title: Testing for gene x environment interaction effects in attention deficit hyperactivity disorder and associated antisocial behavior.
abstract: Gene x environment (G x E) interactions are increasingly thought to have substantial influence on the aetiology and clinical manifestations of complex disorders. In ADHD, although main effects of specific genetic variants and pre- or peri-natal variables have been reported and replicated using pooled analyses, few studies have looked at possible interactions. In a clinical sample of 266 children with ADHD, we tested for interaction between gene variants (in DRD4, DAT1, DRD5, and 5HTT) found to be associated with ADHD in pooled analyses and maternal smoking, alcohol use during pregnancy and birth weight. First, G x E effects on a diagnosis of ADHD were tested using conditional logistic regression analyses. Second, possible modifying effects of G x E on symptoms of associated conduct disorder and oppositional defiant disorder (ODD) were investigated using linear regression analysis. The sample size associated with each of the analyses differed as not each variant had been genotyped for each individual. No effects of G x E on ADHD diagnosis were observed. The results suggest that lower birth weight and maternal smoking during pregnancy may interact with DRD5 and DAT1 (birth weight only) in influencing associated antisocial behavior symptoms (ODD and conduct disorder). These preliminary findings showed no evidence of interaction between previously implicated variants in ADHD and specific environmental risk factors, on diagnosis of the disorder. There may be evidence of G x E on associated antisocial behavior in ADHD, but further investigation is needed.
authors.affiliation: Department of Psychological Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.
authors.forename: K
authors.initials: K
authors.lastname: Langley
authors.forename: D
authors.initials: D
authors.lastname: Turic
authors.forename: F
authors.initials: F
authors.lastname: Rice
authors.forename: P
authors.initials: P
authors.lastname: Holmans
authors.forename: M B M
authors.initials: MB
authors.lastname: van den Bree
authors.forename: N
authors.initials: N
authors.lastname: Craddock
authors.forename: L
authors.initials: L
authors.lastname: Kent
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
authors.forename: M C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: A
authors.initials: A
authors.lastname: Thapar
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects; D000987:Antisocial Personality Disorder / Q000209:etiology* / Q000235:genetics; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D001724:Birth Weight; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D018811:Maternal Exposure; D011247:Pregnancy; D012907:Smoking / Q000009:adverse effects