An association study on the polymorphisms of dopaminergic genes with working memory in a healthy Chinese Han population.

Working memory (WM) is a highly heritable cognitive trait that is involved in many higher-level cognitive functions. In the past few years, much evidence has indicated that the reduction of dopamine activity in human brain can impair the WM system of the neuropsychiatric disorders. In this study, we hypothesized that some genes in the dopamine system were involved in the individual difference of the cognitive ability in healthy population. To confirm this hypothesis, a population-based study was performed to examine the effects of COMT, DAT (1), DRD (1), DRD (2), DRD (3), and DRD (4) on WM spans. Our results indicated there were significant associations of TaqIA and TaqIB in DRD (2) with digital WM span, respectively (χ(2) = 9.460, p = 0.009; χ(2) = 6.845, p = 0.033). On the other hand, we found a significant interaction between Ser9Gly in DRD (3) and TaqIA of DRD (2) on digital WM span (F = 3.207, p = 0.013). COMT, DAT (1) , DRD (1), and DRD (4), however, had no significant effects on digital and spatial WM spans (χ(2)<3.84, p > 0.05). These preliminary results further indicated that certain functional variants in dopamine system, such as TaqIA and TaqIB of DRD (2), were possibly involved in difference of WM in a healthy population.

Association analysis of TPH2, 5-HT2A, and 5-HT6 with executive function in a young Chinese Han population.

The 5-hydroxytryptamine (5-HT) system is widely distributed in the central nervous system. A growing body of evidence has suggested that the neurotransmitter system is implicated in the functions of the prefrontal cortex. So far, several studies have revealed that some functional genetic variants in TPH2, 5-HT2A, and 5-HT6 genes are possibly related to executive function. To investigate the potential influences of TPH2, 5-HT2A, and 5-HT6 on the components of executive function, the authors performed a population-based study with standard cognitive paradigms in a young Chinese Han group. The results indicated that -703 G/T polymorphism of TPH2 was associated with the performance of response inhibition (p = .002) and the T allele carriers (TT and GT) had fewer errors than the noncarriers (GG) did in the response inhibition test. Furthermore, there were no significant associations of the T102C in 5-HT2A and T267C in 5-HT6 with the components of executive function after correcting for multiple tests (p > .05). The present study suggests that TPH2 contributes distinctively to the inhibition domain of executive function, whereas 5-HT2A and 5-HT6 show no striking effects on executive function in the Chinese Han population.

No observable relationship between the 12 genes of nervous system and reasoning skill in a young Chinese Han population.

Reasoning skill is an advanced cognitive ability which is needed for drawing inferences from given information. It is well known that the ability depends on the neural network of the frontal and parietal brain regions. In this study, we hypothesized that some genes involved in neurotransmitter systems were related to reasoning skill. To confirm this hypothesis, we examined the effects of 13 genes (BDNF, NRSF, COMT, DBH, DRD(2), DRD(3), DAT(1), MAOA, GRM(1), GRIN2B, TPH(2), 5-HT(2A), and 5-HT(6)) in neurotransmitter systems on the non-verbal reasoning and verbal reasoning skills. The results indicated there were on significant effects of the 17 functional variants of these genes on the performance of non-verbal reasoning and verbal analogical reasoning skills (χ(2) > 3.84, df = 1, P > 0.05). This study suggests that some of the functional variations in BDNF, COMT, DBH, DRD(2), DRD(3), MAOA, 5-HT(2A), 5-HT(6), GRM(1), and GRIN2B have no observable effects on the certain reasoning skills in a young healthy Chinese Han population.

Effect of BDNF Val66Met polymorphism on digital working memory and spatial localization in a healthy Chinese Han population.

Cognitive abilities are complex human traits influenced by genetic factors. Brain-derived neurotrophic factor (BDNF), a unique polypeptide growth factor, has an influence on the differentiation and survival of neurons in the nervous system. A single-nucleotide polymorphism (rs6265) in the human gene, resulting in a valine to methionine substitution in the pro-BDNF protein, was thought to associate with psychiatric disorders and might play roles in the individual difference of cognitive abilities. However, the specific roles of the gene in cognition remain unclear. To investigate the relationships between the substitution and cognitive abilities, a healthy population-based study and the PCR-SSCP method were performed. The results showed the substitution was associated with digital working memory (p = 0.02) and spatial localization (p = 0.03), but not with inhibition, shifting, updating, visuo-spatial working memory, long-term memory, and others (p > 0.05) among the compared genotype groups analyzed by general linear model. On the other hand, the participants with BDNF (GG) had higher average performance in digital working memory and spatial localization than the ones with BDNF (AA). The findings of the present work implied that the variation in BDNF might play positive roles in human digital working memory and spatial localization.

Polymorphic variation in CHAT gene modulates general cognitive ability: An association study with random student cohort.

The choline O-acetyltransferase (CHAT) gene has been associated with various human disorders that involve cognitive impairment or deficiency. However, the influence of disease-associated variants of CHAT on normal individuals remains dubious. Here we demonstrated the impact of CHAT sequence variants (G-120A) on general human cognitive ability in a cohort of 750 Chinese undergraduate students. A multiple choice questionnaire was used to obtain basic demographic information, such as parents' occupations and education levels. We also administered and scored the Raven's Standard Progressive Matrices (RSPM). A one-way analysis of variance (ANOVA) and Kruskal-Wallis test (K-W) revealed a significant association between sequence polymorphisms of G-120A and individuals' Raven score (p=0.031 for ANOVA and p=0.026 for K-W tests). Moreover, further hierarchical analysis showed a similar trend in the association between G-120A variants and Raven scores only in the female subjects (p=0.008 for ANOVA and p=0.024 for K-W tests) but not in the male subjects. The results of a multiple linear regression confirmed that after we controlled gender, age, birthplace and other non-genetic factors, CHAT G-120A polymorphisms still significantly influenced individual Raven scores (B=-0.70, SE=0.28, t=-2.50, p=0.013). Our results demonstrated that sequence variants of CHAT were associated with human cognitive ability in not only patients with psychiatric disorders but also normal healthy individuals. However, some issues remained indeterminable, such as gender differences and the extent of the influence on individuals' general cognitive abilities; thus, the further research using an independent random sample was required.

An association study of the genetic polymorphisms in 13 neural plasticity-related genes with semantic and episodic memories.

Semantic and episodic memories were two different attributes of long-term memory. In the past few years, plenty of physiological evidence has indicated that neural plasticity is involved in the formation of long-term memory. In the present study, we hypothesized that some functional variants of neural plasticity-related genes were related to episodic and semantic memories. To confirm this hypothesis, we examined the relationship of 13 plasticity-related genes with episodic and semantic memories. The results indicated that there was a statistically significant difference in semantic memory scores among the three genotype groups of T267C in 5-HT ( 6 ) (χ (2) = 16.638, p = 0.0002). However, the functional variations in BDNF, COMT, DBH, DRD ( 2 ), DRD ( 3 ), DRD ( 4 ), MAOA, TPH ( 2 ), 5-HT ( 2A ), GRM ( 1 ), and GRIN2B had no observable effects on the memories. Our preliminary results confirm the hypothesis that a small number of functional variants of the neural plasticity-related genes, such as T267C in 5-HT ( 6 ), play important roles in human specific memory.

Association analysis between 12 genetic variants of ten genes and personality traits in a young chinese Han population.

Some genes involved in neurotransmission synthesis and transmission have been hypothesized to affect personality traits. To investigate the possible roles of these genes in personality traits of 16 Personality Factor Questionnaire, we performed a population-based study in a young Chinese Han cohort. In the study, we selected some functional variations in ten candidate genes (COMT, DBH, DRD(2), DRD(3), DAT, MAOA, GRM(1), GRIN2B, 5-TH(2A), and 5-TH(6)) encoding components in dopamine, glutamate, and 5-hydroxytryptamine pathways. The results showed the T102C in 5-TH(2A) was associated with X3 (emotional and quiet alertness) and B (reasoning) (F = 4.71 and 6.23; p = 0.009 and 0.002), Val158Met in COMT with E (dominance) (F = 7.01; p = 0.0009), while the variations in DBH, DRD(2), DRD(3), MAOA, GRM(1), GRIN2B, and 5-TH(6) were not associated with any of the personality traits. This finding suggests that T102C in 5-TH(2A) and Val158Met in COMT play roles in some human personality traits.