TY - JOUR
T1 - Resequencing and association study of the NFKB activating protein-like gene (NKAPL) in schizophrenia
AU - Chen, Shih Fen
AU - Chao, Yu Lin
AU - Shen, Yu Chih
AU - Chen, Chia Hsiang
AU - Weng, Ching Feng
PY - 2014/8
Y1 - 2014/8
N2 - Objectives: 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.
AB - Objectives: 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.
KW - Han Chinese
KW - NKAPL
KW - Schizophrenia
KW - rs1635
UR - http://www.scopus.com/inward/record.url?scp=84904131527&partnerID=8YFLogxK
U2 - 10.1016/j.schres.2014.05.038
DO - 10.1016/j.schres.2014.05.038
M3 - 文章
C2 - 24972756
AN - SCOPUS:84904131527
SN - 0920-9964
VL - 157
SP - 169
EP - 174
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 1-3
ER -
