TY - JOUR
T1 - Positive association of the Disrupted-in-schizophrenia-1 gene (DISC1) with schizophrenia in the Chinese Han Population
AU - Qu, Mei
AU - Tang, Fulei
AU - Yue, Weihua
AU - Ruan, Yan
AU - Lu, Tianlan
AU - Liu, Zhonghua
AU - Zhang, Handi
AU - Han, Yonghua
AU - Zhang, Darong
AU - Wang, Fei
AU - Zhang, Dai
PY - 2007/4/5
Y1 - 2007/4/5
N2 - Disrupted-in-Schizophrenia-1 (BISC1) is located on 1q42.1, one of the most promising susceptibility loci in schizophrenia linkage studies. A non-synonymous genetic variation rs821616 (Ser704Cys) in DISC1, has recently been shown to be associated with schizophrenia in family-based study [Callicott et al. (2005); Proc Natl Acad Sci USA 102: 8627-8632]. In order to further confirm this issue, we examined four single nucleotide polymorphisms (SNPs) in a chromosomal region spanning 42 kb of this gene, namely rs821616, rs821597, rs4658971, and rs843979, in Chinese sample of 313 schizophrenia patients and 317 healthy controls. Our results showed that two SNPs had strong associations with schizophrenia (rs821616: Allele A > T, χ2 = 7.8006, df = 1, P = 0.0052; Genotype, χ2 = 7.7935, df = 2, P = 0.0203; rs821597: Allele A > G, χ2 = 9.5404, df = 1, P = 0.0020; Genotype, χ2 = 12.2780, df = 2, P = 0.0022). When haplotypes were constructed with two, three, and four markers, a number of haplotype combinations, especially those including rs821616 and rs821597, were significantly associated with schizophrenia. Furthermore, there was a strong evidence for association in a four-marker haplotype analysis (χ2 = 7.686, df = 4, P = 0.005581, corrected P = 0.006199). Although the case-control and family-based association studies both suggest that DISC1 gene may play a role in genetic susceptibility to schizophrenia, the risk haplotypic combinations have subtle differences in the two studies. Our findings provide further evidence for DISC1 as a predisposing gene involved in schizophrenia in the Chinese Han Population.
AB - Disrupted-in-Schizophrenia-1 (BISC1) is located on 1q42.1, one of the most promising susceptibility loci in schizophrenia linkage studies. A non-synonymous genetic variation rs821616 (Ser704Cys) in DISC1, has recently been shown to be associated with schizophrenia in family-based study [Callicott et al. (2005); Proc Natl Acad Sci USA 102: 8627-8632]. In order to further confirm this issue, we examined four single nucleotide polymorphisms (SNPs) in a chromosomal region spanning 42 kb of this gene, namely rs821616, rs821597, rs4658971, and rs843979, in Chinese sample of 313 schizophrenia patients and 317 healthy controls. Our results showed that two SNPs had strong associations with schizophrenia (rs821616: Allele A > T, χ2 = 7.8006, df = 1, P = 0.0052; Genotype, χ2 = 7.7935, df = 2, P = 0.0203; rs821597: Allele A > G, χ2 = 9.5404, df = 1, P = 0.0020; Genotype, χ2 = 12.2780, df = 2, P = 0.0022). When haplotypes were constructed with two, three, and four markers, a number of haplotype combinations, especially those including rs821616 and rs821597, were significantly associated with schizophrenia. Furthermore, there was a strong evidence for association in a four-marker haplotype analysis (χ2 = 7.686, df = 4, P = 0.005581, corrected P = 0.006199). Although the case-control and family-based association studies both suggest that DISC1 gene may play a role in genetic susceptibility to schizophrenia, the risk haplotypic combinations have subtle differences in the two studies. Our findings provide further evidence for DISC1 as a predisposing gene involved in schizophrenia in the Chinese Han Population.
KW - Case-control study
KW - Haplotype
KW - Linkage disequilibrium
KW - SNP
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U2 - 10.1002/ajmg.b.30322
DO - 10.1002/ajmg.b.30322
M3 - Article
C2 - 17286247
AN - SCOPUS:34247465605
SN - 1552-4841
VL - 144
SP - 266
EP - 270
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 3
ER -
