title: Quantitative trait locus analysis of candidate gene alleles associated with attention deficit hyperactivity disorder (ADHD) in five genes: DRD4, DAT1, DRD5, SNAP-25, and 5HT1B.
abstract: It has been widely postulated that the categorical diagnosis of attention deficit hyperactivity disorder (ADHD) should be seen as the extreme end of a set of traits quantitatively distributed in the general population. A consequence of this is that the genes associated with DSM-IV ADHD should also influence these underlying traits in non-affected individuals. The aim of this study was to examine if specific candidate loci previously shown to be associated with DSM-IV ADHD, also act as quantitative trait loci (QTLs) for ADHD-symptoms in the general population. We have genotyped five candidate markers in a population-based sample of male dizygous twin-pairs (n = 329 pairs). We found little evidence to support a role for the previously-nominated alleles of a DRD4 VNTR, a 5HT1B SNP, or a microsatellite marker near to DRD5, in the distribution of ADHD-symptoms scores; however, we found some evidence to suggest that the DAT1 3'UTR VNTR and weak evidence that a microsatellite in SNAP-25 may have a role in continuous measures of ADHD-symptoms hyperactivity above and beyond their role in clinical ADHD.
authors.affiliation: Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, United Kingdom. j.mill@iop.kcl.ac.uk
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mill
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xu
authors.forename: Angelica
authors.initials: A
authors.lastname: Ronald
authors.forename: Sarah
authors.initials: S
authors.lastname: Curran
authors.forename: Tom
authors.initials: T
authors.lastname: Price
authors.forename: Jo
authors.initials: J
authors.lastname: Knight
authors.forename: Ian
authors.initials: I
authors.lastname: Craig
authors.forename: Pak
authors.initials: P
authors.lastname: Sham
authors.forename: Robert
authors.initials: R
authors.lastname: Plomin
authors.forename: Philip
authors.initials: P
authors.lastname: Asherson
mesh_terms: D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002648:Child; D050483:Dopamine Plasma Membrane Transport Proteins; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D015201:Meta-Analysis as Topic; D009419:Nerve Tissue Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci / Q000235:genetics*; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D050825:Synaptosomal-Associated Protein 25; D014429:Twins, Dizygotic / Q000235:genetics*
chemical_list: C493599:DRD4 protein, human; C493605:DRD5 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D044302:Receptor, Serotonin, 5-HT1B; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5