Association of SOX11 Polymorphisms in distal 3'UTR with Susceptibility for Schizophrenia.
3' Untranslated Regions
/ genetics
Adolescent
Adult
Asian People
/ genetics
Case-Control Studies
Cell Line, Tumor
China
Female
Genetic Predisposition to Disease
/ genetics
Genome-Wide Association Study
Humans
Linkage Disequilibrium
Male
Polymorphism, Single Nucleotide
/ genetics
SOXC Transcription Factors
/ genetics
Schizophrenia
/ genetics
Young Adult
SOX11
association
neurodevelopment
schizophrenia
single-nucleotide polymorphism (SNP)
Journal
Journal of clinical laboratory analysis
ISSN: 1098-2825
Titre abrégé: J Clin Lab Anal
Pays: United States
ID NLM: 8801384
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
30
12
2019
revised:
26
02
2020
accepted:
29
02
2020
pubmed:
25
3
2020
medline:
23
6
2021
entrez:
25
3
2020
Statut:
ppublish
Résumé
Diverse and circumstantial evidence suggests that schizophrenia is a neurodevelopmental disorder. Genes contributing to neurodevelopment may be potential candidates for schizophrenia. The human SOX11 gene is a member of the developmentally essential SOX (Sry-related HMG box) transcription factor gene family and mapped to chromosome 2p, a potential candidate region for schizophrenia. Our previous genome-wide association study (GWAS) implicated an involvement of SOX11 with schizophrenia in a Chinese Han population. To further investigate the association between SOX11 polymorphisms and schizophrenia, we performed an independent replication case-control association study in a sample including 768 cases and 1348 controls. After Bonferroni correction, four SNPs in SOX11 distal 3'UTR significantly associated with schizophrenia in the allele frequencies: rs16864067 (allelic P = .0022), rs12478711 (allelic P = .0009), rs2564045 (allelic P = .0027), and rs2252087 (allelic P = .0025). The haplotype analysis of the selected SNPs showed different haplotype frequencies for two blocks (rs4371338-rs7596062-rs16864067-rs12478711 and rs2564045-rs2252087-rs2564055-rs1366733) between cases and controls. Further luciferase assay and electrophoretic mobility shift assay (EMSA) revealed the schizophrenia-associated SOX11 SNPs may influence SOX11 gene expression, and the risk and non-risk alleles may have different affinity to certain transcription factors and can recruit divergent factors. Our results suggest SOX11 as a susceptibility gene for schizophrenia, and SOX11 polymorphisms and haplotypes in the distal 3'UTR of the gene might modulate transcriptional activity by serving as cis-regulatory elements and recruiting transcriptional activators or repressors. Also, these SNPs may potentiate as diagnostic markers for the disease.
Sections du résumé
BACKGROUND
BACKGROUND
Diverse and circumstantial evidence suggests that schizophrenia is a neurodevelopmental disorder. Genes contributing to neurodevelopment may be potential candidates for schizophrenia. The human SOX11 gene is a member of the developmentally essential SOX (Sry-related HMG box) transcription factor gene family and mapped to chromosome 2p, a potential candidate region for schizophrenia.
METHODS
METHODS
Our previous genome-wide association study (GWAS) implicated an involvement of SOX11 with schizophrenia in a Chinese Han population. To further investigate the association between SOX11 polymorphisms and schizophrenia, we performed an independent replication case-control association study in a sample including 768 cases and 1348 controls.
RESULTS
RESULTS
After Bonferroni correction, four SNPs in SOX11 distal 3'UTR significantly associated with schizophrenia in the allele frequencies: rs16864067 (allelic P = .0022), rs12478711 (allelic P = .0009), rs2564045 (allelic P = .0027), and rs2252087 (allelic P = .0025). The haplotype analysis of the selected SNPs showed different haplotype frequencies for two blocks (rs4371338-rs7596062-rs16864067-rs12478711 and rs2564045-rs2252087-rs2564055-rs1366733) between cases and controls. Further luciferase assay and electrophoretic mobility shift assay (EMSA) revealed the schizophrenia-associated SOX11 SNPs may influence SOX11 gene expression, and the risk and non-risk alleles may have different affinity to certain transcription factors and can recruit divergent factors.
CONCLUSIONS
CONCLUSIONS
Our results suggest SOX11 as a susceptibility gene for schizophrenia, and SOX11 polymorphisms and haplotypes in the distal 3'UTR of the gene might modulate transcriptional activity by serving as cis-regulatory elements and recruiting transcriptional activators or repressors. Also, these SNPs may potentiate as diagnostic markers for the disease.
Identifiants
pubmed: 32207210
doi: 10.1002/jcla.23306
pmc: PMC7439430
doi:
Substances chimiques
3' Untranslated Regions
0
SOX11 protein, human
0
SOXC Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23306Subventions
Organisme : Natural Science Foundation of Liaoning Province, China
ID : 2019-ZD-0938
Organisme : National Natural Science Foundation of China
ID : 31500764
Organisme : the National Natural Science Foundation of China
ID : 81601174
Informations de copyright
© 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.
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