Evidence that variation at the serotonin transporter gene influences susceptibility to attention deficit hyperactivity disorder (ADHD): analysis and pooled analysis.
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.
Kent
L
L
Molecular Psychiatry Group, Division of Neuroscience, University of Birmingham, Queen Elizabeth Psychiatric Hospital, Birmingham B15 2QZ, UK. l.s.kent@bham.ac.uk
Doerry
U
U
Hardy
E
E
Parmar
R
R
Gingell
K
K
Hawi
Z
Z
Kirley
A
A
Lowe
N
N
Fitzgerald
M
M
Gill
M
M
Craddock
N
N
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
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins