The SFT2D2 gene is associated with the autoimmune pathology of schizophrenia in a Chinese population

Duilin Liu; Lin Wu; Hui Wei; Caiyun Zhu; Runhui Tian; Wanwan Zhu; Qi Xu

doi:10.3389/fneur.2022.1037777

The SFT2D2 gene is associated with the autoimmune pathology of schizophrenia in a Chinese population

Front Neurol. 2022 Dec 21:13:1037777. doi: 10.3389/fneur.2022.1037777. eCollection 2022.

Authors

Duilin Liu¹, Lin Wu^{1

2}, Hui Wei^{1

3}, Caiyun Zhu^{1

3}, Runhui Tian⁴, Wanwan Zhu^{1

3}, Qi Xu^{1

3}

Affiliations

¹ State Key Laboratory of Medical Molecular Biology, School of Basic Medicine Peking Union Medical College, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Beijing, China.
² Laboratory of Molecular Diagnostics, Beijing Boren Hospital, Beijing, China.
³ Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, China.
⁴ Mental Health Center, The First Bethune Hospital of Jilin University, Changchun, China.

Abstract

Background: The relative risk of GWAS-confirmed loci strongly associated with schizophrenia may be underestimated due to the decay of linkage disequilibrium between index SNPs and causal variants. This study is aimed to investigate schizophrenia-associated signals detected in the 1q24-25 region in order to identify a causal variant in LD with GWAS index SNPs, and the potential biological functions of the risk gene.

Methods: Re-genotyping analysis was performed in the 1q24-25 region that harbors three GWAS index SNPs associated with schizophrenia (rs10489202, rs11586522, and rs6670165) in total of 9801 case-control subjects of Chinese Han origin. Circulating autoantibody levels were assessed using an in-house ELISA against a protein derived fragment encoded by SFT2D2 in total of 682 plasma samples.

Results: A rare variant (rs532193193) in the SFT2D2 locus was identified to be strongly associated with schizophrenia. Compared with control subjects, patients with schizophrenia showed increased anti-SFT2D2 IgG levels. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve (AUC) of 0.803 with sensitivity of 28.57% against specificity of 95% for the anti-SFT2D2 IgG assay.

Discussion: Our findings indicate that SFT2D2 is a novel gene for risk of schizophrenia, while endogenous anti-SFT2D2 IgG may underlie the pathophysiology of the immunological aspects of schizophrenia.

Keywords: GWAS; SFT2D2; autoantibody; re-genotying; schizophrenia.