Investigation of the G protein subunit Galphaolf gene (GNAL) in attention deficit/hyperactivity disorder.
The dopamine system plays an important role in the regulation of attention and motor behavior, subsequently, several dopamine-related genes have been associated with Attention Deficit/Hyperactivity Disorder (ADHD). Among them are the dopamine receptors D1 and D5 that mediate adenylyl cyclase activation through coupling with G(s)-like proteins. We thus hypothesized that the G(s)-like subunit Galpha(olf), expressed in D1-rich areas of the brain, contributes to the genetic susceptibility of ADHD. To evaluate the involvement of the Galpha(olf) gene, GNAL, in ADHD, we examined the inheritance pattern of 12 GNAL polymorphisms in 258 nuclear families ascertained through a proband with ADHD (311 affected children) using the transmission/disequilibrium test (TDT). Categorical analysis of individual marker alleles demonstrated biased transmission of one polymorphism in GNAL intron 3 (rs2161961; P=0.011). We also observed significant relationships between rs2161961 and dimensional symptoms of inattention and hyperactivity/impulsivity (P=0.003 and P=0.008). In addition, because of recent evidence of imprinting at the GNAL locus, secondary analyses were split into maternal and paternal transmissions to assess a contribution of parental effects. We found evidence of strong maternal effect, with preferential transmission of maternal alleles for rs2161961A (P=0.005) and rs8098539A (P=0.035). These preliminary findings suggest a possible contribution of GNAL in the susceptibility to ADHD, with possible involvement of parent-of-origin effects.
Laurin
Nancy
N
Cell and Molecular Biology Division, Toronto Western Research Institute, University Health Network, Toronto, Ont., Canada.
Ickowicz
Abel
A
Pathare
Tejaswee
T
Malone
Molly
M
Tannock
Rosemary
R
Schachar
Russell
R
Kennedy
James L
JL
Barr
Cathy L
CL
D000293:Adolescent; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D005260:Female; D018703:Founder Effect; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010552:Personality Assessment; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D044385:GTP-Binding Protein alpha Subunits; D005819:Genetic Markers; C084618:olfactory G protein subunit alpha olf