Effect of candidate gene polymorphisms on the course of attention deficit hyperactivity disorder.
The main aim of this study was to examine the association between attention-deficit hyperactivity disorder (ADHD)-associated genes and the course of ADHD. Subjects were derived from identically designed case-control family studies of boys and girls with ADHD and a genetic linkage study of families with children with ADHD. Caucasian probands and family members with ADHD and with available genetic data were included in this analysis (N=563). The course of ADHD was compared in subjects with and without putative risk alleles (DRD4 7-repeat allele, DAT1 10-repeat allele, and 5HTTLPR long allele). The persistence of ADHD (full or subthreshold diagnosis in the last month) was plotted using Kaplan-Meier survival functions and tested with Cox proportional hazard models. Survival analyses revealed that by 25 years of age 76% of subjects with a DRD4 7-repeat allele were estimated to have significantly more persistent ADHD compared with 66% of subjects without the risk allele. In contrast, there were no significant associations between the course of ADHD and the DAT1 10-repeat allele (P=0.94) and 5HTTLPR long allele. Our findings suggest that the DRD4 7-repeat allele is associated with a more persistent course of ADHD.
Biederman
Joseph
J
Pediatric Psychopharmacology Department, Massachusetts General Hospital, Boston, MA, USA. jbiederman@partners.org
Petty
Carter R
CR
Ten Haagen
Kristina S
KS
Small
Jacqueline
J
Doyle
Alysa E
AE
Spencer
Thomas
T
Mick
Eric
E
Monuteaux
Michael C
MC
Smoller
Jordan W
JW
Faraone
Stephen V
SV
D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D015810:Linkage Disequilibrium; D008137:Longitudinal Studies; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D016019:Survival Analysis; D055815:Young Adult
C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D050638:Receptors, Dopamine D4