ORCID Profile
0000-0001-8780-0323
Current Organisation
University of California, San Diego
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Publisher: American Psychological Association (APA)
Date: 27-03-2023
DOI: 10.1037/HEA0001251
Publisher: Springer Science and Business Media LLC
Date: 26-02-2020
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.JAAC.2021.11.035
Abstract: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. 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 s le overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. The meta-analysis of overall internalizing symptoms (INT 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 s les will be key in paving the way to future GWAS success.
Publisher: Wiley
Date: 19-09-2023
DOI: 10.1111/ADD.16330
Publisher: Springer Science and Business Media LLC
Date: 30-07-2021
DOI: 10.1038/S41398-021-01480-X
Abstract: Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (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 s le overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGG overall ) 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 s le of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations ( r g ) among rater-specific assessment of AGG ranged from r g = 0.46 between self- and teacher-assessment to r g = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong r g s 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 $$\left| {r_g} \right|$$ 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 $$\left| {r_g} \right|$$ 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.
Publisher: Springer Science and Business Media LLC
Date: 07-06-2021
Publisher: Springer Science and Business Media LLC
Date: 26-11-2018
Location: United States of America
No related grants have been discovered for Sandra A. Brown.