Rare truncating variations and risk of schizophrenia: Whole-exome sequencing in three families with affected siblings and a three-stage follow-up study in a Japanese population

被引：8

作者：

Watanabe, Yuichiro ^{[1
]}

Nunokawa, Ayako ^{[1
,2
]}

Shibuya, Masako ^{[1
]}

Ikeda, Masashi ^{[3
]}

Hishimoto, Akitoyo ^{[4
]}

Kondo, Kenji ^{[3
]}

Egawa, Jun ^{[1
]}

Kaneko, Naoshi ^{[1
,2
]}

Muratake, Tatsuyuki ^{[1
,5
]}

Saito, Takeo ^{[3
]}

Okazaki, Satoshi ^{[4
]}

Shimasaki, Ayu ^{[3
]}

Igeta, Hirofumi ^{[1
]}

Inoue, Emiko ^{[1
]}

Hoya, Satoshi ^{[1
]}

Sugai, Takuro ^{[1
]}

Sora, Ichiro ^{[4
]}

Iwata, Nakao ^{[3
]}

Someya, Toshiyuki ^{[1
]}

机构：

[1] Niigata Univ, Dept Psychiat, Grad Sch Med & Dent Sci, Chuo Ku, 757 Asahimachidori Ichibancho, Niigata 9518510, Japan

[2] Oojima Hosp, 5103 Oojima, Sanjo, Niigata 9550094, Japan

[3] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 4701192, Japan

[4] Kobe Univ, Grad Sch Med, Dept Psychiat, Chuo Ku, 7-5-1 Kusunoki Cho, Kobe, Hyogo 6500017, Japan

[5] Furumachi Mental Clin, Chuo Ku, 608 Furumachidori Gobancho, Niigata 9518063, Japan

来源：

PSYCHIATRY RESEARCH | 2016年 / 235卷

基金：

日本学术振兴会;

关键词：

Affected siblings; Case-control study; Rare truncating variations; Schizophrenia; Whole-exome sequencing; DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDER; GENOME-WIDE ASSOCIATION; VARIANTS; CAMKII; GENE; PROTEIN; BETA; PLASTICITY; SYNAPSES;

D O I：

10.1016/j.psychres.2015.12.011

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

Rare inherited variations in multiplex families with schizophrenia are suggested to play a role in the genetic etiology of schizophrenia. To further investigate the role of rare inherited variations, we performed whole-exome sequencing (WES) in three families, each with two affected siblings. We also performed a three-stage follow-up case-control study in a Japanese population with a total of 2617 patients and 2396 controls. WES identified 15 rare truncating variations that were variously present in the two affected siblings in each family. These variations did not necessarily segregate with schizophrenia within families, and they were different in each family. In the follow-up study, four variations (NWDI W169X, LCORL R7fsX53, CAMK2B L497fsX497, and C9orf89 Q102X) had a higher mutant allele frequency in patients compared with controls, although these associations were not significant in the combined population, which comprised the first-, second- and third-stage populations. These results do not support a contribution of the rare truncating variations identified in the three families to the genetic etiology of schizophrenia. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：13 / 18

页数：6

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