Publications by authors named "Xiaocai Gao"

40 Publications

Genetic Variants of the 9 Gene Are Associated with Nonspecific Intellectual Disability: A Family-Based Association Study.

Genet Test Mol Biomarkers 2020 Oct 29;24(10):625-631. Epub 2020 Sep 29.

School of Medicine, Northwest University, Xi'an, China.

Mutations within the myotubularin-related protein 9 gene (9) have been identified in several families with nonsyndromic intellectual disability (NSID), a generalized neurodevelopmental disorder; however, the relationship between 9 and NSID needs to be verified using a larger sample size. To explore whether genetic variants in the 9 gene are linked to susceptibility of NSID among the Chinese population. Seven single nucleotide polymorphisms (SNPs) of the 9 gene (rs4559208, rs3824211, rs2164272, rs2164273, rs1897951, rs6991606, and rs7815802) were analyzed using family-based association testing among 258 Han Chinese NSID families. Three SNPs of 9 were significantly associated with NSID ( = 2.152,  = 0.031 for rs4559208;  = 2.403,  = 0.016 for rs2164273; and  = 2.758,  = 0.006 for rs7815802). Three alleles of these SNPs were more likely to be transferred from the carrier parents to the affected offspring. Haplotypes constructed using these SNPs also showed a similar transmitting trend ( = 2.505,  = 0.012,  = 8.835, and global  = 0.032). Carriers with the G-G-C haplotype showed a higher risk of NSID (odds ratio = 1.46, 95% confidence interval [1.01-2.09],  = 0.04) than others. functional predictions supported an etiological role for these three SNPs in NSID biology. This study provides additional insights into the association of NSID with specific alleles, and haplotypes within the 9 gene. Genotypic analyses of the 9 gene should be considered for patients presenting with NSID of unknown etiology.
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http://dx.doi.org/10.1089/gtmb.2020.0145DOI Listing
October 2020

The 5-HTTLPR polymorphism impacts moral permissibility of impersonal harmful behaviors.

Soc Cogn Affect Neurosci 2019 08;14(8):911-918

College of Life Science, Northwest University, 710069 Xi'an, China.

Inspired by the roles of serotonin in an emotional aversion to harmful actions, we examined to what extent serotonin transporter gene (5-HTT)-linked polymorphic region (5-HTTLPR), a proxy for measuring serotonin function, underpinned the individual differences in moral judgment through cross-sectional analysis and two-wave comparison. The cross-sectional analysis with a larger cohort (N = 1197) showed that the SS carriers of the 5-HTTLPR polymorphism, corresponding to the low ratio of serotonin recycling from the synaptic cleft, rated impersonal harmful actions (e.g. flipping a switch to divert a train to hit one person instead of five people) as more permissible as compared with the L-allele carriers. The two-wave comparison with a subsample from the larger cohort (N = 563) indicated that the association between 5-HTTLPR polymorphism and moral permissibility of impersonal harmful actions was stable from wave 1 to wave 2. Thus, these findings highlight the importance of the 5-HTTLPR polymorphism to harmful moral behaviors.
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http://dx.doi.org/10.1093/scan/nsz060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6847979PMC
August 2019

Revisiting the relationships of 2D:4D with androgen receptor (AR) gene and current testosterone levels: Replication study and meta-analyses.

J Neurosci Res 2020 02 29;98(2):353-370. Epub 2019 Jul 29.

Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an, China.

The relationships of digit ratio (2D:4D) with the length of AR (CAG)n, and testosterone levels from saliva and blood have been extensively debated over the years. This research including three studies further clarifies such controversies. To do so, we re-examined the relationships between the length of AR (CAG)n, 2D:4D, and current testosterone levels, through replication study and meta-analysis for each study. The results indicate: (a) the length of AR (CAG)n is not significantly associated with 2D:4D; (b) current testosterone levels are not significantly associated with the ratio; and (c) the length is not significantly associated with testosterone levels. Thus, AR (CAG)n and current testosterone levels are not significantly related to 2D:4D at individual level.
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http://dx.doi.org/10.1002/jnr.24502DOI Listing
February 2020

Mutations of ARX and non-syndromic intellectual disability in Chinese population.

Genes Genomics 2019 01 25;41(1):125-131. Epub 2018 Sep 25.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), Institute of Population and Health, Northwest University, Xi'an, 710069, China.

Mutations of Aristaless-related homeobox (ARX) gene were looked as the third cause of non-syndromic intellectual disability (NSID), while the boundary between true disease-causing mutations and non-disease-causing variants within this gene remains elusive. To investigate the relationship between ARX mutations and NSID, a panel comprising six reported causal mutations of the ARX was detected in 369 sporadic NSID patients and 550 random participants in Chinese. Two mutations, c.428_451 dup and p.G286S, may be disease-causing mutations for NSID, while p.Q163R and p.P353L showed a great predictive value in female NSID diagnosis with significant associations (X = 19.60, p = 9.54e-6 for p.Q163R; X = 25.70, p = 4.00e-07 for p.P353L), carriers of these mutations had an increased risk of NSID of more than fourfold. Detection of this panel also predicted significant associations between genetic variants of the ARX gene and NSID (p = 3.73e-4). The present study emphasized the higher genetic burden of the ARX gene on NSID in the Chinese population, molecular analysis of this gene should be considered for patients presenting NSID of unknown etiology.
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http://dx.doi.org/10.1007/s13258-018-0745-6DOI Listing
January 2019

Independent self-construal mediates the association between CYP19A1 gene variant and subjective well-being.

Conscious Cogn 2017 10 6;55:205-213. Epub 2017 Sep 6.

Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi'an 710069, China; College of Life Science, Northwest University, Xi'an 710069, China; Institute of Population and Health, Northwest University, Xi'an 710069, China. Electronic address:

Testosterone and estrogen are involved in self-related behavioral dispositions and experiences of subjective well-being. In this study, we investigated to what extent the aromatase (CYP19A1) gene, which encodes an enzyme in converting testosterone into estrogen, contributes to subjective well-being and in another self-related disposition: independent and interdependent self-construal. In study 1, a meta-analysis showed that the GG genotype of CYP19A1 (a G/A substitution at Val80, rs700518) was associated with higher testosterone and lower estradiol. In study 2, an empirical study of individuals with the GG (n=115), AG (n=286) and AA (n=193) genotypes indicated that individuals with the GG genotype exhibited higher independent self-construal and higher subjective well-being. The association between the GG genotype of CYP19A1 Val80 and subjective well-being was mediated by the independent self-construal. Our findings reinforce the idea that personality traits such as independent self-construal explain the link between genetic variant and subjective well-being.
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http://dx.doi.org/10.1016/j.concog.2017.08.012DOI Listing
October 2017

The CAG polymorphism in androgen receptor (AR) gene impacts the moral permissibility of harmful behavior in females.

Psychoneuroendocrinology 2017 Jun 7;80:74-79. Epub 2017 Mar 7.

China Center for Special Economic Zone Research, Shenzhen University, Shenzhen 518060, China; Research Center for Brain Function and Psychological Science, Shenzhen University, Shenzhen 518060, China. Electronic address:

The moral permissibility of harm is strikingly varied among individuals. In light of the connection between testosterone levels and utilitarian moral judgment, this study examined to what extent a CAG polymorphism in the androgen receptor gene, a genetic polymorphism with the ability to regulate testosterone function, contributes to individual differences in moral judgment. Four hundred and thirty-nine Chinese Han participants completed permissibility ratings of harm in moral dilemmas and moral transgression scenarios. Results showed a significant association between the CAG polymorphism and moral permissibility of harm in females. Females with more copies of the S allele, which is associated with higher availability of testosterone, were more likely to judge harmful utilitarian acts and unintentionally harmful acts as permissible, while these effects were absent in males. The findings provide the first evidence for a link between the androgen receptor gene and moral judgment and highlight the role of androgens in moral foundations.
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http://dx.doi.org/10.1016/j.psyneuen.2017.03.008DOI Listing
June 2017

Investigating the genetic basis of attention to facial expressions: the role of the norepinephrine transporter gene.

Psychiatr Genet 2016 12;26(6):266-271

aKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education bShaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an cLaboratory of Medical Molecular Biology, Henan University of Science and Technology, Luoyang, China.

Objective: Levels of norepinephrine (NE) in the brain are related to attention ability in animals and risk of attention-deficit hyperactivity disorder in humans. Given the modulation of the norepinephrine transporter (NET) on NE levels in the brain and the link between NE and attention impairment of attention-deficit hyperactivity disorder, it was possible that the NET gene underpinned individual differences in attention processes in healthy populations.

Methods: To investigate to what extent NET could modulate one's attention orientation to facial expressions, we categorized individuals according to the genotypes of the -182 T/C (rs2242446) polymorphism and measured individuals' attention orientation with the spatial cueing task.

Results: Our results indicated that the -182 T/C polymorphism significantly modulated attention orientation to facial expressions, of which the CC genotype facilitated attention reorientation to the locations where cued faces were previously presented. However, this polymorphism showed no significant effects on the regulations of emotional cues on attention orientation.

Conclusion: Our findings suggest that the NET gene modulates the individual difference in attention to facial expressions, which provides new insights into the roles of NE in social interactions.
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http://dx.doi.org/10.1097/YPG.0000000000000146DOI Listing
December 2016

Catechol-O-methyltransferase (COMT) gene modulates private self-consciousness and self-flexibility.

Conscious Cogn 2016 08 12;44:186-192. Epub 2016 Aug 12.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Northwest University, Xi'an 710069, China; Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China; Laboratory of Medical Molecular Biology, Henan University of Science and Technology, Luoyang 471003, China. Electronic address:

Dopamine levels in the brain influence human consciousness. Inspired by the role of Catechol-O-methyltransferase (COMT) in inactivating dopamine in the brain, we investigated to what extent COMT could modulate individual's self-consciousness dispositions and self-consistency by genotyping the COMT Val158Met (rs4680) polymorphism and measuring self-consciousness and self-consistency and congruence in a college student population. The results indicated that COMT Val158Met polymorphism significantly modulated the private self-consciousness. The individuals with Val/Val genotype, corresponding to lower dopamine levels in the brain, were more likely to be aware of their feelings and beliefs. The results also indicated that this polymorphism modulated one's self-flexibility. The individuals with Val/Val genotype showed higher levels of stereotype in self-concept compared with those with Met/Met genotype. These findings suggest that COMT is a predictor of the individual differences in self-consciousness and self-flexibility.
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http://dx.doi.org/10.1016/j.concog.2016.08.001DOI Listing
August 2016

Genetic Polymorphism of GABRR2 Modulates Individuals' General Cognitive Ability in Healthy Chinese Han People.

Cell Mol Neurobiol 2017 Jan 27;37(1):93-100. Epub 2016 Feb 27.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), Institute of Population and Health, College of Life Science, Northwest University, Xi'an, 710069, China.

Previous studies have indicated that the cognitive impairment or deficit is associated with GABAergic signaling in central nervous system. Inspired by the finding that receptor GABRR2 modulates concentration of GABA and phasic inhibitory GABAergic transmission in brain. This study investigated to what extent a genetic variant (c.1423C>T, rs282129) of GABRR2 gene modulates individuals' general cognitive ability in 987 Chinese Han people. Results showed a significant influence of GABRR2 gene polymorphism on individuals' Raven's Standard Progressive Matrices (RSPM) performance (F = 3.58, P = .028 by ANOVA and χ  = 9.35, P = .009 by K-W test, respectively), even if non-genetic factors were partialed out (gender, major, types of birthplace, and socioeconomic index) (B = -.67, SE = .26, t = 2.63, P = .009). The finding provided a strong evidence, to our knowledge, for the view that genetic variant of GABRR2 gene may contribute to the difference of individuals' general cognitive ability, independently.
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http://dx.doi.org/10.1007/s10571-016-0347-2DOI Listing
January 2017

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

Neurosci Lett 2016 Mar 6;617:122-6. Epub 2016 Feb 6.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), Institute of Population and Health, College of Life Science, Northwest University, Xi'an 710069, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.neulet.2016.02.002DOI Listing
March 2016

A New Role for LOC101928437 in Non-Syndromic Intellectual Disability: Findings from a Family-Based Association Test.

PLoS One 2015 19;10(8):e0135669. Epub 2015 Aug 19.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Institute of Population and Health, Northwest University, Xi'an, China.

Non-syndromic intellectual disability (NSID) is mental retardation in persons of normal physical appearance who have no recognisable features apart from obvious deficits in intellectual functioning and adaptive ability; however, its genetic etiology of most patients has remained unknown. The main purpose of this study was to fine map and identify specific causal gene(s) by genotyping a NSID family cohort using a panel of markers encompassing a target region reported in a previous work. A total of 139 families including probands, parents and relatives were included in the household survey, clinical examinations and intelligence tests, recruited from the Qinba mountain region of Shannxi province, western China. A collection of 34 tagged single nucleotide polymorphisms (tSNPs) spanning five microsatellite marker (STR) loci were genotyped using an iPLEX Gold assay. The association between tSNPs and patients was analyzed by family-based association testing (FBAT) and haplotype analysis (HBAT). Four markers (rs5974392, rs12164331, rs5929554 and rs3116911) in a block that showed strong linkage disequilibrium within the first three introns of the LOC101928437 locus were found to be significantly associated with NSID (all P<0.01) by the FBAT method for a single marker in additive, dominant and recessive models. The results of haplotype tests of this block also revealed a significant association with NSID (all P<0.05) using 2-window and larger HBAT analyses. These results suggest that LOC101928437 is a novel candidate gene for NSID in Han Chinese individuals of the Qinba region of China. Although the biological function of the gene has not been well studied, knowledge about this gene will provide insights that will increase our understanding of NSID development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0135669PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545728PMC
May 2016

Association between ε2/3/4, promoter polymorphism (-491A/T, -427T/C, and -219T/G) at the apolipoprotein E gene, and mental retardation in children from an iodine deficiency area, China.

Biomed Res Int 2014 25;2014:236702. Epub 2014 Mar 25.

Bio-X Institute, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China ; Institute for Neuropsychiatric Science and Metabonomics, Changning Mental Health Center, Shanghai 200335, China ; Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of Chinese Academy Sciences, Shanghai 200031, China.

Background: Several common single-nucleotide polymorphisms (SNPs) at apolipoprotein E (ApoE) have been linked with late onset sporadic Alzheimer's disease and declining normative cognitive ability in elder people, but we are unclear about their relationship with cognition in children.

Results: We studied -491A/T, -427T/C, and -219G/T promoter polymorphisms and ε2/ε3/ε4 at ApoE among children with mental retardation (MR, n = 130), borderline MR (n = 124), and controls (n = 334) from an iodine deficiency area in China. The allelic and genotypic distribution of individual locus did not significantly differ among three groups with Mantel-Haenszel χ (2) test (P > 0.05). However, frequencies of haplotype of -491A/-427T/-219T/ε4 were distributed as MR > borderline MR > controls (P uncorrected = 0.004), indicating that the presence of this haplotype may increase the risk of disease.

Conclusions: In this large population-based study in children, we did not find any significant association between single locus of the four common ApoE polymorphisms (-491A/T, -427T/C, -219T/G, and ε2/3/4) and MR or borderline MR. However, we found that the presence of ATTε4 haplotype was associated with an increased risk of MR and borderline MR. Our present work may help enlarge our knowledge of the cognitive role of ApoE across the lifespan and the mechanisms of human cognition.
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http://dx.doi.org/10.1155/2014/236702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984859PMC
January 2015

Development of neurodevelopmental disorders: a regulatory mechanism involving bromodomain-containing proteins.

J Neurodev Disord 2013 Feb 20;5(1). Epub 2013 Feb 20.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, People's Republic of China.

Neurodevelopmental disorders are classified as diseases that cause abnormal functions of the brain or central nervous system. Children with neurodevelopmental disorders show impaired language and speech abilities, learning and memory damage, and poor motor skills. However, we still know very little about the molecular etiology of these disorders. Recent evidence implicates the bromodomain-containing proteins (BCPs) in the initiation and development of neurodevelopmental disorders. BCPs have a particular domain, the bromodomain (Brd), which was originally identified as specifically binding acetyl-lysine residues at the N-terminus of histone proteins in vitro and in vivo. Other domains of BCPs are responsible for binding partner proteins to form regulatory complexes. Once these complexes are assembled, BCPs alter chromosomal states and regulate gene expression. Some BCP complexes bind nucleosomes, are involved in basal transcription regulation, and influence the transcription of many genes. However, most BCPs are involved in targeting. For example, some BCPs function as a recruitment platform or scaffold through their Brds-binding targeting sites. Others are recruited to form a complex to bind the targeting sites of their partners. The regulation mediated by these proteins is especially critical during normal and abnormal development. Mutant BCPs or dysfunctional BCP-containing complexes are implicated in the initiation and development of neurodevelopmental disorders. However, the pathogenic molecular mechanisms are not fully understood. In this review, we focus on the roles of regulatory BCPs associated with neurodevelopmental disorders, including mental retardation, Fragile X syndrome (FRX), Williams syndrome (WS), Rett syndrome and Rubinstein-Taybi syndrome (RTS). A better understanding of the molecular pathogenesis, based upon the roles of BCPs, will lead to screening of targets for the treatment of neurodevelopmental disorders.
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http://dx.doi.org/10.1186/1866-1955-5-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585942PMC
February 2013

A family-based association study of dopamine receptor D4 and mental retardation in Qinba region of China.

Neurosci Lett 2012 May 15;516(1):1-4. Epub 2012 Feb 15.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Institute of Population and Health, Northwest University, Xi'an 710069, China.

Dopamine receptor D4 (DRD4) is activated by the neurotransmitter dopamine and links to many neurological and psychiatric conditions because of its close relationship with prefrontal cortex and other important brain regions. To explore the possibility that genetic variants of DRD4 gene predispose to children with mental retardation (MR), five target SNPs of DRD4 were selected and genotyped in the samples of 163 MR pedigrees from the Qinba region of China. Two SNPs (rs752306 and rs3758653) showed weak association with MR (the P values were 0.022 and 0.015 for dominant model, and 0.027 and 0.015 for recessive model, respectively). Although they did not bear the multiple testing corrections, the haplotype which contained rs3758653 exhibited a significant association with MR (global P values were 0.018 for dominant model and 0.028 for recessive model, respectively). The in silico analysis also indicated that rs752306 and rs3758653 would be biologically meaningful SNPs. Therefore, the present study suggested that the genetic variants of DRD4 gene may play an important role in human MR. Further investigations, such as confirmation with other independent samples and functional studies, may elucidate their effect on gene expression and MR susceptibility.
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http://dx.doi.org/10.1016/j.neulet.2012.02.017DOI Listing
May 2012

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

Cell Mol Neurobiol 2012 Aug 24;32(6):1011-9. Epub 2012 Feb 24.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Institute of Population and Health, Northwest University, Xi'an, China.

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.
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http://dx.doi.org/10.1007/s10571-012-9817-3DOI Listing
August 2012

A family-based association study of DIO2 and children mental retardation in the Qinba region of China.

J Hum Genet 2012 Jan 3;57(1):14-7. Epub 2011 Nov 3.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Institute of Population and Health, Northwest University, Xi'an, China.

Deiodinase enzyme II (DIO2) has an important role in individuals' thyroid hormones' level, the development of central and peripheral nervous systems and characterized by mental retardation (MR). The DIO2 gene was genotyped by using five haplotype-tagging single-nucleotide polymorphisms (SNPs) in 157 Chinese MR high-density family pedigrees, including 452 nuclear families and >1460 persons. The single marker and haplotype analyses were performed by Family-based Association Tests (FBAT). Three SNPs had P-values <0.05 in at least one inherited model survived with the correction. Several haplotypes composed of these SNPs were also associated with MR. The in silico analyses identified that one of the SNPs, rs1388378, may be a functional SNP. However, further in vitro studies of this SNP should be considered in elucidating its effect on gene expression and the possible role in MR susceptibility.
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http://dx.doi.org/10.1038/jhg.2011.121DOI Listing
January 2012

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

J Mol Neurosci 2012 Feb 5;46(2):352-61. Epub 2011 Jul 5.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Institute of Population and Health, Xi'an, 710069, China.

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.
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http://dx.doi.org/10.1007/s12031-011-9592-5DOI Listing
February 2012

Variants in COMT and DBH influence on response inhibition ability in Chinese Han females.

Cell Mol Neurobiol 2011 Nov 19;31(8):1163-9. Epub 2011 Jun 19.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Institute of Population and Health, Northwest University, Xi'an 710069, China.

Catechol-O-methyltransferase (COMT) and dopamine-beta hydroxylase (DBH) are key enzymes to breakdown dopamine. Some previous studies have indicated that val158met in COMT and 19 bp insertion/deletion in 5' flank of DBH are related to the performance of executive function. To further investigate the associations of the two genes with executive function, we performed a population-based study in a Chinese Han population. The results indicated that val158met in COMT and the 19 bp insertion/deletion of DBH were associated with the average reaction time of response inhibition in female group (P = 0.01, P = 0.03), respectively. Furthermore, there was a significant interaction of the two genes on the reaction time (P = 0.006). This present study suggests that not only do COMT and DBH influence independently on response inhibition in females, but also exert a significant interaction on response inhibition.
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http://dx.doi.org/10.1007/s10571-011-9717-yDOI Listing
November 2011

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

J Neurogenet 2011 Mar 4;25(1-2):27-34. Epub 2011 Apr 4.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Institute of Population and Health, Xi'an, China.

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.
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http://dx.doi.org/10.3109/01677063.2011.569804DOI Listing
March 2011

Polymorphisms in the DLG3 gene is not associated with non-syndromic mental retardation in the Chinese Han population of Qin-Ba mountain.

Cell Mol Neurobiol 2011 Jul 3;31(5):695-700. Epub 2011 Mar 3.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Institute of Population and Health, College of Life Science, Northwest University, People's Republic of China.

Discs-large-related 3 (DLG3), a member of the membrane-associated guanylate kinases (MAGUKs) protein family, playing an important role in regulating NMDA signal pathway and contributing to synaptic plasticity, may have an influence on the susceptibility of non-syndromic mental retardation (NSMR). To investigate the possible genetic contribution of DLG3 gene to the NSMR of Chinese Han population, we performed an association study of 556 subjects (118 NSMR, 116 borderline NSMR, and 322 controls in 275 males and 281 females) from Qin-Ba mountain region of Shaanxi province in the northwest of China by five common SNPs in the gene. The results showed that there was no positive association between the genetic variations of DLG3 and NSMR. In conclusion, the results of this study indicated that DLG3 did not associate with NSMR in Chinese Han population; however, further studies are needed.
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http://dx.doi.org/10.1007/s10571-011-9666-5DOI Listing
July 2011

Variations in 5-HT2A influence spatial cognitive abilities and working memory.

Can J Neurol Sci 2011 Mar;38(2):303-8

Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Institute of Population and Health Henan University of Science and Technology, Luoyang, China.

Background: 5-hydroxytryptamine receptor 2A (5-HT2A) participates in diverse psychiatric disorders by regulating the activity of serotonin. Some previous studies have also suggested that the receptor is involved in cognitive abilities of disease groups. We hypothesize that some functional genetic variants in 5-HT2A have certain specific influences on cognitive abilities in a normal population.

Method: To confirm this hypothesis, two polymorphisms (rs6313 and rs4941573) in 5-HT2A were selected, and a population-based study was performed in a young healthy Chinese Han cohort.

Results: The results indicated that the rs6313 and rs4941573 were associated with touching blocks and mental rotation-3D error ratio in males, and the rs4941573 was associated with visuo-spatial working memory in the whole cohort.

Conclusion: All the findings suggest that 5-HT2A participates in human spatial cognitive abilities and spatial working memory.
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http://dx.doi.org/10.1017/s0317167100011513DOI Listing
March 2011

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

Cell Mol Neurobiol 2011 May 15;31(4):519-26. Epub 2011 Jan 15.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Institute of Population and Health, Xi'an, 710069, China.

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.
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http://dx.doi.org/10.1007/s10571-010-9645-2DOI Listing
May 2011

Gender differences in cognitive ability associated with genetic variants of NLGN4.

Neuropsychobiology 2010 14;62(4):221-8. Epub 2010 Aug 14.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi'an, China.

Neuroligin-4 (NL4), encoded by the NLGN4 gene on the X chromosome, is a neuronal-specific brain membrane protein which plays an important role in the formation of functional presynaptic elements and axon specialization. The genetic variants of NLGN4 affect the biological function of NL4, resulting in the manifestation of different psychiatric disorders. The present study investigates the influence of these genetic variants on cognitive performance. The cognitive abilities of 351 subjects were evaluated using the Chinese Wechsler Intelligence Scale Children. The haplotypes were assigned with the PHASE program. The ANOVA method was applied to investigate the relationship between single SNP, the identified target haplotypes and cognitive performance in a random sample. We observed that the X(C) allele of rs5916271 and X(A) allele of the re6638575 carriers had significantly higher cognitive ability performances than the noncarrier boys (p < 0.05). The target haplotype composed of 2 allele (X(CA+)) carriers also displayed a higher cognitive performance than that of the noncarriers boys. The genetic polymorphism of NLGN4 also had a significant effect on the boys' cognitive ability and other intelligence factors. Future research will involve determining the relationship between NLGN4 and personal cognitive ability.
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http://dx.doi.org/10.1159/000319948DOI Listing
February 2011

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

J Mol Neurosci 2010 Sep 13;42(1):120-6. Epub 2010 May 13.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Institute of Population and Health, Xi'an 710069, China.

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.
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http://dx.doi.org/10.1007/s12031-010-9373-6DOI Listing
September 2010

Genetic variations of FACL4 have no obvious influence on cognitive ability in young Chinese children.

Psychiatry Res 2010 Jun 10;178(1):202-4. Epub 2010 May 10.

Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, College of Life Science, Institute of Population and Health, Northwest, University, Xi'an, China.

The influence of genetic variants of FACL4 on individual cognitive ability was examined in a random sample of 213 boys and 224 girls. Both conventional genetic methods and analysis of variance were applied in this study. We found no significant relationship between FACL4 and cognitive function.
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http://dx.doi.org/10.1016/j.psychres.2009.11.020DOI Listing
June 2010

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

J Mol Neurosci 2009 Jul 8;38(3):250-6. Epub 2009 May 8.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), Institute of Population & Health, College of Life Science, Northwest University, Xi'an, China.

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.
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http://dx.doi.org/10.1007/s12031-009-9205-8DOI Listing
July 2009

Mental retardation and Xq12-Xq23: candidate loci for nonspecific mental retardation in the male population of the QinBa region.

Psychiatr Genet 2009 Feb;19(1):27-31

College of Life Science, Institute of Population and Health, Northwest University, Xi'an, China.

Objectives: The higher prevalence of nonspecific mental retardation (NSMR) presents an important socioeconomic and medical issue for families and the whole QinBa region in China. The obvious family aggregation and high heritability indicated that genetic causes play a role in the NSMR population in QinBa. This study discusses the relationship between Xq12-Xq23 region and NSMR in the QinBa area.

Method: We chose six short tandem repeats--DXS7132, DXS6979, DXS1191, DXS1230, DXS1072, and DXS6804, located in Xq12-Xq23--and analyzed the distribution difference of their alleles between the NSMR and control boys.

Results: A significant allele distribution difference was found between NSMR and control boys (all P<0.05) for DXS7132, DXS1191, DXS1230, DXS1072, and DXS6804 but not for DXS6979.

Conclusion: Our results suggest that Xq12-Xq23 may be the candidate region where there are one or more loci, linked to NSMR in the QinBa region. Further study needs to be carried out for locating the gene responsible for NSMR in this region and a larger sample size and more genetic markers are needed.
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http://dx.doi.org/10.1097/YPG.0b013e3283121d05DOI Listing
February 2009

Positive association of neuroligin-4 gene with nonspecific mental retardation in the Qinba Mountains Region of China.

Psychiatr Genet 2009 Feb;19(1):1-5

College of Life Science, Institute of Population and Health, Northwest University, Xi'an, China.

Objective: Neuroligin-4 is essential for proper brain function. Some studies indicate a close relationship between neuroligin-4 and several human psychiatric conditions.

Methods: The case-control method was used to study the association between nonspecific mental retardation (NSMR) and genetic variants of neuroligin-4 gene (NLGN4). Five single nucleotide polymorphisms (SNPs: rs5916271, rs7049300, rs6638575, rs3810686, and rs1882260) were genotyped by PCR-RFLP/SSCP method in the NLGN4.

Results: Individual SNP analysis shows significant differences at SNPs rs3810686 and rs1882260 for allele frequency when NSMR cases and controls [odds ratio (OR)=1.589, 95% confidence interval (CI)=1.035-2.438, chi2=4.53, df=1, P=0.033; OR=2.050, 95% CI=1.211-3.470, chi2=7.38, df=1, P=0.007, respectively] were compared. Further haplotype analysis indicates that there are two haplotype sets, rs3810686-rs1882260 and rs6638575-rs3810686-rs1882260, which show statistical differences between NSMR cases and controls (chi2=6.79, df=2, global P=0.034; chi2=9.29, df=2, global P=0.0096, respectively).

Conclusion: The results suggest a positive association between the genetic variants of the NLGN4 and NSMR in the Chinese children from Qinba Mountains Region.
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http://dx.doi.org/10.1097/YPG.0b013e3283088e54DOI Listing
February 2009

Genetic variations in FTSJ1 influence cognitive ability in young males in the Chinese Han population.

J Neurogenet 2008 ;22(4):277-87

School of Life Science, Institute of Population and Health, Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, China

Human cognitive ability is a trait that is known to be significantly influenced by genetic factors. Previous linkage data provide evidence suggesting that gene FtsJ homolog 1 (Escherichia coli) is associated with mental retardation. The gene may have a relation to individual differences in cognitive ability because it is most critical for brain development. In the present research, three tag single-nucleotide polymorphism (SNPs) (rs2268954, rs2070991, and rs5905692) in FtsJ homolog 1 (E. coli) are selected and genotyped by the PCR-SSCP method. An analysis of variance is performed to determine the relationship between the SNPs and cognitive ability of the Chinese Han population of youth in Qinba mountain. There are significant correlations between the variance in FtsJ homolog 1 (E. coli) and general cognitive ability, verbal comprehension, and preceptual organization. These findings suggest that genetic variations in FtsJ homolog 1 (E. coli) possibly influence human cognitive ability.
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http://dx.doi.org/10.1080/01677060802337299DOI Listing
June 2009