Dataset Information

Identification of Rare, Single-Nucleotide Mutations in NDE1 and Their Contributions to Schizophrenia Susceptibility.

ABSTRACT: Nuclear distribution E homolog 1 (NDE1), located within chromosome 16p13.11, plays an essential role in microtubule organization, mitosis, and neuronal migration and has been suggested by several studies of rare copy number variants to be a promising schizophrenia (SCZ) candidate gene. Recently, increasing attention has been paid to rare single-nucleotide variants (SNVs) discovered by deep sequencing of candidate genes, because such SNVs may have large effect sizes and their functional analysis may clarify etiopathology.We conducted mutation screening of NDE1 coding exons using 433 SCZ and 145 pervasive developmental disorders samples in order to identify rare single nucleotide variants with a minor allele frequency ?5%. We then performed genetic association analysis using a large number of unrelated individuals (3554 SCZ, 1041 bipolar disorder [BD], and 4746 controls). Among the discovered novel rare variants, we detected significant associations between SCZ and S214F (P = .039), and between BD and R234C (P = .032). Furthermore, functional assays showed that S214F affected axonal outgrowth and the interaction between NDE1 and YWHAE (14-3-3 epsilon; a neurodevelopmental regulator).This study strengthens the evidence for association between rare variants within NDE1 and SCZ, and may shed light into the molecular mechanisms underlying this severe psychiatric disorder.

SUBMITTER: Kimura H

PROVIDER: S-EPMC4393687 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Identification of Rare, Single-Nucleotide Mutations in NDE1 and Their Contributions to Schizophrenia Susceptibility.

Kimura Hiroki H Tsuboi Daisuke D Wang Chenyao C Kushima Itaru I Koide Takayoshi T Ikeda Masashi M Iwayama Yoshimi Y Toyota Tomoko T Yamamoto Noriko N Kunimoto Shohko S Nakamura Yukako Y Yoshimi Akira A Banno Masahiro M Xing Jingrui J Takasaki Yuto Y Yoshida Mami M Aleksic Branko B Uno Yota Y Okada Takashi T Iidaka Tetsuya T Inada Toshiya T Suzuki Michio M Ujike Hiroshi H Kunugi Hiroshi H Kato Tadafumi T Yoshikawa Takeo T Iwata Nakao N Kaibuchi Kozo K Ozaki Norio N

Schizophrenia bulletin 20141020 3

<h4>Background</h4>Nuclear distribution E homolog 1 (NDE1), located within chromosome 16p13.11, plays an essential role in microtubule organization, mitosis, and neuronal migration and has been suggested by several studies of rare copy number variants to be a promising schizophrenia (SCZ) candidate gene. Recently, increasing attention has been paid to rare single-nucleotide variants (SNVs) discovered by deep sequencing of candidate genes, because such SNVs may have large effect sizes and their f ...[more]

PMID: 25332407

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Project description:BackgroundAccumulating studies have reported inconsistent association between ErbB4 single nucleotide polymorphisms (SNPs) and predisposition to schizophrenia. To better interpret this issue, here we conducted a meta-analysis using published case-control studies.MethodsWe conducted a systematic search of MEDLINE (Pubmed), Embase (Ovid), Web of Science (Thomson-Reuters) to identify relevant references. The association between ErbB4 SNPs and schizophrenia was assessed by odds ratios (ORs) and 95% confidence intervals (CIs). Between-study heterogeneity was evaluated by I squared (I) statistics and Cochran's Q test. To appraise the stability of results, we employed sensitivity analysis by omitting 1 single study each time. To assess the potential publication bias, we conducted trim and fill analysis.ResultsSeven studies published in English comprising 3162 cases and 4264 controls were included in this meta-analysis. Meta-analyses showed that rs707284 is statistically significantly associated with schizophrenia susceptibility among Asian and Caucasian populations under the allelic model (OR = 0.91, 95% CI: 0.83-0.99, P = 0.035). Additionally, a marginal association (P < 0.1) was observed between rs707284 and schizophrenia risk among Asian and Caucasian populations under the recessive (OR = 0.85, 95% CI: 0.72-1.01, P = 0.065) and homozygous (OR = 0.84, 95% CI: 0.68-1.03, P = 0.094) models. In the Asian subgroup, rs707284 was also noted to be marginally associated with schizophrenia under the recessive model (OR = 0.84, 95% CI: 0.70-1.00, P = 0.053). However, no statistically significant association was found between rs839523, rs7598440, rs3748962, and rs2371276 and schizophrenia risk.ConclusionThis meta-analysis suggested that rs707284 may be a potential ErbB4 SNP associated with susceptibility to schizophrenia. Nevertheless, due to the limited sample size in this meta-analysis, more large-scale association studies are still needed to confirm the results.

Dataset Information

Identification of Rare, Single-Nucleotide Mutations in NDE1 and Their Contributions to Schizophrenia Susceptibility.

Publications

Identification of Rare, Single-Nucleotide Mutations in NDE1 and Their Contributions to Schizophrenia Susceptibility.

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