ADHD candidate gene study in a population-based birth cohort: association with DBH and DRD2.
OBJECTIVE
Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset disorder with a significant impact on public health. Although a genetic contribution to risk is evident, predisposing genetic determinants remain largely unknown despite extensive research. So far, the most promising candidate genes have been those involved in dopamine and serotonin pathways. This study tests a series of allelic variants within such candidate genes to determine their potential influence on ADHD susceptibility.


METHODS
We used a population sample ascertained from a birth cohort of a subpopulation of Finland, characterized by founder effect and isolation, thus minimizing genetic heterogeneity. The subjects were systematically ascertained using DSM-IV diagnostic criteria for ADHD from the Northern Finland Birth Cohort 1986 of more than 9,000 individuals, resulting in the study sample of 188 ADHD cases and 166 controls. We genotyped markers in 13 candidate genes, including critical components of dopamine and serotonin pathways.


RESULTS
We report evidence for association of ADHD with allelic variants of the dopamine beta-hydroxylase (DBH) and dopamine receptor D2 (DRD2) genes.


CONCLUSIONS
Our study supports the involvement of the dopamine pathway in the etiology of ADHD; specifically the genes DBH and DRD2 deserve more attention in further studies.
Nyman
Emma S
ES
National Public Health Institute, Helsinki, Finland.
Ogdie
Matthew N
MN
Loukola
Anu
A
Varilo
Teppo
T
Taanila
Anja
A
Hurtig
Tuula
T
Moilanen
Irma K
IK
Loo
Sandra K
SK
McGough
James J
JJ
Järvelin
Marjo-Riitta
MR
Smalley
Susan L
SL
Nelson
Stanley F
SF
Peltonen
Leena
L
D000293:Adolescent; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D015331:Cohort Studies; D017931:DNA Primers / Q000235:genetics; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D011159:Population Surveillance / Q000379:methods*; D050637:Receptors, Dopamine D3 / Q000235:genetics*
D017931:DNA Primers; C493593:DRD3 protein, human; D005819:Genetic Markers; D050637:Receptors, Dopamine D3; D004299:Dopamine beta-Hydroxylase