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The interaction of ASAH1 and NGF gene involving in neurotrophin signaling pathway contributes to schizophrenia susceptibility and psychopathology.

Abstract：

:The neurodevelopmental hypothesis of schizophrenia has been widely accepted. In light of our previous microarray data, two neurodevelopment-related genes were focused on inclduing the N-acylsphingosine amidohydrolase 1 gene (ASAH1) and the nerve growth factor gene (NGF). The evidence that ASAH1 and NGF are associated with schizophrenia is far from conclusive. Furthermore, their interactions in schizophrenia have not been investigated. Total 413 patients and 578 controls were included. Eleven single-nucleotide polymorphisms (SNPs) in ASAH1 and NGF were selected. A multifactor dimensionality reduction (MDR) was applied to investigate gene-gene interactions in schizophrenia, and the traditional odds ratio methods was applied to validate it. The effects of ASAH1, NGF and their interaction on the severity of the disease were analyzed by 3 × 3 covariance analysis of (ANCOVA). The biological interaction between ASAH1 and NGF was examined. KEGG was used to identify the related signaling pathways. After correction by Bonferroni, there were no differences in the genotypic, allelic, or haplotypic frequencies of 11 SNPs between patients and controls. However, the interaction of certain SNPs had effect on susceptibility to schizophrenia, including two high-risk and one low-risk genotypic combinations (OR = 1.49 [1.11-2.00]; OR = 1.45 [1.09-1.92], and OR = 0.64 [0.41-0.98]). ASAH1-rs7830490 and its interaction with NGF-rs4332358 were associated with the general psychopathological subscale score (F adjusted = 3.94, p adjusted = 0.01; F adjusted = 2.36, p adjusted = 0.03). We also found that ASAH1 and NGF interacted with CaMK2B involving in the neurotrophin signaling pathway. Our results suggest that the interaction of ASAH1 and NGF with CaMK2B involved in neurotrophin signaling pathway may contribute to schizophrenia susceptibility and psychopathology.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Su Y,Yang L,Li Z,Wang W,Xing M,Fang Y,Cheng Y,Lin GN,Cui D

doi

10.1016/j.pnpbp.2020.110015

subject

Has Abstract

pub_date

2021-01-10 00:00:00

pages

110015

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(20)30331-6

journal_volume

104

pub_type

杂志文章

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The interaction of ASAH1 and NGF gene involving in neurotrophin signaling pathway contributes to schizophrenia susceptibility and psychopathology.