title: Sex-specific influence of DRD2 on ADHD-type temperament in a large population-based birth cohort.
abstract: Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder with a significant public-health impact. Previously, we described a candidate gene study in a population-based birth cohort that demonstrated an association with ADHD-affected males and the dopamine receptor D2 (DRD2). The current study evaluates potential associations of dopamine receptor genes and Cloninger temperament traits within this same sample. Participants with stringent lifetime ADHD diagnoses were ascertained systematically from the genetically isolated Northern Finland 1986 Birth Cohort (n=9432), resulting in 178 cases and 157 controls. Markers in all known dopamine receptor genes were genotyped. We report an association of DRD2 with low Persistence in females (rs1079727 P=0.02, rs1124491 P=0.02, rs1800497 P=0.03). The associated DRD2 minor allelic haplotype (CAA, P=0.03) is the same haplotype we previously associated with ADHD in males in this birth cohort. The current study further supports previous results on the role of DRD2 in individuals with ADHD. Investigations suggest that DRD2 may have an impact on both males and females, but the particular outcome appears sex-specific, manifesting as ADHD in males and low Persistence in females. Furthermore, these findings suggest that the putative role of low Persistence as an endophenotype for ADHD deserves further investigation.
authors.affiliation: Public Health Genomics Unit, Institute for Molecular Medicine Finland FIMM, University of Helsinki and National Institute for Health and Welfare, Helsinki, Finland. emma.nyman@thl.fi
authors.forename: Emma S
authors.initials: ES
authors.lastname: Nyman
authors.forename: Anu
authors.initials: A
authors.lastname: Loukola
authors.forename: Teppo
authors.initials: T
authors.lastname: Varilo
authors.forename: Anja
authors.initials: A
authors.lastname: Taanila
authors.forename: Tuula
authors.initials: T
authors.lastname: Hurtig
authors.forename: Irma
authors.initials: I
authors.lastname: Moilanen
authors.forename: Sandra
authors.initials: S
authors.lastname: Loo
authors.forename: James J
authors.initials: JJ
authors.lastname: McGough
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.forename: Susan L
authors.initials: SL
authors.lastname: Smalley
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Nelson
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005387:Finland; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D008297:Male; D036801:Parturition; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012727:Sex Characteristics; D013694:Temperament
chemical_list: D017448:Receptors, Dopamine D2