In:
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Wiley, Vol. 174, No. 8 ( 2017-12), p. 798-807
Abstract:
The synapse‐associated protein 97/discs, large homolog 1 of Drosophila ( DLG1 ) gene encodes synaptic scaffold PDZ proteins interacting with ionotropic glutamate receptors including the N ‐methyl‐D‐aspartate type glutamate receptor (NMDAR) that is presumed to be hypoactive in brains of patients with schizophrenia. The DLG1 gene resides in the chromosomal position 3q29, the microdeletion of which confers a 40‐fold increase in the risk for schizophrenia. In the present study, we performed genetic association analyses for DLG1 gene using a Japanese cohort with 1808 schizophrenia patients and 2170 controls. We detected an association which remained significant after multiple comparison testing between schizophrenia and the single nucleotide polymorphism (SNP) rs3915512 that is located within the newly identified primate‐specific exon (exon 3b) of the DLG1 gene and constitutes the exonic splicing enhancer sequence. When stratified by onset age, although it did not survive multiple comparisons, the association was observed in non‐early onset schizophrenia, whose onset‐age selectivity is consistent with our recent postmortem study demonstrating a decrease in the expression of the DLG1 variant in early‐onset schizophrenia. Although the present study did not demonstrate the previously reported association of the SNP rs9843659 by itself, a meta‐analysis revealed a significant association between DLG1 gene and schizophrenia. These findings provide a valuable clue for molecular mechanisms on how genetic variations in the primate‐specific exon of the gene in the schizophrenia‐associated 3q29 locus affect its regulation in the glutamate system and lead to the disease onset around a specific stage of brain development.
Type of Medium:
Online Resource
ISSN:
1552-4841
,
1552-485X
DOI:
10.1002/ajmg.b.v174.8
DOI:
10.1002/ajmg.b.32595
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2143866-3
SSG:
12
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