title: LPHN3 and attention-deficit/hyperactivity disorder: interaction with maternal stress during pregnancy.
abstract: BACKGROUND
  Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous behavioral disorder, complex both in etiology and clinical expression. Both genetic and environmental factors have been implicated, and it has been suggested that gene-environment interactions may play a pivotal role in the disorder. Recently, a significant association was reported between ADHD and LPHN3 (which codes for latrophilin 3), and replicated in independent samples.
  
  
  METHODS
  We have examined the association between tag single nucleotide polymorphisms (SNPs) in LPHN3 within the region previously implicated in ADHD. Family based association tests (FBAT) were conducted (n = 380 families) with the categorical diagnosis of ADHD, behavioral and cognitive phenotypes related to ADHD, and response to treatment (given a fixed dose of methylphenidate, 0.5 mg/day). Stratified FBAT analyses, based on maternal smoking and stress during pregnancy, was conducted.
  
  
  RESULTS
  Whereas limited association was observed in the total sample, highly significant interaction between four LPHN3 tag SNPs (rs6551665, rs1947274, rs6858066, rs2345039) and maternal stress during pregnancy was noted. Analysis conducted in the sub-group of mothers exposed to minimal stress during pregnancy showed significant associations with ADHD, behavioral and cognitive dimensions related to ADHD, as well as treatment response. Although extensive association was observed with the candidate SNPs, the findings are partially inconsistent with previously published results with the opposite alleles over-transmitted in these studies.
  
  
  CONCLUSIONS
  These results provide evidence for the interaction between a genetic and environmental factor independently shown to be associated with ADHD. If confirmed in independent large studies, they may present a step forward in unraveling the complex etiology of ADHD.
authors.affiliation: Douglas Mental Health University Institute, McGill University, Verdun, QC, Canada.
authors.forename: Zia
authors.initials: Z
authors.lastname: Choudhry
authors.forename: Sarojini M
authors.initials: SM
authors.lastname: Sengupta
authors.forename: Natalie
authors.initials: N
authors.lastname: Grizenko
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Fortier
authors.forename: Geeta A
authors.initials: GA
authors.lastname: Thakur
authors.forename: Johanne
authors.initials: J
authors.lastname: Bellingham
authors.forename: Ridha
authors.initials: R
authors.lastname: Joober
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology* / Q000235:genetics; D002648:Child; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000523:psychology*; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000523:psychology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D018000:Receptors, Peptide / Q000235:genetics*
chemical_list: C513284:ADGRL3 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide