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Yang L.H.,Columbia University | Phillips M.R.,Shanghai JiaoTong University | Phillips M.R.,Emory University | Li X.,Beijing Hui Long Guan Hospital | And 7 more authors.
British Journal of Psychiatry | Year: 2013

Background Although outcomes among people with schizophrenia differ by social context, this has rarely been examined across rural v. urban settings. For individuals with schizophrenia, employment is widely recognised as a critical ingredient of social integration. Aims To compare employment for people with schizophrenia in rural v. urban settings in China. Method In a large community-based study in four provinces representing 12% of China's population, we identified 393 people with schizophrenia (112 never treated). We used adjusted Poisson regression models to compare employment for those living in rural (n = 297) v. urban (n = 96) settings. Results Although rural and urban residents had similar impairments due to symptoms, rural residents were three times more likely to be employed (adjusted relative risk 3.27, 95% CI 2.11-5.07, P50.001). Conclusions People with schizophrenia have greater opportunities to use their capacities for productive work in rural than urban settings in China. Contextual mechanisms that may explain this result offer a useful focus for future research.


Zhai Y.,Centers for Disease Control and Prevention | Yin S.,Qingdao Mental Health Center | Zhang D.,Qingdao University
Journal of Alzheimer's Disease | Year: 2016

Antipsychotic drugs have been inconsistently associated with death risk of Alzheimer's disease (AD) patients. Herein we review and quantitatively summarize the evidence from epidemiological studies. Pertinent studies were identified by searching PubMed and Cochrane Library Register of Controlled Trials through 20 December 2015. The DerSimonian and Laird random effect model was adopted as the pooling method. Twelve studies from nine articles with 11,463 participants were included. The pooled RR of observational studies was 1.36 (95 CI, 0.83-2.24; I2 = 94.9) for antipsychotic drugs users versus individuals who were not exposed to antipsychotic drugs. When the three studies that were key contributors to the high heterogeneity were excluded, the pooled RR was 2.08 (95 CI 1.39 to 3.13). The result of one double-blind randomized clinical trial indicated that antipsychotic drugs nearly doubled the risk of death in AD patients. In conclusion, there is no evidence of absence of association between antipsychotic drugs' use with death risk of AD patients. Careful assessments of potential benefits and risks should be made before prescribing antipsychotics for treatment of psychosis symptoms and behavioral problems of AD patients.


Xing Y.-Y.,Qingdao Municipal Hospital | Yu J.-T.,Qingdao Municipal Hospital | Yu J.-T.,Ocean University of China | Cui W.-Z.,Qingdao Mental Health Center | And 5 more authors.
Journal of Alzheimer's Disease | Year: 2012

Variants in the clusterin gene have been associated with Alzheimer's disease (AD) through replicated genome-wide studies, but the underlying mechanisms remain unknown. In this study the association of the AD clusterin common risk polymorphism rs9331888 with blood clusterin levels was tested in 104 AD subjects and 104 healthy controls. Blood clusterin levels were significantly elevated in AD patients (p < 0.05). The rs9331888 AD-risk variant was associated with low clusterin mRNA and protein levels in an allele-dose dependent manner in both groups (p < 0.001). This study indicates that the rs9331888 AD-risk variant is associated with low blood clusterin levels. © 2012-IOS Press and the authors. All rights reserved.


Yu J.-T.,Qingdao Municipal Hospital | Yu J.-T.,Ocean University of China | Miao D.,Ocean University of China | Cui W.-Z.,Qingdao Mental Health Center | And 6 more authors.
Current Alzheimer Research | Year: 2012

Toll-like receptor 4 (TLR4) represents a reasonable functional and positional candidate gene for Alzheimer's disease (AD) as it is located within the previous identified linkage region of AD on chromosome 9q, and functionally is involved in the microglia-mediated inflammatory response, amyloid-β (Aβ) plaque formation and Aβ clearance. To test whether variants in the TLR4 gene are associated with late-onset AD (LOAD), we organized a multicenter study of 785 subjects (399 cases and 386 matched controls) in a Han Chinese population. Ten single nucleotide polymorphisms (SNPs) that span the TLR4 gene, from approximately 5 kb of the predicted 5'-untranslated region (UTR) to approximately 6 kb of the predicted 3'- UTR, were selected and their associations with LOAD risk factors were assessed. With respect to allelic diversity, the minor alleles of seven SNPs (rs10759930, rs1927914, rs1927911, rs12377632, rs2149356, rs7037117, and rs7045953) in TLR4 showed consistent protective effects against the risk of developing LOAD. With regard to genotypic diversity, individuals carrying at least one minor allele of each SNP above had a consistently lower risk of LOAD than those with no copies of the minor alleles (ORs ranging from 0.445 to 0.637). rs7045953, located in the 3'-UTR of TLR4, was most strongly associated with LOAD, and when incorporated into a haplotype with rs10759930, the strongest association was detected (P = 1.7×10 -6, Pc =1.0×10 -4). Our data suggests that the TLR4 gene contributes to the susceptibility for LOAD in Han Chinese. © 2012 Bentham Science Publishers.


Tan L.,Qingdao University | Yu J.-T.,Qingdao University | Zhang W.,Qingdao University | Wu Z.-C.,Qingdao University | And 6 more authors.
Alzheimer's and Dementia | Year: 2013

Objective: Five genomewide association studies (GWAS) in white populations have recently identified and confirmed 9 novel Alzheimer's disease (AD) susceptibility loci (CLU, CR1, PICALM, BIN1, ABCA7, MS4A gene cluster, CD2AP, CD33, and EPHA1). These studies have been conducted almost exclusively in white populations and it is unclear whether these observations generalize to populations with different ethnicities. Methods: We recruited 1224 unrelated northern Han Chinese subjects comprising 612 patients with a clinical diagnosis of late-onset AD (LOAD) according to the criteria of the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association and 612 healthy age- and sex-matched control subjects. Because of our previous study investigating CLU, CR1, and PICALM in the Han population, we limited the current analysis to BIN1, ABCA7, MS4A gene cluster, CD2AP, CD33, and EPHA1. Results: In a multivariate analysis, associations of MS4A6A (rs610932; odds ratio = 0.632, Bonferroni corrected P =.019) and CD33 (rs3865444; odds ratio = 1.492, Bonferroni corrected P =.017) with LOAD were replicated successfully. When these data were stratified by apolipoprotein E (APOE) ε4 status, both rs610932 and rs610932 were evident only among subjects without the APOE ε4 allele. For BIN1, assuming a dominant model of inheritance, a positive association for rs7561528 in APOE ε4 carriers was observed. This association, however, did not remain significant after Bonferroni correction. As for ABCA7, CD2AP, and EPHA1 single nucleotide polymorphisms from recent GWAS, despite the similar directional effects, no significant differences in genotype and estimated allele frequency distribution between patients and control subjects were observed. Conclusions: This study provides the first independent evidence that MS4A and CD33 loci are associated with the risk of LOAD in northern Han Chinese population. Genotypes at the two loci confer risk predominantly in APOE ε4-negative subjects. © 2013 The Alzheimer¢s Association. All rights reserved.


Zhang X.,Qingdao University | Liu J.,Qingdao University | Guo Y.,Qingdao University | Jiang W.,Qingdao University | Yu J.,Qingdao Mental Health Center
Depression and Anxiety | Year: 2015

Background Oligodendrocyte transcription factor 2 (OLIG2) is primarily concentrated in the brain and spinal cord ventricular zone, where this protein stimulates oligodendrocytes and specific neurons, determines motor neuron and oligodendrocyte differentiation, and sustains replication in early development. Recent studies have demonstrated that OLIG2 gene is associated with mental disorders, such as schizophrenia, mood disorder, and obsessive-compulsive disorder (OCD). Methods The aim of the present study was to explore whether OLIG2 gene is associated with OCD in a Chinese Han population through the assessment and analysis of three single nucleotide polymorphisms (SNPs), namely, rs762178, rs1059004, and rs9653711, selected from OLIG2 gene sequences from 400 OCD samples and 459 healthy controls in a case-controlled association study. Results We demonstrated three principal results. First, SNP rs762178 was associated with OCD, female OCD, and early-onset OCD; rs1059004 was associated with OCD and early-onset OCD; and rs9653711 was also associated with OCD and early-onset OCD. Second, the pairs of loci rs762178 and rs1059004, rs1059004 and rs9653711, and rs762178 and rs9653711 exhibited linkage disequilibrium. Third, the three-locus A-C-G haplotype was associated with early-onset OCD. Conclusions The present study is the first to verify the associations of SNPs rs762178, rs1059004, and rs9653711 of the OLIG2 gene with OCD in a Chinese Han population. Thus, OLIG2 might serve as a potential target for OCD treatment in future studies. Further studies should verify the current findings. © 2015 Wiley Periodicals, Inc.


Yu J.-T.,Ocean University of China | Yu J.-T.,Qingdao University | Sun Y.-P.,Qingdao University | Ou J.-R.,Ocean University of China | And 4 more authors.
Neurobiology of Aging | Year: 2011

Toll-like receptor 2 (TLR2) represents a reasonable functional and positional candidate gene for Alzheimer's disease (AD) as it is located under the linkage region of AD on chromosome 4q, and is functionally involved in the microglia-mediated inflammatory response and amyloid β (Aβ) clearance. In the current study, 7 single nucleotide polymorphisms (SNPs) that span the TLR2 were selected and their associations with late-onset AD (LOAD) risk were assessed in a case-control sample comprising 785 individuals in a Han Chinese population. No significant differences in the frequency of TLR2 alleles, genotypes, and haplotypes in the AD cases were detected compared with the controls. TLR2 gene might not play a major role in the genetic predisposition to late-onset Alzheimer's disease in this population. © 2011 Elsevier Inc.


PubMed | Ocean University of China, Nanjing Medical University, Qingdao University and Qingdao Mental Health Center
Type: Journal Article | Journal: Oncotarget | Year: 2016

The myocyte enhancer factor (MEF2) family of transcription factors plays a vital role in memory and learning due to its functions in regulating synapse number and reducing dendritic spines. Myocyte enhancer factor 2 C (MEF2C) is regarded as modulator of amyloid-protein precursor (APP) proteolytic processing, in which amyloid- (A) is produced. A common single nucleotide polymorphism (SNP, rs190982) in MEF2C gene was identified to be related to late-onset Alzheimers disease (LOAD) in Caucasians in a large meta-analysis of genome-wide association studies (GWAS). Here, we recruited unrelated 984 LOAD patients and 1348 healthy controls matched for gender and age to ascertain whether the rs190982 polymorphism is related to LOAD in Han Chinese. No difference in the genotype and allele distributions of the MEF2C rs190982 polymorphism was found between LOAD cases and healthy controls (genotype: P = 0.861; allele: P = 0.862), even after stratification for APOE 4 allele as well as statistical adjustment for age, gender and APOE 4 status. Furthermore, the meta-analysis in 4089 Chinese individuals did not detect the association of rs190982 within MEF2C with the risk for LOAD (OR = 1.03, 95%CI = 0.90-1.18). Overall, the current evidence did not support the relation between rs190982 polymorphism within MEF2C and the LOAD risk in Northern Han Chinese.


PubMed | Ocean University of China, Nanjing Medical University, Taishan Medical University, Qingdao University and Qingdao Mental Health Center
Type: | Journal: Molecular neurobiology | Year: 2016

Progranulin (PGRN) plays an important role in Alzheimers disease (AD) through participating in altering neurite outgrowth and neuronal survival. Previous studies identified that rs5848 in the 3-untranslated region (3-UTR) of the PGRN gene (GRN) is strongly associated with AD in Caucasians. In order to assess the involvement of the GRN polymorphism in the risk of late-onset AD (LOAD), we analyzed the genotype and allele distributions of rs5848 in 2350 Han Chinese subjects (AD, 992; control, 1358). The minor T allele of rs5848 was significantly associated with an increased risk of LOAD (P=0.005, odds ratio (OR)=1.197, 95% confidence interval (CI)=1.057-1.355). Moreover, the association was further validated in the multivariate logistic regression analysis (dominant model: OR=1.195, P=0.038, recessive model: OR=1.386, P=0.025; additive model: OR=1.187, P=0.009). Interestingly, we observed that the interaction between apolipoprotein E (APOE) and rs5848 significantly altered the risk for AD. The rs5848 polymorphism was only significantly associated with LOAD in APOE 4 allele carriers. Then we included five studies (including the present study) and conducted a meta-analysis which consisted of 3236 cases (male, 1152; female, 2084) and 3405 (male, 1436; female, 1969) controls. The result of the meta-analysis supported T allele of rs5848 within GRN as a risk factor for AD. In conclusion, our results demonstrated that rs5848 polymorphism within GRN was associated with LOAD.


Chi S.,Qingdao University | Teng L.,Qingdao University | Song J.-H.,Qingdao University | Zhou C.,Qingdao University | And 3 more authors.
Journal of Affective Disorders | Year: 2013

Background: Anxiety is common in stroke survivors and may adversely affect recovery. Polymorphisms of tryptophan hydroxylase2 (THP2) gene have been shown to be associated with anxiety disorders and other affective disorders. This study was aimed to investigate the association of two polymorphisms of THP2 gene, rs4570625 and rs4565946, with poststroke anxiety disorders in a Han Chinese population. Methods: This case control study included 112poststroke anxiety patients and 246 non-anxious controls. All participants completed Hamilton Anxiety Rating Scale and DNA was extracted from blood and genotyped for the two polymorphisms of THP2 gene. Results: Results revealed that the G allele of rs4570625 was associated with the increased risk of poststroke anxiety. In the female subgroup, both the GG genotype and G allele were observed to be significantly higher in case than in control. No significant difference in genotype and allele frequencies of the rs4565946 was found between case and control. Haplotype analysis identified that patients with the G-C haplotype had significantly increased the risk of poststroke anxiety. Limitations: More than 20 TPH2 polymorphisms have been detected, some of which are tightly-linked and may function together, only two SNPs of TPH2 were investigated in this study. Conclusions: The findings suggest that these polymorphisms in TPH2 gene are involved in development of poststroke anxiety in the Han Chinese population. © 2012 Elsevier B.V. All rights reserved.

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