https://scholars.lib.ntu.edu.tw/handle/123456789/476371
標題: | Genetic associations and expression of extra-short isoforms of disrupted-in-schizophrenia 1 in a neurocognitive subgroup of schizophrenia | 作者: | CHIH-MIN LIU Liu Y.-L. HAI-GWO HWU Fann C.S.-J. Yang U.-C. Hsu P.-C. Chang C.-C. WEI J. CHEN TZUNG-JENG HWANG MING-HSIEN HSIEH CHEN-CHUNG LIU YI-LING CHIEN |
公開日期: | 2019 | 卷: | 64 | 期: | 7 | 起(迄)頁: | 653-663 | 來源出版物: | Journal of Human Genetics | 摘要: | Disrupted-in-schizophrenia 1 (DISC1) was reported to be associated with schizophrenia. In a previous study, we found significant association with schizophrenia patients with deficient sustained attention assessed by continuous performance test (CPT). This study aimed to identify risk polymorphisms in this specific neurocognitive subgroup and investigate the expression of different isoforms of DISC1. A total of 83 genetic variants were identified through direct sequencing in 50 controls and 100 schizophrenia patients. Fourteen variants were genotyped in 600 controls and 912 patients. Patients were subgrouped by familial loading (multiplex or simplex) and performance on CPT. The frequency of AA genotype of rs11122324 at the 3′-UTR of Es and Esv1 isoforms and of rs2793091 at intron 4 were significantly higher in multiplex schizophrenia patients than those in controls (corrected p < 0.05). In further subgrouping, the frequency of AA genotype of the two SNPs were significantly higher in multiplex schizophrenia patients with deficient sustained attention than those in controls (corrected p < 0.005). The mRNA expression levels of two extra-short isoforms (Es and Esv1) in the EBV-transformed lymphocytes of schizophrenia were significantly higher than those of controls. Luciferase reporter assays demonstrated that the A-allele of rs11122324 significantly upregulated DISC1 extra-short isoforms transcription compared with the G-allele. We found two SNPs (rs11122324 and rs2793091) of DISC1 may be specifically associated with multiplex schizophrenia patients with deficient sustained attention. The SNP rs11122324 may be a risk polymorphism, which may have functional influence on the transcription of Es and Esv1 through increasing their expression. ? 2019, The Author(s), under exclusive licence to The Japan Society of Human Genetics. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/476371 | DOI: | 10.1038/s10038-019-0597-1 | SDG/關鍵字: | messenger RNA; DISC1 protein, human; isoprotein; nerve protein; RNA isoform; adult; Article; cognition; controlled study; female; gene expression; gene frequency; genetic association; genetic risk; genetic variability; genotype; human; luciferase assay; lymphocyte; major clinical study; male; mRNA expression level; schizophrenia; allele; disorders of higher cerebral function; exon; genetic predisposition; genetics; metabolism; schizophrenia; single nucleotide polymorphism; Taiwan; Alleles; Exons; Female; Genetic Predisposition to Disease; Humans; Male; Nerve Tissue Proteins; Neurocognitive Disorders; Polymorphism, Single Nucleotide; Protein Isoforms; RNA Isoforms; Schizophrenia; Taiwan |
顯示於: | 醫學系 |
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