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

Justin M Luningham, Anne M Hendriks, Eva Krapohl, Hill Fung Ip, Catharina E M van Beijsterveldt, Sebastian Lundström, Eero Vuoksimaa, Tellervo Korhonen, Paul Lichtenstein, Robert Plomin, Lea Pulkkinen, Richard J Rose, Jaakko Kaprio, Meike Bartels, Dorret I Boomsma, Gitta H Lubke

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
JournalJournal of Child Psychology and Psychiatry
DOIs
Publication statusE-pub ahead of print - 16 Jan 2020

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Aggression
Outcome Assessment (Health Care)
Siblings
Phenotype
Gene-Environment Interaction
Interpersonal Relations
Sample Size
Psychology

Bibliographical note

© 2020 Association for Child and Adolescent Mental Health.

Cite this

Luningham, Justin M ; Hendriks, Anne M ; Krapohl, Eva ; Fung Ip, Hill ; van Beijsterveldt, Catharina E M ; Lundström, Sebastian ; Vuoksimaa, Eero ; Korhonen, Tellervo ; Lichtenstein, Paul ; Plomin, Robert ; Pulkkinen, Lea ; Rose, Richard J ; Kaprio, Jaakko ; Bartels, Meike ; Boomsma, Dorret I ; Lubke, Gitta H. / Harmonizing behavioral outcomes across studies, raters, and countries : application to the genetic analysis of aggression in the ACTION Consortium. In: Journal of Child Psychology and Psychiatry. 2020.
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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.",
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Harmonizing behavioral outcomes across studies, raters, and countries : application to the genetic analysis of aggression in the ACTION Consortium. / Luningham, Justin M; Hendriks, Anne M; Krapohl, Eva; Fung Ip, Hill; van Beijsterveldt, Catharina E M; Lundström, Sebastian; Vuoksimaa, Eero; Korhonen, Tellervo; Lichtenstein, Paul; Plomin, Robert; Pulkkinen, Lea; Rose, Richard J; Kaprio, Jaakko; Bartels, Meike; Boomsma, Dorret I; Lubke, Gitta H.

In: Journal of Child Psychology and Psychiatry, 16.01.2020.

Research output: Contribution to JournalArticleAcademicpeer-review

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

N1 - © 2020 Association for Child and Adolescent Mental Health.

PY - 2020/1/16

Y1 - 2020/1/16

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.

U2 - 10.1111/jcpp.13188

DO - 10.1111/jcpp.13188

M3 - Article

JO - Journal of Child Psychology and Psychiatry

JF - Journal of Child Psychology and Psychiatry

SN - 0021-9630

ER -