Association of Genetic Variants at 22q11.2 Chromosomal Region with Cognitive Performance in Japanese Patients with Schizophrenia.
Association of Genetic Variants at 22q11.2 Chromosomal Region with Cognitive Performance in Japanese Patients with Schizophrenia.
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22q11.2 染色体区域的遗传变异与日本精神分裂症患者认知表现的关联。
DOI：
10.1016/j.scog.2019.100134
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发表时间：
2019
影响因子：
--
通讯作者：
Shimoda K
中科院分区：
文献类型：
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作者：
Akiyama K;Saito A;Saito S;Ozeki Y;Watanabe T;Fujii K;Shimoda K
22q11.2杂合性多基因缺失增加了精神分裂症的风险，并伴有明显的认知障碍。我们探索了22q11.2上的基因是否与特发性精神分裂症患者的认知表现有关。240名精神分裂症患者和240名健康对照接受了日语版的精神分裂症认知简评(BACS)，并使用金门试验(Illumina®)对22q11.2区域115个标签单核苷酸多态(Tag SNPs)进行了基因分型。在PLINK 1.07中使用线性回归分析BACS认知域的z分数与SNPs和单倍型之间的关系。另一组149名双相情感障碍患者被纳入进行认知评估，并选择SNPs使用实时荧光聚合酶链式反应(Real-time PCR)进行基因分型。精神分裂症和双相情感障碍患者在BACS亚域的认知损害表现出定性的可比性，这表明两组患者在由此产生的认知效果大小方面相对于对照组具有显著的相关性。Rs4819522(Tbx1)和rs2238769(UFD1L)分别与精神分裂症患者的符号编码显著和名义上相关。单倍型分析显示，在精神分裂症患者中，包含rs4819522的A等位基因和rs2238769的G等位基因的单倍型与符号编码呈显著负相关。未发现任何单倍型对双相情感障碍患者认知功能的影响。我们的结果对于理解与符号编码相关的UFD1LandTBX1基因单倍型在精神分裂症患者中的作用具有重要意义。在一组新诊断的患者和其他种族中进行进一步的重复研究是有必要的。
22q11.2 heterozygous multigene deletions confer an increased risk of schizophrenia with marked impairment of cognition. We explored whether genes on 22q11.2 are associated with cognitive performance in patients with idiopathic schizophrenia. A total of 240 schizophrenia patients and 240 healthy controls underwent the Japanese-language version of the Brief Assessment of Cognition in Schizophrenia (BACS) and were genotyped for 115 tag single-nucleotide polymorphisms (tag SNPs) at the 22q11.2 region using the golden gate assay (Illumina®). Associations between z-scores of the BACS cognitive domains and SNPs and haplotypes were analyzed using linear regression in PLINK 1.07. An additional set of 149 patients with bipolar disorder were included for cognitive assessment and selected SNPs were genotyped using real-time PCR. Patients with schizophrenia and bipolar disorder showed qualitatively comparable profiles of cognitive impairment across BACS subdomains, as revealed by significant correlation between the two groups in the resulting cognitive effect sizes relative to controls. rs4819522 (TBX1) and rs2238769 (UFD1L) were significantly and nominally associated, respectively, with symbol coding in patients with schizophrenia. Haplotype analyses revealed that haplotypes containing the A allele at rs4819522 and G allele at rs2238769 showed significant negative associations with symbol coding in patients with schizophrenia. There was no effect of any haplotypes on cognition in patients with bipolar disorder. Our results have implications for the understanding of the role of haplotypes ofUFD1LandTBX1genes associated with symbol coding in patients with schizophrenia. Further replication studies in a cohort of newly diagnosed patients and other ethnicities are warranted.