressive symptoms measured by a categorical variable derived from the Center for Epidemiologic Studies Depression Scale, based on a cutoff score of 12.ResultsAmong the 15 450 respondents (mean [SD] age, 59.5 [9.9] years; 7987 women [51.7%]), 4422 (28.6%) were exposed to parental physical maltreatment; 986 (6.4%), to sibling aggression; and 2504 (16.2%), to peer bullying in childhood. Respondents experiencing intrafamilial aggression were more likely to be bullied by peers (parental physical maltreatment odds ratio [OR], 2.53 [95% CI, 2.25-2.83]; sibling aggression OR, 3.05 [95% CI, 2.46-3.78]). Children with these adverse experiences were at a higher risk of adult depression symptoms (parental physical maltreatment OR, 1.28 [95% CI, 1.15-1.42]; sibling aggression OR, 1.40 [95% CI, 1.13-1.74]; peer bullying OR, 1.78 [95% CI, 1.56-2.01]). Peer bullying mediated 30% (95% CI, 19%-42%) of the association between childhood parental maltreatment and adult depression and 35% (95% CI, 15%-54%) of the association between sibling aggression and depression symptoms in adulthood.Conclusions and relevanceThis study found that being bullied by peers was a mediator of the association between childhood intrafamilial aggression and depression in adulthood. The findings have important implications to mitigate the effect of early-life stress and promote life-course mental health through dealing with childhood intrafamilial aggression and peer bullying experiences coordinately.

Project description:Background: Increased epigenetic age acceleration (EAA) in survivors of childhood cancer is associated with specific treatment exposures, unfavorable health behaviors, and presence of certain chronic health conditions. To better understand inter-individual variability, we investigated the genetic basis underlying EAA. Methods: Genome-wide association studies of EAA based on multiple epigenetic clocks (Hannum, Horvath, PhenoAge, and GrimAge) were performed. MethylationEPIC BeadChip array and whole-genome sequencing data were generated with blood-derived DNA from participants in the St. Jude Lifetime Cohort Study (discovery: 2,138 pre-existing and 502 newly generated data, all survivors; exploratory: 282 community controls). Linear regression models were fit for each epigenetic age against allelic dose of each genetic variant, adjusting for age at sampling, sex, and cancer treatment exposures. Fixed-effects meta-analysis was used to combine summary statistics from two discovery data sets. LD (Linkage disequilibrium) score regression was used to estimate single-nucleotide polymorphism (SNP)-based heritability. Results: For EAA-Horvath, a genome-wide significant association was mapped to SELP gene with the strongest SNP rs732314 (meta-GWAS: β=0.57, P=3.30×10-11). Moreover, the stratified analysis of the association between rs732314 and EAA-Horvath showed substantial heterogeneity between children and adults (meta-GWAS: β=0.97 vs. 0.51, I2=73.1%) as well as between survivors with and without chest/abdominal/pelvic-RT exposure (β=0.64 vs. 0.31, I2=66.3%). For EAA-Hannum, an association was mapped to HLA locus with the strongest SNP rs28366133 (meta-GWAS: β=0.78, P=3.78×10-11). There was no genome-wide significant hit for EAA-PhenoAge or EAA-GrimAge. Interestingly, among community controls, rs732314 was associated with EAA-Horvath (β=1.09, P=5.43×10-5), whereas rs28366133 was not associated with EAA-Hannum (β=0.21, P=0.49). The estimated heritability was 0.33 (SE=0.20) for EAA-Horvath and 0.17 (SE=0.23) for EAA-Hannum, but close to zero for EAA-PhenoAge and EAA-GrimAge. Conclusions: We identified novel genetic variants in SELP gene and HLA region associated with EAA-Horvath and EAA-Hannum, respectively, among survivors of childhood cancer. The new genetic variants in combination with other replicated known variants can facilitate identification of survivors at higher risk in developing accelerated aging, and potentially inform drug targets for future intervention strategies among vulnerable survivors.

Dataset Information

Genetic association study of childhood aggression across raters, instruments, and age.

Publications

Genetic association study of childhood aggression across raters, instruments, and age.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets