Preferential transmission of paternal alleles at risk genes in attention-deficit/hyperactivity disorder.
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.
Hawi
Ziarih
Z
Department of Psychiatry and Genetics, Trinity College, Dublin, Ireland. zhhawi@tcd.ie
Segurado
Ricardo
R
Conroy
Judith
J
Sheehan
Karen
K
Lowe
Naomi
N
Kirley
Aiveen
A
Shields
Denis
D
Fitzgerald
Michael
M
Gallagher
Louise
L
Gill
Michael
M
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*
D050483:Dopamine Plasma Membrane Transport Proteins; D005819:Genetic Markers; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5