Unrevealing the shared genetic mechanisms underlying C-reactive protein and schizophrenia

Zihao Yang; David Li; Ying He; Xiaogang Chen; Zongchang Li

doi:10.1016/j.pnpbp.2023.110785

Unrevealing the shared genetic mechanisms underlying C-reactive protein and schizophrenia

Prog Neuropsychopharmacol Biol Psychiatry. 2023 Aug 30:126:110785. doi: 10.1016/j.pnpbp.2023.110785. Epub 2023 May 5.

Authors

Zihao Yang¹, David Li¹, Ying He², Xiaogang Chen², Zongchang Li³

Affiliations

¹ Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital, Central South University, Changsha, PR China.
² Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital, Central South University, Changsha, PR China; China National Technology Institute on Mental Disorders & Hunan Key Laboratory of Psychiatry and Mental Health, Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, PR China.
³ Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital, Central South University, Changsha, PR China; China National Technology Institute on Mental Disorders & Hunan Key Laboratory of Psychiatry and Mental Health, Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, PR China. Electronic address: zongchangli@csu.edu.cn.

PMID: 37150315
DOI: 10.1016/j.pnpbp.2023.110785

Abstract

Longitudinal observational studies and Mendelian randomization research have obtained contradictory conclusions regarding the association between C-reactive protein (CRP) level and schizophrenia risk. However, the shared genetic mechanisms underlying CRP and schizophrenia remain poorly understood. Here, we examined the global and local genetic correlations using summary statistics from large-scale genome-wide association studies (GWAS) on CRP level and schizophrenia. Furthermore, we identified their shared genetic variants by applying the conditional false discovery rate approach and performed functional analyses of shared variants to explore the shared genetic mechanisms underlying CRP level and schizophrenia. We found a significant negative genetic correlation at the whole genome level and five significant local genetic correlations between CRP level and schizophrenia. Eight-three shared genetic loci were identified, from which single-nucleotide polymorphism (SNP) presents mixed effects on the increased CRP level and schizophrenia risk. Additionally, we identified 64 and 73 candidate genes that were mapped from SNPs with"concordant effect"(ceSNPs) and"discordant effect"(deSNPs) on the CRP level and schizophrenia risk respectively. Functional analyses revealed that genes mapped from ceSNPs and deSNPs exhibited similar patterns of human brain developmental expression trajectories and biological processes, but differed in expression levels and cell-type-specific enrichment in brain tissues. Our findings demonstrated mixed effects of shared genetic architecture between CRP level and schizophrenia, proving a deeper insight into the shared genetic aetiology underlying the CRP level and schizophrenia.

Keywords: CRP; Genetic correlation; Schizophrenia; Shared genetic mechanisms.

MeSH terms

C-Reactive Protein* / genetics
C-Reactive Protein* / metabolism
Genetic Loci
Genetic Predisposition to Disease / genetics
Genome-Wide Association Study
Humans
Polymorphism, Single Nucleotide / genetics
Schizophrenia* / genetics

Substances

C-Reactive Protein