Rare PDCD11 variations are not associated with risk of schizophrenia in Japan
Rare PDCD11 variations are not associated with risk of schizophrenia in Japan
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DOI：
10.1111/pcn.12549
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发表时间：
2017-11-01
影响因子：
11.9
通讯作者：
Someya, Toshiyuki
中科院分区：
文献类型：
--
作者：
Hoya, Satoshi;Watanabe, Yuichiro;Someya, Toshiyuki
目的：罕见的基因变异被认为是精神分裂症的实质性风险。我们进行了一个三阶段的研究，以确定罕见的变化，有很大的影响，对发展精神分裂症的风险。方法：在第一阶段，我们优先考虑罕见的错义变异使用全外显子组测序（WES）数据从三个家庭，包括先证者，受影响的兄弟姐妹，和父母。在第二阶段，我们对96名患者的PDCD11编码区进行了靶向重测序。在第三阶段，我们对1357名精神分裂症患者和1394名对照者进行了罕见PDCD 11变异与精神分裂症的关联研究。（Asp961Asn）和p.（Val1240Leu），由家庭内的两个受影响的兄弟姐妹共享。PDCD11编码区的靶向重测序鉴定了三种罕见的非同义变异：（Asp961Asn），p.（Phe1835del）和p.（Arg1837His）。病例对照研究表明，精神分裂症与四种罕见的PDCD11变异之间没有显著相关性。（Asp961Asn），p.（Val1240Leu），p.（Phe1835del）和p.结论：我们的数据不支持罕见的PDCD11变异在日本人群中赋予精神分裂症实质性风险的作用。
Aim: Rare gene variations are thought to confer substantial risk for schizophrenia. We performed a three-stage study to identify rare variations that have a strong impact on the risk of developing schizophrenia.Methods: In the first stage, we prioritized rare missense variations using whole-exome sequencing (WES) data from three families, consisting of a proband, an affected sibling, and parents. In the second stage, we performed targeted resequencing of the PDCD11 coding region in 96 patients. In the third stage, we conducted an association study of rare PDCD11 variations with schizophrenia in a total of 1357 patients and 1394 controls.Results: Via WES, we identified two rare missense PDCD11 variations, p.(Asp961Asn) and p.(Val1240Leu), shared by two affected siblings within families. Targeted resequencing of the PDCD11 coding region identified three rare non-synonymous variations: p.(Asp961Asn), p.(Phe1835del), and p.(Arg1837His). The case-control study demonstrated no significant associations between schizophrenia and four rare PDCD11 variations: p.(Asp961Asn), p.(Val1240Leu), p.(Phe1835del), and p.(Arg1837His).Conclusion: Our data do not support the role of rare PDCD11 variations in conferring substantial risk for schizophrenia in the Japanese population.