title: Evidence that variation at the serotonin transporter gene influences susceptibility to attention deficit hyperactivity disorder (ADHD): analysis and pooled analysis.
abstract: Reduced central serotonergic activity has been implicated in poor impulse regulation and aggressive behaviour in animals, adults and also young children.(1,2) Two recently published studies have implicated variation at a polymorphism in the promoter of the serotonin transporter (5HTT; hSERT) in influencing susceptibility to ADHD.(3,4) Consistent with these results we have also found a trend for the long allele of the promoter polymorphism to influence susceptibility to ADHD in a sample of 113 ADHD parent proband trios (65 transmissions vs 49 non-transmissions, chi(2) = 2.25, P = 0.13). A pooled analysis of our, and these published results demonstrated a significant over representation of the long allele of the promoter in ADHD probands compared to controls (chi(2) = 7.14, P = 0.008). We have also examined two other 5HTT polymorphisms (the VNTR in intron 2 and the 3' UTR SNP). TDT analysis demonstrated preferential transmission of the T allele of the 3' UTR SNP (chi(2) = 4.06, P = 0.04). In addition, ETDT analysis of haplotypes demonstrated significant preferential transmission of haplotypes containing the T allele of the 3' UTR SNP with the long allele of the promoter polymorphism (chi(2) = 13.18, 3 df, P = 0.004) and the 10 repeat of the VNTR (chi(2) = 8.77, 3 df, P = 0.03). This study provides further evidence for the possible involvement of the serotonin transporter in susceptibility to ADHD.
authors.affiliation: Molecular Psychiatry Group, Division of Neuroscience, University of Birmingham, Queen Elizabeth Psychiatric Hospital, Birmingham B15 2QZ, UK. l.s.kent@bham.ac.uk
authors.forename: L
authors.initials: L
authors.lastname: Kent
authors.forename: U
authors.initials: U
authors.lastname: Doerry
authors.forename: E
authors.initials: E
authors.lastname: Hardy
authors.forename: R
authors.initials: R
authors.lastname: Parmar
authors.forename: K
authors.initials: K
authors.lastname: Gingell
authors.forename: Z
authors.initials: Z
authors.lastname: Hawi
authors.forename: A
authors.initials: A
authors.lastname: Kirley
authors.forename: N
authors.initials: N
authors.lastname: Lowe
authors.forename: M
authors.initials: M
authors.lastname: Fitzgerald
authors.forename: M
authors.initials: M
authors.lastname: Gill
authors.forename: N
authors.initials: N
authors.lastname: Craddock
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins