Samenvatting
Background: Aggressive behavior in children and adolescents
is caused by complex interactions of genetic and environmental
factors (GxE-interactions). In this respect, environmental
adversities lead to aggression in some individuals
depending on their genetic make-up. Using data from the
Avon Longitudinal Study of Parents and Children (ALSPAC),
we conducted a genome-wide study of gene-based interactions
with four established environmental risk factors for
aggressive behavior.
Methods: Genome-wide genotyping data were available for
8941 children and adolescents. For up to 5214 of these,
we had data for eight disruptive behavior-related traits
that measure aggression. Environmental adversities were
maternal paracetamol use, life events and smoking during
pregnancy, and child maltreatment after birth. Following
GxE-interaction analyses, we investigated whether specific
canonical pathways were enriched in our data.
Results: We discovered 686 significant gene-based GxEinteractions
(involving 589 unique genes) that survived correction
for multiple testing ( α≈7.90E-08) and explained up
to 39% of the phenotypic variance associated with each
interaction. In total, 326 genes interacted with maternal
smoking, 272 genes with maternal life events, 73 genes
with paracetamol use, and 2 genes with child maltreatment.
Across all interactions, the top 5 genes were AKR1C1,
CSMD1, FBXL14, PODNL1, and TMEM132D. Further, opioid
signaling emerged as the only canonical pathway that was
significantly enriched in multiple sets of GxE-implicated
genes.
Discussion: The interaction of multiple genes with four environmental
factors is related to aggressive behavior in children and adolescents. Some of these genes have been previously
implicated in aggression, including NOS1AP, NOS3,
RBFOX1, and TMEM132D. In addition, opioid signaling is
a key molecular cascade underlying the identified GxEinteractions.
is caused by complex interactions of genetic and environmental
factors (GxE-interactions). In this respect, environmental
adversities lead to aggression in some individuals
depending on their genetic make-up. Using data from the
Avon Longitudinal Study of Parents and Children (ALSPAC),
we conducted a genome-wide study of gene-based interactions
with four established environmental risk factors for
aggressive behavior.
Methods: Genome-wide genotyping data were available for
8941 children and adolescents. For up to 5214 of these,
we had data for eight disruptive behavior-related traits
that measure aggression. Environmental adversities were
maternal paracetamol use, life events and smoking during
pregnancy, and child maltreatment after birth. Following
GxE-interaction analyses, we investigated whether specific
canonical pathways were enriched in our data.
Results: We discovered 686 significant gene-based GxEinteractions
(involving 589 unique genes) that survived correction
for multiple testing ( α≈7.90E-08) and explained up
to 39% of the phenotypic variance associated with each
interaction. In total, 326 genes interacted with maternal
smoking, 272 genes with maternal life events, 73 genes
with paracetamol use, and 2 genes with child maltreatment.
Across all interactions, the top 5 genes were AKR1C1,
CSMD1, FBXL14, PODNL1, and TMEM132D. Further, opioid
signaling emerged as the only canonical pathway that was
significantly enriched in multiple sets of GxE-implicated
genes.
Discussion: The interaction of multiple genes with four environmental
factors is related to aggressive behavior in children and adolescents. Some of these genes have been previously
implicated in aggression, including NOS1AP, NOS3,
RBFOX1, and TMEM132D. In addition, opioid signaling is
a key molecular cascade underlying the identified GxEinteractions.
| Originele taal-2 | English |
|---|---|
| Pagina's (van-tot) | S175-S176 |
| Aantal pagina's | 2 |
| Tijdschrift | European Neuropsychopharmacology |
| Volume | 29 |
| DOI's | |
| Status | Published - 1-okt.-2019 |