Does Parental Expressed Emotion Moderate Genetic Effects in ADHD? An Exploration Using a Genome Wide Association Scan

Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5;147B(8):1359-68. doi: 10.1002/ajmg.b.30860.

Abstract

Studies of gene x environment (G x E) interaction in ADHD have previously focused on known risk genes for ADHD and environmentally mediated biological risk. Here we use G x E analysis in the context of a genome-wide association scan to identify novel genes whose effects on ADHD symptoms and comorbid conduct disorder are moderated by high maternal expressed emotion (EE). SNPs (600,000) were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. ADHD symptom severity and comorbid conduct disorder was measured using the Parental Account of Childhood Symptoms interview. Maternal criticism and warmth (i.e., EE) were coded by independent observers on comments made during the interview. No G x E interactions reached genome-wide significance. Nominal effects were found both with and without genetic main effects. For those with genetic main effects 36 uncorrected interaction P-values were <10(-5) implicating both novel genes as well as some previously supported candidates. These were found equally often for all of the interactions being investigated. The observed interactions in SLC1A1 and NRG3 SNPs represent reasonable candidate genes for further investigation given their previous association with several psychiatric illnesses. We find evidence for the role of EE in moderating the effects of genes on ADHD severity and comorbid conduct disorder, implicating both novel and established candidates. These findings need replicating in larger independent samples.

MeSH terms

  • Adolescent
  • Alleles
  • Attention Deficit Disorder with Hyperactivity / diagnosis
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Attention Deficit Disorder with Hyperactivity / psychology*
  • Child
  • Child, Preschool
  • Excitatory Amino Acid Transporter 3 / genetics
  • Expressed Emotion*
  • Female
  • Gene Frequency
  • Genetic Markers
  • Genome, Human
  • Genome-Wide Association Study*
  • Humans
  • Interviews as Topic
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Models, Genetic
  • Neuregulins
  • Parent-Child Relations
  • Parents / psychology*
  • Polymorphism, Single Nucleotide
  • Probability
  • Quantitative Trait Loci

Substances

  • Excitatory Amino Acid Transporter 3
  • Genetic Markers
  • Intracellular Signaling Peptides and Proteins
  • NRG3 protein, human
  • Neuregulins
  • SLC1A1 protein, human