Study Report

Basic Info

Reference	Kimura, H., 2014 PMID: 25332407
Citation	Kimura, H., et al. (2014). "Identification of Rare, Single-Nucleotide Mutations in NDE1 and Their Contributions to Schizophrenia Susceptibility." Schizophr Bull.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	cases: 3554 SZ and 1041 BD; controls: 4746 controls
SNP/Region/Marker Size	3 variants
Predominant Ethnicity	Mongloid
Population	Japanese
Age Group	adult : cases: SCZ mean=48.4, SD=14.6; BD mean=51.0, SD=14.1. controls: mean=43.2, SD=14.7.

Detail Info

Sample Diagnosis	Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (TR) criteria
Sample Status	All of the cases were included if they met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (TR) criteria for SCZ, BD, and PDD (specifially, Autistic disorder, Asperger's disorder, PDD not otherwise specifid). In addition, the patients' capacity to consent was confimed by a family member when needed.
Technique	Genotyping was performed using Taqman (Applied Biosystems) custom probes.
Statistical Method	Analysis was performed on an HT7900 instrument (Applied Biosystems) according to the standard protocol. All allele-wise association analyses were carried out by calculating the P values for each SNP using Fisher's exact test (one-tail). Differences were considered significant when the P value was less than 0.05. Statistical calculations were done using SPSS v21 (SPSS Inc.) and Plink v1.07. Furthermore, we calculated adjusted P value (100000 permutations) as implemented in Plink v1.07. Calculation of statistical power was performed by the Genetic Power Calculator with the multiplicative model.
Result Summary	Among the discovered novel rare variants, we detected signifiant associations between SCZ and S214F (P=0.039), and between BD and R234C (P=0.032). Furthermore, functional assays showed that S214F affected axonal outgrowth and the interaction between NDE1 and YWHAE (14-3-3 epsilon; a neurodevelopmental regulator).

Genetic factors reported by this study for BD

Other variants reported by this study for BD (count: 3)

Variant Name	Related Gene	Type	Allele Change	Statistical Values	Author Comments	Result Category
NDE1 Chr16:15785177 C/T	NDE1	missense	C/T	BD: MAF=0.0097, P-value=0.032	We detected a signifiant association between BD and this var...... We detected a signifiant association between BD and this variant. More...	Positive
NDE1 Chr16:15785118 C/T	NDE1	missense	C/T	BD: MAF=0, P-value=0.82	No significant association was observed. No significant association was observed.	Negative
NDE1 Chr16:15785033 C/G	NDE1	missense	C/G	BD: MAF=0.0098, P-value=0.17, OR=0.41	No significant association was observed. No significant association was observed.	Negative

Genes reported by this study for BD (count: 1)

Gene	Statistical Values/Author Comments	Result Category
NDE1	A signifiant association was detected between a variant within this gene and BD. A signifiant association was detected between a variant within this gene and BD.	Positive

Genetic factors reported by this study for SZ and/or MDD

Other variants reported by this study for SZ/MDD

Disease	Variant Name	Related Gene	Type	Statistical Values	Description	Result Category
SZ	NDE1 Chr16:15785033 C/G	NDE1	missense	SZ: MAF=0.0015, P-value=0.15, OR=0.65	No significant association was observed.	Negative
SZ	NDE1 Chr16:15785118 C/T	NDE1	missense	SZ: MAF=0.00076, P-value=0.039, OR=7.1	We observed a signifiant association between SCZ and this variant.	Positive
SZ	NDE1 Chr16:15785177 C/T	NDE1	missense	SZ: MAF=0.00013, P-value=0.46	No significant association was observed.	Negative

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	NDE1	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.	Positive