Association of SOX11 Polymorphisms in distal 3 ' UTR with Susceptibility for Schizophrenia

Cheng-Peng Sun, Dong Sun, Zhi-Lin Luan*, Xin Dai, Xu Bie, Wen-Hua Ming, Xiao-Wan Sun, Xiao-Xiao Huo, Tian-Lan Lu, Dai Zhang

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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    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 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 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 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.

    Original languageEnglish
    Article number23306
    Number of pages11
    JournalJournal of clinical laboratory analysis
    Issue number8
    Publication statusPublished - Aug-2020


    • association
    • neurodevelopment
    • schizophrenia
    • single-nucleotide polymorphism (SNP)
    • SOX11
    • SHESIS

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