Figure - available from: BMC Neuroscience
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Hypothetical illustration of two types of variability. The top portion shows three individuals who differ in the spread (moment-to-moment variability) around a regression line after slope is covaried out. The bottom portion represents variability of RT slope between individuals. Some individuals become faster (or slower) over the 20 presentations of a given trial type. We are primarily interested in RT slope variability in this paper
Source publication
Background
Attention provides vital contribution to everyday functioning, and deficits in attention feature in many psychological disorders. Improved understanding of attention may eventually be critical to early identification and treatment of attentional deficits. One step in that direction is to acquire a better understanding of genetic associat...
Citations
Objective:
Nicotine acts through the dopamine pathway in the brain affecting reward processing through cigarette consumption. Thus, both genetic and epigenetic factors related to dopamine metabolism may influence individual's smoking behavior.
Materials and methods:
We studied variations of two variable numbers of tandem repeats (VNTRs), 40 and 30 bp in length, in SLC6A3 gene together with six DNA methylation sites located in a first intron of the gene in relation to several smoking-related phenotypes in a study population consisting of 1230 Whites of Russian origin.
Results:
Both the 5R allele of 30 bp VNTR and the 9R allele of 40 bp VNTR in SLC6A3 were associated with a reduced risk to tobacco smoking [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.37-0.75; OR 0.62, 95% CI 0.43-0.88]. Although the carriers of 9R allele also had high Fagerström test for nicotine dependence scores (OR 1.65, 95% CI 1.04-2.60), they were still more likely to succeed in smoking cessation (OR 0.59, 95% CI 0.40-0.88). Also, current smokers had more than 2.5-fold likelihood to have increased SLC6A3 methylation levels than former smokers (OR 2.72, 95% CI 1.63-4.53).
Conclusions:
The SLC6A3 5R of 30 bp and 9R of 40 bp VNTR variants may lead to a reduced risk to start smoking through decreased dopamine availability, and can also affect the success in subsequent smoking cessation attempts. Moreover, the elevated mean methylation values in the first intron of SLC6A3 may be related to nicotine dependence via a more active dopamine transporter.
Background
ADHD is a chronic neurodevelopmental disorder and is thought to be associated with circadian system.
Methods
We performed a pathway-based study to test individual single nucleotide polymorphisms (SNPs) and the overall evidence of genetic polymorphisms involved in the circadian pathway in association with children ADHD susceptibility among a Chinese population. A community-based case-control study was conducted among Chinese children, and 168 ADHD patients and 233 controls were recruited using a combination diagnosis based on the DSM-IV ADHD rating scale, SNAP-IV rating scale, and semi-structured clinical interview.
Results
The results of single-loci analyses identified that PER1 rs2518023 and ARNTL2 rs2306074 were nominally association with ADHD susceptibility (P<0.05). Next, we applied multifactor dimensionality reduction (MDR), and classification and regression tree (CART) analyses to explore high-order gene–gene interactions among the functional SNPs to ADHD risks. The results indicated that interactions among the PER1 rs2518023, ARNTL2 rs2306074 and NR1D1 rs939347 were associated with the risk of ADHD in children. Individuals carrying the combination genotypes of the PER1 rs2518023 GG or GT, ARNTL2 rs2306074 TC or TT and NR1D1 rs939347 GA or AA displayed a significantly higher risk for ADHD than who carry the PER1 rs2518023 TT and CRY2 rs2292910 CA/CC genotypes (adjusted OR=4.37, 95% CI=2.16-8.85, P<0.001).
Conclusions
These findings revealed the importance of genetic variations related to the circadian clock system to the susceptibility of children ADHD.
The purpose of our study was to test the hypothesis that prenatal tobacco smoking exposure (PSE) could modulate the association of genetic variants with ADHD. A community based case-control study was conducted among Chinese children and 168 ADHD patients and 233 controls were recruited by using combination diagnosis of DSM-IV, SNAP-IV and semi-structured clinical interview. Logistic regression analysis was performed to estimate the effect of prenatal tobacco smoking exposure and genotype frequencies on ADHD susceptibility individually by adjustment for potential confounders. Multiplicative and additive interaction analysis were performed to evaluate the interactions between risk genes and PSE with regard to ADHD. Prenatal tobacco smoke exposure was a significant risk factor of ADHD even after adjusted for other potential confounders. ADRA2A rs553668, DRD2 rs1124491 and SLC6A4 rs6354 were identified to be associated with ADHD. A significant multiplicative and additive gene-environment interactions were observed between the PSE and the ADRA2A rs553668 in relation to ADHD and ADHD-ODD. The risk of the genetic variants in ADHD was increased significantly if the child had prenatal tobacco exposure. The genetic risk for ADHD could be influenced by the presence of environmental risks. The environmental and the genetic risks are not distinct to each other. More gene-environment interaction studies were needed to reveal the etiology of ADHD.
