title: Resequencing and association study of the NFKB activating protein-like gene (NKAPL) in schizophrenia.
abstract: OBJECTIVE
  Schizophrenia is a highly inheritable disorder, but many aspects of its etiology and pathophysiology remain poorly understood. Recently, in the Han Chinese population, a SNP rs1635 located within the exon of the NKAPL gene (encoding NFKB activating protein-like) achieved genome-wide significance in schizophrenia.
  
  
  METHODS
  In order to find the causal variants of the NKAPL gene in schizophrenia, we searched for genetic variants in the promoter region, and exons (including both UTR ends) using direct sequencing in a sample of patients with schizophrenia (n=515) and non-psychotic controls (n=456), all Han Chinese from Taiwan, and conducted an association and rudimentary functional study.
  
  
  RESULTS
  We identified 5 common SNPs (defined as minor allele frequency (MAF)>0.01) in the NKAPL gene. In a case-control association analysis, the minor allele (A) of rs1635 was significantly more common among patients than controls (P=0.0003, OR=1.41, 95% CI=1.17-1.71). A haplotype analysis of the 5 common SNPs indicated a risk haplotype (rs12000C-rs1635A-rs9461446C-rs3734564G-rs1679709G) associated with schizophrenia (P=2.77e-005, OR=1.53, 95% CI=1.25-1.87). In addition, we identified 4 patient-specific rare SNPs (MAF<0.01) (c.137G>A, c.213G>A, c.752C>T (rs370337122), and c.844G>A (rs147161729)) within the NKAPL gene. In silico analysis demonstrated their functional impact on the protein; however, there was also 1 control-specific rare SNP (c.119G>A) detected within the NKAPL gene, indicating that the clinical relevance of these putatively pathological rare SNPs is not straightforward.
  
  
  CONCLUSIONS
  This study suggested that rs1635 in the NKAPL gene appeared to play a role in conferring susceptibility to schizophrenia. In addition, some rare SNPs in the NKAPL gene with possibly damaging effects may be important in our patients. Our study provides genetic clues to indicate the involvement of NKAPL in schizophrenia.
authors: Department of Life Science and Institute of Biotechnology, National Dong-Hwa University, Hualien, Taiwan.
authors: Shih-Fen
authors: SF
authors: Chen
authors: Department of Psychiatry, Tzu-Chi General Hospital at Hualien, and School of Medicine, Tzu-Chi University, Hualien, Taiwan.
authors: Yu-Lin
authors: YL
authors: Chao
authors: Department of Psychiatry, Tzu-Chi General Hospital at Hualien, and School of Medicine, Tzu-Chi University, Hualien, Taiwan. Electronic address: shengmp@gmail.com.
authors: Yu-Chih
authors: YC
authors: Shen
authors: Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, and Chang Gung University, School of Medicine, Taoyuan, Taiwan.
authors: Chia-Hsiang
authors: CH
authors: Chen
authors: Department of Life Science and Institute of Biotechnology, National Dong-Hwa University, Hualien, Taiwan. Electronic address: cfweng@mail.ndhu.edu.tw.
authors: Ching-Feng
authors: CF
authors: Weng
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D056970:Co-Repressor Proteins / Q000235:genetics*; D003198:Computer Simulation; D005091:Exons; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D013624:Taiwan
chemical_list: D056970:Co-Repressor Proteins; C569368:NKAPL protein, human; D009687:Nuclear Proteins
keywords: Han Chinese; NKAPL; Schizophrenia; rs1635