Novel missense SETD1A variants in Japanese patients with schizophrenia: Resequencing and association analysis
Novel missense SETD1A variants in Japanese patients with schizophrenia: Resequencing and association analysis
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日本精神分裂症患者的新型错义 SETD1A 变异：重测序和关联分析
DOI：
10.1016/j.psychres.2022.114481
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发表时间：
2022
影响因子：
11.3
通讯作者：
Someya Toshiyuki
中科院分区：
文献类型：
--
作者：
Morikawa Ryo;Watanabe Yuichiro;Igeta Hirofumi;Arta Reza K.;Ikeda Masashi;Okazaki Satoshi;Hoya Satoshi;Saito Takeo;Otsuka Ikuo;Egawa Jun;Tanifuji Takaki;Iwata Nakao;Someya Toshiyuki
SETD 1A基因是精神分裂症的重要危险基因。为了进一步研究SETD 1A在日本人群精神分裂症遗传病因学中的作用，我们进行了重新测序和关联分析。首先，我们对974名精神分裂症患者的SETD 1A编码区进行了重新测序。然后，我们对2,027名精神分裂症患者和2,664名对照者进行了基因分型，通过重新测序进行了优先排序。接下来，我们在3，001名精神分裂症患者和2，664名对照者中检查了SETD 1A与精神分裂症之间的关联。最后，我们进行了一个回顾性的图表审查的患者优先SETD 1A变异。我们通过重测序鉴定了两个新的错义突变体（p.Ser575Pro和p.Glu857Gln）。我们没有通过基因分型在4，691个个体中检测到这些变异。在关联分析中，这些变异与精神分裂症没有显著关联。此外，我们发现，精神分裂症患者与p.Glu857Gln变异有发育迟缓。总之，novelSETD 1Amissense变体仅在日本精神分裂症患者中发现。然而，我们的研究并没有提供这些变异对日本人群精神分裂症遗传病因学的贡献的证据。
SETD1Ahas been identified as a substantial risk gene for schizophrenia. To further investigate the role ofSETD1Ain the genetic etiology of schizophrenia in the Japanese population, we performed resequencing and association analyses. First, we resequenced theSETD1Acoding regions of 974 patients with schizophrenia. Then, we genotyped variants, prioritized via resequencing, in 2,027 patients with schizophrenia and 2,664 controls. Next, we examined the association betweenSETD1Aand schizophrenia in 3,001 patients with schizophrenia and 2,664 controls. Finally, we performed a retrospective chart review of patients with prioritizedSETD1Avariants. We identified two novel missense variants (p.Ser575Pro and p.Glu857Gln) via resequencing. We did not detect these variants in 4,691 individuals via genotyping. These variants were not significantly associated with schizophrenia in the association analysis. Additionally, we found that a schizophrenia patient with the p.Glu857Gln variant had developmental delays. In conclusion, novelSETD1Amissense variants were exclusively identified in Japanese patients with schizophrenia. However, our study does not provide evidence for the contribution of these variants to the genetic etiology of schizophrenia in the Japanese population.