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  • Title: Investigation of allelic heterogeneity of the CCK-A receptor gene in paranoid schizophrenia.
    Author: Zheng C, Fu Q, Shen Y, Xu Q.
    Journal: Am J Med Genet B Neuropsychiatr Genet; 2012 Sep; 159B(6):741-7. PubMed ID: 22825913.
    Abstract:
    The cholecystokinin type A receptor (CCKAR) gene has been found to be associated with positive symptoms in patients with schizophrenia but the results reported to date are inconsistent. Considering the involvement of allelic heterogeneity in poor replication of the CCKAR finding, we genotyped five single nucleotide polymorphisms (SNPs) located in the 5' putative regulatory region of the CCKAR gene in a Chinese case-control sample and then applied the 5-SNP haplotype analysis to extract allelic heterogeneity information. The results showed that three individual haplotypes were strongly associated with increased risk of schizophrenia (corrected P = 2.9 × 10(-4), P = 2.5 × 10(-5), and P = 1.4 × 10(-5), respectively) and their combination gave an odds ratio (OR) of 6.12 with 95% CI 3.67-10.21 (P = 6.7 × 10(-15)). The haplotypes were also associated with some clinical symptoms including hallucination, suspiciousness, and hostility. Our work provided further evidence in support of the CCKAR hypothesis of schizophrenia and also suggested that haplotype-based association analysis may be a powerful approach for identification of allelic heterogeneity of a disease-underlying gene, which is very likely to be attributable to poor replication of an initial finding due to the reduction of sample power and the complexity of genetic architectures.
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