CSMD1 rs10503253 increases schizophrenia risk in a Tunisian population-group

Ons Mihoub; Arij Ben Chaaben; Wahid Boukouaci; Mohamed Lajnef; Fayza Ayari; Hamdi El Kefi; Hanen Ben Ammar; Hajer Abazza; Zouhair El Hechmi; Fathi Guemira; Marion Leboyer; Ryad Tamouza; Maher Kharrat

doi:10.1016/j.encep.2023.08.002

CSMD1 rs10503253 increases schizophrenia risk in a Tunisian population-group

Encephale. 2023 Sep 23:S0013-7006(23)00146-X. doi: 10.1016/j.encep.2023.08.002. Online ahead of print.

Authors

Affiliations

¹ Laboratory of Human Genetics (LR99ES10), Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia; Inserm U955 IMRB, Translational Neuropsychiatry Laboratory and Paris-Est Créteil University, 94010 Créteil, France. Electronic address: ons.mihoub@etudiant-fmt.utm.tn.
² Laboratory of Human Genetics (LR99ES10), Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.
³ Inserm U955 IMRB, Translational Neuropsychiatry Laboratory and Paris-Est Créteil University, 94010 Créteil, France.
⁴ Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia.
⁵ Department of Psychiatry, Military Hospital of Tunis, Tunis, Tunisia.
⁶ Department of Psychiatry F, Razi Hospital, Mannouba, Tunisia.
⁷ Inserm U955 IMRB, Translational Neuropsychiatry Laboratory, AP-HP, DMU IMPACT, Fédération Hospitalo-Universitaire de médecine de précision en psychiatrie (FHU ADAPT), Paris Est Créteil University and Fondation Fondamental, 94010 Créteil, France.

PMID: 37748985
DOI: 10.1016/j.encep.2023.08.002

Abstract

Objectives: Schizophrenia is a complex and chronic neuropsychiatric disorder. Recent genome-wide association studies have identified several at risk genetic variants, including two single nucleotide polymorphisms, namely the rs10503253 and the rs1270942 respectively located in the CSMD1 and the CFB loci. The present case-control study was designed to assess potential associations between the two variants and the risk of developing schizophrenia and disease severity. Further we demonstrate the relationship between these variants and clinical characteristics in a population-group from Tunisia.

Patients and methods: In total, 216 patients diagnosed with schizophrenia along with176 healthy controls were included in this case-control study. The molecular analysis of the two polymorphisms was performed using tetra the Primer Amplification Refractory Mutation System-Polymerase Chain method. The statistical analysis was done using Compare V2.1 software, and correlations between genetic results and clinical characteristics were examined by Kruskal-Wallis testing.

Results: The frequency of the rs10503253A allele was found significantly higher among patients with schizophrenia as compared to healthy controls and associated with high negative PANSS scores. While no association was found concerning the implication of the rs1270942 variant in schizophrenia risk, a positive correlation with high positive PANSS scores was further observed.

Conclusion: The present finding confirms the previously reported association between the Cub and Sushi multiple Domain 1 rs10503253A allele and the risk to develop schizophrenia and identified the rs1270942 variant as a potential disease risk modifier. Such observations may be important for the definition of the susceptible immunogenetic background in North African individuals at risk to develop mental disorders.

Keywords: CFB; CSMD1; Complement system; Polymorphism; Polymorphisme; Schizophrenia; Schizophrénie; Système complément.