Interplay between genome-wide implicated genetic variants and environmental factors related to childhood antisocial behavior in the UK ALSPAC cohort

I Hyun Ruisch,Andrea Dietrich,Jan K Buitelaar,Pieter J Hoekstra,Jeffrey C Glennon

doi:10.1007/s00406-018-0964-5

Abstract

We investigated gene–environment (G × E) interactions related to childhood antisocial behavior between polymorphisms implicated by recent genome-wide association studies (GWASs) and two key environmental adversities (maltreatment and smoking during pregnancy) in a large population cohort (ALSPAC). We also studied the MAOA candidate gene and addressed comorbid attention-deficit/hyperactivity disorder (ADHD). ALSPAC is a large, prospective, ethnically homogeneous British cohort. Our outcome consisted of mother-rated conduct disorder symptom scores at age 7;9 years. G × E interactions were tested in a sex-stratified way (α = 0.0031) for four GWAS-implicated variants (for males, rs4714329 and rs9471290; for females, rs2764450 and rs11215217), and a length polymorphism near the MAOA-promoter region. We found that males with rs4714329-GG (P = 0.0015) and rs9471290-AA (P = 0.0001) genotypes were significantly more susceptible to effects of smoking during pregnancy in relation to childhood antisocial behavior. Females with the rs11215217-TC genotype (P = 0.0018) were significantly less susceptible to effects of maltreatment, whereas females with the MAOA-HL genotype (P = 0.0002) were more susceptible to maltreatment effects related to antisocial behavior. After adjustment for comorbid ADHD symptomatology, aforementioned G × E’s remained significant, except for rs11215217 × maltreatment, which retained only nominal significance. Genetic variants implicated by recent GWASs of antisocial behavior moderated associations of smoking during pregnancy and maltreatment with childhood antisocial behavior in the general population. While we also found a G × E interaction between the candidate gene MAOA and maltreatment, we were mostly unable to replicate the previous results regarding MAOA–G × E’s. Future studies should, in addition to genome-wide implicated variants, consider polygenic and/or multimarker analyses and take into account potential sex stratification.

Highlights

Conduct disorder (CD) is a pediatric behavioral disorder with a prevalence of approximately 4–16% in boys and about 1–9% in girls [1]
We focused on two key environmental risk factors for antisocial behavior, namely maternal smoking during pregnancy and childhood maltreatment [7, 15, 16, 21], in the interplay with recently identified genetic variants from genome-wide association studies (GWASs) of antisocial behavior, while controlling for potential confounding by comorbid attention-deficit/hyperactivity disorder (ADHD) and addressing specific statistical concerns
We found that heterozygotes of the rs11215217 single-nucleotide polymorphisms (SNPs) appeared to be less susceptible, and carriers of both low- and high-activity allele of the monoamine oxidase A (MAOA)-length polymorphic region (LPR) appeared to be more susceptible to effects of childhood maltreatment in relation to antisocial behavior

Summary

Introduction

Conduct disorder (CD) is a pediatric behavioral disorder with a prevalence of approximately 4–16% in boys and about 1–9% in girls [1]. CD symptomatology or antisocial behaviors can be considered as continuous traits that are caused by both genetic and environmental risk factors. The interplay between genes and environment, known as gene–environment (G × E) interactions, can provide insight into why some individuals are more susceptible to certain adverse genetic or environmental factors than others. These G × E interactions are assumed to be of great importance in multifactorial traits such as antisocial behavior [5,6,7]

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