title: Preferential transmission of paternal alleles at risk genes in attention-deficit/hyperactivity disorder.
abstract: Family, twin, and adoption studies have demonstrated a significant genetic contribution to the etiology of attention-deficit/hyperactivity disorder (ADHD). Pharmacological, neuroimaging, and animal-model findings suggest imbalances in monoaminergic (dopaminergic, serotonergic, and noradrenergic) neurotransmission in ADHD. We have examined monoaminergic candidate genes for possible genetic association with ADHD in the Irish population, focusing particularly on genes of the dopaminergic and serotonergic systems. We have observed that several of these genes are associated with ADHD, including DAT1, DBH, DRD4, DRD5, and 5HT1B. Here, we present what appears to be a systematic overtransmission of paternal alleles at candidate genes associated with ADHD. For the nine genes included in the analysis, the overall odds ratio for paternal transmission was 2, compared with 1.3 for maternal transmission (paternal vs. maternal chi 2=9.6; P=.0019). Transmission to females, from either parent, was significantly stronger than to males. Possible reasons for this preferential transmission include imprinting and ascertainment bias, although results of further analyses show that the latter is unlikely.
authors.affiliation: Department of Psychiatry and Genetics, Trinity College, Dublin, Ireland. zhhawi@tcd.ie
authors.forename: Ziarih
authors.initials: Z
authors.lastname: Hawi
authors.forename: Ricardo
authors.initials: R
authors.lastname: Segurado
authors.forename: Judith
authors.initials: J
authors.lastname: Conroy
authors.forename: Karen
authors.initials: K
authors.lastname: Sheehan
authors.forename: Naomi
authors.initials: N
authors.lastname: Lowe
authors.forename: Aiveen
authors.initials: A
authors.lastname: Kirley
authors.forename: Denis
authors.initials: D
authors.lastname: Shields
authors.forename: Michael
authors.initials: M
authors.lastname: Fitzgerald
authors.forename: Louise
authors.initials: L
authors.lastname: Gallagher
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
mesh_terms: D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000235:genetics*; D016009:Chi-Square Distribution; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D009679:Nuclear Family; D016017:Odds Ratio; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D050641:Receptors, Dopamine D5 / Q000235:genetics*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D005819:Genetic Markers; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5