rs13211507

A case-control study of 2,019 schizophrenia patients and 2,579 Japanese controls found the rs12807809-rs12278912 haplotype in the NRGN gene (chromosome 11q24.2) significantly associated with schizophrenia (global P = 0.0042). The TG haplotype was associated with increased risk (OR = 1.14, P = 0.0019), while the TA haplotype was protective (OR = 0.85, P = 0.0053). Gene expression analysis demonstrated the high-risk TG haplotype had significantly lower NRGN expression than the protective TA haplotype (P = 0.007 in HapMap samples, P = 0.002 in combined case-control samples).

This comprehensive review examines the genomics of schizophrenia and pharmacogenomics of antipsychotic drugs, synthesizing evidence on over 200 genes associated with psychotic disorders. The authors discuss five categories of genes relevant to antipsychotic response: disease-associated genes, mechanism-of-action genes, drug metabolism genes (particularly CYP2D6, CYP2C19, CYP2C9, CYP3A4), drug transporter genes, and pleiotropic genes. The review details pharmacogenomic profiles of 20+ antipsychotic drugs and demonstrates significant ethnic and interindividual variation in drug metabolism phenotypes, with examples including CYP2D6 extensive metabolizers (55.71% of population), intermediate metabolizers (34.7%), poor metabolizers (2.28%), and ultra-rapid metabolizers (7.31%).

This review comprehensively summarizes the latest genetic studies on schizophrenia, including family studies (heritability ~80%), genome-wide association studies, epigenetic mechanisms, candidate gene investigations, and next-generation sequencing findings. Key GWAS findings identified 108 schizophrenia-associated loci including variants in MIR137 (rs1625579), TCF4 (rs12966547), CSMD1 (rs10503253), CACNA1C (rs4765905), ANK3 (rs10761482), and MHC region variants, with evidence for polygenetic inheritance involving both common SNPs and rare copy number variations.

This comprehensive review synthesizes genomic and pharmacogenomic research in schizophrenia, discussing over 200 candidate genes associated with psychotic disorders, genetic mechanisms including copy number variants and microRNA alterations, and pharmacogenomic factors affecting antipsychotic efficacy and safety. Key genes covered include dopamine receptors (DRD1-5), dysbindin (DTNBP1), DISC1, neurotrophic factors, and metabolic enzymes such as CYP2D6, CYP3A4, and COMT, with emphasis on genotype-phenotype correlations in antipsychotic response and side effects.