title: Genetic association and identification of a functional SNP at GSK3β for schizophrenia susceptibility.
abstract: OBJECTIVE
  GSK3β is a key gene in neurodevelopment, and also an important target of antipsychotics. Several lines of evidence including association and gene expression studies have suggested GSK3β as a susceptibility gene for schizophrenia, but the underlying genetic mechanism is still unknown. In this study, we test whether the genetic variants in GSK3β contribute to the risk of schizophrenia in Chinese population.
  
  
  METHODS
  We first conducted an association analysis of 9 representative SNPs spanning the entire genomic region of GSK3β in two independent Han Chinese case-control samples from southwestern China (the Kunming sample and the Yuxi sample, a total of 2550 subjects).Then using EMSA and reporter gene assays, we tested the functional impact of the identified risk SNP on transcriptional factor binding affinity and promoter activity.
  
  
  RESULTS
  We observed weak allelic associations of three GSK3β SNPs (rs3755557, rs7431209 and rs13320980) with schizophrenia in the combined Han Chinese samples. Further analysis using genotypes (under recessive genetic model) supported the association of rs3755557 (p = 0.01, corrected), which is located in the GSK3β promoter region. The functional assays demonstrated that the risk SNP (rs3755557) could influence the transcription factor binding affinities, resulting in a higher promoter activity of the risk allele.
  
  
  CONCLUSIONS
  Our findings suggest that GSK3β is likely a risk gene for schizophrenia, and its expression alteration caused by the risk SNP in the promoter region may contribute to the etiology of schizophrenia.
authors: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors: Ming
authors: M
authors: Li
authors: Yin
authors: Y
authors: Mo
authors: Xiong-jian
authors: XJ
authors: Luo
authors: Xiao
authors: X
authors: Xiao
authors: Lei
authors: L
authors: Shi
authors: Ying-mei
authors: YM
authors: Peng
authors: Xue-bin
authors: XB
authors: Qi
authors: Xing-yan
authors: XY
authors: Liu
authors: Li-de
authors: LD
authors: Yin
authors: Hong-bo
authors: HB
authors: Diao
authors: Bing
authors: B
authors: Su
mesh_terms: D000328:Adult; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D002461:Cell Line, Transformed; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D014162:Transfection
chemical_list: C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3