TY - JOUR
T1 - Harmonizing behavioral outcomes across studies, raters, and countries
T2 - application to the genetic analysis of aggression in the ACTION Consortium
AU - Luningham, Justin M.
AU - Hendriks, Anne M.
AU - Krapohl, Eva
AU - Fung Ip, Hill
AU - van Beijsterveldt, Catharina E.M.
AU - Lundström, Sebastian
AU - Vuoksimaa, Eero
AU - Korhonen, Tellervo
AU - Lichtenstein, Paul
AU - Plomin, Robert
AU - Pulkkinen, Lea
AU - Rose, Richard J.
AU - Kaprio, Jaakko
AU - Bartels, Meike
AU - Boomsma, Dorret I.
AU - Lubke, Gitta H.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
KW - Aggression
KW - developmental psychopathology
KW - integrative data analysis
KW - phenotype reference panel
KW - twin modeling
UR - http://www.scopus.com/inward/record.url?scp=85078589696&partnerID=8YFLogxK
U2 - 10.1111/jcpp.13188
DO - 10.1111/jcpp.13188
M3 - Article
AN - SCOPUS:85078589696
SN - 0021-9630
VL - 61
SP - 807
EP - 817
JO - Journal of Child Psychology and Psychiatry and Allied Disciplines
JF - Journal of Child Psychology and Psychiatry and Allied Disciplines
IS - 7
ER -
