2015年5月
Identification of Rare, Single-Nucleotide Mutations in NDE1 and Their Contributions to Schizophrenia Susceptibility.
Schizophrenia bulletin
- 巻
- 41
- 号
- 3
- 開始ページ
- 744
- 終了ページ
- 53
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1093/schbul/sbu147
BACKGROUND: 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. METHODS AND RESULTS: 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). CONCLUSIONS: 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.
- リンク情報
-
- DOI
- https://doi.org/10.1093/schbul/sbu147
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201702212768289079
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/25332407
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393687
- URL
- http://europepmc.org/abstract/med/25332407
- URL
- http://orcid.org/0000-0002-6199-8711
- ID情報
-
- DOI : 10.1093/schbul/sbu147
- ISSN : 0586-7614
- ISSN : 1745-1701
- J-Global ID : 201702212768289079
- ORCIDのPut Code : 15167403
- PubMed ID : 25332407
- PubMed Central 記事ID : PMC4393687