Investigation of the G protein subunit Gαolf gene (GNAL) in attention deficit/hyperactivity disorder

Abstract

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 Gα olf , expressed in D1-rich areas of the brain, contributes to the genetic susceptibility of ADHD. To evaluate the involvement of the Gα 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.

Parent-of-origin effects of FAS and PDLIM1 in attention-deficit/hyperactivity disorder

“…We also found similar maternal transmission in GNAL (p = 0.0081 for rs1477941, p = 0.002 for J Psychiatry Neurosci 2012;37(1) rs10468679 and p = 0.0003 for rs8087897) to those reported by Laurin and colleagues. 11 Furthermore, Table S3 in Appendix 1 confirms the paternal transmission (p = 0.0019 for rs12288512) in BDNF found by Kent and colleagues. 7 In addition, we confirmed the paternal transmission (p = 0.022 for rs3863145) for DAT1 reported by Hawi and colleagues.…”

“…These genes have been reported to have paternal or maternal transmission or parent-of-origin effects in ADHD in previous studies. [6][7][8][9][10][11][12][13][14][15] In the cleaned SNP data, we did not find any SNPs in the DRD4 gene. Furthermore, we could not confirm the paternal or maternal transmission or parent-oforigin effects (p < 0.01) for HTR1B, SLC6A4, DRD4, DRD5 and FADS2.…”

Genotype-Phenotype Analysis, Neuropsychological Assessment, and Growth Hormone Response in a Patient with 18p Deletion Syndrome

“…However, dystonia rarely occurs among 18p deletion patient who are hemizygous for GNAL . GNAL also was a susceptible gene for ADHD with preferential transmission of maternal alleles [DasBanerjee et al, 2008;Laurin et al, 2008]. Although the patient in our study did not have dystonia, she did have manifestations of ADHD with a possible contribution of GNAL loss.…”

Normal gut microbiota modulates brain development and behavior

“…This suggestion does not exclude the possibility that exposure to gut microbiota metabolites, generated by the flora of the pregnant mother, could also influence brain development during embryogenesis. Gut microbiota may also be able to modify expression of risk genes (16,36) or be part of mechanisms that alter cognitive functions observed in patients with gastrointestinal diseases (37,38). Finally, the observed behavioral changes imposed by the presence of the gut flora in rodents, reported in this paper, may have wider implications when considering psychiatric disorders in humans.…”