Harmonizing behavioral outcomes across studies, raters, and countries: application to the genetic analysis of aggression in the ACTION Consortium

Harmonizing behavioral outcomes across studies, raters, and countries: application to the genetic analysis of aggression in the ACTION Consortium · SciRah

^aDepartment of Population Health Sciences School of Public Health Georgia State University Atlanta GA USA
^bDepartment of Psychology University of Notre Dame Notre Dame IN USA
^cDepartment of Population Health Sciences, School of Public Health, Georgia State University, Atlanta, GA, USA
^dDepartment of Psychology, University of Notre Dame, Notre Dame, IN, USA
^eAmsterdam Public Health research institute Faculty of Behavioural and Movement Sciences Vrije Universiteit Amsterdam Amsterdam The Netherlands
^fNetherlands Twin Register Department of Biological Psychology Vrije Universiteit Amsterdam Amsterdam The Netherlands
^gAmsterdam Public Health research institute, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
^hNetherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
ⁱMedical Research Council Social, Genetic, and Developmental Psychiatry Centre Institute of Psychiatry, Psychology, and Neuroscience King's College London London UK
^jMedical Research Council Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK
^kCentre for Ethics, Law and Mental Health (CELAM) University of Gothenburg Gothenburg Sweden
^lGillberg Neuropsychiatry Centre University of Gothenburg Gothenburg Sweden
^mCentre for Ethics, Law and Mental Health (CELAM), University of Gothenburg, Gothenburg, Sweden
ⁿGillberg Neuropsychiatry Centre, University of Gothenburg, Gothenburg, Sweden
^oInstitute for Molecular Medicine Finland University of Helsinki Helsinki Finland
^pInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
^qDepartment of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
^rDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
^sDepartment of Psychology University of Jyvaskyla Jyvaskyla Finland
^tDepartment of Psychology, University of Jyvaskyla, Jyvaskyla, Finland
^uDepartment of Psychological and Brain Sciences Indiana University Bloomington IN USA
^vDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA
^wDepartment of Public Health University of Helsinki Helsinki Finland
^xDepartment of Public Health, University of Helsinki, Helsinki, Finland
^yAmsterdam Neuroscience Amsterdam The Netherlands
^zAmsterdam Neuroscience, Amsterdam, The Netherlands
✉Corresponding author

Abstract

BACKGROUND: Aggression 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. METHODS: Individual 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. RESULTS: The 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. CONCLUSIONS: Opposite-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.

TL;DROpposite-sex twins displayed unique social dynamics of aggressive behaviors in a joint analysis of a large, multinational dataset, suggesting the integrative data analysis framework has the potential to elucidate broad, generalizable results in the investigation of common psychological traits in children. (Semantic Scholar)

Harmonizing behavioral outcomes across studies, raters, and countries: application to the genetic analysis of aggression in the ACTION Consortium

Abstract

Plain-language summary

Discussion