Rare FBOX18 variations and risk of schizophrenia: whole-exome sequencing in two parent-affected offspring trios followed by resequencing and case-control studies.
Rare FBOX18 variations and risk of schizophrenia: whole-exome sequencing in two parent-affected offspring trios followed by resequencing and case-control studies.
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罕见的 FBOX18 变异和精神分裂症的风险：对两个受父母影响的后代三人组进行全外显子组测序，然后进行重新测序和病例对照研究。
DOI：
10.1111/pcn.12526
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发表时间：
2017
影响因子：
11.9
通讯作者：
Someya T
中科院分区：
文献类型：
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作者：
Hoya S;Watabe Y;Hishimoto A;Nunokawa A;Inoue E;Igeta H;Otsuka I;Shibuya M;Egawa J;Sora I;Someya T
目的 罕见变异被认为在精神分裂症的遗传病因学中发挥作用；为了进一步研究它们的作用，我们在日本人群中进行了一项三阶段研究。方法在第一阶段，我们对两个受父母影响的后代三人组进行了全外显子组测序（WES）。在第二阶段，我们对 96 名患者的 FBXO18 编码区进行了重新测序。在第三阶段，我们在两个独立人群（总共包括 1376 名患者和 1496 名对照）中测试了罕见的非同义 FBXO18 变异与精神分裂症的关联。结果 在这两个三人组中，WES 反复鉴定出 FBXO18 基因中罕见的移码变异 (L116fsX)。对 FBXO18 编码区域进行重新测序，我们检测到三种罕见的非同义变异（V15L、L116fsX 和 V1006I）。然而，在病例对照研究中，这些罕见的FBXO18变异与精神分裂症之间没有显着关联。结论我们目前的研究没有提供证据证明罕见的非同义FBXO18变异对日本人群精神分裂症遗传病因的贡献。然而，为了得出明确的结论，应使用足够大的样本量进行进一步的研究。
AimRare variations are suggested to play a role in the genetic etiology of schizophrenia; to further investigate their role, we performed a three‐stage study in a Japanese population.MethodsIn the first stage, we performed whole‐exome sequencing (WES) of two parent‐affected offspring trios. In the second stage, we resequenced theFBXO18coding region in 96 patients. In the third stage, we tested rare non‐synonymousFBXO18variations for association with schizophrenia in two independent populations comprising a total of 1376 patients and 1496 controls.ResultsA rare frameshift variation (L116fsX) in theFBXO18gene was recurrently identified by WES in both trios. ResequencingFBXO18coding regions, we detected three rare non‐synonymous variations (V15L, L116fsX, and V1006I). However, there were no significant associations between these rareFBXO18variations and schizophrenia in the case–control study.ConclusionOur present study does not provide evidence for the contribution of rare non‐synonymousFBXO18variations to the genetic etiology of schizophrenia in the Japanese population. However, to draw a definitive conclusion, further studies should be performed using sufficiently large sample sizes.