Non-carriers of the CHRM1 rs2075748-T and rs1942499-A haplotype have normal levels of transcription of the CHRM1 gene and expression of the M1R, which leads to greater sensitivity to variations in CLZ/NDMC ratio, which consequently affects working memory processes. Carriers of CHRM1 rs2075748-T and rs1942499-A haplotype have lower transcription of the CHRM1 gene and expression of M1R, leading to faster saturation of CLZ and NDMC binding sites on the M1R prior to reaching clinically detectable effects of CLZ/NDMC ratio on working memory processes.

CHRM1: muscarinic acetylcholine receptor M1; CLZ: clozapine; M1R: M1 muscarinic acetylcholine receptor; NDMC: N-desmethylclozapine.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart for identifying clinical studies included in this meta-analysis.

PGx findings for antipsychotic response and adverse effects are summarized here.

a Complete gene names can be found in Table S2 of the Supplementary Materials. b Association between gene variant and the phenotype reported by at least one study.